JP3150717B2 - Method for producing polysulfone-based resin selectively permeable membrane - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing a selectively permeable polysulfone resin membrane, and more particularly to a method for producing a selectively permeable polysulfone resin membrane for medical applications such as hemodialysis and hemofiltration.

[0002]

2. Description of the Related Art Permselective membranes made of materials such as cupra ammonium rayon, cellulose acetate, polyacrylonitrile, and polymethyl methacrylate are widely used in artificial kidneys, but such medical devices are used because they come into direct contact with blood. Sterilization is indispensable in order to prevent biological infection due to contamination of blood with bacteria or the like at the time, and gas sterilization using ethylene oxide gas, heat sterilization using an autoclave, and the like are performed as such sterilization methods. However, since it has become clear in recent years that ethylene oxide gas causes allergy to living organisms, a heat sterilization method using an autoclave has been widely used.

On the other hand, polysulfone-based resins have been studied as medically selective permeable membranes because they have excellent heat resistance and can be sterilized by heat in an autoclave. Was. However, on the other hand, permselective membranes made of polysulfone-based resins have a high adsorptivity to protein components in blood due to their hydrophobicity, and the membrane surface is easily contaminated.
There is a drawback that blood filtration tends to cause a problem such as a decrease in permeation rate over time.

As means for hydrophilizing the polysulfone-based resin selectively permeable membrane in order to solve the drawbacks, JP-B-2-18695, JP-A-61-93801, and JP-A-61-238306 disclose such means. A permselective membrane comprising a polysulfone-based resin and polyvinylpyrrolidone as a hydrophilic polymer compound is disclosed. However, the permselective membranes according to these publications have a large mixing ratio of polyvinylpyrrolidone with respect to the polysulfone-based resin, and the amount of polyvinylpyrrolidone remaining as an unextracted component in the membrane is large, so that blood requiring high safety is required. It is not suitable as a selectively permeable membrane for medical use such as dialysis. In particular, when exposed to a severe environment such as heat sterilization by an autoclave, when the amount of residual polyvinylpyrrolidone is large, the amount of polyvinylpyrrolidone eluted also increases, and sufficient safety may not be ensured.

[0005]

SUMMARY OF THE INVENTION In view of the drawbacks of the prior art, the present invention relates to a selectively permeable membrane in the medical field, such as hemodialysis, which reduces the filtration rate due to adsorption of blood proteins and the like to the membrane surface. An object of the present invention is to solve the problems and to provide a method for producing a polysulfone-based resin selectively permeable membrane that can be used in a safer state.

[0006]

Means for Solving the Problems The inventors of the present invention have made intensive studies on solving the above problems, and have reached the following conclusions. That is, the present invention has the following configuration. A method for producing a polysulfone-based resin selectively permeable membrane from a membrane-forming solution obtained by mixing a polysulfone-based resin and polyvinylpyrrolidone, wherein: a) the molecular weight of polyvinylpyrrolidone is 300,000 or more; When a stock solution having a mixing ratio of 0.5% or more and 10% or less is used and the stock solution is discharged from a spinneret, the mixing ratio of the good solvent to the polysulfone resin is 6%.
An aqueous solution of 0% or less is used as an internal injection solution, and the water permeability is 630 ml / m ² . H. A method for producing a polysulfone-based resin selectively permeable hemodialysis and / or hemofiltration membrane, characterized in that the membrane is at least mmHg.

As the polysulfone resin to be used, those commercially available under the trade names Udel (Amoco Performance Products), Radel (the same) and Victrex (ICI) are readily available. Although it can be conveniently used, it is of course not limited to these. Further, polyvinylpyrrolidone is a hydrophilic polymer compound having a molecular weight of 10,000, 40,000,
160,000 and 360,000 are K-15, K-30,
Although commercially available under the trade names K-60 and K-90, polyvinylpyrrolidone has a higher effect of hydrophilizing the membrane as it has a higher molecular weight. In the invention, the molecular weight is 300,0
More than 00 polyvinylpyrrolidone is used. 30
A large amount of polyvinylpyrrolidone must remain in the membrane in order to impart a hydrophilicity effect to the membrane using polyvinylpyrrolidone having a molecular weight of less than 000, but this increases the amount of eluate from the membrane. Will do.
Conversely, if the residual amount of polyvinylpyrrolidone having a molecular weight of less than 300,000 in the membrane is reduced to reduce the eluate, the hydrophilizing effect becomes insufficient. Over time, and no sufficient effect can be exhibited. In hemodialysis and hemofiltration, it is also an object of the present invention to remove unnecessary waste such as urea by diffusion and filtration and to remove a certain amount of excess water stored in the body. In general, hemodialysis and hemofiltration are performed by a constant pressure operation, and it is preferable that a constant filtration rate is always obtained in a constant pressure filtration state for removing a certain amount of water. When the speed is reduced, it is necessary to set the filtration pressure higher in accordance with the reduction in the filtration speed, which causes inconvenience in operation.

Accordingly, the molecular weight of the polyvinylpyrrolidone used is 300,000 or more. At this time, the filtration rate decreases with time by controlling the residual amount of polyvinylpyrrolidone in the membrane. Despite having a sufficient hydrophilic effect without
In addition, a membrane with a small amount of eluted material, that is, a membrane that satisfies the safety standard in a test according to the dialysis type artificial kidney apparatus standard can be obtained.

The stock solution used in the present invention basically comprises a polysulfone-based resin, polyvinylpyrrolidone and a solvent for dissolving them, but is not limited to these compounds only. If necessary, other additives may be used. May be mixed. For example, water, alcohols such as ethanol and isopropyl alcohol, and glycols such as glycerin, tetraethylene glycol and propylene glycol can be used.

These additives are used as pore-forming agents, and the type and additives of the additives may be selected so as to obtain a desired film performance. Such a method is a subject of the present invention. Absent. The solvent is not particularly limited as long as it can dissolve the polysulfone-based resin and polyvinylpyrrolidone and, in some cases, other additives in common, but is not particularly limited.
An aprotic polar solvent such as methyl-2-pyrrolidone, N, N-dimethylacetamide, N, N-dimethylformamide, dimethylsulfoxide and the like, and a mixed solvent thereof can be preferably used.

To prepare the membrane stock solution, a polysulfone-based resin, polyvinylpyrrolidone, a solvent and, if necessary, an additive may be mixed and dissolved, but in order to give the membrane an appropriate strength, the polysulfone-based resin is 10% by weight. The content is not less than 30% by weight, preferably not less than 15% by weight and not more than 20% by weight. More importantly, the amount of polyvinylpyrrolidone added is such that the mixing ratio of polyvinylpyrrolidone to the polysulfone resin is 0.5% or more and 10% or less.

A membrane prepared from a stock solution having a ratio of less than 0.5% has a high hydrophilizing effect by polyvinylpyrrolidone having a molecular weight of 300,000 or more because polyvinylpyrrolidone remaining in the membrane is small. Nevertheless, the polysulfone-based resin cannot exhibit a sufficient hydrophilizing effect to cancel the hydrophobicity of the resin.
Therefore, the resulting selectively permeable membrane has a high adsorptivity to blood proteins and is liable to cause contamination of the membrane surface.

On the other hand, the upper limit of the mixing ratio is preferably 10% or less. Since polyvinylpyrrolidone is a water-soluble polymer compound, polyvinylpyrrolidone remaining in the film may elute little by little when used. When an eluate test is performed on a permselective membrane prepared using a membrane-forming stock solution having a mixing ratio of more than 10% based on a dialysis-type artificial kidney apparatus, the residual amount of polyvinylpyrrolidone in the membrane is too large. Fail to pass its safety standards. Polyvinylpyrrolidone is a compound whose safety is so high that it has been used as a plasma substitute in the medical field, but it is needless to say that polyvinylpyrrolidone does not enter the body as it is unnecessary for the living body. For that purpose, it is important that polyvinylpyrrolidone is not left unnecessarily in the membrane. By controlling the mixing ratio to 10% or less, the safety as a selectively permeable membrane for medical use is dramatically improved.

For forming the membrane, a known technique for a conventionally known hollow fiber membrane may be used. That is, for the hollow fiber membrane, the membrane forming stock solution may be discharged from the sheath portion of the double hollow die, an internal injection solution for maintaining the hollow shape from the core portion, and then immersed in the coagulation solution. At this time, in order to obtain a hollow fiber membrane having desired performance, it is important to adjust the coagulability of the coagulating solution or the internal injection solution with respect to the membrane forming stock solution,
For example, N, which is a good solvent for polysulfone resin,
The coagulability can be adjusted by the mixing ratio of N-dimethylacetamide, N-methyl-2-pyrrolidone, dimethylsulfoxide and water, or a mixed solvent of these good solvents and water. The best combination may be determined as appropriate for the die temperature, the coagulation liquid temperature, and the dry length, but the die temperature is 30 to 50 ° C., and the coagulation liquid temperature is 40 to 60.
C and the dry length are preferably 20 to 60 cm.

[0015]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS The embodiments of the present invention will be described below in detail with reference to examples.

[0016]

Example 1 Polysulfone (Udel P-1700) 1
8%, polyvinylpyrrolidone (K-90, M = 3600)
00) A film forming stock solution (mixing ratio: 5.6%) consisting of 1% and N, N-dimethylacetamide 81% was prepared by heating and dissolving. The undissolved fine particles and the like were removed from the film-forming stock solution, defoamed under reduced pressure, and then extruded from the sheath of a double hollow die kept at 40 ° C. At this time, N, N-
A mixed solution of dimethylacetamide / water = 60/40 was simultaneously discharged, immersed in a coagulation liquid at 30 ° C. while maintaining a dry length of 30 cm, and washed with water to obtain a hollow fiber membrane.
This hollow fiber membrane had an inner diameter of 195 μm and an outer diameter of 288 μm, and showed a water permeability of 238 ml / m ² · H · mmHg.

[0017]

EXAMPLE 2 A stock solution consisting of 16% of polysulfone, 0.5% of polyvinylpyrrolidone (K-90, M = 360000), 25% of tetraethylene glycol and 58.5% of N, N-dimethylacetamide (mixing ratio: 3 .1%). Example 1 except that water was used as the internal injection liquid
A hollow fiber membrane was obtained in the same manner as described above. This hollow fiber membrane has an inner diameter of 19
630ml / m ²・ H ・ mm with 1μm, 290μm outer diameter
Hg showed water permeability.

[0018]

COMPARATIVE EXAMPLE 1 A stock solution consisting of 18% of polysulfone, 1% of polyvinylpyrrolidone (K-30, M = 40000) and 81% of N, N-dimethylacetamide (mixing ratio: 5.
(3%) was dissolved by heating. N,
A hollow fiber membrane was obtained in the same manner as in Example 1 except that a mixed solution of N-dimethylacetamide / water = 70/30 was used. This hollow fiber membrane had a water permeability of 380 ml / m ² · H · mmHg at an inner diameter of 197 µm and an outer diameter of 290 µm.

[0019]

Comparative Example 2 A stock solution comprising 18% of polysulfone, 5% of polyvinylpyrrolidone (K-90, M = 360000) and 5% of N, N-dimethylacetamide (mixing ratio: 2)
(7.8%) was dissolved by heating. A hollow fiber membrane was obtained in the same manner as in Example 1 except that a mixed solution of N, N-dimethylacetamide / water = 40/60 was used as the internal injection liquid. This hollow fiber membrane has an inner diameter of 188 μm and an outer diameter of 283 μm
Showed a water permeability of 220 ml / m ² · H · mmHg.

[0020]

Comparative Example 3 Polysulfone 18%, polyvinylpyrrolidone (K-90, M = 360000) 0.05%, N, N
-A stock solution of 81.95% dimethylacetamide (mixing ratio 0.3%) was prepared. A hollow fiber membrane was obtained in the same manner as in Example 1 except that a mixed solution of N, N-dimethylacetamide / water = 70/30 was used as an internal injection solution. This hollow fiber membrane had an inner diameter of 195 μm and an outer diameter of 296 μm, and showed a water permeability of 198 ml / m ² · H · mmHg.

[0021]

Reference Example 1 The hollow fiber membranes of Examples 1 and 2 and Comparative Examples 1 to 3 were subjected to the following safety tests based on the dialysis type artificial kidney apparatus standard. After weighing 1.5 g of the dried hollow fiber and adding 150 ml of distilled water for injection, extraction was performed at 70 ° C. for one hour, and the ultraviolet absorption spectrum of the extract was measured at a wavelength showing the maximum absorption at 220 to 350 nm. . The hollow fiber membrane of Comparative Example 2 did not pass the safety standard, but the other hollow fiber membranes passed the safety standard.

[0022]

Reference Example 2 Using the hollow fiber membranes of Examples 1 and 2 and Comparative Examples 1 to 3, mini-modules having an effective membrane area of 0.2 m ² were prepared. Heparin-added bovine blood 20 m
The solution was passed at a flow rate of 1 / min, and the change over time in the filtration rate was measured while maintaining the filtration pressure at 200 mmHg. Comparative Example 1
In the hollow fiber membranes of Nos. 3 and 3, the filtration rate was drastically reduced, and the filtration rate after 4 hours was only 50% or less of the initial value. However, other hollow fiber membranes showed a filtration rate of 80% or more, and the decrease was slight.

[0023]

[Table 1]

[0024]

[Table 2]

[0025]

According to the present invention, a hydrophobic membrane made of a polysulfone resin can be hydrophilized, and the filtration rate can be prevented from decreasing over time due to contamination of the membrane surface such as blood proteins. It can be a permselective membrane with few substances and excellent in safety for living bodies, and can be an excellent permselective membrane in medical applications such as hemodialysis and hemofiltration. Further, the present invention is a method suitable as a method for producing a selectively permeable membrane for medical use, but it is also used for ultrafiltration membranes and microfiltration membranes not only for medical applications but also for general industrial applications where membrane surface contamination is likely to occur. be able to.

────────────────────────────────────────────────── ─── Continuation of the front page (56) References JP-A-3-258330 (JP, A) JP-A-3-284326 (JP, A) JP-A-63-99325 (JP, A) (58) Field (Int. Cl. ⁷ , DB name) B01D 71/68 B01D 71/44 WPI (DIALOG)

Claims (1)

(57) [Claims] 1. A method for producing a polysulfone-based resin selectively permeable membrane from a membrane-forming stock solution in which a polysulfone-based resin and polyvinylpyrrolidone are mixed, wherein : a) the molecular weight of polyvinylpyrrolidone is 300,000 or more; and b) polysulfone When using a film forming stock solution in which the mixing ratio of polyvinylpyrrolidone to the system resin is 0.5% or more and 10% or less and discharging the film forming stock solution from a spinneret.
The mixing ratio of the good solvent to the polysulfone resin is 6
0% or less aqueous solution is used as the internal injection liquid, and the water permeability is
630 ml / m ² . H. mmHg or higher membrane , characterized by selective permeation hemodialysis and polysulfone resin.
And / or a method for producing a blood filtration membrane. "