JP3424807B2 - Hollow fiber membrane - Google Patents

Description

Description: TECHNICAL FIELD [0001] The present invention relates to a hollow fiber membrane obtained by a dry-wet spinning method and suitably used for ultrafiltration, dialysis, and diafiltration. [0002] In recent years, dialysis complications accompanying the increase in long-term dialysis patients have attracted attention, and not only low-molecular-weight substances such as urea and creatinine but also medium-high-molecular-weight substances (low-molecular proteins) have been removed. ing. It has also been suggested that the effects of improving clinical symptoms such as pruritus and pain and improving lipid metabolism are due to the removal of substances having a molecular weight of 10,000 to 30,000. The membranes used in these treatments are called high performance membranes, which allow larger substances to be removed by increasing the pore size compared to conventional dialysis membranes. The properties required for a high-performance membrane are that it has high water permeability and a sharp cutoff property (excellent in removing molecular substances of 10,000 to 30,000 and does not leak albumin with a molecular weight of 66,000, which is a useful blood protein). is necessary. Conventionally, a cellulose-based hollow fiber membrane represented by a cellulose ester has a high performance of removing low-molecular substances, but the performance of removing a low-molecular-weight protein region is not sufficient as compared with a polysulfone-based hollow fiber membrane. [0003] The present invention aims to solve the above-mentioned drawbacks, and an object of the present invention is to provide a cellulose-based hollow fiber membrane having high water permeability and sharp solute cutoff properties. Is to provide. [0004] That is, the present invention provides the following hollow fiber membranes. Permeation rate when passing pure water at 37 ° C. is 200 to
500 ml / m ² · hr · mmHg, blood flow 2
The clearance of β ₂ -microglobulin in vitro at 00 ml / min is 30 ml / min · m
² or more, clearance of urea is 170ml / min.m
^{2. A} hollow fiber membrane, wherein the sieving coefficient of albumin is ² or more, and the yield strength of the hollow fiber membrane is 10 g / filament or more. The hollow fiber membrane as described above, wherein the hollow fiber membrane comprises cellulose triacetate as a main component. The hollow fiber membrane according to any one of the above, wherein the thickness is 10 to 30 µm. [0005] The hollow fiber membrane of the present invention has a water permeation speed (hereinafter, UFR) of 200 to 500 m when permeating pure water at 37 ° C.
l / m ² · hr · mmHg. U
When the FR is less than 200 ml / m ² · hr · mmHg, the size of the pores opened on the membrane surface is too small or the number of pores is too small, so that the removability of the target low molecular substance such as urea is insufficient. In other words, it becomes impossible to achieve both high-dimensional removal of low-molecular substances and medium-molecular substances or more, for example, because of low molecular weight or high permeability of substances having medium molecular weight or more such as β ₂ -microglobulin. UFR is 500ml / m ² · h
If it exceeds r · mmHg, the strength of the hollow fiber is reduced, so that the spinnability and modularity are reduced. In addition, since the pore diameter becomes too large, it becomes impossible to suppress the leakage of albumin to a low level. The yield strength of the hollow fiber membrane is 10
g / filament or more. When the yield strength is lower than 10 g / filament, the handleability of modularization is deteriorated and the yield is reduced. Examples of the hollow fiber membrane material in the present invention include regenerated cellulose, modified cellulose, polysulfone, acrylonitrile, etc. Any material may be used as long as it has a small amount of protein adsorption, but cellulose having excellent water permeability and solute permeability. Acetate is preferred, and cellulose triacetate is particularly preferred from the viewpoint of biocompatibility. The thickness of the hollow fiber membrane of the present invention is preferably in the range of 10 to 100 μm from the viewpoint of improving spinnability and modularity. In order to obtain higher transmission performance, 10
-30 μm is particularly preferred. The spinning method of the hollow fiber membrane of the present invention is not particularly limited, and can be obtained by a spinning method such as melting, dry, wet, and dry-wet methods. The film is preferably formed by a dry-wet spinning method using an agent. Any hollow forming agent may be used as long as it is inert to the spinning dope. For example, liquid paraffin or isopropyl myristate can be used as the liquid, and dry air, nitrogen, helium, argon or the like can be used as the gas. The hollow fiber membrane of the present invention can be produced, for example, as follows, but the present invention is not limited to the following. Membrane materials 16 such as cellulose acetate
25 parts by weight, solvent 45 to 75.6 parts by weight, non-solvent 8.4
A spinning dope consisting of ３９39 parts by weight is dissolved by heating to 130-190 ° C., extruded from the outside of a double-tube spinneret, and extruded from a liquid paraffin from the inside. After the extruded spinning dope passed through the gas atmosphere, the weight ratio of solvent / non-solvent / water was adjusted to 6/4/90 to 27/3/70 to 0-5.
Coagulated in a coagulating liquid at 0 ° C., and the excess solvent and non-solvent are washed in a washing bath. In order to obtain the hollow fiber membrane of the present invention, a spinning solution comprising a membrane material such as cellulose triacetate, a solvent and a non-solvent is discharged from a spinneret into a gaseous atmosphere and then guided to a coagulation bath to produce a hollow fiber membrane. Preferably, the concentration of the membrane material such as cellulose triacetate is adjusted to 16 to 25% by weight, and the concentration of the solvent in the coagulation bath composed of solvent / non-solvent / water is adjusted to 6 to 27% by weight. Next, the membrane fiber is impregnated with glycerin by passing the hollow fiber through a 30 to 70% by weight aqueous glycerin solution, and wound up through a drying step. The solvent is not particularly limited as long as it dissolves cellulose acetate, but N, N-dimethylacetamide, N, N-dimethylformamide, γ-butyrolactone, N-methylpyrrolidone, dimethylsulfoxide, N, N- It is preferable to use a polar solvent such as dimethylimidazolidinone.
These can be used alone or in combination. Examples of the non-solvent include polyhydric alcohols such as ethylene glycol, triethylene glycol, polyethylene glycol, and glycerin, and lower alkyl ether derivatives thereof, and these can be used alone or as a mixture. The cellulosic hollow fiber membrane produced by such a method is excellent in water permeability and sharp in solute cut-off, so that it is suitably used for ultrafiltration, dialysis, and diafiltration. Is used for hemodialysis, hemofiltration dialysis and the like. Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to the examples. [Example 1] Cellulose triacetate 1
9 parts by weight, 56.7 parts by weight of N-methylpyrrolidone, and 24.3 parts by weight of triethylene glycol were dissolved by heating at 170 ° C., and further degassed under vacuum to obtain a spinning solution of cellulose triacetate. This was filtered through a sintered filter having a pore diameter of 20 μm to remove impurities, and then discharged at 1.1 cc / min from the outside of the double-tube structure base, and simultaneously, liquid paraffin was discharged from the inside of the base. After passing through the air, the hollow fiber spinning solution is led to a coagulation bath of 40 ° C. composed of N-methylpyrrolidone / triethylene glycol / water = 10.5 / 4.5 / 85 (weight ratio), and then a washing bath. After passing through a 60% glycerin water bath and a drying step, it was wound into a cheese shape by a winder. The inner diameter of the obtained hollow fiber was 198 μm, the film thickness was 15 μm, and the yield strength was 32 g. The thus obtained hollow fiber 5,000 to 5,000
20,000 pieces were bundled and put into a plastic molded product to produce a module for performance evaluation. Measurement method 1. Measurement of Pure Water Permeation Rate (UFR) The above-prepared module was sufficiently washed with pure water, pure water adjusted to 37 ° C. was passed through the hollow fiber membrane, and the amount of filtered water was measured.
The water permeation speed UFR was calculated using the following equation. UFR (ml / m ² · hr · mmHg) = filtration amount / inlet pressure / time / membrane area Urea and β ₂ - measurement urea microglobulin clearance and β ₂ - microglobulin clearance was measured in accordance with the "performance evaluation method of the film" (High Performance Membrane Research Group). CL (ml / min) = (inlet concentration−outlet concentration) / inlet concentration / supply liquid flow physiological saline solution outside the hollow fiber membrane of the module, and 200 ml / min blood (plasma) inside the hollow fiber. And measured at a filtration flow rate of 15 ml / min. Measure the solute concentration of the undiluted solution at the inlet of the hollow fiber membrane, the solute concentration of the undiluted solution at the outlet, and the amount of the supplied solution to determine the clearance CL.
Was calculated. 3. Measurement of albumin sieving coefficient The sieving coefficient SC of albumin was 5.0 g / d in accordance with “Evaluation method of membrane performance” (High Performance Membrane Research Society).
The measurement was performed using 1 l of an albumin-phosphate buffer (pH 7.4). SC = (2 × filtrate concentration) / (inlet concentration + outlet concentration) The concentration of the undiluted solution at the inlet of the hollow fiber membrane, the concentration of the undiluted solution at the outlet and the concentration of the filtrate were measured, and the sieving coefficient SC was measured.
Was calculated. 4. Measurement of yield strength of hollow fiber Using Tensilon UTMII manufactured by Toyo Baldwin,
Pulling speed 100mm / min, distance between chucks 100
mm. Comparative Example 1 Cellulose Triacetate 3
2 parts by weight, 61.2 parts by weight of N-methylpyrrolidone and 6.8 parts by weight of triethylene glycol were dissolved by heating at 170 ° C., and further degassed under vacuum to obtain a spinning solution of cellulose triacetate. This was filtered through a sintered filter having a pore diameter of 20 μm to remove impurities, and then discharged at 1.1 cc / min from the outside of the double-tube structure base, and simultaneously, liquid paraffin was discharged from the inside of the base. After passing through the air, the hollow fiber spinning solution is composed of N-methylpyrrolidone / triethylene glycol / water = 27/3/70 (weight ratio) 25
C., followed by a water-washing bath, a 60% glycerin water bath, and a drying process, followed by winding into a cheese by a winder. The inner diameter of the obtained hollow fiber is 198 μm, and the film thickness is 16 μm.
m, and the yield strength was 25 g. A module was fabricated and performance was evaluated in the same manner as in Example 1.
Because of low R, low molecular weight substances (urea) and high molecular weight substances (β _2-
Microglobulin) clearance performance could not be compatible. Comparative Example 4 Cellulose Triacetate 1
7 parts by weight, 49.8 parts by weight of N-methylpyrrolidone, and 33.2 parts by weight of triethylene glycol were heated and dissolved at 170 ° C., and further degassed under vacuum to obtain a spinning solution of cellulose triacetate. This was filtered through a sintered filter having a pore diameter of 20 μm to remove impurities, and then discharged at 1.3 cc / min from the outside of the double-tube structure base, and simultaneously, liquid paraffin was discharged from the inside of the base. After passing through the air, the hollow-fiber stock solution is composed of N-methylpyrrolidone / triethylene glycol / water = 9/6/85 (weight ratio) 33
C., followed by a water-washing bath, a 60% glycerin water bath, and a drying process, followed by winding into a cheese by a winder. The inner diameter of the obtained hollow fiber is 196 μm, and the film thickness is 17 μm.
m and the yield strength was 18 g. A module was fabricated and performance was evaluated in the same manner as in Example 1. The results are summarized in Table 1. Comparative Example 2 Cellulose Triacetate 1
8 parts by weight, 57.4 parts by weight of N-methylpyrrolidone, and 24.6 parts by weight of triethylene glycol were heated and dissolved at 170 ° C., and further degassed under vacuum to obtain a spinning solution of cellulose triacetate. This was filtered through a sintered filter having a pore diameter of 20 μm to remove impurities, and then discharged at 1.1 cc / min from the outside of the double-tube structure base, and simultaneously, liquid paraffin was discharged from the inside of the base. After passing through the air, the hollow fiber spinning solution is led to a coagulation bath of N-methylpyrrolidone / triethylene glycol / water = 35/15/50 (weight ratio) at 40 ° C., followed by a water washing bath and a 60% glycerin water bath. After passing through a drying process, it was wound into a cheese shape by a winder. The inner diameter of the obtained hollow fiber is 201 μm and the film thickness is 14
μm, and the yield strength was 9 g. An attempt was made to produce a module and evaluate its performance in the same manner as in Example 1, but the module could not be assembled due to low yield strength. Comparative Example 3 Cellulose Triacetate 1
5 parts by weight, 59.5 parts by weight of N-methylpyrrolidone and 25.5 parts by weight of triethylene glycol were dissolved by heating at 170 ° C., and further degassed under vacuum to obtain a spinning solution of cellulose triacetate. This was filtered through a sintered filter having a pore diameter of 20 μm to remove impurities, and then discharged at 1.1 cc / min from the outside of the double-tube structure base, and simultaneously N-methylpyrrolidone / triethylene glycol / water = from the inside of the base. A solidifying liquid composed of 35/15/50 (weight ratio) was discharged. After passing through the air, the hollow fiber-like spinning stock solution becomes N-
Methylpyrrolidone / triethylene glycol / water = 35
/ 15/50 (weight ratio) to a coagulation bath at 40 ° C., and after passing through a washing bath, was wound up with a skein winding machine. The inner diameter of the obtained hollow fiber membrane is 201 μm and the film thickness is 65 μm.
μm, and the yield strength was 21 g. This is 60w
After being immersed in a t% aqueous glycerin solution, the solution was centrifuged to remove excess glycerin to prepare a module. Performance evaluation was performed in the same manner as in Example 1, but the UFR was too high (the pore size was too large) and the sieving coefficient of albumin was too large. [Table 1] As is clear from Table 1, the hollow fiber membranes obtained in Examples 1 and 2 have a high water permeation rate, are compatible with a high level of clearance performance of low molecular weight substances and medium molecular weight substances, and are useful proteins. Had a sharp cut-off property to suppress the leakage of albumin. As is apparent from the above description, according to the present invention, the sharpness which is high in water permeability, has a high level of removability of low-molecular substances and medium-molecular substances, and has little leakage of albumin. It is possible to provide a blood purification hollow fiber membrane having an excellent cutoff property. Further, since a cellulose-based hollow fiber membrane having excellent breaking strength and breaking elongation can be obtained, modularization is easy.

────────────────────────────────────────────────── ─── Continuation of the front page (56) References JP-A-10-85569 (JP, A) JP-A-9-70431 (JP, A) JP-A-9-154936 (JP, A) (58) Field (Int.Cl. ⁷ , DB name) B01D 69/08 B01D 71/16

Claims (1)

(57) [Claims] [Claim 1] The water permeation speed when permeating pure water at 37 ° C is
200-500 ml / m is ² · hr · mmHg, the blood flow rate 200 ml / beta2-microglobulin clearance in in vitro in min is 30 ml / min · m ² or more, clearance urea 170 ml / min
・ M ² or more, the sieving coefficient of albumin is 0.012 or more and 0.05 or less, and the yield strength of the hollow fiber membrane is 10 g / filament or more, and the film thickness is
10 ~ 30μm, inactive liquid for spinning solution
Cellulose tris for use as vacant forming agents
Acetate hollow fiber membrane.