JPH11309355A - Polysulfone hollow fiber type blood purifying membrane and its production - Google Patents

Abstract

PROBLEM TO BE SOLVED: To prepare a polysulfone blood purifying membrane improved in biocompalibility, extremely reduced in the elution of polyvinyl pyrrolidone on the inner surface side of hollow fiber and improve in separation characteristics. SOLUTION: In a polysulfone hollow fiber type blood purifying membrane, a selective separation layer having separation function substantially is present on the inner surface side of each hollow fiber membrane and contains 1-10 wt.% of polyvinyl pyrrolidone wherein 5-50% thereof is soluble in water and the concn. thereof of an inner surface is 30-45%. This polysulfone hollow fiber type blood purifying membrane is a hollow fiber membrane improved in blood compatibility, extremely reduced in the elution of polyvinyl pyrrolidone to a blood side and excellent in mol.wt. fractionality. By this constitution, an artificial kidney extremly significant in future dialytic treatment can be provided.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a polysulfone-based hollow fiber type blood purification membrane and a method for producing the same. More specifically, the present invention relates to a polysulfone blood purification membrane having improved blood compatibility and separation characteristics, and a method for producing the same.

[0002]

2. Description of the Related Art In recent years, ultrafiltration, reverse osmosis, gas separation, and the like, which are separation techniques using a selectively permeable separation membrane, have been put to practical use in various fields, and are suitable for various uses. Separation membranes made from materials are commercially available. As the material of the permselective separation membrane, polymers such as cellulose, cellulose acetate, polyamide, polyacrylonitrile, polyvinyl alcohol, polymethyl methacrylate, polysulfone, and polyolefin polymers are used. Among them, polysulfone-based polymers have attracted attention as medical and industrial separation membrane materials in recent years because of their excellent physicochemical properties such as heat resistance, acid resistance, alkali resistance, and oxidation resistance.

However, since a polysulfone-based polymer is a hydrophobic material, a permselective separation membrane made of the polysulfone-based polymer has better water wettability than a permselective separation membrane made of a hydrophilic polymer. Absent. Therefore, in the case of medical use, it is pointed out that plasma proteins are easily adsorbed, and air bubbles remaining in the membrane escape to the blood due to poor air bubbles, and blood coagulation occurs by activating platelets. Have been.

[0004] Therefore, studies have been made to improve the water wettability by imparting hydrophilicity to a permselective separation membrane made of a polysulfone-based polymer. As one method, a hydrophilic polymer is contained in a polysulfone-based polymer. In addition, a permselective separation membrane and a method for producing the same have been proposed. But,
When the content of the hydrophilic polymer is low, the water wettability deteriorates, causing blood coagulation. Conversely, when the content of the hydrophilic polymer is high, the amount of the hydrophilic polymer eluted from the membrane after film formation increases. There is a problem.

JP-A-61-238306, 63-9
No. 7666 discloses a method for producing a polysulfone-based separation membrane using a polysulfone-based polymer, a hydrophilic polymer, and a system in which an additive such as a non-solvent or a swelling agent is added to the polysulfone-based polymer as a stock solution. But
There is no description of a method for reducing elution of a hydrophilic polymer.
Also, JP-A-63-97205 and JP-A-63-97634.
JP-A-4-300636 discloses that a hydrophilic polymer is insolubilized by subjecting a polysulfone-based separation membrane produced by the above method to radiation treatment and / or heat treatment.
A method for reducing elution of a hydrophilic polymer is disclosed. However, the blood compatibility is deteriorated probably because the hydrophilic polymer is insolubilized by the crosslinking.

JP-A-6-165926 discloses that a polysulfone hollow fiber membrane containing a polyglycol and a vinylpyrrolidone polymer is washed with water and hot water, and treated with a solution having a poor solvent action on the polysulfone polymer. And producing a hollow fiber membrane. However, treatment with a solvent having this poor solvent action is 9
It is performed at 0 ° C., and extraction and removal are not enough.

Regarding the spinning draft, Japanese Patent Publication No. 5-54
No. 373, which contains 1 to 10% by weight of a hydrophilic polymer produced by spinning a low-viscosity stock solution comprising a hydrophobic polymer, a hydrophilic polymer, and a common solvent thereof;
A process for producing hollow fibers for blood treatment having a water absorption capacity of 吸 10% is disclosed, in which the speed of the spinning composition leaving the spinneret and the speed of taking off the produced fibers are the same, ie spinning. It is preferable that the draft rate is 1. However, if the draft rate is actually 1,
It is difficult to increase the spinning speed. If the discharge rate of the stock solution is increased to increase the spinning speed, the pressure loss of the spinneret will increase,
The discharge linear velocity of the spinning dope increases, and uneven discharge of the spinning dope is likely to occur, causing problems such as instability of spinning and disturbance of the membrane structure. In addition, Japanese Patent Laid-Open No. 6-1
No. 65926 states that if the nozzle draft is extremely increased or decreased, the structure becomes unstable. Therefore, the nozzle draft is usually set in the range of 2 to 5, but if the draft rate exceeds 2, the nozzle draft becomes hollow. Problems have been pointed out, such as a structure in which the inner surface of the yarn is torn, and albumin, which is a useful protein, tends to leak.

In recent years, as the cause of dialysis complication, beta ₂ - microglobulin (β ₂ -MG) and low molecular protein include a high-performance dialysis membrane which they can be removed efficiently from the blood is desired . In the above-mentioned conventional techniques, sufficient studies have not been made on the fractionation properties, and they are not always satisfactory. That is, if the permeation performance of the membrane is increased to improve the removal of low-molecular proteins, leakage of useful proteins such as albumin becomes a problem.

[0009]

DISCLOSURE OF THE INVENTION The present invention has solved the problems of the prior art, has improved blood compatibility, and has very little elution of polyvinylpyrrolidone to the inner surface of the hollow fiber membrane.
Moreover, it is an object of the present invention to provide a polysulfone-based blood purification membrane having improved separation characteristics of the membrane and a method for producing the same.

[0010]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies to achieve the above object, and as a result, found that a hollow fiber type polysulfone-based hollow fiber type blood purification membrane containing polyvinylpyrrolidone (hereinafter referred to as PVP) contains PVP. Is made insoluble in water and the PVP concentration on the inner surface of the hollow fiber membrane is adjusted appropriately, so that the elution of PVP from the inner surface is small, blood compatibility is excellent, and the hollow fiber is clean. It has been found that a membrane can be provided. Also, PVP with a suitable solvent
Was extracted to wash the hollow fiber membrane, and it was found that a clean hollow fiber membrane with less PVP elution from the inner surface could be provided. Furthermore, by spinning from an undiluted spinning solution having an appropriate viscosity at an appropriate spinning draft rate, the thickness of a selective separation layer having an effect of substantially sifting solute molecules in a membrane can be appropriately controlled, and a hollow layer can be formed. It has been found that a polysulfone-based blood purification membrane having a sharp fractionation property, which has no tearing structure on the inner surface of the fibrous membrane and can efficiently remove unnecessary substances and recover useful substances efficiently.

That is, according to the present invention, a selective separation layer having a substantial separation function is present on the inner surface side of the hollow fiber membrane, and
In a polysulfone-based hollow fiber type blood purification membrane containing polyvinylpyrrolidone, 1 to 10% by weight of polyvinylpyrrolidone is contained, 5 to 50% of the polyvinylpyrrolidone is soluble in water, and polyvinylpyrrolidone on the inner surface is Is a polysulfone blood purification membrane characterized by having a concentration of 30% to 45%.

The present invention also comprises a polysulfone-based polymer in an amount of 15 to 20% by weight and a weight ratio of polyvinylpyrrolidone to the polysulfone-based polymer of 0.25 to 0.25.
After spinning a hollow fiber membrane using a polymer solution of 0.5 to 0.5, and insolubilizing a part of polyvinylpyrrolidone in the hollow fiber membrane by a physicochemical method. This is a method for producing a purification membrane.

According to the present invention, the hollow fiber membrane after spinning is further washed by extracting polyvinylpyrrolidone with a solvent that dissolves polyvinylpyrrolidone or an alcoholic solvent that is a mixed solvent of a good solvent and a poor solvent for the polysulfone polymer. A method for producing a polysulfone blood purification membrane, characterized in that a polysulfone polymer and polyvinylpyrrolidone dissolved in a common solvent have a viscosity of 150.
A spinning dope of 0 to 6000 mPa · s was drafted at a draft rate of 1.
A method for producing a polysulfone-based hollow fiber type blood purification membrane, comprising spinning at a discharge linear velocity of 90 m / min or less at 1 to 1.9. Hereinafter, the present invention will be described in detail.

The polysulfone-based polymer referred to in the present invention is a general term for a polymer compound having a sulfone bond and is not particularly limited.

Embedded image

Embedded image The polysulfone-based polymer resin having a repeating unit shown in (1) is widely commercially available and is preferably used because it is easily available. The former polysulfone resin is available from Amoco Performance Products, Inc.
Is sold under the trade name of "Ultrazone" by BSF Inc. There are several types depending on the degree of polymerization and the like.

The PVP of the present invention is a water-soluble polymer compound obtained by vinyl-polymerizing N-vinylpyrrolidone, and is a trade name of "Plasdone" by IS P. "Koridon" from S.F.
There are polyvinylpyrrolidone of several molecular weights each, marketed under the trade name. If the PVP content in the hollow fiber membrane is low, the PVP on the inner surface of the hollow fiber membrane that comes into contact with blood
Since the concentration does not increase and the hydrophilicity of the membrane deteriorates, blood coagulation tends to occur when it comes into contact with blood. As described later, the PVP content in the hollow fiber membrane can be increased by increasing the PVP concentration in the polymer solution used for spinning, but the viscosity of the polymer solution increases and spinning becomes impossible. For this reason, in the present invention, PVP is 1 to 1 in the hollow fiber membrane.
It is contained in the hollow fiber membrane in the range of 0% by weight. Preferably it is in the range of 2.5 to 8% by weight.

The PVP content in the hollow fiber membrane can be easily calculated from the elemental analysis values of nitrogen and sulfur. The hollow fiber membrane was analyzed by pyrolysis gas chromatography,
It can also be easily obtained by analyzing the peak derived from P. PVP is a polymer that is easily soluble in water, and easily elutes from the hollow fiber membrane into water or blood. When all the contained PVP is insolubilized, the elution from the hollow fiber membrane is completely eliminated, but the effect of hydrophilizing the membrane surface is weakened. For this reason, in the present invention, a part of PVP is insolubilized by crosslinking, and the amount of PVP soluble in water is 5 to 50% of the total amount contained in the hollow fiber membrane. Within this range, elution from the hollow fiber membrane is suppressed, and the effect of hydrophilizing the membrane surface is maintained.

The amount of PVP that is soluble in water is the amount of PVP in the membrane that has not been insolubilized by crosslinking, and is determined as follows. That is, the hollow fiber membrane was changed to N-methyl-2-
Dissolve completely with pyrrolidone. Next, water is added to the polymer solution to precipitate a polysulfone-based polymer. After standing, the amount of PVP in the resulting supernatant is quantified by liquid chromatography. An important factor for the blood compatibility of the hollow fiber membrane is the hydrophilicity of the membrane surface, and in a polysulfone-based hollow fiber membrane containing PVP, the PVP concentration on the inner surface of the membrane is important. If the surface PVP concentration is too low, the membrane surface becomes hydrophobic, plasma proteins are easily adsorbed, and blood is easily coagulated. That is, blood compatibility becomes poor. Conversely, if the surface PVP concentration is too high, the amount of PVP eluted into blood or the like increases, giving undesired results for the purposes and applications of the present invention. Therefore, the concentration of the inner surface PVP in the present invention is in the range of 30% to 45%, preferably 33%.
４０40%.

The PVP concentration on the inner surface of the hollow fiber membrane is determined by X-ray photoelectron spectroscopy (ESCA). In other words, the ESCA measurement of the inner surface of the hollow fiber membrane was performed by arranging the samples on a double-sided tape, cutting them in the direction of the fiber axis with a cutter, and expanding the hollow fiber membrane so that the inside faced up. And measure by the usual method. That is, C1s, O1
From the area intensities of the s, N1s, and S2p spectra, the surface concentration of nitrogen (A) and the surface concentration of sulfur (B) were determined using a relative sensitivity coefficient attached to the apparatus. Surface PVP concentration = A × 100 / (A × 111 + B) × 44
2) Calculate the surface PVP concentration from the above.

In the present invention, the elution of PVP from the hollow fiber membrane is evaluated by the elution amount when the inner surface of the hollow fiber membrane is circulated and extracted with a 40% aqueous ethanol solution. Specifically, it is evaluated by incorporating a hollow fiber membrane into a module, circulating a 40% aqueous ethanol solution on the blood side at 37 ° C. for 4 hours, and measuring the amount of extracted PVP. 37 as an extraction medium
Although blood at ° C. is appropriate, the amount of eluted hydrophilic polymer is too small and the amount of interfering substances is large, so that it is difficult to quantify the extracted PVP. As an extraction medium, water also has a weak extraction power, and it is difficult to determine the amount of PVP to be extracted. A 40% aqueous ethanol solution is suitable as the extraction medium.

In the present invention, as described above, a part of PVP is insolubilized by crosslinking, and elution from the hollow fiber membrane is suppressed. Furthermore, in the present invention, elution of PVP from the hollow fiber membrane is suppressed, and the amount of polyvinylpyrrolidone eluted when the inside of the hollow fiber membrane is circulated and extracted with a 40% alcohol aqueous solution is 0.5 mg or less per 1 m ^{2 of} membrane area. More preferably, there is. Such a hollow fiber membrane can be obtained as follows.

The polysulfone-based hollow fiber type blood purification membrane of the present invention is formed by a dry-wet spinning method described later. In the membrane immediately after spinning, (a) PVP which exists between polysulfone-based polymer particles and is easily removed by water washing or hot water washing,
(B) PV that is weakly bite into polysulfone-based polymer particles and is difficult to remove by water washing or hot water washing, but can be eluted
It is presumed that P and (c) PVP that bites into the polysulfone-based polymer particles and is not extracted and removed exists. In the conventional technique, even if the (a) type PVP can be removed by washing, the (b) type PVP is not sufficiently removed, and the PVP that has not been insolubilized from the membrane in use gradually decreases. It is thought to elute. In the present invention, in order to reduce the elution of PVP from the membrane, (b)
A method for cleaning and removing as much as possible the type of PVP is proposed.

The first method of washing and removing according to the present invention is a method of washing the formed polysulfone hollow fiber membrane with a mixed solvent of a good solvent and a poor solvent for the polysulfone polymer. As a matter of course, this mixed solvent has a mixing ratio set within a range that does not dissolve the polysulfone-based polymer, and dissolves PVP that has not been insolubilized. In such a mixed solvent, the polysulfone-based polymer particles cause swelling action, soften the polysulfone-based polymer in the surface layer of the membrane, and improve the flow diffusion property of PVP. It is considered that the inside of the membrane can be cleaned by pulling out, and as a result, elution can be highly reduced.

As good solvents for the polysulfone polymer used in the first method, dimethylacetamide (hereinafter referred to as DMAC), N-methyl-2-pyrrolidone,
Dimethyl sulfoxide (hereinafter, referred to as DMSO), dimethylformamide and the like can be exemplified, and they are used alone or as a mixture. Among them, DMAC and / or DMSO are preferably used. Examples of the poor solvent for the polysulfone-based polymer include water, isopropyl alcohol, ethanol, propylpropylene glycol, and tetraethylene glycol. Among them, water is preferably used. The mixing ratio of the good solvent and the poor solvent of the polysulfone polymer cannot be unconditionally determined because the conditions differ depending on the type of the solvent or the processing temperature, but the good solvent of the polysulfone polymer is used as 30 to 95% by weight. Is preferred. For example, 30-60% by weight of DMAC
An aqueous solution, a 30 to 60% by weight aqueous solution of N-methylpyrrolidone, a 50 to 95% by weight aqueous solution of DMSO, and the like are used. In addition, a good solvent for the polysulfone polymer and a poor solvent for the polysulfone polymer do not need to be used alone,
A mixed solution of a mixture of two or more good solvents and poor solvents may be used. The treatment temperature may be any temperature, but when an aqueous solution of a good solvent for the polysulfone polymer is used, the boiling point of water or lower is desired for operation,
10-98 degreeC is a preferable range, 30-98 degreeC is more preferable, and 50-95 degreeC is desirable.

The second method of washing and removing according to the present invention is a method of washing the formed polysulfone-based hollow fiber membrane with a high-temperature alcohol-based solvent. The polysulfone-based polymer particles constituting the membrane swell, weakly incorporated PVP is easily released, and the diffusion rate of PVP increases. For this reason, it is presumed that PVP which is difficult to remove by the water washing or hot water washing treatment is removed by washing. Therefore, when the processing temperature is low, cleaning and removal become insufficient, and a higher one is desired,
If it is too high, a change in the film structure occurs and the film performance fluctuates.
Therefore, in the present invention, a cleaning treatment at 130 to 160 ° C. is desired. Preferably it is 135-155 degreeC, More preferably, it is 140-150 degreeC.

The alcohol solvent that can be used in the present invention includes:
All PVP good solvents having a swelling effect on the polysulfone-based polymer can be mentioned, but an alcohol-based solvent having a boiling point or decomposition point of 130 ° C. or higher is preferred from the viewpoint of simplicity of operation and equipment. Among them, glycerin is preferably used. The water content of the alcohol-based solvent is preferably low, and 5% or less is recommended.
% Or less, and more preferably 0.5% or less. In both the first method and the second method, it is not necessary to use, as the formed polysulfone-based hollow fiber membrane, the one obtained by previously removing the easily removed PVP and the solvent of the spinning dope through a water washing or hot water washing step. It is presumed that even if the solvent of the spinning solution remains, it is more effective for the PVP to be washed and removed when the membrane is in an expanded state.

In both the first method and the second method, the following methods can be exemplified as processing methods. (1) The film is heated to an arbitrary temperature while the cleaning liquid is immersed.
(2) The film is immersed in the cleaning liquid adjusted to the set temperature.
(3) The cleaning liquid adjusted to the set temperature is showered on the membrane.
(4) Run the film in the cleaning solution adjusted to the set temperature.
Either method is possible, and it is sufficient that the formed polysulfone-based hollow fiber membrane is sufficiently brought into contact with the cleaning liquid adjusted to the set temperature. The processing time varies depending on the processing method, and is preferably 10 minutes or more, and more preferably 30 minutes or more in the methods (1) to (3), which are batch operations. In the continuous operation (4), the residence time needs to be 15 seconds or more, and more preferably 20 seconds or more. Naturally, the solvent used after the treatment is washed with water and / or
Alternatively, it is preferable to remove by washing with hot water.

When the inner surface of the polysulfone-based hollow fiber type blood purification membrane of the present invention is observed with a scanning electron microscope, the structure in which fibrous polysulfone-based polymers (fibrils) are gathered side by side in the hollow fiber axis direction. And there are gaps between fibrils in some places. As described below, the fibrils are torn between the fibrils depending on the conditions of the film formation, and the gaps become large. In a hollow fiber membrane having such an inner surface,
Loss of surface smoothness leads to poor blood compatibility, and also adversely affects solute molecule removal. Therefore, in the hollow fiber membrane of the present invention, 0.8 μm
It is desired not to have more than m torn gaps.

The sieving of solute molecules is determined by the size of the solute molecules and the pore size of the membrane. That is, solute molecules smaller than the pore size of the membrane can pass through the membrane, but solute molecules larger than the pore size of the membrane cannot. According to this principle, solute molecules are sieved. In the case of a membrane having a non-uniform membrane structure, sieving occurs when the pore diameter is reduced in the membrane cross-sectional direction, that is, in the selective separation layer according to the present invention. Generally, the pore size of the membrane is small at the dense structure of the polymer portion. Therefore, the selective separation layer in the present invention can be read from a transmission electron microscope image of the cross section of the membrane. That is, the transmission electron microscope image of the cross section of the film is sectioned at a certain width, and image analysis is performed to determine the ratio (tissue ratio) occupied by the polymer portion. When this operation is performed from the inside of the hollow fiber membrane to the outside of the hollow fiber membrane, the distribution of the tissue ratio in the cross section direction of the hollow fiber membrane becomes clear. As will be described later, there is a pore size distribution in the membrane. In consideration of this, in the present invention, when the image analysis is performed on the selective separation layer with the width of the image analysis being 0.5 to 1.0 μm, the highest tissue ratio is obtained. From the value that was high, it was defined as a part within 30%, and its thickness was measured.

The fractionation properties of the membrane are described by a multilayer structure model. That is, a structure in which a number of layers obtained by slicing the film in parallel to the film surface (and thus perpendicular to the film cross section) is stacked is assumed. It is considered that the solute molecules are sieved for each layer, and that the entire membrane is subjected to multi-stage filtration. The average pore size differs for each layer, but if one layer is taken up, there is a distribution of pore sizes in that layer, so only the layer with the smallest average pore size has the effect of sieving solutes. The layer having a slightly larger pore size can also capture large solute molecules that have passed through. In other words, a solute molecule that has passed through a large pore size layer in a layer having a small average pore size is sufficiently captured by pores having a slightly larger average pore size but smaller size than the solute molecule. Therefore, as the selective separation layer, a layer from the layer having the smallest average pore diameter to the layer having a slightly larger average pore diameter is effective.

The thickness of the selective separation layer is important for the sharpness of the fractionation characteristics. When the selective separation layer is thin, if the average pore size is slightly increased to improve the permeability of the removed substance,
Albumin, a useful plasma protein, is more easily permeated.
There is a pore size distribution in the selective separation layer. It is presumed that if the average pore size is increased, the number of pores through which albumin can permeate increases. When the selective separation layer is thin, there is no other selective separation layer that traps albumin that has once leaked from a portion having a large pore diameter, and thus the membrane permeates the membrane as it is. In addition, even when a structural defect occurs in the selective separation layer due to a slight change in spinning conditions or the like, leakage of a high molecular weight substance is particularly remarkable. On the other hand, when the selective separation layer is thick, even if the membrane structure is relatively loose, the thicker the thickness, the less the leakage of albumin, that is, the sharper the molecular weight fractionation characteristics. This is because the selective separation layer of the membrane is thick,
This is because even if albumin permeates in one layer, it is trapped in any layer of the selective separation layer, and as a result, the probability of permeation through the membrane decreases. However, if the selective separation layer is too thick, the transmission resistance becomes too large.
μm, more preferably 3 μm
To 12 μm, more preferably 5 μm to 10 μm.

Regarding the position of the selective separation layer, regardless of whether it is located inside the hollow fiber membrane, at the center of the cross section, or both inside the hollow fiber membrane and outside the hollow fiber membrane, Although good, generally, blood is flowed inside the hollow fiber membrane, and in order to prevent protein in the blood, which causes clogging of the membrane pores, from entering the membrane, in the present invention, the selective separation layer is formed by the hollow fiber membrane. It is preferably inside.

In forming the polysulfone-based hollow fiber type blood purification membrane in the present invention, a dry-wet membrane formation technique which is a generally known technique can be used. That is, first, both the polysulfone-based polymer and PVP are dissolved in a common solvent to prepare a uniform spinning solution. Examples of the common solvent in which both the polysulfone-based polymer and PVP are dissolved include, for example, various solvents such as DMAC, DMSO, N-methyl-2-pyrrolidone, dimethylformamide, sulfolane, dioxane, or a mixture of two or more of the above. A solvent consisting of Further, an additive such as water may be added to the spinning dope for controlling the pore size.

When the viscosity of the spinning stock solution is too low, large macrovoids appear remarkably inside the membrane. In the case of a hollow fiber membrane for blood purification, when a large number of such macrovoids are present, blood coagulation occurs during hemodialysis. This is likely to occur, and it is preferable that the hollow fiber membrane used for hemodialysis has no macrovoids. The macro void referred to here is a space having a maximum diameter of 5 μm in a space where no polymer exists in the film.
m or more. On the other hand, if the viscosity of the stock solution is too high, the pressure before the spinneret is too high, and stable spinning cannot be performed. Therefore, in the present invention, the viscosity of the spinning dope needs to be 1500 to 6000 mPa · s,
The range is preferably from 0 to 4000 mPa · s. The viscosity referred to in the present invention is a value obtained by measuring a spinning dope with a rotary viscometer at the same temperature as the spinneret temperature under film-forming conditions.

The viscosity of the spinning dope is determined by the molecular weight of PVP, the concentration of the polysulfone-based polymer and PVP in the spinning dope,
Each factor has a significant effect on the formation of the membrane structure, depending on the temperature of the spinning stock solution and the like. In the present invention, by appropriately selecting the raw materials to be used and setting the conditions of concentration and temperature,
Adjust the viscosity of the stock solution to the above range. If the amount of the polysulfone-based polymer resin added is too small, the formation of the film becomes difficult and the film strength becomes too weak, or if too large, phenomena such as poor spinnability and too small pore diameter occur, It is preferably 15 to 20% by weight,
More preferably, it is about 19% by weight. However, this range is not absolute, and depending on the properties of the target hollow fiber membrane, it can be made smaller or larger than this range, and the membrane properties change by changing other spinning conditions. Therefore, an optimal combination may be appropriately selected.

The purpose of adding PVP to the spinning dope is to leave PVP in the hollow fiber membrane to impart hydrophilicity to the membrane. Therefore, the molecular weight of the PVP used is important. In other words, if the molecular weight of PVP is too small, the PVP may be used at the time of coagulation of the spinning solution and at the time of washing the obtained hollow fiber membrane.
Since P is easily eluted from the membrane, it is necessary to add a larger amount of PVP to the spinning solution to leave PVP necessary for imparting hydrophilicity to the hollow fiber membrane in the hollow fiber membrane. Becomes Therefore, in order to increase the residual ratio of PVP in the hollow fiber membrane, it is preferable that the molecular weight is large, and the K-value defined by the following formula is 88 to 95, preferably 89 to 94.

[0036]

(Equation 1) Here, Z is the relative viscosity of the solution of concentration C, and C is the concentration of (weight / volume)%.

The polysulfone polymer in the spinning dope and P
The relative amount of VP is extremely important in determining the PVP concentration on the inner surface of the obtained hollow fiber membrane. Because, on the inner surface of the hollow fiber membrane, rapid solidification occurs due to the contact between the hollow inner solution and the spinning solution, and the ratio of the absolute amount of the polysulfone polymer and PVP present on the solidified surface is fixed to the inner surface as it is. This is because that. When the weight ratio of PVP to the polysulfone-based polymer in the spinning solution is too small,
Surface PVP concentration does not increase. If the weight ratio of PVP to the polysulfone-based polymer is too large, the strength of the membrane becomes weak, and the amount of PVP eluted from the membrane cannot be ignored. So, while maintaining the strength more than necessary,
When the PVP concentration on the inner surface of the hollow fiber is adjusted to 30% to 45%, the weight ratio of PVP to the polysulfone polymer in the spinning dope is 0.25 to 0.5, preferably 0.3 to 0.48. , More preferably 0.35
To 0.45.

As the hollow inner liquid, water or a coagulating liquid mainly composed of water can be used, and depending on the intended membrane performance of the hollow fiber membrane,
The composition and the like may be determined, and cannot be unconditionally determined. In general, a mixed solution of a solvent and water used for a stock spinning solution is suitably used. For example, 0-60% by weight of DM
An AC aqueous solution or the like is used, and particularly preferably 0 to 40% by weight. When forming a hollow fiber membrane, a tube-in-orifice-type double spinneret is used, and the spinning solution and the hollow inner solution for coagulating the spinning solution are simultaneously extruded from the spinneret into the air at 20 to 80 cm. And then immersed in a coagulation bath mainly composed of water placed below the spinneret, coagulated and wound.

The spinning draft rate referred to in the present invention is the ratio of the linear velocity at which the stock solution is discharged from the annular slit die of the tube-in-orifice type double spinning nozzle to the winding speed of the hollow fiber membrane. And a value obtained by dividing the winding speed by the linear discharge speed of the stock spinning solution. In the case of a low spin draft, the slit width of the spinneret needs to be reduced accordingly. In the case of a hollow fiber membrane for blood purification, the range of the film thickness usually used is 20 to 60 μm. Therefore, when the spinning draft rate is low, increasing the spinning speed increases the discharge linear velocity of the stock solution and increases the pressure loss at the spinneret, so that spinning tends to be unstable. In addition, since the discharge unevenness of the undiluted solution occurs, the film structure is disturbed, and the dispersion of the water permeability and the solute permeability is increased. Furthermore, problems are pointed out that the narrow slit width makes it difficult to align the spinneret, and that the spinneret itself becomes difficult to manufacture and costs high. Conversely, if the spinning draft is too high, that is, if the winding speed is too high relative to the linear discharge speed of the stock solution from the spinneret, the hollow fiber inner surface is strongly pulled while solidifying immediately below the spinneret. As a result, the dense layer on the inner surface of the membrane becomes torn, and a pore having a particularly large pore diameter is easily generated, which causes a problem of leakage of albumin, a useful protein. This problem can be improved to some extent, but not sufficiently, by reducing the viscosity of the stock solution by changing the composition of the stock solution or increasing the temperature of the stock solution. Therefore, in the present invention, the spinning draft rate needs to be 1.1 to 1.9, and is preferably in the range of 1.1 to 1.5.

The linear velocity at which the stock solution is discharged is the linear speed at which the stock solution is discharged from the spinneret during spinning, and the discharge flow rate of the stock solution per unit time is divided by the cross-sectional area of the stock solution discharged from the spinneret. Value. When the discharge linear velocity of the undiluted solution is increased, the ununiform discharge of the undiluted solution becomes large, and a hole having a large pore diameter is formed due to the unevenness of the structure of the film, thereby causing albumin leakage. In the present invention, the discharge linear velocity of the stock solution needs to be 90 m / min or less, and is 70 m / min.
min or less, and more preferably 60 m / min.
More preferably, it is not more than min.

In order to control the selective separation layer, the following film forming process is important. First, the type and concentration of the liquid in the hollow is important, and when the concentration of the solvent in the liquid in the hollow is increased, the coagulation force is weakened, so that the solidification proceeds slowly.
A dense cohesive structure cannot be obtained, and the selective separation layer has a sparse structure. Next, the viscosity of the spinning solution is important. If the viscosity is high, the movement of the polysulfone-based polymer during coagulation is suppressed, and the selective separation layer becomes thicker than when the viscosity is low under the same conditions. The viscosity of the spinning dope depends on the molecular weight of the hydrophilic polymer, the concentration of the polysulfone-based polymer and the hydrophilic polymer in the spinning dope, the temperature of the spinning dope, and all factors have a significant effect on the formation of the selective separation layer. Exert. Spinning draft is also an important factor, and in order to have a thick selective separation layer,
It is better to increase the spinning draft rate. Other factors influencing the formation of the selective separation layer include the distance between the spinneret and the free running section from the coagulation bath, the size of the spinneret, the temperature and composition of the coagulation bath, the spinning speed, and the solvent used for the spinning solution. However, it is necessary to set in consideration of the solute permeation performance and the purpose.

The hollow fiber membrane spun and wound as described above is post-treated by a known method. That is, the solvent and excess PVP are removed by washing with hot water or the like,
After giving glycerin as needed, it is dried by dry heat. Also, a method of winding the hollow fiber membrane after winding it after washing it with hot water or the like after drying and drying it with hot water instead of post-processing after winding it is also within the scope of the present invention. Is adjusted to 1500 to 6000 mPa · s, and the spinning draft is set to 1.1 to 1.9 or less under the condition that the discharge linear speed from the spinneret is 90 m / min or less.

[0043]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail with reference to Examples and Comparative Examples, but the present invention is not limited thereto. The water permeability and the sieving coefficient in the present invention are measured as follows. That is, the dried polysulfone-based selectively permeable hollow fiber membrane 100
A mini-module (effective length 25 cm) composed of books was assembled and molded, and the amount of water permeation was measured in a unit of ml / Hr / m ² / mmHg by a flow method under a pressure condition of 200 mmHg.
Subsequently, the sieving coefficients of β ₂ -MG and albumin were measured using bovine plasma. Yarn strength is ORIENTEC T
Using ENSILON; RTC-1210, the hollow fiber membrane was pulled until breaking, and the maximum load applied at that time was taken as strength.

[0044]

Example 1 17 parts by weight of a polysulfone resin (manufactured by Amoco Performance Products, P-1700), polyvinylpyrrolidone (manufactured by BSF, K-
92) A uniform spinning dope comprising 7 parts by weight and 76 parts by weight of DMAC was prepared. This spinning dope has a viscosity of 340 at 65 ° C.
It was 0 mPa · s. While keeping this spinning stock solution at 65 ° C., a slit width of 5% together with a 15% DMAC hollow inner solution was used.
It was discharged from a 9.5 μm annular die, immersed in 55 ° C. water provided 60 cm below, and wound up at a speed of 70 m / min. The discharge rate of the spinning dope was adjusted so that the thickness of the hollow fiber during drying was adjusted to 45 μm.
It was 9.3 m / min, and the draft rate was 1.42. The obtained hollow fiber membrane bundle was suspended, and a 40% by weight aqueous DMAC solution heated to 85 ° C. was showered for 80 minutes. Thereafter, the resultant was washed with hot water at 90 ° C. and immersed in a 20% glycerin aqueous solution to adhere glycerin. Subsequently, it was dried with hot air at 75 ° C. for 11 hours. Subsequently, the hollow fiber membrane was treated with 600 ppm of sodium disulfite and 300 ppm of sodium carbonate.
Was immersed in an aqueous solution in which was dissolved, and irradiated with 25 kGy of γ-ray to obtain a polysulfone blood purification membrane. The obtained hollow fiber membrane was dyed with an aqueous solution of osmium tetroxide, dehydrated, embedded in an epoxy resin, cured, and then formed into an ultrathin section of about 60 nm using an ultramicrotome.
FX) Observations were made. Using the obtained TEM image, 0.1.
The tissue ratio was measured at an interval of 7 μm from the inner surface side of the hollow fiber membrane to the outer surface side using an image analyzer (IP-1000: manufactured by Asahi Kasei Corporation). Table 1 shows the measurement results and the film evaluation results.
Shown in FIG. 1 shows the state of the inner surface of this film. There is no torn structure and the surface is smooth.

[0045]

Example 2 Extraction and washing of a hollow fiber membrane were carried out at 80 ° C. and 40% DM.
A polysulfone-based blood purification membrane was obtained in the same manner as in Example 1, except that glycerin at 130 ° C. was showered for 3 hours instead of the 80-minute shower with an AC aqueous solution. Table 1 shows the obtained results.

Example 3 Example 1 was repeated except that extraction washing with a shower was not performed for 80 minutes in a 40% aqueous solution of DMAC at 80 ° C.
A polysulfone blood purification membrane was obtained in the same manner as described above. Table 1 shows the obtained results.

[0046]

Example 4 17 parts by weight of a polysulfone resin (manufactured by Amoco Performance Products, P-1700), polyvinylpyrrolidone (manufactured by BSF, K-
89) A uniform spinning dope composed of 7 parts by weight and 76 parts by weight of DMAC was prepared. This spinning dope has a viscosity of 165 at 80 ° C.
It was 0 mPa · s. While keeping this spinning solution at 80 ° C., the slit width was 5% with the hollow inner solution of 15% DMAC.
It was discharged from a 9.5 μm annular die, immersed in 55 ° C. water provided 60 cm below, and wound up at 70 m / min. Thereafter, a polysulfone-based blood purification membrane was obtained in the same manner as in Example 1. Table 1 shows the obtained results.

[0047]

Example 5 16 parts by weight of a polysulfone resin (manufactured by Amoco Performance Products, P-1700), polyvinylpyrrolidone (manufactured by BSF, K-
89) A uniform spinning dope consisting of 7.8 parts by weight and 76.2 parts by weight of DMAC was prepared. This spinning dope has a viscosity of 70 ° C.
Was 2500 mPa · s. This spinning stock solution is 70 ° C
, And discharged from an annular die having a slit width of 59.5 μm together with a 15% DMAC hollow inner solution, immersed in 55 ° C. water provided 60 cm below, and wound up at 70 m / min. Thereafter, a polysulfone-based blood purification membrane was obtained in the same manner as in Example 1. Table 1 shows the obtained results.

[0048]

Example 6 17 parts by weight of a polysulfone resin (manufactured by Amoco Performance Products, P-1700), polyvinylpyrrolidone (manufactured by BSF, K-
92) A uniform spinning dope comprising 5.5 parts by weight and 78.5 parts by weight of DMAC was prepared. This spinning dope has a viscosity of 50 ° C.
Was 2400 mPa · s. This spinning stock solution is 50 ° C
, And discharged from an annular die having a slit width of 59.5 μm together with a 15% DMAC hollow inner solution, immersed in 55 ° C. water provided 60 cm below, and wound up at 70 m / min. Thereafter, a polysulfone-based blood purification membrane was obtained in the same manner as in Example 1. Table 1 shows the obtained results.

[0049]

Example 7 17 parts by weight of a polysulfone resin (manufactured by Amoco Performance Products, P-1700), polyvinylpyrrolidone (manufactured by BSF, K-
89) A uniform spinning dope comprising 6.3 parts by weight and 76.7 parts by weight of DMAC was prepared. This spinning dope has a viscosity of 55 ° C.
Was 2820 mPa · s. 55 ° C.
, And discharged from an annular die having a slit width of 59.5 μm together with a 15% DMAC hollow inner solution, immersed in 55 ° C. water provided 60 cm below, and wound up at 70 m / min. Thereafter, a polysulfone-based blood purification membrane was obtained in the same manner as in Example 1. Table 1 shows the obtained results.

[0050]

Comparative Example 1 A polysulfone-based hemodialysis membrane was obtained in the same manner as in Example 6, except that irradiation with γ-rays was not performed. Table 1 shows the obtained results.

Comparative Example 2 A hollow fiber membrane was made of sodium disulfite at 600 pp.
A polysulfone-based hemodialysis membrane was obtained in the same manner as in Example 6, except that the sample was immersed in water instead of immersed in an aqueous solution in which m and 300 ppm of sodium carbonate were dissolved, and irradiated with 50 kGy γ-rays. Table 1 shows the obtained results.

[0051]

[Comparative Example 3] Instead of discharging a spinning solution together with a 15% hollow inner solution from an annular die having a slit width of 59.5 µm,
A polysulfone-based blood purification membrane was obtained in the same manner as in Example 1, except that the liquid was discharged from an annular die having a slit width of 125 μm. Table 1 shows the obtained results. At this time, the draft rate was 3.2. The inner surface of this film has a structure that is severely torn by the influence of the draft, and this is shown in FIG.

Comparative Example 4 The same procedure as in Example 1 was carried out except that the spinning solution was discharged from an annular die having a slit width of 50 μm instead of being discharged from an annular die having a slit width of 59.5 μm together with a 15% DMAC hollow inner solution. A polysulfone blood purification membrane was obtained. Table 1 shows the obtained results. At this time, the draft rate was 1.0. Although the inner surface of this film has a low draft, it does not have a torn structure, but structural irregularities are seen due to the influence of the discharge unevenness of the stock solution. This is shown in FIG.

[0052]

Comparative Example 5 17 parts by weight of a polysulfone resin (manufactured by Amoco Performance Products, P-1700), polyvinylpyrrolidone (manufactured by BSF, K-
92) A uniform spinning dope composed of 3.5 parts by weight and 79.5 parts by weight of DMAC was prepared. This spinning dope has a viscosity of 50 ° C.
Was 1250 mPa · s. This spinning stock solution is 50 ° C
, And discharged from an annular die having a slit width of 59.5 μm together with a 15% DMAC hollow inner solution, immersed in 55 ° C. water provided 60 cm below, and wound up at 70 m / min. Thereafter, a polysulfone-based blood purification membrane was obtained in the same manner as in Example 1. Table 1 shows the obtained results.

[0053]

[Table 1]

With respect to the hollow fiber membranes of Examples 1 to 7 and Comparative Examples 1 to 5, the residual blood was evaluated. That is, 16cm
120 long hollow fiber membranes were assembled in a module and washed with 20 ml of physiological saline. Thereafter, blood taken out of the carotid artery of the dog via a peristaltic pump was flowed at a flow rate of 2 ml / min inside the hollow fiber for 10 minutes. After extruding the blood with 5 ml of physiological saline, the module was disassembled and the degree of residual blood was evaluated. As a result, residual blood was observed in the hollow fibers of Comparative Examples 2, 3, and 5, but in the hollow fiber membranes of the other Comparative Examples and Examples, there was little or no residual blood.

[0055]

As described above, the polysulfone blood purification membrane of the present invention has improved blood compatibility, the amount of polyvinylpyrrolidone eluted to the blood side is extremely small, and
Hollow fiber membrane with excellent molecular weight fractionation properties. According to the present invention, it is possible to provide an artificial kidney which is very significant in the future dialysis treatment.

[Brief description of the drawings]

FIG. 1 is an image obtained by observing the inner surface of a hollow fiber membrane of Example 1 with a scanning electron microscope (upper: 10,000 times, lower: 30,000 times). The inner surface is smooth, and it is observed that the fibrils are arranged side by side in the axial direction of the hollow fiber.

FIG. 2 is an image obtained by observing the inner surface of the hollow fiber membrane of Comparative Example 3 with a scanning electron microscope (upper: 10,000 times, lower: 30,000 times). There is a gap of about 2 μm on the inner surface as if torn.

FIG. 3 is an image obtained by observing the inner surface of the hollow fiber membrane of Comparative Example 4 with a scanning electron microscope at a magnification of 1000 times. Structural non-uniformity is observed due to the influence of the non-uniform liquid ejection. The middle part and the lower part show images enlarged by 15,000 times, respectively, where a portion where the fibrils are coarse is a and a portion where the fibrils are dense is b.

Claims (12)

[Claims] 1. A selective separation layer having a substantial separation function is present on the inner surface side of a hollow fiber membrane, and in a polysulfone-based hollow fiber type blood purification membrane containing polyvinylpyrrolidone, 1 to 10% by weight of polyvinylpyrrolidone is used. % Of the polyvinylpyrrolidone is soluble in water, and the concentration of polyvinylpyrrolidone on the inner surface of the hollow fiber membrane is in the range of 30% to 45%. Hollow fiber blood purification membrane. 2. The polysulfone hollow fiber blood purification membrane according to claim 1, wherein the concentration of polyvinylpyrrolidone on the inner surface of the hollow fiber is 33% to 40%. 3. The polysulfone-based hollow according to claim 1, wherein the amount of polyvinylpyrrolidone eluted when the inside of the hollow fiber membrane is circulated and extracted with a 40% alcohol aqueous solution is 0.5 mg or less per 1 m ^{2 of} membrane area. Thread type blood purification membrane. 4. The polysulfone hollow fiber blood purification membrane according to claim 1, wherein the inner surface of the hollow fiber membrane does not have a torn gap of 0.8 μm or more. 5. The polysulfone-based hollow fiber blood purification membrane according to claim 1, wherein the thickness of the selective separation layer is 2 to 15 μm. 6. After spinning a hollow fiber membrane using a polymer solution containing 15 to 20% by weight of a polysulfone polymer and having a weight ratio of polyvinylpyrrolidone to the polysulfone polymer of 0.25 to 0.5. A method for producing a polysulfone-based hollow fiber type blood purification membrane, wherein a part of polyvinylpyrrolidone in the hollow fiber membrane is insolubilized by a physicochemical method. 7. The polysulfone-based hollow fiber according to claim 6, wherein the hollow fiber membrane after spinning is brought into a wet state having a saturated water content or more, and then irradiated with radiation to insolubilize a part of polyvinylpyrrolidone. Of manufacturing a blood purification membrane. 8. The spinning hollow fiber membrane is characterized in that polyvinylpyrrolidone is extracted and washed with a solvent that dissolves polyvinylpyrrolidone or an alcoholic solvent, which is a mixed solvent of a good solvent and a poor solvent for the polysulfone polymer. The method for producing a polysulfone-based hollow fiber type blood purification membrane according to claim 6. 9. The polysulfone-based hollow fiber blood purification membrane according to claim 8, wherein the good solvent for the polysulfone-based polymer is dimethylacetamide and / or dimethylsulfoxide, and the poor solvent for the polysulfone-based polymer is water. Manufacturing method. 10. The hollow fiber membrane after spinning is heated to 130 to 160 ° C.
The method for producing a polysulfone-based hollow fiber blood purification membrane according to claim 6, wherein the membrane is extracted and washed with an alcohol-based solvent. 11. The method for producing a polysulfone-based hollow fiber type blood purification membrane according to claim 10, wherein the alcohol-based solvent is glycerin. 12. A spinning dope having a viscosity of 1500 to 6000 mPa · s, in which a polysulfone polymer and polyvinylpyrrolidone are dissolved in a common solvent thereof, at a draft rate of 1.1 to 1.9 and a discharge linear speed of 90 m / min or less. The method for producing a polysulfone-based hollow fiber type blood purification membrane according to claim 6, wherein spinning is performed.