JPH1085570A - Manufacture of selectively permeable hollow yarn membrane - Google Patents

Abstract

PROBLEM TO BE SOLVED: To manufacture a hollow yarn membrane of superior performance of removing harmful substances in low and medium molecular weight areas by using an aqueous solution containing the specified amount in the total of polyvalent alcohol and an organic solvent solution as a core agent, jetting out a raw liquid prepared by melting a cellulose derivative of specified amount in the specified organic solvent solution from a nozzle and spinning under specified condition. SOLUTION: An aqueous solution contining in total polyvalent alcohol and an organic solvent of 5-30wt.% is used as a core agent in spinning a raw liquid prepared by melting a cellulose derivative of 5-18wt.% in a cellulose derivative melting organic solvent solution containing polyvalent alcohol of 0-50wt.%. The water solution is jetted out of a tube-in-orifice- shaped nozzle and passed through inside gas and then passed through a coagulating liquid composed of a water solution of concentration of total of polyvalent alcohol and the organic solvent higher than that of the core agent by 20-45wt.% and solidifed therein. The membrane structure is formed into the two-layer structure provided with an extremely thin membrane dense layer of specified void content formed on the inner face and a porous substrate layer. Thus a cellulose derivative selectively permeable hollow yarn membrane of superior performances of permeability and fractionation can be manufactured.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing a selectively permeable hollow fiber membrane particularly useful for blood purification. For example, manufacture of artificial dialysis membranes for patients with renal insufficiency, especially hollow fiber membranes suitable for removing medium-high molecular weight substances such as β ₂ -microglobulin, which has recently attracted attention in relation to long-term complications of dialysis patients About the method. Also, simply hemofiltration dialysis,
The present invention relates to a method for producing a hollow fiber membrane which is also suitable for hemofiltration.

[0002]

2. Description of the Related Art In recent years, in connection with long-term complications of dialysis patients, β which is considered to be a causative substance of dialysis amyloidosis
_2- MG (molecular weight 11,800), parathyroid hormone (molecular weight of about 9,
500), molecular weight 2 thought to be related to joint pain and bone pain
The need to remove harmful substances in the relatively medium to high molecular weight region, such as ~ 40,000 substances, has been avoided. On the other hand, loss of albumin (molecular weight: 66,000), which is essential for the human body, must be avoided as much as possible.

[0003] That is, there is a demand for a permselective membrane having excellent permeability for substances having a molecular weight of 40,000 or less and 50,000 or less, and having good rejection of substances having a molecular weight of 60,000 or more and having a good sharp cut of the molecular weight. .

Hitherto, the development of hollow fiber membranes using a cellulose derivative as a raw material has been actively conducted.
As disclosed in Japanese Patent Application Laid-Open No. 8-24165, spinning of a non-coagulable triacetate spinning solution such as liquid paraffin, higher alcohol, or isopropyl myristate as a core agent when wet spinning a hollow fiber is required. In order to improve the spinnability at the time, it is necessary to increase the concentration of triacetate in the spinning dope. Therefore, a dense structure layer is formed on the outer surface of the hollow fiber.

[0005] For these reasons, the conventional cellulose derivative hollow fiber has a smaller density difference between the dense layer and the porous layer than the synthetic polymer membrane, is close to a uniform layer as a whole, and has a sufficient substance permeability. Did not.

[0006] Synthetic polymers such as polysulfone have been obtained which relatively satisfy the above requirements as seen in, for example, Japanese Patent Publication No. 2-18695 and Japanese Patent Publication No. 5-54337.

On the other hand, Japanese Patent Application Laid-Open No. 8-970 discloses a hollow fiber membrane in which N ₂ gas is used as a core agent to improve the permeability of cellulose derivatives, particularly triacetate.
According to this, the ultrafiltration coefficient of pure water is 10 to 200 ml /
A hollow fiber membrane having a m ² · mmHg · hr and a β ₂ -MG sieving coefficient of 0.2 or more. Even after 4 hours from the start of blood filtration, the blood permeability of the membrane and the β ₂ -MG sieve A hemodialysis membrane having a coefficient of 90% or more as compared with the value at the start of hemofiltration is obtained.

However, in the spinning method of triacetate using a gas as a core material disclosed in the publication, spinning at a low polymer concentration is difficult because spinning is difficult. 10 to 120m as shown in
1 / Hr · mmHg · m ² is relatively low, and it is difficult to obtain a hollow fiber having a high ultrafiltration coefficient. When a gas is used as the core material, since the core material does not have coagulation properties, it is difficult to form a dense layer on the inner surface. A two-layer film like a synthetic polymer cannot be obtained. Therefore, it is difficult to obtain a membrane capable of greatly removing medium-high molecular weight substances such as β ₂ -MG, which is a problem due to long-term complications in hemodialysis.

[0009] As described above, the membrane made of the cellulose derivative, particularly triacetate, obtained by the conventional production method has a film structure in which the density difference between the dense layer and the porous layer is unclear, and therefore the permeability and the fractionability are also low. It was not enough compared to a membrane made of a synthetic polymer such as polysulfone.

[0010]

SUMMARY OF THE INVENTION An object of the present invention is to solve such problems of the prior art. Particularly, in hemodialysis or hemofiltration dialysis, a medium molecular weight region such as β ₂ -MG is used. To provide a method for obtaining a selectively permeable hollow fiber membrane comprising a cellulose derivative which is excellent in both the performance of removing harmful substances of the above and the performance of removing harmful substances in a low molecular weight region such as urea, and has a small loss of albumin. The purpose is.

[0011]

Means for Solving the Problems As a result of the inventor's intense efforts to achieve the above object, the present inventors have adjusted the core structure and the coagulating solution to a specific relationship and spun to thereby achieve a conventional membrane structure. Rather than a uniform membrane, it has a dense layer with a specific porosity of an ultra-thin film on the inner surface, and the support layer can have a two-layer structure of a porous layer. The present inventors have found that a hydrophilic hollow fiber membrane can be obtained, and have reached the present invention.

That is, the present invention provides a method for preparing a polyhydric alcohol from 0 to 50.
In a solution of a cellulose derivative-soluble organic solvent containing 5% by weight of a cellulose derivative, 5 to 18% by weight of a cellulose derivative was dissolved.
Using an aqueous solution containing 0 wt% as a core, the mixture is discharged from a tube-in-orifice-shaped nozzle and passed through a gas, and then the total concentration of the polyhydric alcohol and the organic solvent is 20 to 45 wt% as compared with the core. This is a method for producing a permselective hollow fiber, characterized in that the fiber is passed through a coagulation liquid composed of a high aqueous solution and solidified.

Typical examples of the hollow fiber membrane obtained by the present invention include an inner diameter of 100 to 300 μm, a thickness of 30 to 60 μm, a porosity of 60 to 90%, and an ultrafiltration coefficient of pure water. 200-800 ml / m ² · mmHg · h
and permselective hollow fibers in which the sieving coefficient of r and β ₂ -microglobulin is 0.6 or more and the loss of albumin is further reduced.

The structure of the membrane wall of the hollow fiber membrane obtained by the production method of the present invention has an extremely thin dense layer which determines the separation and permeation characteristics of a substance on the inner surface, and shares the mechanical properties of the membrane on the outer side. It has a support layer, and the support layer has a two-layer or multilayer structure, which is a porous layer having almost no permeation resistance of the target substance.

Hereinafter, the present invention will be described in more detail. The material forming the hollow fiber membrane in the present invention is a cellulose derivative, particularly acetyl cellulose. Among them, those generally used are polymers substantially consisting of cellulose diacetate and cellulose triacetate. Among these, cellulose triacetate is particularly preferred. Note that “substantially” means that other high molecular weight substances and additives may be contained as long as the properties of the cellulose derivative are not impaired.

The solvent that can be used in the hollow fiber spinning solution of the present invention is a cellulose derivative-soluble organic solvent, which is also water-miscible. Specific examples include N-methylpyrrolidone, dimethylformamide, dimethylsulfoxide, dimethylamide, dimethylacetamide and the like.
Particularly preferred is N-methylpyrrolidone. The polyhydric alcohol that can be mixed with the organic solvent acts as a non-solvent for the cellulose derivative. Examples of such polyhydric alcohols include propylene glycol, ethylene glycol, triethylene glycol, polyethylene glycol and the like, with propylene glycol being particularly preferred.

The combination of the organic solvent and the polyhydric alcohol is preferably a combination of N-methylpyrrolidone and propylene glycol.

The concentration of the cellulose derivative in the spinning dope is 5 to 5.
18 wt%, preferably 10 to 15 wt%. If it exceeds 18% by weight, the porous layer as the support layer tends to be densified, and the performance of removing β ₂ -MG or the like is greatly reduced. If the amount is less than 5 wt%, the viscosity of the spinning dope becomes too low, and the spinning becomes difficult.

The ratio (wt) of the organic solvent / polyhydric alcohol in the spinning dope is usually 100/0 to 50/50, preferably 85/15 to 65/35, and particularly preferably 83/50.
17-75 / 25.

The core agent is for forming a thin dense layer having excellent fractionability on the inner surface of the hollow fiber. The organic solvent and the polyhydric alcohol used in the spinning solution are combined in a total amount of 5 to 30% by weight.
Preferably, the aqueous solution contains, more preferably, 10 to 20.
It is an aqueous solution containing a low concentration of wt%. The solidification rate exceeds 30 wt% is difficult to form an extremely slows down dense layer becomes lower than 5 wt% too thick thickness of the dense layer, removal performance of high molecular weight proteins in such as beta ₂ -MG is poor .

In the coagulation bath, it is necessary to form a porous layer by slowly coagulating the outer layer of the hollow fiber. For this reason, the concentration of the organic solvent and the polyhydric alcohol (insoluble) in total is lower than that of the core agent. 20-45 wt%, preferably 2
It is necessary to increase by 5 to 40 wt%. Specifically, an aqueous solution containing a high concentration of 30 to 70 wt% in total, preferably 40 to 60 wt% is preferable. If it exceeds 70% by weight, the coagulation becomes too slow and the spinning properties deteriorate, and if it is less than 30% by weight, the porous layer tends to be densified, and the ability to remove β ₂ -MG or the like becomes low. The hollow fiber membrane obtained in the present invention has a dense layer having a thickness of 2 μm or less and a porosity of 30% or less on at least the inner surface.

The characteristic of the performance of the hollow fiber membrane is a high level which cannot be obtained with a conventional membrane having a relatively uniform structure, and the ultrafiltration coefficient of pure water is 200 to 800 ml / m ² ···
mmHg · hr, β ₂ -MG has a sieving coefficient of 0.6 or more, has a good albumin rejection (for example, the sieving coefficient of albumin in bovine plasma is 0.02 or less), It is a hollow fiber membrane with excellent fractionation performance.

[0023]

EXAMPLES Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited to these examples. The sieving coefficient of β ₂ -MG and the sieving coefficient of albumin were measured based on “Protocol and Function Classification of Bovine Plasma in-vitro Evaluation of Blood Purifier” by the Scientific Committee of the Japan Society for Dialysis Therapy. The UFR is based on the dialyzer performance evaluation standard (S5
7.9), "Single pass circulation method".

Examples 1 to 3 and Comparative Example 1 N-methylpyrrolidone (NMP) using cellulose triacetate (degree of acetylation: 60.5, degree of polymerization: 360, manufactured by Daicel Chemical Industries, Ltd.) as a solvent Using a spinning stock solution dissolved in a system in which propylene glycol (PG) as a polyhydric alcohol was mixed at the ratio shown in Table 1, NMP and P
The aqueous solution having the composition of G was used as a core material and discharged into the air from a double tube nozzle, introduced into a coagulating solution under the conditions shown in Table 1, solidified, washed with water, and wound after glycerin adhesion treatment. . The obtained hollow fiber membrane was dried, inserted into a circular tubular case, and both ends were adhered and fixed with polyurethane, thereby producing a hollow fiber membrane dialyzer having an effective area of about 1.5 m ² . in-vit
The ultrafiltration coefficient (UFR) of pure water, the sieving coefficient of β ₂ -MG and the sieving coefficient of albumin were measured by ro. Table 1 shows the results
Shown in

[Comparative Example 2] Using a liquid paraffin as a core agent, a conventionally obtained hollow fiber having a uniform and dense membrane structure with a reduced film thickness was obtained. Table 1 shows the results.

[0026]

[Table 1]

Examples 4 and 5, Comparative Example 3 Example 1 except that dimethyl sulfoxide (DMSO) was used as a solvent and triethylene glycol was used as a non-solvent polyhydric alcohol.
The same operation as described above was performed to produce a hollow fiber membrane dialyzer. The results are shown in Table 2.

[0028]

[Table 2]

Claims (4)

[Claims] 1. A spinning solution in which a cellulose derivative is dissolved in an amount of 5 to 18 wt% in a cellulose derivative-soluble organic solvent solution containing a polyhydric alcohol in an amount of 0 to 50 wt%. An aqueous solution containing 30 wt% is used as a core material and discharged from a tube-in-orifice-shaped nozzle. After passing through a gas, the total concentration of the polyhydric alcohol and the organic solvent is 20 to 4 times higher than that of the core material.
A method for producing a permselective hollow fiber, comprising passing through a coagulation liquid comprising a 5 wt% higher aqueous solution and solidifying. 2. The method for producing a permselective hollow fiber according to claim 1, wherein the concentration of the polyhydric alcohol in the organic solvent solution is 15 wt% to 35 wt%. 3. The method for producing a selectively permeable hollow fiber according to claim 1, wherein the organic solvent is N-methylpyrrolidone and the polyhydric alcohol is propylene glycol. 4. The method according to claim 1, wherein the organic solvent is dimethyl sulfoxide and the polyhydric alcohol is triethylene glycol.
Or the method for producing a selectively permeable hollow fiber according to 2.