JPS61254201A - Hollow fibrous serum separation membrane - Google Patents

Abstract

PURPOSE:To obtain a hollow fibrous membrane of which the separation capacity is highly held and the thermal deformation ratio at 121 deg.C for 20min in a free state is 2% or less, by reducing the number of solute impervious pores while holding the number of solute pervious pores. CONSTITUTION:Cellulose ester is dissolved in a solvent such as N-methyl-2- pyrrolidone or dimethylformamide and polyethylene glycol being a swelling agent and the resulting solution is spun into a hollow yarn shape along with an internal solution consisting of the same solvent and the same swelling agent. This spun hollow yarn is guided to a coagulation bath consisting of the same solvent and the same swelling agent. In this case, the value calculated by subtracting the concn. of the solvent and swelling agent in the internal solution from that of the solvent and swelling agent in the coagulation bath is set to 0-20. Because each of the change ratios of the hollow yarn in the axial and diameter directions, after said yarn was immersed in water at 121 deg.C for 20min in such a state that both ends thereof are made free, can be suppressed to 2% or less, autoclave sterilization in water at 121 deg.C, in such a state that both ends are fixed, is enabled.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Field of Application) The present invention relates to a hollow fibrous plasma separation membrane used to separate plasma from blood.

(Prior art J) In recent years, plasma separation membranes have been used for plasmapheresis therapy, donated plasma supplied from normal people, and plasma collection from donated blood. Required properties include safety as a medical material and separability that allows a large amount to be separated from blood without changing the composition of plasma components as much as possible.First of all, regarding safety, there is no damage to blood cell components during separation. It is necessary for the membrane to be able to withstand external shocks when it is assembled into a plasma separator.In practice, there is a possibility of unexpected shocks being applied during transportation, and when defoaming inside the hollow fibers. Since the separator is struck with forceps, the mechanical strength of the membrane must be sufficiently high.In other words, if this mechanical strength is low, the membrane will be damaged and blood cells will flow out from inside the hollow fiber, causing serious problems. It is.

Next, regarding separability, there is no change in the composition of high-viscosity plasma, which is the target of plasmapheresis treatment, and normal plasma, which is donated! In the former case, separation for 1 minute increases the therapeutic effect,
In the latter case, it is necessary to increase the value of stored plasma.

However, this mechanical strength and separation performance are contradictory properties, and the plasma separation membranes conventionally used have not been able to resolve these contradictory properties. That is, if the mechanical strength is increased in order to improve safety, the separation performance will be lowered, and patients and plasma donors will be restrained for a long time, which will increase the burden. In addition, increasing separability conversely reduces strength, which requires careful attention to safety and poses many problems in handling.

Furthermore, separators incorporating plasma separation membranes must be ultimately sterilized. EOG sterilization, formalin sterilization, R-ray sterilization, autoclave sterilization, etc. are used as sterilization methods, but autoclave sterilization is desired because it is reliable and effective without worrying about residual sterilization agents. However, when conventional cellulose ester membranes are assembled into a separator and sterilized in an autoclave with both ends fixed, their shape changes due to poor thermal stability, making it difficult to maintain the membrane properties before sterilization. .

(Problems to be Solved by the Invention) As a result of intensive studies by the present inventors to eliminate the above-mentioned drawbacks associated with conventional plasma separation membranes, the present inventors have discovered a membrane with high mechanical strength and separation performance, and which has both ends fixed. The inventors have discovered a hollow fibrous plasma separation membrane that does not cause any shape change during autoclave sterilization under normal conditions, and have arrived at the present invention.

(Means for solving the problem) That is, the present invention provides a film made of cellulose ester with a thickness of 8
Ultrafiltration speed UY (m//Wt
-hr -wtHy) and blue dextran 2000
The sieving coefficient ♂ satisfies the following equations (1) and (2) at the same time,
In addition, the deformation rate in both the axial and radial directions after being in contact with water at 121"C for 20 minutes with both ends of the membrane free is 2.
% or less.

500≦Y<2000 (1)-2,OX
10-'xY+0.6≦♂≦1.0 (21 The sieving coefficient of the above Blue Dextran 2000 is determined as follows.
Manufactured by armacia Fine Chemicals,
The average molecular weight (2,000,000 Daltons) is 0. Dissolved in IN phosphate buffer (pH=7.0), 0.025% by weight
A feed solution was prepared after filtering through a 0.45 μm membrane. On the other hand, a module 7 was prepared by bundling 42 hollow fibrous plasma separation membranes and fixing both ends with adhesive so that the effective permeation area was 151, so that the solution could pass through the inside of the hollow fibers at both ends. Install this module as shown in Figure 1 (6 in Figure 1). Pure water 10 is supplied by a liquid feed pump 11 to perform defoaming. After complete defoaming, the three-way cock 12 is switched and a 0.025% by weight aqueous solution is supplied by the liquid feed pump 2 to prevent air from being mixed in, replacing it with pure water. Immediately after replacing, use screw cock 9 to check that the average value of pressure gauges 4 and 7 is 100.
11! Adjust within 5 minutes so that the HP is reached, and the start time is when the adjustment is completed. Pressure 1001! 'After 15 minutes of maintaining at WHp, the liquid to be filtered from module 6 is collected for 2 minutes. At the same time, the i liquid supplied to module 6 and the liquid after passing (not after filtration) are collected. Absorbance α1. of the filtrate, feed and flow through at a wavelength of 254 nm. α2 and α
5 and α1/(α2+αS) as blue dextran 2
The sieving coefficient was set to 000.

The sieving coefficient of such blue dextran is 12XIF'X
When Y + is in the range of 0.6 to 1.0 and the ultrafiltration rate is in the range of 500 to 2000, the average pore area of the membrane is increased and the pore size distribution is narrowed. By reducing the number of pores through which solute does not pass while maintaining the number of pores through which solute passes, high separation performance can be maintained, the mechanical strength of the membrane can be increased by the reduction in pores which do not pass through, and the membrane thickness can be kept to 80 μm or less. It has become possible.

That is, the ultrafiltration speed is 2000 m//m hr-1! I
'm) If it exceeds LP, the separability will improve, but the mechanical properties will deteriorate, and if it is less than 500 m//d-hr-mHy, the strength will increase, but the separability will deteriorate, which is not preferable. Also, the dextran sieving coefficient is -2, Ox to”
-' x Y + less than 0.6 is not preferable because the blood decomposition after filtration changes greatly. In addition, the shaft after being immersed in 121℃ water for 20 minutes with both ends of the membrane free,
The fact that the rate of change in the radial direction is suppressed to 2 inches or less means that autoclave sterilization in 121"C water is possible with both ends fixed. If both of these rates of change exceed 2%, autoclaving is possible. This is not preferable since the film thickness may sometimes be distributed in the axial and radial directions, resulting in changes in film characteristics.

The hollow fibrous plasma separation membrane of the present invention is made of cellulose ester. A separation membrane having the above characteristics is produced, for example, by the following method. Cellulose esters (cellulose diacetate, cellulose triacetate, cellulose nitrate, etc.) are dissolved in a solvent (N-methyl-2-
pyrrolidone, dimethylformacide, etc.) and a swelling agent (polyethylene glycol).
Spun into a medium-walled thread together with a solution (inner solution) consisting of a swelling agent. The spun hollow fibers are introduced into a coagulation bath containing the same solvent and swelling agent. At this time, the concentration of (swelling agent in solvent) in the coagulation bath (Co
ut) and the concentration of (solvent + swelling agent) in the internal solution (C!in)
It is important to select from the following ranges.

O≦Cout-C1n≦x0 (wt%) (Effect of the invention) The hollow fibrous plasma separation membrane according to the present invention thus obtained has high mechanical strength and plasma separation performance, and can be sterilized in an autoclave. It is effectively used for plasmapheresis treatment, blood donations that receive plasma from normal people, plasma collection from donated blood, etc.

(Examples) Examples of the present invention will be described below, but the present invention is not limited to these examples.

Example 1 A plasma separation membrane having a membrane thickness of 74 μm was manufactured in the following manner.

Spinning stock solution; 30″M amount of cellulose triacetate,
Dissolved in a mixed solvent obtained by mixing N-methyl-2-pyrrolidone and polyethylene glycol (400) in a weight ratio of 6:4.

Spinning: After heating the spinning dope to 120°C, it is spun out from a nozzle at 84°C, passed through air, and introduced into a coagulation bath. A coagulation bath is introduced into the hollow fiber during spinning.

Coagulation: N-methyl-2 as coagulation bath (hollow fiber internal liquid)
- Coagulation with an aqueous solution containing 68% by weight of pyrrolidone and polyethylene glycol (400), and an aqueous solution containing N-methyl-2-pyrrolidone and polyethylene glycol (400) as a coagulation bath (hollow fiber external temperature).

Post-treatment: After solidification, washing with water, then 50°C, 90% by weight
Treat in a glycerin bath for 1 hour and dry.

The performance of the hollow fiber membrane obtained is listed in Table 1.

Table 1 (Note) XI) A film with length L (=150!l) and thickness dμm
After being immersed in 1'C water for 20 minutes, the length (L) and film thickness (6) were measured and the rate of change was determined from the following formula.

X2) Constant speed transfer #j for one membrane of length l0CX1
The load at break of the sow measured using an H-type tensile tester.

X3) Percentage beyond the limit calculated by the following formula based on the membrane surface standard of 0.5tyj = (separated plasma flow rate/supplied blood flow rate)
X 100 However, blood supply flow Ji 100m//min
And so.

Table 2 shows the results of measuring all the characteristic values of two known plasma separation membranes.

Table 2

[Brief explanation of the drawing]

FIG. 1 shows a flow sheet for measuring the sieving coefficient of Blue Dextran 2000.

Claims (1)

[Claims] Hollow fiber membrane made of cellulose ester with a thickness of 80 μm or less, ultrafiltration rate Y [ml/m^2・hr・m
mHg] and the sieving coefficient x of Blue Dextran 2000 satisfy the following equations (1) and (2) at the same time, and the axial direction and A plasma separation membrane with a deformation rate of 2% or less in both radial directions. 500≦Y<2000 (1) −2×10＾−＾4×Y+0.6≦x≦1.0 (2)