JPH10165775A - Production of permselective hollow yarn membrane - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a permselective hollow yarn membrane superior in mol.wt. fractionation properties within a medium and high mol.wt. region, in hollow yarn spinning of a cellulose derivative, by using a soln. with moisture content of a specific value as a core agent introduced into hollow yarn and setting a spinning draft to a specific value. SOLUTION: This hollow yarn membrane has permselectivity and is composed of a cellulose derivative and has an inner diameter of 150-300μm and a thickness of 20-60μm. In order to produce the hollow yarn membrane having an extremely thin dense layer formed on the inner surface thereof, it is necessary to use a core agent having coagulability to a dope emitted from a cap, that is, capable of desolvating a dope soln. at a time of spinning. By using an aq. soln. of an org. solvent as the core agent at a time of spinning, the dense layer can be formed on the inner surface of the hollow yarn membrane. Herein, the moisture content of the aq. soln. as the core agent must be 50wt.% or more, pref., 70wt.% or more. It is necessary to set a spining draft to 5 or less, desirably 3 or less.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a method for producing a selectively permeable hollow fiber membrane. Specifically, the cellulose derivative is discharged from the annular slit by dry-wet spinning,
An object of the present invention is to provide a method for stably producing a hollow fiber membrane having good molecular weight fractionation by employing a specific core agent and a specific spinning draft when obtaining a hollow fiber membrane.

More specifically, the hollow fiber membrane obtained by the present invention has a selective permeability exhibiting excellent separation performance, and is suitable for blood treatment such as hemodialysis and hemofiltration dialysis. An object of the present invention is to provide a permselective hollow fiber membrane suitable for removing harmful substances.

[0003]

2. Description of the Related Art Permselective hollow fiber membranes have been practically used in reverse osmosis and hemodialysis. In particular, hollow fiber hemodialyzers are often used at present for purifying blood of patients with renal failure. In this case, a large number of dialysis membranes, for example, hollow fiber membranes, are housed in a housing, blood of a patient is allowed to flow inside the hollow, and dialysate is allowed to flow outside, that is, a gap between the hollow fibers, and the hollow fiber membrane wall is formed. Through the dialysis, waste substances in the blood are removed to correct the electrolyte concentration, and a pressure difference is applied between the inside and outside of the hollow fiber to remove excess water in the blood by ultrafiltration.

[0004] Further, hollow fibers are sometimes used to separate only plasma from blood or remove specific components from the plasma to treat autoimmune diseases and the like.

[0005] Recently, it has been confirmed that a therapeutic effect can be obtained by using a hollow fiber in protein permeable hemodialysis or protein permeable hemodialysis.

[0006] As described above, the hollow fiber for blood treatment must selectively allow a specific substance to permeate according to the purpose.
Its properties are determined by the material, porosity (size, number, etc.) of the hollow fiber, film thickness, and the like.

By the way, β ₂ -microglobulin (β ₂ -MG, molecular weight 11, 80, which is recently associated with long-term complications of dialysis patients and is considered as a causative substance of dialysis amyloidosis.
0), parathyroid hormone (molecular weight of about 9,500) considered to be associated with pruritus and hyperlipidemia, erythroblast inhibitory factor (molecular weight of about 1,000) involved in anemia, joint pain, and bone pain The necessity of removing harmful substances in a relatively medium-high molecular weight region, such as substances having a molecular weight of 20,000 to 40,000, which are considered to be considered, is called for. On the other hand, albumin essential for the human body (molecular weight 66,00
The loss of 0) must be avoided as much as possible. That is, there is a demand for a permselective membrane which is excellent in permeability of substances having a molecular weight of 40,000 to 50,000 or less, has good blocking properties for substances having a molecular weight of 60,000 or more, and has good sharp cutoff of the molecular weight cutoff.

However, conventionally, as a synthetic polymer such as polysulfone, a polymer which relatively satisfies the above requirements has been obtained as disclosed in Japanese Patent Publication No. 2-18695 and Japanese Patent Publication No. 5-54337. However, in the case of cellulose derivatives, particularly triacetate, for example, JP-B-58-24
As disclosed in JP-A-165-165, in order to use a non-coagulable triacetate spinning solution such as liquid paraffin, higher alcohol, or isopropyl myristate as a core agent for wet spinning a hollow fiber, In this case, the triacetate concentration must be increased to increase the spinnability during spinning. In addition, a layer having a dense structure is formed on the outer surface of the hollow fiber in order to solidify the spinning stock solution from the nozzle and then solidify the outer surface of the hollow fiber with the coagulating liquid.

[0009] For these reasons, conventionally, the cellulose derivative hollow fiber has a smaller density difference between the dense layer and the porous layer of the structure than the synthetic polymer membrane, and is close to a uniform layer as a whole.
The permeability of the substance was not sufficient. For this purpose, the thickness of the film has been reduced to improve the transmittance, but this is not sufficient. Further, since the density difference between the dense layer and the porous layer having the membrane structure is unclear, there is room for improvement in the fractionation characteristics of the substance.

[0010]

SUMMARY OF THE INVENTION An object of the present invention is to solve such problems of the prior art, and to use a cellulose derivative polymer to approximate the structure of a conventional synthetic polymer. It provides a dense and dense structure and imparts high molecular weight fractionation characteristics. Particularly, in hemodialysis and hemofiltration dialysis, a method for producing a selectively permeable hollow fiber membrane capable of removing harmful substances in the medium-high molecular weight region such as β ₂ -MG and improving the outflow prevention of useful substances such as albumin is provided. Is what you do.

[0011]

Means for Solving the Problems The inventors of the present invention have made intensive studies to solve the above-mentioned problems, and as a result, in a hollow fiber spinning of a cellulose derivative by a dry-wet method, the water content as a core agent introduced into the inside of the hollow fiber is reduced. A thin dense layer is formed on the inner surface of the hollow fiber by using a solution of 50% or more and making the draft in spinning, that is, the ratio of the take-up speed of the hollow fiber to the discharge linear speed of the dope in the spinneret, 5 or less. In addition, a hollow fiber membrane having a porous structure on the outside and a cellulose derivative having a good molecular weight fractionation property in a medium-high molecular weight region can be produced stably without trouble such as thread breakage during spinning. I found it.

[0012]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in more detail. That is, the hollow fiber membrane in the present invention is a material having selective permeability, the material of which is a cellulose derivative, particularly acetylcellulose, and among those generally used, substantially cellulose diacetate, It is a polymer composed of cellulose triacetate. Note that “substantially” means that other polymers, additives, and the like may be contained as long as the properties of the cellulose derivative are not impaired.

The structure of the membrane wall of the hollow fiber membrane of the present invention is characterized by an ultrathin dense layer which functions to separate and permeate the separation and permeation properties of the substance and the mechanical properties, and a material which can mechanically withstand the fluid pressure but is capable of withstanding the fluid pressure. A two-layer or multi-layer structure conventionally realized with a synthetic polymer, which has a porous layer that has almost no permeation resistance, is preferable. In particular, when blood is processed through the inner surface of the hollow fiber membrane, it is desirable that there is a dense layer at least on the inner surface of the hollow fiber. If there is a porous layer on the inner surface, there is a concern that blood proteins may adhere to that portion or penetrate into the pores, thereby impeding the permeation of substances.

In order to produce such a membrane having an ultra-thin dense layer on the inner surface of the hollow fiber membrane, a core agent which has coagulability with respect to the dope discharged from the spinneret during spinning, that is, which can desolvate the solution of the dope. You need to use

As the solvent for the cellulose derivative, N-methylpyrrolidone, dimethylformamide, dimethylacetamide, dimethylsulfoxide and the like are generally used. Water has good compatibility with these organic solvents, and Shows coagulability with dope. Therefore, a dense layer can be formed on the inner surface of the hollow fiber membrane by using an aqueous solution as a core agent during spinning.

As the aqueous solution, an aqueous solution of the above-mentioned solvent can be generally used, but may further contain a swelling agent, a non-solvent and other additives. Swelling agents include formamide, urea, triethyl phosphate, glyoxal, butanol,
Isopropanol and the like, and non-solvents include ethylene glycol, triethylene glycol, polyethylene glycol, glycerin, propylene glycol and alcohols.

If the water content of the aqueous solution is less than 50%, an ultra-thin dense layer for imparting the molecular weight fractionation performance of a medium-high molecular weight substance will not be formed. The water content of the aqueous solution as the core agent must be 50% by weight or more, and is preferably 7% by weight.
0% by weight or more.

On the other hand, when the water content of the aqueous solution is high, the dope discharged from the spinneret rapidly solidifies, so that the spinnability is lowered and the yarn breaks easily. For this reason, the spinning draft needs to be 5 or less. It is desirably 3 or less.

In the case of blood purification, which is the main use of the permselective hollow fiber membrane obtained in the present invention, the hollow fiber generally has an inner diameter of 150 to 300 μm. It is practical to make the outer diameter of 0.5 mmφ or less from the viewpoint of die working, and is also desirable in terms of working accuracy. More preferably, it is 0.4 mmφ or less.

In general, the thickness of the hollow fiber membrane according to the present invention is desirably small in view of the permeability of a substance. It is preferably at least 20 μm from the viewpoint of strength. On the other hand 60
Above μm, the permeability of the substance decreases.

As described above, the method for producing a hollow fiber membrane of the present invention, when used in a hemodialyzer or hemofiltration dialysis, has a β _2-
Highly selective removal of harmful substances in the medium and high molecular weight areas such as MG and a small amount of albumin that is beneficial to the human body. It is a manufacturing method that can be performed.

Although the method for producing the hollow fiber membrane of the present invention is not particularly limited, a tube-in-orifice nozzle is desirably prepared by using a spinning stock solution obtained by dissolving a cellulose derivative in an organic solvent and using an aqueous solution as a core agent. A method is adopted in which the liquid is discharged more, passes through a gas, and then passes through a water-soluble coagulating liquid and solidifies.

[0023]

EXAMPLES The present invention will be described more specifically below with reference to examples, but the present invention is not limited to these examples.

Examples 1 to 4 and Comparative Examples 1 to 5 13 parts of cellulose triacetate and triethylene glycol 20
Part was dissolved uniformly in 67 parts of dimethyl sulfoxide as a spinning dope, and from an annular slit type nozzle, an aqueous solution of dimethyl sulfoxide was used as a core material and discharged into the air. After solidification, washing with water and glycerin adhesion treatment, it was wound up. The hollow fiber had an inner diameter of about 200 μm and a film thickness of about 45 μm. The obtained hollow fiber membranes are dried, bundled, inserted and filled in a cylindrical container, and both ends are adhered and fixed with polyurethane to prepare a hemodialyzer having an effective area of about 1.5 m ^2. Mass transfer coefficient (K ₀ ) of dextran 10,000 at room temperature and sieving coefficient of albumin using bovine plasma (S
C) was measured.

As a method of measuring K ₀ , a hollow cylindrical fiber container is filled with a bundle of hollow fibers at a filling rate of about 52%, both ends are sealed with an adhesive, and then cut to open a hollow portion. Using a dialyzer having an effective membrane surface area of 1.5 m ^{2 according to} the above, an aqueous solution of 0.1% by weight of dextran 10,000 at 200 ml / min was flowed at 37 ° C. to the blood side, that is, the hollow side at 200 ml / min. By measuring the concentration in the effluent on the blood side when water is flowed at 500 ml / min on the liquid side, that is, on the hollow fiber gap side, K ₀ is calculated by the following equation.
Is obtained. Dextran concentration in the sampling solution is
For example, it is measured by the anthrone-sulfuric acid method.

[0026]

(Equation 1)

[0027] Q _B: blood-side flow rate [ml / sec] Q _D: flow rate of the dialysate side [ml / sec] DA: in the dialysance of dextran 10,000,
The measurement method is in vitro by the Japanese Dialysis Medical Association Scientific Committee
o Based on the evaluation working group evaluation method. A: Effective membrane area of hollow fiber membrane [cm ² ]: Membrane area based on the inner diameter of the hollow fiber membrane in a wet state.

The method for measuring the sieving coefficient (SC) of albumin is based on the in vitro evaluation protocol and functional classification (draft) ('94 .11.12) of bovine plasma in blood purifiers by the Scientific Committee of the Japanese Society for Dialysis Therapy. The measurement of albumin concentration was performed by A / GB-Test Wako (Wako Pure Chemical Industries, Ltd.). Table 1 shows the results.

[0029]

[Table 1]

Table 1 shows spinning conditions, spinning conditions, and in
It shows the in vitro performance. The method for producing a hollow fiber of the present invention is a method for stably producing a selectively permeable hollow fiber membrane having a large K _{0 of} 10,000 dextran, a small sieving coefficient of albumin, and a good fractionation property. Has become.

[0031]

According to the method for producing a cellulose derivative selectively permeable hollow fiber membrane of the present invention, a cellulose derivative hollow fiber membrane can be stably spun with less thread breakage, and has a high permeability in a medium-high molecular weight region. And a selectively permeable hollow fiber membrane having an excellent fractionation property of low permeation of albumin.

Claims (5)

[Claims] 1. A polymer substantially consisting of a cellulose derivative is dissolved in an organic solvent, and then this solution is linearly extruded from an annular slit, and simultaneously a solution having a water content of 50% by weight or more is extruded. Characterized in that it is introduced inside the body, and the spinning draft is taken off at less than 5;
A method for producing a permselective hollow fiber membrane substantially consisting of cellulose ester having a thickness of 0 to 300 µm and a thickness of 20 to 60 µm. 2. The permselective hollow fiber membrane according to claim 1, wherein the outer diameter of said annular slit is 0.5 mmφ or less. 3. The method for producing a permselective hollow fiber membrane according to claim 1, wherein said cellulose derivative is cellulose triacetate. 4. The selectively permeable hollow fiber membrane according to claim 1, wherein the organic solvent is one kind of solvent selected from N-methylpyrrolidone, dimethylformamide, dimethylacetamide, and dimethylsulfoxide or a mixture of two or more kinds. Production method. 5. The method for producing a selectively permeable hollow fiber membrane according to claim 1, wherein said selectively permeable hollow fiber membrane has a dense layer at least on an inner surface.