JPH1085569A - Manufacture of selectively permeable hollow yarn membrane - Google Patents

Abstract

PROBLEM TO BE SOLVED: To manufacture a hollow yarn membrane having a superior performance in removing harmful substances of low and medium molecular weight areas by spinning through a nozzle under the specified conditions an aqueous solution as a core material containing a specified amount of the total of polyvalent alcohol and a spinning solution prepared by melting a cellulose derivative of specified amount in the specified organic solvent solution. SOLUTION: An aqueous solution containing the total of polyvalent alcohol and spinning raw liquid as an organic solvent of 5-30wt.%, in which a cellulose derivative is melted, is contained as a core agent 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 for 0.0001-0.02 seconds, and immersed in a coagulating liquid. 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 harmful substances in both areas of medium molecular weight such as B2 -MG and low molecular weight such as urea can be removed, and a selectively permeable hollow yarn membrane composed of a cellulose derivative with little albumin loss 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, production of artificial dialysis membranes for patients with renal insufficiency, especially hollow fiber membranes suitable for the removal of medium and high molecular weight substances represented by 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 10.
A hollow fiber membrane having a sieving coefficient of 0.2 or more of 200 ml / m ² · mmHg · hr and β ₂ -MG of 0.2 or more,
A hemodialysis membrane is obtained, characterized in that the blood permeability of the membrane and the sieving coefficient of β ₂ -MG show 90% or more of the values at the start of hemofiltration even after a lapse of time.

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.

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 difference in density between the dense layer and the porous layer is unclear, and therefore, the membrane has poor permeability and fractionability. It was not enough compared to a membrane made of a synthetic polymer such as polysulfone.

[0011]

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.

[0012]

Means for Solving the Problems As a result of the inventor's intensive efforts to achieve the above object, the present invention has been made to adjust the time required for the spinning stock solution and the core agent to pass through the gas after discharging and adjust the spinning time to a specific relationship. By doing so, the membrane structure can be changed to a two-layer structure in which a dense layer having a specific porosity of an extremely thin film is provided on the inner surface and the support layer is a porous layer, instead of the conventional uniform film, and the permeability and the separation performance are improved. The present inventors have found that a cellulose derivative selectively permeable hollow fiber membrane having excellent image performance 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.
A tube-in-orifice was prepared by using a spinning dope obtained by dissolving a cellulose derivative in a cellulose derivative-soluble organic solvent solution containing 5% by weight as a core agent and an aqueous solution containing a polyhydric alcohol and the organic solvent in a total amount of 5 to 30% by weight. A method for producing a selectively permeable hollow fiber, characterized in that the fiber is discharged from a liquid nozzle, passed through a gas for 0.0001 to 0.02 seconds, and then immersed in a coagulation liquid.

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 sieving coefficient of albumin is 0.02 or less and the loss of albumin is small.

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, especially acetyl cellulose.

Among them, those generally used are polymers substantially composed 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 which 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 stock solution for spinning is not particularly limited, but is usually 5 to 18% by weight, preferably 10 to 15% by weight. 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 solution is usually 100/0 to 50/50, preferably 85/15 to 65/35, and more preferably 83/35.
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%. If it exceeds 30 wt%, the solidification rate becomes extremely slow, and it is difficult to form a dense layer. If it is lower than 5 wt%, the dense layer becomes too thick, and the ability to remove medium-high molecular weight proteins such as β ₂ -MG deteriorates. .

In the coagulation bath, it is necessary to form a porous layer by gently 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. 20-45 wt%, preferably 2
It is preferable 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.

In the present invention, after the above-mentioned spinning solution and the core agent are discharged from the nozzle, they pass through the gas zone for 0.0001 second to 0.02 second before being immersed in the above-mentioned coagulating liquid and coagulated. The feature is to make it.

By passing through the gas zone, the solidification of the inner layer of the hollow fiber proceeds faster than that of the outer layer, and a thin dense layer which determines the separation and permeability of the substance is formed on the inner surface. A porous layer serving as a support layer sharing the characteristics is formed, and thus a hollow fiber having high-performance permselectivity is obtained.

If the time is shorter than 0.0001 seconds, a dense layer is also formed in the outer layer, and the ability to remove medium-high molecular weight proteins such as β ₂ -MG is reduced. Conversely, if the time is longer than 0.02 seconds, the densification of the inner layer proceeds too much, and the dense layer becomes too thick, so that a film having the required high performance permselectivity cannot be obtained.

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.

[0030]

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 the “protocol and function classification of in-vitro evaluation of bovine plasma in blood purifiers” by the Scientific Committee of the Japanese Society for Dialysis Therapy. The UFR is based on the dialyzer performance evaluation standard (S57.9) of the Japan Society of Artificial Organs, “Sin
and the "gle pass circulation method".

Examples 1-3 and Comparative Examples 1-2 N-methylpyrrolidone (NMP), cellulose triacetate (degree of acetylation: 60.5, degree of polymerization: 360, manufactured by Daicel Chemical Industries, Ltd.) Using a spinning stock solution obtained by dissolving propylene glycol (PG) as a solvent polyhydric alcohol at a ratio shown in Table 1, the same NMP shown in Table 1 was used.
Using an aqueous solution having the composition of PG and PG as a core material, the mixture is discharged and passed through a double tube nozzle into air at a distance shown in Table 1, then introduced into a coagulating liquid, solidified, washed with water, and treated with glycerin. After winding. 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
-Ultrafiltration coefficient (UFR) and β ₂ of pure water in vitro
-The sieving coefficient of MG and the sieving coefficient of albumin were measured. The results are shown in Table 1.

[Comparative Example 3] Liquid paraffin was used as a core agent, and a conventionally obtained hollow fiber having a uniform and dense membrane structure with a reduced film thickness was obtained.

Table 1 shows the results.

[0035]

[Table 1]

Claims (2)

[Claims] 1. A spinning solution obtained by dissolving a cellulose derivative in a cellulose derivative-soluble organic solvent solution containing 0 to 50% by weight of a polyhydric alcohol, containing a total of 5 to 30% by weight of a polyhydric alcohol and the above organic solvent. Using an aqueous solution as a core material, discharging from a tube-in-orifice-shaped nozzle, passing through a gas for 0.0001 to 0.02 seconds, and then immersing in a coagulation liquid, producing a selectively permeable hollow fiber. Method. 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%.