JPH07116484A - Micro-porous membrane of polyethersulfone and sulfonated polyethersulfone having endotoxin-absorptive power - Google Patents

Abstract

PURPOSE:To easily and efficiently remove endotoxin by absorption to an extremely low concentration by processing a micro-porous membrane of polyethersulfone and sulfonated polyethersulfone having good fluidity using cationic resins to impart zeta potential to the surface of the membrane. CONSTITUTION:Polyethersulfone resin and sulfonated polyethersulfone resin are used to manufacture a micro-porous membrane by a conventinal method. Thereafter the micro-porous membrane of polyethersulfone and sulfonated polyethersulfone is dipped in a solution of cationic resin such as polyamide.epichlorohydrin, which membrane is then drid and heat treated, wherein alkali is added to the solution of polyamide.epichlorohydri resin to provide pH 12-13 thereby effectively performing the treatment. As a result, positive zeta potential is imparted to the surface of the membrane, so that the micro-porous membrane of polyethersulfone and sulfonated polyethersulfone, wherein an endotoxin-absorptive power is held, can be provided.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention is used for removing harmful endotoxin from a liquid such as an injection solution, a dialysate solution or an infusion solution which directly enters a living body through a vein, and is used in an industrial production process of these solutions. The present invention relates to a microporous membrane that can be used.

[0002]

BACKGROUND OF THE INVENTION Endotoxin is a complex of lipopolysaccharide and protein that constitutes the outer membrane of the cell wall of Gram-negative bacteria. It is a harmful substance that causes fever and shock when it enters the body, and is used for intravenous injection. Needs to remove this in advance. By the way, as a method for removing endotoxin from the above liquid, ion chromatography, gel chromatography, affinity chromatography (Japanese Patent Publication No. 16389) and the like have been proposed.
However, these ion chromatography, gel chromatography, and affinity chromatography are not practically advantageous methods because the equilibrium adsorption amount is small and it is difficult to set conditions such as PH, ionic strength, and regeneration conditions. In addition, the ultrafiltration method using a reverse osmosis membrane or an ultrafiltration membrane has a molecular size of 0.001 in order to remove endotoxin.
Since it is about μm, it is necessary to use a membrane having a molecular weight cut-off of about 6000, and the low flow rate characteristic makes the apparatus large in size in order to increase the throughput. Furthermore, there is a disadvantage that high pressure is required for filtration and running cost increases.

[0003]

SUMMARY OF THE INVENTION The present invention has been made in view of the above circumstances and is capable of removing endotoxin up to an extremely low concentration with high treatment efficiency (that is, low pressure) and high flow rate. It is intended to obtain the obtained polyethersulfone and sulfonated polyethersulfone microporous membrane.

[0004]

[Means for Solving the Problems] In order to achieve the above object, the present inventors have conducted various studies, paying attention to the fact that endotoxin contained in water is charged with anion (anion), and The excellent poly (ether sulfone) and sulfonated poly (ether sulfone) microporous membranes are treated with a resin having a cationic property, and the zeta potential on the surface of the membrane is made positive to retain the endotoxin adsorption ability. It was successful. Explaining the manufacturing process of the microporous membrane of the present invention having the above-mentioned structure, it is a raw material of the microporous membrane,
A microporous membrane is prepared by a conventional method using a polyethersulfone resin and a sulfonated polyethersulfone resin (FIG. 1). As the cationic resin, polyamide / epichlorohydrin resin having a quaternary ammonium salt group is used. Immersing the poly (ether sulfone) and sulfonated poly (ether sulfone) microporous membrane in the polyamide / epichlorohydrin resin solution which is this cationic resin,
Heat treatment after drying. At the time of this treatment, alkali is added to the polyamide-epichlorohydrin resin solution to adjust the pH to 12-13.
By doing so, the processing is performed more effectively.
As a result, a polyethersulfone and a sulfonated polyethersulfone microporous membrane in which a positive zeta potential is applied to the membrane surface to retain the endotoxin adsorption ability are obtained (FIG. 2).

[0005]

EXAMPLE A membrane having a pore size of 0.2 μm was prepared from a sulfonated polyethersulfone resin, and another polyamide / epichlorohydrin resin aqueous solution (solid content 0.6%, pH 1) was prepared separately.
2 to 13) for 5 minutes, air-dried, and further heat-treated at 100 ° C. for 10 minutes to complete the microporous membrane of the present invention.

[0006]

[Results of endotoxin removal test (1)] The microporous membrane obtained above was set as a φ47 mm sample in a holder that had been dry heat sterilized at 250 ° C. for 1 hour in advance, and then 20 m.
Washed with 1 of endotoxin free water. After that, a 50 ml / min / φ47 mm endotoxin aqueous solution (concentration: 201 EU / ml) was filtered, and the endotoxin concentration of the filtrate was determined by gel inversion (gelation sensitivity 0.03).
EU / ml). As a result, the endotoxin concentration in the filtrate was 0.03 EU / ml or less up to 400 ml, indicating a high endotoxin adsorption amount. The endotoxin adsorption removal state is shown by FIG. In contrast to this, when a removal test was carried out under the same conditions without treatment with the polyamide-epichlorohydrin resin aqueous solution, endotoxin adsorption was not observed at all.

[0007]

[Endotoxin removal test results (2)] A microporous membrane obtained in the example was folded to form a cartridge filter having a folded membrane area of 4000 cm ² , which was previously sterilized by dry heat at 250 ° C for 1 hour. It was set in the cartridge housing.
Then, the endotoxin aqueous solution (concentration 20 EU / ml) was filtered at a flow rate of 5 l / min / 4000 cm ² ,
The endotoxin concentration of the filtrate was measured by the gel inversion method (gelation sensitivity 0.03 EU / ml). As a result, 1
The endotoxin concentration of the filtrate is 0.03 EU up to 200 l.
/ Ml or less, showing a high endotoxin adsorption amount. The endotoxin adsorption removal state is shown by FIG.
In contrast to this, a cartridge filter similar to the above was prepared using a microporous membrane which was not treated with an aqueous solution of a polyamide-epichlorohydrin resin under the same conditions, and a removal test was carried out. Was not seen at all.

[0008]

The present invention is as described above, and the intended purpose, that is, it is possible to remove endotoxin from an endotoxin-containing liquid to a very low concentration with high treatment efficiency, and a high flow rate of polyethersulfone can be obtained. And a sulfonated polyethersulfone microporous membrane for medical treatment,
There are great expectations for its use in fields such as pharmaceuticals.

[Brief description of drawings]

FIG. 1 is a schematic enlarged longitudinal sectional view of a poly (ether sulfone) and a sulfonated poly (ether sulfone) microporous membrane before treatment with a cationic resin.

FIG. 2 is a schematic enlarged vertical sectional view of the same as above, after treatment with a cation resin.

FIG. 3 is a schematic enlarged vertical cross-sectional view showing a state of adsorbing and removing endotoxin.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Office reference number FI technical display location C08L 71/10 LQK 81/02 LRG

Claims (1)

[Claims] 1. Polyethersulfone and sulfonated polyethersulfone microporous membranes, wherein a cationic resin is applied with a positive zeta potential to retain endotoxin adsorption ability.