JPH0611325B2 - Porous hollow fiber membrane - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a blood purification membrane for selectively removing harmful substances that adsorb proteins in plasma.

[Prior Art] Recently, plasma exchange therapy has been clinically applied to the treatment of intractable diseases, and its effect is being gained. However, this removes all plasma components and replenishes supplemental fluids such as fresh plasma, plasma preparations, albumin, etc., and not only the active ingredients in plasma cannot be recovered, but also the lack of plasma or plasma preparations as supplemental fluids. ,
Many problems such as the occurrence of serum hepatitis and allergies have been pointed out.

For this reason, a two-stage separation method and a low temperature filtration method have been devised as a method for removing a polymer substance (hereinafter referred to as a harmful substance) that causes a disease from the plasma obtained by separating blood cells by membrane separation. However, it is very difficult to selectively remove only harmful substances depending on the pore size of the membrane because the molecular weight of the harmful substances differs depending on the disease and it is very difficult to control the pore size to a specified size. There are limits because of this.

On the other hand, a method for removing harmful substances using an adsorbent has also been investigated. As a method for adsorbing and removing bilirubin and other harmful substances that adsorb plasma proteins, a porous copolymer obtained by polymerizing acrylonitrile or the like is disclosed in JP-B-58. -29139. Although this adsorbs bilirubin and the like in plasma, its ability is not yet sufficient, and it has not yet been put to practical use.

[Problems to be Solved by the Invention] It is an object of the present invention to provide a porous hollow fiber filtration membrane capable of selectively removing plasma protein-adsorptive harmful substances only by filtering plasma or serum. To do.

[Means for Solving Problems] C That is, the gist of the present invention is that the surface of the micropores is made of a polyacrylonitrile polymer, the film thickness is 5 μm to 300 μm, the specific surface area is at least 10 m ² / g, and the inner wall surface is It is a porous hollow fiber filtration membrane having a large number of micropores penetrating to the outer wall surface and having a human serum albumin permeability of 80% or more.

When the thickness of the membrane of the present invention is less than 5 μm, the adsorption area is small, and when it exceeds 300 μm, the plasma permeability is lowered. The material of the porous film is not particularly limited,
It is necessary that the immunoactive substance is immobilized on the surface of the micropores. The material of the porous membrane may be a polyacrylonitrile-based polymer, but it is not particularly limited to obtain a porous hollow fiber membrane having the features of the present invention by spinning the polyacrylonitrile-based polymer. Since it is difficult in many cases, it is preferable that the polyacrylonitrile polymer is fixed to the surface of the micropores of the porous hollow fiber membrane made of another material. In this case, the added amount is 5 to 20% with respect to the base material.
Is preferred. Examples of the material of the porous hollow fiber membrane include polyvinyl alcohol, cellulose acetate, polyolefin and the like. Further, as an example of the method of introducing the polyacrylonitrile-based polymer into the surface of the membrane micropores, graft polymerization can be mentioned. The polyacrylonitrile-based polymer referred to in the present invention means a polymer containing 70% or more of polyacrylonitrile, methacrylonitrile or α-chloropolyacrylonitrile.

As the porous hollow fiber membrane, one obtained by stretching a highly oriented crystalline unstretched hollow fiber made of polyolefin or the like at a relatively low temperature is preferably used because it has a large internal surface area of fine pores.

The porous membrane used in the present invention has a specific surface area of at least 10 m ²
/ G or more is required. If the specific surface area is less than 10 m ² / g, the removal efficiency of harmful substances in blood is not sufficient. This specific surface area can be measured by a nitrogen gas adsorption method. The porous membrane has a human serum albumin permeability of 80.
% Or more is required. As for the human serum albumin permeability, a hollow fiber having an effective length of 7 cm is used when the membrane is a hollow fiber, and a physiological saline solution of 0.1% human serum albumin serum is circulated inside the hollow fiber under the condition that the transmembrane pressure difference is 50 mmHg. The concentration of human serum albumin contained in the filtrate was
It can be calculated by the following formula using the value obtained by measuring the absorbance at 0 nm.

When the human serum albumin permeability is less than 80%, when blood is filtered, harmful substances can be removed, but useful plasma components are not sufficiently permeated, which is not preferable.

The size of the fine pores of the membrane is preferably 1 to 4 kg / cm ² in terms of bubble point, from the viewpoint of plasma permeability. The bubble point can be measured by using ASTM F316-80 or a method according thereto (in the case of hollow fiber) using ethanol as a test solution. The porous membrane may be a flat membrane, but is preferably a hollow fiber because the device can be made compact. In the case of hollow fibers, the inner diameter is preferably 150 to 500 μm. The porosity is 3
It is preferably 0% or more in terms of plasma or serum filtration, and more preferably 40% or more.

[Examples] The present invention will be described in more detail with reference to the following examples.

Example 1 As a porous membrane having a large number of minute pores penetrating from the inner wall surface to the outer wall surface, an inner diameter of 270 μm, a film thickness of 60 μm, a porosity of 60 vol%, a bubble point measured in ethanol of 3.2 kg / cm ² , Internal surface area 3 measured by N ₂ adsorption method
Using 2 m ² / g polyethylene porous hollow fiber membrane EHF (trade name, manufactured by Mitsubishi Rayon Co., Ltd.), acrylonitrile was subjected to electron beam graft copolymerization by pre-irradiation in air. The amount of acrylonitrile added was about 9% based on the polyethylene hollow fiber. Using this hollow fiber, a plasma filtration mini-module having an effective length of 7 cm and a membrane area of 200 cm ² (hollow fiber inner diameter standard) was prepared. The transmittance of human serum albumin γ globulin in this mini-module was 96%. Using this mini-module, plasma containing 15.8 mg / dl of unconjugated bilirubin was flown into the hollow fiber at a rate of 4 ml / min at 37 ° C. and filtered through the hollow fiber membrane surface at a rate of 0.3 ml / min for 60 minutes. . The unfiltered plasma was recirculated to the unfiltered plasma by a circulation filtration method. Bilirubin concentration in plasma after filtration is 6.3 mg / dl
Met. In contrast, the loss of total protein, albumin and immunoglobulin was slight.

Comparative Example 1 Using the same polyethylene porous hollow fiber membrane as that used in Example 1, a mini module was prepared without graft copolymerization, and after hydrophilizing treatment with ethyl alcohol, the same conditions as in Example 1 were applied. Then, the same plasma as in Example 1 was filtered. Bilirubin concentration in plasma after filtration is 12.1 mg / d
It was l.

Comparative Example 2 0.4 g of 0.8 denier acrylic fiber (having almost the same weight as the hollow fiber used in Example 1) from which the fiber oil was removed by boiling in methanol for 2 hours was treated with the same plasma as used in Example 1. 18 ml (about the same weight as the plasma treated in Example 1) was added and incubated at 37 ° C. for 2 hours. The plasma bilirubin concentration in the supernatant was 14.1 mg / dl.

Comparative Example 3 Acrylonitrile 55 g, divinylbenzene (purity 50
%) 45 g, acetophenone 180 g, decalin 120
g, 1 g of azobisisobutyronitrile, 1 g of 2,2'-azobis (2,4-dimethylvaleronitrile), 6 g of partially saponified polypinyl alcohol, and 1280 g of ion-exchanged water in which 13 g of sodium chloride are dissolved, and stirred While 45
1 hour at ℃, 2 hours each at 50 ℃ and 60 ℃, 70 more
Polymerization was carried out by heating at 4 ° C. for 4 hours, and after the polymerization was completed, it was washed with methanol and then with water to obtain porous crosslinked polyacrylonitrile beads. The specific surface area of the beads was 190 m ² / g. 0.4 g of this adsorbent was incubated in the same manner as in Comparative Example 2 with 18 ml of the same plasma as used in Example 1. The plasma bilirubin concentration in the supernatant was 10.2 mg / dl.

[Effects of the Invention] The porous hollow fiber membrane of the present invention has a remarkably large active surface area because the surface of its micropores is made of a polyacrylonitrile-based polymer, and plasma is better than granular adsorbents or acrylic fibers having acrylonitrile immobilized on the surface. It has the characteristics that the treatment efficiency when treated with is much higher and the loss of useful substances is less.

Claims (1)

[Claims] 1. A micropore surface made of a polyacrylonitrile polymer, having a film thickness of 5 μm to 300 μm, a specific surface area of at least 10 m ² / g, and having a large number of micropores penetrating from the inner wall surface to the outer wall surface. A porous hollow fiber filtration membrane having a human serum albumin permeability of 80% or more.