JPH0321645B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel hollow fiber membrane, and relates to a hollow fiber membrane for dialysis suitable for purifying body fluids by dialysis.

Cellulose esters have traditionally been processed into hollow fiber membranes and used in various processes, such as desalination of brine and seawater, ultrafiltration of aqueous solutions containing various solutes, and energy-saving separation processes.

On the other hand, various research and development efforts have been made on cellulose ester-based hollow fiber membranes as hollow fiber membrane materials used for blood purification of renal failure patients due to their compatibility with living organisms and ease of production. In addition, the characteristics required for hollow fiber membranes used in hemodialysis include: no blood leakage from the hollow fibers, the ability to easily remove small molecular weight waste products from the body such as urea, uric acid, and creatinine, and balanced water permeability. There are times when you have something like that.

However, in cellulose ester hollow fiber membranes for blood purification, the amount of permeated water, that is, the ultraviolet rate UFR (ml/ ^m2・hr・mmHg), can be determined relatively easily.
Although it is possible to increase the solute permeability coefficient, it has been difficult to increase the solute permeability coefficient while balancing the permeate amount.

Therefore, the present inventors have conducted intensive studies on hollow fiber membranes that maintain a good balance between the ultraviolet rate UFR and the permeability coefficient of solutes (for example, urea permeability coefficient PUN), and as a result, have discovered the present invention.

In the present invention, the balance between the two was evaluated using the membrane constant M defined by the following equation (a).

M=P×10 ⁵ /√ (a) The present inventors considered the permeation of water and solute through a membrane using a pore mechanism. The radius of the pores in the membrane is rcm, the membrane thickness is Δdcm, the number of pores is n/cm ² , and the viscosity of water is ηg/
Let it be cm・sec. The permeability coefficient of the solute membrane is Pcm/sec
Let the diffusion coefficient of solute be Dcm ² /sec. Also, the amount of movement of water per unit time is Vcm/sec. Movement amount V
cm/sec is ultraviolet rate UFRml/m ²・hr・mmHg
and (b).

UFR=V/ΔP×4.8×10 ¹⁰ (b) Vcm/sec is from Hagen Poiseulle's Law (c)
It is given by Eq.

V=nπr ⁴ ΔP/8ηΔd (c) Δpg/cmsec ² represents the pressure difference at the entrance and exit of the pore.

The permeability coefficient P of the solute in the membrane is determined by equation (d) using the pore area and the solute diffusion coefficient Dcm ² /sec.
When formula (d) is transformed using formula (c), formula (e) is obtained.

P=Dnπr ² /Δd (d) P=√8× (e) It can be seen from equation (e) that the balance between the amount of permeated water and the permeability coefficient of solute is determined by the number of pores n. (b) and
From equation (e), the present inventors defined the membrane constant M in equation (a) as a parameter for evaluating the balance between UFR and PUN.

The shape of dialysis modules for artificial kidneys is becoming smaller in order to reduce the amount of blood filled in the module. When miniaturized, the properties required of hollow fiber membranes are such that in order to maintain the same water permeability per module, it is necessary to increase the UFR. Furthermore, in order to compensate for the decrease in membrane area, it is necessary to increase the solute permeability coefficient of the membrane.

As an example of cellulose acetate hollow fiber membrane, JP-A-54-42420 can be mentioned;
When the UFR is about 5 to about 6 ml/ ^m2・hr・mmHg, the permeability coefficient of urea is about 50×10 ^-5 to about 75×10 ^-5 cm/
Hollow fiber membranes that are sec are described. And when evaluated using the film constant according to the present invention, UFR is 5
ml/m ²・hr・mmHg, urea permeability coefficient is 75×10 ^-5
For a hollow fiber membrane with cm/sec, it is 33.5.

Based on pore theory, the present inventors found that in order to balance the amount of permeated water and the solute permeability coefficient, it is possible to obtain a hollow fiber membrane with a high membrane constant when the inulin permeability exceeds 30%. I found out what I can do.

However, as the pores become larger and the number of pores increases, the strength of the hollow fibers inevitably decreases, causing damage during the module assembly process, making it impossible to use the fibers as a hemodialysis module. The present inventors have discovered a hollow fiber membrane that has an appropriate membrane constant and does not cause any performance deterioration or damage to the hollow fiber membrane during module assembly.

The present invention is a hollow fiber membrane for dialysis, which has an ultrafiltration rate UFR (ml/m ² hr mmHg) within the range of equation (1), and a urea permeability coefficient PUN (cm/sec). Among them, there are some that are characterized by having a performance having the relationship expressed by formula (ii) and having an inulin transmittance SC (%) within the range expressed by formula (iii).

10≧UFR≧4 (1) P _UN ×10 ⁵ /√≧40 (ii) SC≧30 (iii) Cellulose esters that can be used in the hollow fiber membrane for dialysis in the present invention include cellulose diacetate, cellulose triacetate, Cellulose esters such as cellulose propionate, cellulose butyrate, cellulose acetate propionate, and cellulose acetate ghylate may be used alone or in mixtures thereof.

The cellulose ester hollow fiber membrane of the present invention is
Using a liquid that is incompatible with an alkaline aqueous solution as the core liquid, the cellulose ester spinning dope is extruded from an annular orifice through an annular slit in the outer tube of a spinneret with a double-tube structure, and the core liquid is extruded from the inner tube of the spinneret. At the same time, the spinning stock solution is first introduced into a gas atmosphere and then introduced into an aqueous coagulation bath, and after washing the adhering coagulation liquid with water,
1 to 30 with 0.1% to 13% by weight alkaline aqueous solution
It is manufactured by treating the alkali aqueous solution with an acetic acid aqueous solution and then washing with water. In particular, in order to maintain the UFR, P _UN and SC of the present invention within a predetermined range, the spinning stock solution is It is desirable to set the concentration of cellulose ester therein to 30% by weight or more.

Hereinafter, the present invention will be explained in more detail with reference to specific examples, but the present invention is not limited to this scope.

In addition, the urea permeability coefficient P _UN (cm/
sec) and inulin permeability SC (%) were calculated using the following formula.

(1) P _UN (cm/sec) P _UN =Q _B /A lnC ₁ /C ₂ where Q _B ; Flow rate of feed liquid (ml/sec) A; Effective membrane area (cm ² ) C ₁ ; Raw solution inlet Urea concentration at the stock solution outlet C ₂ ; Urea concentration at the stock solution outlet (2) SC (%) SC = C ₄ /C ₃ ×100 where C ₃ ; Inulin concentration in the stock solution C ₄ ; Inulin concentration in the permeate Example 1 31 parts by weight of cellulose diacetate, 48 parts by weight of dimethylformamide, polyethylene glycol
Mix and dissolve 21 parts by weight of 200 and use this as a spinning stock solution.
Spinning was carried out using an annular orifice nozzle.
A spinning dope was supplied from the outer tube, while liquid paraline was discharged as a core liquid. The hollow stock solution that came out of the annular orifice was run in 15 cm of air, then solidified, then washed with water, run in a 5% by weight sodium hydroxide aqueous solution for 6 seconds, and then passed through an acetic acid aqueous solution bath and a water washing bath. The hollow fibers were then passed through a 40% by weight aqueous glycerin bath, and then passed through a zone of dry air at 60° C. in countercurrent to the hollow fibers, and wound onto a bobbin using a winder. The obtained cellulose acetate hollow fibers had a perfect circular shape, an inner diameter of 200 μm, and a film thickness of 22 μm. of this membrane
UFR is 5.5ml/ ^m2・hr.mm. The permeability coefficients for Hg and urea were 94×10 ^-5 cm/sec. The permeability of inulin was 35%. The membrane constant is 40.1,
It is superior to conventional cellulose ester hollow fiber membranes. Furthermore, the falling strength of the hollow fiber membrane per single fiber was 27 g, and no trouble occurred when the hollow fiber was used to form a module. Incidentally, the descending strength is measured by conducting a tensile test at a yarn length of 10 cm and a tensile speed of 10 cm/min, and measuring the strength corresponding to the descending point of the obtained strength-elongation curve.

Example 2 The dimethylformamide of Example 1 was converted into N-methylpyrrolidone and polyethylene glycol 200
A spinning dope was prepared in the same manner as in Example 1, except that ethylene glycol was used, and the dope and core liquid were extruded from an annular orifice nozzle, passed through the air, introduced into a coagulation bath, coagulated, and then washed with water. death,
Run in a 7% by weight sodium hydroxide aqueous solution, then pass through an acetic acid aqueous solution bath, a water washing bath, and then 41
% by weight through a glycerin aqueous solution bath, then
The hollow fibers were passed through countercurrent to dry air at 60°C and wound onto a bobbin using a winder. The obtained cellulose acetate hollow fiber membrane has a perfect circular shape with an inner diameter of
It was 200μ and the film thickness was 21μ. UFR of this hollow fiber membrane
is 5.1ml/ ^m2・hr.mmHg, and the permeability coefficient of urea is 93
×10 ^-5 cm/sec. The permeability of inulin is
It was 41%. The membrane constant is 41.2, which is superior to conventional cellulose ester hollow fiber membranes. Further, the falling strength of the hollow fiber per single yarn was 25 g, and no trouble occurred when the hollow fiber was made into a module.

Comparative Example 1 33 parts by weight of cellulose diacetate, 54 parts by weight of N-methylpyrrolidone and 13 parts by weight of ethylene glycol were mixed and dissolved to prepare a spinning stock solution, which was spun using an annular orifice nozzle to obtain an inner diameter of 202μ and a film thickness of 20μ.
A cellulose acetate hollow fiber membrane was obtained. The UFR of this hollow fiber was 3 ml/m ² ·hr · mmHg, and the permeability coefficient of urea was 70×10 ^-5 cm/sec. The membrane constant was 40.4. On the other hand, in order to obtain a module having the same level of performance as the amount of permeated water in the module produced in Example 2, it was necessary to increase the packing density or the module container by 1.7 times. However, the packing density
If the capacity is 1.7 times, it will be difficult to form a module, and on the other hand, if the capacity of the module is 1.7 times, the blood volume within the module will also be 1.7 times, which is not preferable because the extracorporeal circulation amount of blood will be significantly reduced.

Comparative Example 2 The same spinning solution as in Example 1 was spun and coagulated in the same manner as in Example 1, and then washed with water to reduce the inner diameter.
A cellulose acetate hollow fiber membrane having a diameter of 200 μm and a thickness of 22 μm was obtained (the treatment with an aqueous sodium hydroxide solution and an aqueous acetic acid solution after spinning, washing with water, and coagulation as in Example 1 was not performed). The obtained hollow fiber membrane has a UFR of
5.3ml/m ²・hr・mmHg, PUN is 82×10 ^-5 cm/sec
It was hot. The membrane constant was calculated to be 35.6. When a module was prepared using such a hollow fiber membrane and its urea clearance was measured, it was found to be only 137 ml/min. On the other hand, when the module of Example 1 was used, the urea clearance was 157 ml/min.

Incidentally, urea clearance was determined using the following formula.

C=Q _B・1−exp{N _T (1−Q _B /Q _D )}/Q _B /Q _D −exp{
N _T (1-Q _B /Q _D )} Here, N _T = K ₀ · S / Q _B Q _B , Q _D ; Blood flow rate and dialysate flow rate (ml/min) K _O : Overall mass transfer coefficient (cm /min) S; module membrane area (cm ² ) and K _O =Q _B /S (1-Q _B /Q _D )1n (C/Q _D -1) / (
C/Q _B -1)

Claims (1)

[Scope of Claims] 1. A cellulose acetate-based hollow fiber membrane for dialysis spun from a spinning stock solution containing 30% by weight or more of cellulose acetate, which has an ultrafiltration rate of UFR.
(ml/ ^m2・hr・mmHg), UFR and urea permeability coefficient
Relationship with PUN (cm/sec) and inulin permeability SC
A hollow fiber membrane for dialysis, characterized in that (%) satisfies the following range and the yield strength per single hollow fiber is 20 g or more. 4≦UFR≦10 (i) PUN×10 ⁵ /√≧40 (ii) SC≧30 (iii)