JPH038422A - Hollow fiber membrane - Google Patents

Abstract

PURPOSE:To enhance the removability of urotoxin in blood by forming the hollow fiber membrane of regenerated cellulose which contains polyethylene glycol, has <=0.10 coefft. of sieving albumin in blood filtration and bas a specific average membrane pore radius, etc. CONSTITUTION:A spinning liquid of cuprammonium rayon having about 4 to 12% cellulose concn. is discharged together with a non-solidifiable hollow part forming agent, such as perchloroethylene, from double spinning mouth pieces and is passed in a nonsolidifiable atmosphere. The spun fiber is then introduced into a solidifying bath, such as sulfuric acid or ammonium sulfate and is solidified to obtain the hollow fiber membrane of the regenerated cellulose. The resulted hollow fiber membrane has the hollow part penetrated continuously in the axial direction of the fiber, has 40 to 250Angstrom average membrane pore radius at the time of wetting, and 60 to 95% hydrous voids, contains the polyethylene glycol and has <=0.10 value of the coefficient of sieving the albumin at the time of blood filtration.

Description

[Detailed Description of the Invention] [Field of Industrial Application] The present invention provides a hollow fiber with good handling properties that suppresses the loss of useful proteins in the blood such as albumin, and can efficiently remove toxic substances in the blood with a molecular weight of 100 or more. Regarding membranes.

Specifically, in blood purification therapy, it is a membrane that selectively removes high-molecular-weight toxic substances having a molecular size of ~66,000 molecules smaller than albumin, represented by β2-microglobulin, over a wide range, and which is a module. The present invention relates to a hollow fiber membrane for dialysis with good molding efficiency.

[Conventional technology]

Complications such as anemia, hypertension, hyperpigmentation, and bone and joint disorders are frequently observed in patients who are continuously receiving blood purification therapy due to chronic renal failure, etc., and research is needed to investigate the causes and countermeasures. It is progressing. In general, the ability of blood purification membranes to remove substances is taken up as a factor other than the living body, and as a result, substances that cannot be removed or substances that can be removed in significantly smaller amounts than the amount produced by the living body accumulate in the body, resulting in various problems. It is believed that complications may occur. However, there is no example in which the mechanism of complications including the identification of the pathogenic substance has been clarified (membranes that can efficiently remove poisonous substances with a molecular weight of at most 15,000 molecules, including urea with a molecular weight of 60, have not been generally sought. However, blood purification therapy has continued to be carried out mainly using hollow fiber membranes made of regenerated cellulose (average pore radius of about 30 Å or less), which satisfies this requirement.

In recent years, it has been revealed that the accumulation of β2-microglobulin in the body is greatly involved in the onset of dialysis amyloidosis, including pre-hair syndrome among various complications, and β2-microglobulin can be efficiently removed. Blood purification membranes are now in demand. Also, taking this opportunity,
The idea of removing substances in the molecular size range smaller than albumin (3,166,000 molecules) and then examining their therapeutic effects rapidly spread.

It is known that conventional regenerated cellulose membranes for blood purification, which have a membrane pore radius of 30 Å or less, cannot be expected to have a substantial ability to remove substances having a molecular weight larger than β2-microglobulin. On the other hand, if the membrane pore radius is made too large without sufficient consideration of the hemodialysis/filtration characteristics of the membrane, the sieving coefficient of albumin will also increase, resulting in the loss of albumin, which is a useful blood component. Conventional so-called protein cruising membranes using synthetic polymeric materials fall into this category.

On the other hand, mainly synthetic polymer-based membrane materials
- Adsorption-removal hollow fiber membranes targeted at microglobulin removal have been developed (for example, JP-A-63-1098
71'). However, since this method does not primarily rely on the diffusion permeation removal of substances, which is the basic concept of dialysis, but relies on adsorption phenomena, it is impossible to remove more than the saturated adsorption amount of the material, and it is not clinically sufficient. In order to obtain a sufficient amount of β2-microglobulin to be removed, a considerable amount of hollow fiber membrane is required.

In addition, in order to maintain the practical strength of the hollow fiber membrane, the total volume porosity (corresponding to the water-containing porosity in this specification) is 75%.
It is said that the following should be done. Since the higher the water-containing porosity of the membrane, the better the diffusion removal ability of the substance becomes, this value is not satisfactory for a diffusion-dependent hollow fiber membrane.

On the other hand, large-pore hollow fiber membranes using regenerated cellulose as a material are known to be used for virus separation, etc. (for example, JP-A-58-89626, JP-A-58
-89628, JP-A-59-204911, JP-A-61
-254202), but since this is intended for the production of virus-free plasma, it has an extremely large membrane pore size and membrane structure that actively allows substances that should not pass through blood purification membranes, such as albumin and globulin, to pass through. It has blood filtration properties. In other words, the regenerated cellulose membrane has a pore size intermediate between such large-pore membranes and conventional blood purification membranes, and has a membrane structure and hemodialysis/filtration characteristics that meet the objectives of the present invention. Hollow fiber membranes with this feature were unknown.

Further, conventional hollow fiber membranes are impregnated with some kind of water-soluble substance in order to maintain their substance permeation performance, and glycerin is generally used as such a substance.

The present inventors have previously confirmed that a hollow fiber membrane impregnated with a large amount of glycerin can be a hollow fiber membrane that generally satisfies the good substance permeability properties aimed at by the present invention.

[Problem to be solved by the invention]

All of these conventionally known high-molecular weight toxic substance removal membranes remove substances by relying heavily on adsorption or filtration mechanisms, and are expected to be used in hemodialysis therapy, which is the most common blood purification method. Removal by diffusion mechanisms was almost impossible.

Furthermore, those made from internally synthesized polymers lose a considerable amount of useful proteins such as albumin.
Because the focus is on selective adsorption to β2-microglobulin, there are problems such as it being unsuitable for removing other high molecular weight toxic substances, and as a blood purification membrane it is only suitable for extremely limited uses. There was. In addition, these materials have relatively low material strength, and there are also problems in that the water-containing porosity of the hollow fiber membrane, which largely controls the diffusion removal ability of substances, cannot be increased too much, and the membrane thickness cannot be made very thin.

There are various types of blood purification therapy, and even the same blood purification membrane exhibits different performance if used in different ways. In the most common hemodialysis therapy, loss of useful protein components is not a practical problem if the sieving coefficient for albumin is 0.15 or less, but it is desirable that it be smaller, and no special precautions are required when using it. . It should be less than 0.10.

However, conventional membranes intended to suppress the loss of albumin have had the problem of not having sufficient ability to remove substances such as β2-microglobulin.

The main mechanisms for removing waste substances in blood purification therapy include ■ filtration removal, ■ diffusion removal, and ■ adsorption removal. It has been said that whales have no choice but to perform filtration or adsorption. However, in normal hemodialysis therapy where only about 2 to 31 volumes of water are removed per treatment, we cannot expect much from "filtration removal". In other words, there is a need for a membrane that can also effectively perform "diffusion removal." Furthermore, conventional polymeric most toxic substance removal membranes generally have a problem in that their ability to remove low molecular weight toxic substances such as urea and creatinine is somewhat inferior to that of conventional blood purification membranes.

In order to solve these problems, the present inventors devised a hollow fiber membrane impregnated with a large amount of glycerin, with an adhesion rate of 20% or more, and achieved certain results, but its performance exceeded the intended purpose. It did not reach an optimal level that could be fully satisfied within the preferred range.

In addition, physical properties specific to impregnated glycerin, such as interfacial tension, hygroscopic properties, and viscosity, may cause the hollow fiber membrane to feel sticky, and the filaments may stick when the hollow fiber membrane is bundled. There are issues that need to be improved, such as poor handling when bundling to form a membrane separation module, poor module molding due to poor filament dispersibility, and poor efficiency in developing hollow fiber membrane performance as a module. This problem was noticeable in fiber membranes. In addition, since glycerin gradually evaporates at temperatures above 150°C, in the manufacturing process of hollow fiber membranes in which glycerin is applied and then dried, glycerin greatly controls the performance of the resulting hollow fiber membranes. There was also a problem with the hollow fiber membrane manufacturing method that it was difficult to control the adhesion rate.

The first object of the present invention is to suppress the loss of albumin, which is a nutritional protein, to a level that does not pose a practical problem (i.e., 10 g or less, preferably 5 g or less per treatment), and to High molecular weight poisonous substances including β2-microglobulin can be widely removed by filtration and diffusion mechanisms - in other words, hollow fiber membranes with better apparent fractionation properties are preferable to glycerin-containing hollow fiber membranes. Second, the hollow fiber membrane containing a large amount of glycerin with an adhesion rate of 20% or more has the above-mentioned difficulties in controlling performance during production of the hollow fiber membrane, poor handling when assembling the module, and problems as a module. The object of the present invention is to simultaneously achieve two purposes: to provide a hollow fiber membrane that does not cause problems such as poor efficiency in developing hollow fiber membrane performance.

[Means to solve the problem]

The above objects of the present invention are achieved by the following hollow fiber membrane.

That is, it has a hollow portion that continuously penetrates in the fiber axis direction, and the average membrane pore radius when wet is 40 to 250 Å, preferably 60 Å.
~200 Å, more preferably 60 to 180 Å, a water-containing porosity of 60 to 95%, preferably 76 to 95%, more preferably 80 to 95%, contains polyethylene glycol, and has a sieving coefficient of albumin in hemofiltration. This is a hollow fiber membrane made of regenerated cellulose, characterized in that the

The term "wet" as used herein means after the hollow fiber membrane has been immersed in pure water at 37° C. for one hour or more. Further, the "average pore radius of the membrane" can be estimated by the following equations based on pore theory based on actual measurements or partial assumptions of the water filtration rate, diffusion rate, water-containing porosity, etc. of the membrane. Note that "water-containing porosity" means the volume fraction of water in the wet hollow fiber membrane, but here, it is calculated using a simple formula for calculating the water-containing porosity when the manufacturing conditions are known. Ta. If the manufacturing conditions are unknown, they can be measured by a conventional method using a vicinometer or the like, and the values can be used.

Here, f (q) = (1-2,105q+ 2.0865
q″−1,7068q’+ 0.72603q’)/
(1-0,75857q')SD=(1q)"q""rl/1p τ = From equations 10 and 0, Ak(-): In-plane porosity τ(-): Pore theory (oil passage model) according to the oil passage ratio g (
Pa-sec): Viscosity of water (0,691x 10-
) L p (crl / cIIY / se
c/Pa): Membrane water filtration coefficient (37'C, 20(
(Actually measured using a hollow fiber membrane module with a membrane area of approximately 100'cA under 100μg) PIII (cm/5ec): Water diffusion transfer coefficient of membrane (3
(Actually measured at 7°C)
): By actually measuring the thickness of the hollow fiber membrane when wet, that is, Pm and Lp, r can be found using the equation (2).

Furthermore, by finding H based on the following equation, Ak, τ
Other membrane structural parameters are also determined.

r, (CIll) : Average pore radius of the membrane r, (C
al): Molecular diameter of water (1,07×10-”)
D (c+a/5ee): Diffusion coefficient of water (2,97
X10-') H(-): Membrane water content porosity Vs (c4/win): Spinning solution discharge amount ρs (g/
Id): Spinning solution density C<->: Cellulose weight fraction ω in the spinning solution (c11/
m1n): Winding speed ρ, 1g/d): True density of cellulose (assumed to be 1.52) r, (am): Outer radius of the hollow fiber membrane when wet r = (cm
): Inner radius of the hollow fiber membrane when wet (-): Stretching rate in the longitudinal direction of the yarn when transitioning from a dry state to a wet state (37°C
Note: H, V, ρSr, C and ω are actually measured at the time of hollow fiber membrane preparation, and ro and l”i are actually measured using a x200x microscope magnifying glass.

However, the regenerated cellulose hollow fiber membrane of the present invention has β2
- Regarding the removal of microglobulin, the amount removed by diffusion is equal to or greater than the amount removed by the filtration mechanism.

Contributing factors to the diffusion include the membrane pore radius, lI thickness, membrane water-containing porosity, and the like.

The hollow fiber membrane of the present invention is made of regenerated cellulose.

When regenerated cellulose is used as a membrane material, it can be made extremely thin due to its excellent mechanical strength, and its excellent hydrophilicity allows it to maintain practical strength while maintaining a high water-containing porosity that is effective for the diffusion mechanism. Therefore, it also has a good ability to remove low molecular weight substances that is not found in other materials.

Therefore, it is particularly suitable for use as an artificial kidney.

Regarding β2-microglobulin removal, a removal rate of 20% or more is desired for clinical use, but a membrane or its general substance with a β2-microglobulin sieving coefficient of 0.3 or more, preferably 0.5 or more The transfer coefficient is 2
This removal rate can be achieved by using a membrane that has X I O-'ax/sec or higher, or a membrane that has both characteristics. The term "removal rate" used here refers to the change in blood β2-microglobulin concentration of dialysis patients before and after dialysis.
It is calculated by correcting concentration using the hematocrit value.

The hollow fiber membrane according to the present invention having the above characteristics can be produced, for example, by the following method.

Cellulose concentration 4-12%, prepared by a known method
, preferably 4 to 8% cuproammonium rayon spinning solution, and a gaseous or liquid known non-coagulable hollow-forming agent (e.g. liquid halogenated carbon such as percrene, trichrene, trichlorotrifluoroethane, etc.: isopropylene). Various esters such as myristate: air, nitrogen; so-called freon gas such as tetrafluoromethane and hexafluoroethane, various halon gases), or methanol, ethanol, propatool, acetone, methyl ethyl ketone:
Along with a hollow part forming agent that exhibits microcoagulability in the spinning solution, such as an aqueous solution containing at least one selected from formic acid, acetic acid, propionic acid, glycerin and other polyols, or a mutually mixed solution thereof, It is discharged from a double spinneret, passed through a non-coagulating atmosphere, and then led to a coagulation bath. Coagulants include caustic soda, sulfuric acid, hydrochloric acid,
Aqueous solutions such as acetic acid, ammonium sulfate, acetone, and lower alcohols can be used, but sulfuric acid or ammonium sulfate aqueous solutions are preferably used. The use of sulfuric acid or ammonium sulfate aqueous solution can be easily provided by the hollow fiber membrane of the present invention, which has a larger pore size than conventional products. Furthermore, the use of these coagulants does not result in a homogeneous membrane, but rather provides a hollow fiber membrane with a small effective thickness.

By suppressing the membrane pore radius of the rate-determining layer (layer that regulates the size of permeable substances) of such hollow fiber membranes to 100 Å or less, it is advantageous for the diffusion and removal of the most deeply toxic polymeric substances, which are smaller in size than albumin. On the other hand, there is an advantage that the apparent molecular weight fractionation, that is, the selective removal ability, which can suppress the loss of useful blood components having a molecular weight larger than that of albumin, is much improved compared to the case of only filtration removal.

After scouring the coagulated fibers with water and inorganic acid, a membrane pore size retaining agent is applied, and then a drying process is performed to form the desired hollow fibers.
get the benefits. Liquid polyethylene glycol is used as the membrane pore size retaining agent. "Liquid polyethylene glycol" as used herein refers to an average molecular weight of 150 to 6, which is liquid at room temperature.
In addition to those of 00, average molecular ffi 200 containing these
00 or less; also includes solutions in organic solvents such as acetone, ethanol, trichlene, toluene, etc., and solutions in low molecular weight polyethylene glycols that are liquid at room temperature. At that time, the adhesion rate of polyethylene glycol is 20 to 200
The weight percentage is preferably 50 to 180% by weight, more preferably 70 to 150% by weight.

The membrane pore size can be designed depending on which waste products with a molecular weight of β2-microglobulin or higher are to be targeted for removal. Examples include using a combination of coagulation with an aqueous solution or sulfuric acid (aqueous solution) and liquid polyethylene glycol as a membrane pore size retaining agent.

Conventionally, glycerin has been put to practical use as a membrane pore size retaining agent and is widely used in existing hollow fiber membranes, but by replacing this with liquid polyethylene glycol as in the present invention, it is possible to obtain hollow fiber membranes with the same solute removal performance. The adhesion rate of the membrane pore size retaining agent required to obtain this can be reduced by 10% to 40% based on the weight of the polymer material.

Figures 1 and 2 show cases in which the coating rate of the membrane pore size retaining agent on the hollow fiber membrane was changed by varying the concentration and amount of the membrane pore size retaining agent applied under the same conditions as in Example 2 described below. The correlation between the adhesion rate of membrane pore size retaining agent and various solute removal performances was shown by comparing a glycerin-containing hollow system and a polyethylene glycol-containing hollow fiber. In other words, in Figure 1, β
- Sieving coefficient (SC) of lactoglobulin (β-LG)
Figure 2 shows the dependence of the sieving coefficient (SC) of albumin (Alb) on the pore size retention agent deposition rate. ). It has been shown that the polyethylene glycol-containing regenerated cellulose hollow fiber of the present invention is a membrane with superior molecular i fractionation characteristics due to differences in the molecular size of the membrane pore size retaining agent and the interaction of hydroxyl groups.

Furthermore, hollow fiber membranes containing polyethylene glycol reduce problems such as poor handling due to the sticky feel of the hollow fiber membranes, poor module molding due to poor dispersibility between filaments, and poor efficiency in developing hollow fiber membrane performance as a module. This effect is due to the material advantage that liquid polyethylene glycol has a smaller sticky feeling due to differences in physical properties such as interfacial tension, moisture absorption properties, and viscosity between liquid polyethylene glycol and glycerin, and the above-mentioned adhesion rate. achieved as a synergistic effect of reduction.

Furthermore, compared to glycerin, liquid polyethylene glycol volatilizes less during the heating and drying process, so even in the manufacturing process of hollow fiber membranes, which is dried after applying it, the adhesion rate will be lower during the process. In addition to manufacturing advantages such as being easily controlled by changing the volume applied to the hollow fiber membrane and the concentration at the time of application in the case of diluted solutions, hollow fiber membranes containing liquid polyethylene glycol have low hygroscopicity. Therefore, the physical properties of the hollow fiber membrane during product storage become stable over time. In addition, spinning stock solution (dope)
It is also possible to mix polyethylene glycol with it.

The significance of the liquid polyethylene glycol contained in the regenerated cellulose hollow fiber membrane of the present invention is that it maintains the desired structure when the hollow fiber membrane is completed, and that it provides good handling when assembled into a membrane separation device such as an artificial kidney. The objective is to ensure the following: and to suppress a decrease in the performance expression efficiency of the hollow fiber membrane within the membrane separation device due to assembly problems. In addition, when the hollow fiber membrane of the present invention is assembled as a membrane separation device (after enjoying the effect of the second objective of the present invention), if the inside of the device is to be cleaned or filled with liquid for practical use. Although the cellulose adhesion rate of polyethylene glycol may be reduced, the structure and performance intended for the hollow fiber membrane are maintained unless re-dried, so the first objective of the present invention is not impaired.

〔Example〕

EXAMPLES The present invention will be described in more detail with reference to Examples below. In the examples, "%" means % by weight unless otherwise specified.

The sieving coefficient was measured by a parallel filtration method at a transmembrane differential pressure of 5 QmmHg at the time of measurement.

A cuproammonium rayon solution containing 8% cellulose prepared by a known method as a back-spinning solution and trichlorotrifluoroethane as a hollow space forming agent were each used at a rate of 5.8 ml/llllin from a double spinneret.

Discharged into the air at a rate of 2.44d/sin, approximately 25C1
After being allowed to fall by its own weight, it was coagulated with a 25% Cl2O% ammonium sulfate aqueous solution, and then introduced onto a conveyor for the scouring process. On a conveyor where no forced mechanical tension is applied to this filament, 50°C warm water; 50°C, 2% sulfuric acid water;
After scouring with one shower in the order of ℃ warm water, unwind,
Polyethylene glycol 40 by membrane pore retaining agent applying device
0 (= “Macrogol 400 J” listed in the Japanese Pharmacopoeia)
After applying 100% liquid and 1.1 d/llln/2 filaments, it was run in a tunnel type drying oven at 155°C and then wound up at a speed of 90 m/win.

The amount of polyethylene glycol 400 attached to the hollow fiber membrane thus obtained was 105
%Met.

Furthermore, using the obtained hollow fiber membrane, a membrane area of approximately 1.5
When 100 m artificial kidney modules were assembled using a urethane-based botting agent, the yield was 100 good products without problems such as poor adhesion.

The structural specifications and in vitro membrane permeation performance of this hollow fiber membrane were as shown in Table 1. inV i shown in Table 1
The TRO test results show that not only β2-microglobulin but also β-lactoglobulin (= β-LG, molecular weight 35,000), which is a membrane permeability indicator substance, can be efficiently removed, while the permeation of albumin is extremely low, and albumin permeation is extremely low. Blocks the permeation of substances with larger molecular sizes,
It was shown that substances with molecular sizes smaller than this can be removed over a wide range of substance groups.

1 operation I The spinning solution discharge rate was 6.17II11/min, trichlorotrifluoroethane was used as the hollow part forming agent, and the discharge rate was 2.45! nl/win, and the amount of 30% aqueous solution of polyethylene glycol 400 applied is 1.0 relative/win.
lll1n/2 filament, drying temperature 155°C1
The winding speed was 100 m/min, and the other conditions were as in Example 1.
Accordingly, a hollow fiber membrane having a polyethylene glycol 400 adhesion amount of 24% based on cellulose was obtained.

Furthermore, when an artificial kidney module with a membrane area of approximately 1.5 mm was assembled using the obtained hollow fiber membrane using a urethane-based botting agent, the yield was 99 good products without problems such as poor adhesion. Met.

As shown in Table 1, this hollow fiber membrane exhibited effective removal performance for substances with a smaller molecular size than albumin.

A hollow fiber membrane was prepared using a 70% aqueous solution of polyethylene glycol 400, which was applied at a rate of 2.0 m/min/2 filaments, and in accordance with Example 2, in which the amount of polyethylene glycol 400 deposited was 131% relative to cellulose. Obtained.

Furthermore, using the obtained hollow fiber membrane, a membrane area of approximately 1.5
When 100 rrf artificial kidney modules were assembled using a urethane botting agent, the yield was 100 good products without problems such as poor adhesion.

As shown in Table 1, the hollow fiber membrane exhibited effective removal performance for substances with a molecular size smaller than that of albumin.

1JJL Example: The spinning solution discharge rate was 5.8 m/min, trichlorotrifluoroethane was used as the hollow part forming agent, the discharge rate was 2°83 mf/min, and polyethylene glycol 200 (average molecular group = approximately 200 mf/min) was used. ) The amount of 100% liquid applied is 1.5 mfl /min / 2 filaments,
The drying temperature was 160° C., the winding speed was 90 m/min, and the other conditions were as in Example 1 to obtain a hollow fiber membrane having a polyethylene glycol 200 adhesion amount of 120% based on cellulose.

Furthermore, using the obtained hollow fiber membrane, the membrane area was approximately 1.51.
When the artificial kidney module prepared in No. 1 was made ioo,tm using a urethane potting agent, the yield of good products without problems such as poor adhesion was 100.

As shown in Table 1, the hollow fiber membrane exhibited effective removal performance for substances with a molecular size smaller than that of albumin.

A cuproammonium rayon solution with a cellulose concentration of 8% prepared by a known method as a spinning solution, and trichlorotrifluoroethane as a hollow part forming agent were each used at a rate of 13.0 In1/min and 2.781 d using a double spinneret. /
The mixture was discharged into the air at a rate of 20 min and allowed to fall by its own weight by about 30 cm, and then coagulated with a 25° Cl2O% ammonium sulfate aqueous solution and led onto a conveyor for the scouring process.

50°C warm water; 50°C 12% sulfuric acid water;
After performing shower-type scouring in the order of °C warm water, unraveling, applying polyethylene glycol 400 (PEG400) using a membrane pore size retaining agent applying device, and running a 150"C tunnel type drying oven at 100 m/min. A hollow fiber membrane with a PEG400 coating amount of 150% per cellulose was obtained at a winding speed of .

The structural specifications and in vitro membrane permeation performance of this hollow fiber membrane were as shown in Table 1.

A cuproammonium rayon hollow fiber membrane, which has been conventionally used for artificial kidneys, was obtained according to a known method. As shown in Table 1, although this has an excellent ability to remove low molecular weight substances such as urea, it has a low ability to remove substances in the high molecular weight range such as β2 microglobulin, and is not suitable for the first purpose of the present invention. .

Hinu 1 70 of polyethylene glycol 400 in Example 3
% aqueous solution was changed to a 70% aqueous solution of glycerin, and a hollow fiber membrane was obtained under the same conditions except for the above. The glycerin adhesion rate of the hollow fiber membrane obtained at this time was 110%, and a comparison with Example 3 showed that glycerin evaporates more easily than polyethylene glycol 400.

Furthermore, using the obtained hollow fiber membrane, an artificial kidney module with a membrane area of approximately 1.5 mm was assembled using a urethane-based botting agent under the same conditions as in each example, and problems such as poor adhesion were found. The yield of non-defective products was 43.

The properties of this hollow fiber membrane were as shown in Table 1.

This Ml Tsuji 1 According to the manufacturing method of cellulose large pore membrane shown in JP-A-59-204912, the inner diameter is 250 mm and the membrane thickness is 25 I! ra,
A cuproammonium rayon hollow fiber membrane with an average pore radius of 300 was obtained. This is β2 as shown in Table 1.
- Although the sieving coefficient of microglobulin was 1.0, which showed extremely high removal ability, the sieving coefficient of albumin, which is a useful protein in the blood, was also high at 1.00, which is inappropriate for the purpose of the present invention. Met.

[Function and Effects of the Invention] The following is an explanation of the following: [Function and Effects of the Invention] It has a hollow portion that extends continuously in the fiber axis direction, has an average membrane pore radius of 40 to 250 Å when wet, and has a water-containing porosity of 76 to 95%.
and the sieving coefficient of albumin in blood filtration is 0.1
The hollow fiber membrane of the present invention, in which polyethylene glycol is attached at a ratio of 20 to 200% by weight based on the net weight of the hollow fiber membrane material, has a sieving coefficient of β2 microglobulin of 0.3 or more or its general substance. The transfer coefficient is 2
X 10-'cm/sec or more, it is suitable for filtration and diffusion removal of β2-microglobulin, and has excellent ability to remove high molecular weight substances other than β2-microglobulin. The loss of useful proteins such as these can be suppressed to a level that does not pose a practical problem.

That is, the hollow fiber membrane according to the present invention eliminates waste products having a molecular weight lower than albumin without substantially losing useful blood components having a molecular weight larger than that of albumin.
To provide a blood purification membrane capable of removing a wide range of substances including substances in the high molecular weight region typified by microglobulin.

Furthermore, by attaching polyethylene glycol as a membrane pore size retaining agent, the above-mentioned effects can be obtained even with a low membrane pore size retaining agent attachment rate, and moreover, the apparent molecular weight fractionation characteristics can be improved. Further, when the hollow fiber membranes are bundled, there is little adhesion between the filaments, and their dispersibility is not impaired, so problems such as poor module molding and poor efficiency in developing hollow fiber membrane performance as a module are solved.

[Brief explanation of drawings]

Figure 1 shows the dependence of the sieving coefficient (SC) of β-lactoglobulin (β-LG) on the pore size retention agent attachment rate, and Figure 2 shows the dependence of the sieving coefficient (SC) of albumin (Alb) on pore size retention. It shows dependence on agent adhesion rate. Figure 1 Figure 2

Claims (1)

[Claims] (1) It has a hollow part that penetrates continuously in the fiber axis direction, the average membrane pore radius when wet is 40 to 250 Å, and the water-containing porosity is 60 to 60.
A regenerated cellulose hollow fiber membrane containing 95% polyethylene glycol and having an albumin sieving coefficient in blood filtration of 0.10 or less.