JP2008178814A - Cellulose acetate-based non-symmetrical hollow fiber membrane - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a permselective hollow fiber membrane imparting coarse and dense structure in the membrane thickness direction of the hollow fiber membrane by using a cellulose acetate-based polymer, and high water permeability, molecular cutoff characteristics, and solute permeability, while enhancing the productivity of the hollow fiber membranes with handling difficulty and the productivity of modules. <P>SOLUTION: In the hollow fiber membrane of non-symmetrical structure mainly consisting of cellulose acetate-based polymer, having a dense layer on the inner face, the hollow fiber membrane has an inner diameter of 150-250 μm, a membrane thickness of 10-<30 μm, an opening ratio of the outer surface of 15-30%, and an average opening area of 0.01-<0.05 μm<SP>2</SP>per one opening. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a selectively permeable hollow fiber membrane comprising a cellulose acetate polymer. Specifically, using cellulose acetate polymer, it has a dense layer on the inner surface, forms an asymmetrical dense structure that increases the pore diameter toward the outer surface, and also provides productivity and safety for blood purification. It is about technology to improve.

  The permselective hollow fiber membrane has been widely used in the field from reverse osmosis to microfiltration. Currently, hollow fiber hemodialyzers are often used to purify the blood of patients with renal failure. This is because a housing contains a large number of dialysis membranes, for example, hollow fiber membranes, the patient's blood is passed through the hollow portions, and the dialysate is passed through the outside, that is, the hollow fiber membrane gaps. By removing the waste products in the blood by dialysis through the filter, the electrolyte concentration is corrected, and the medium molecular weight substances and excess water in the blood are removed by filtration by applying a pressure difference inside and outside the hollow fiber membrane. It is. Furthermore, a hollow fiber membrane may be used to separate only plasma from blood or remove specific components from the plasma to treat autoimmune diseases and the like. Recently, it has been confirmed that a therapeutic effect can be obtained by using a hollow fiber membrane for protein permeable hemodialysis or protein permeable hemofiltration dialysis.

  By the way, in recent years, it is related to long-term complications in dialysis patients, and the parathyroid gland is considered to be related to β2-microglobulin (β2-MG, molecular weight: 11,800), pruritus, and hyperlipidemia, which are considered to be causative agents of dialysis amyloidosis. Necessity of removal of toxic substances in the relatively medium high molecular weight region such as hormones (molecular weight: about 9,500), erythroblast-inhibiting factor involved in anemia, substances with molecular weight of 20,000 to 40,000 that are considered to be related to joint pain and bone pain Is screaming. On the other hand, the loss of albumin (molecular weight: 66,000) useful for the human body must be avoided as much as possible. That is, there is a demand for a selectively permeable membrane excellent in the permeability of a substance having a molecular weight of 40 to 50,000 or less and having a high molecular weight of 60,000 or more and having a good molecular weight and sharp-cutting property.

  Thus, the hollow fiber membrane for blood processing must selectively permeate a specific substance according to the purpose. The performance is determined by the material of the hollow fiber membrane, the membrane structure, the porosity (pore size, number, etc.), the film thickness, and the like.

In order to obtain the above-mentioned membrane performance, a hollow fiber membrane having a water permeability (UFR) as high as possible is necessary. Conventionally, synthetic polymers such as polysulfone, as seen in Patent Documents 1 and 2, for example, The thing which comparatively satisfy | filled the said request | requirement is obtained. However, it is unclear whether the synthetic polymer membrane uses a hydrophilizing agent such as polyvinyl pyrrolidone or due to the membrane structure, but the dimensional stability of the hollow fiber membrane is not clear. Low and very difficult to handle. In addition, since the hydrophilizing agent is hydrophilic, it may elute in the blood and gradually accumulate in the body, and there is a concern that the hydrophilizing agent that is originally a foreign substance may adversely affect the living body. The In order to eliminate concerns about such adverse effects, it was necessary to perform a treatment for suppressing the elution of the membrane for strengthening the washing and crosslinking, and the handling was complicated and the production was difficult.
Japanese Patent Publication No. 2-18695 Japanese Patent Publication No. 5-54373

In addition, in cellulose acetate polymers, as seen in Patent Document 3, for example, liquid cores when wet spinning a hollow fiber membrane is liquid coagulant such as liquid paraffin, higher alcohol, isopropyl myristate, etc. Since no (low) material is used, the asymmetric structure as described above cannot be obtained.
Japanese Patent Publication No.58-24165

For example, Patent Documents 4 and 5 disclose cellulose triacetate films having an asymmetric structure having a dense layer on the inner surface. Using a solidified aqueous solution as the internal liquid, it has been possible to obtain a film structure of a two-layer or multi-layer structure that has been conventionally realized with a synthetic polymer. However, it is described that it is very difficult to stabilize the hollow fiber membrane production because the spinnability is lowered when the aqueous solution concentration of the internal solution is lowered. Thus, in order to use as a hemodialyzer, not only the productivity of the hollow fiber membrane is ensured, but the total productivity cannot be improved unless the assembly property of the module is also secured. Therefore, there is room for improvement in order to improve the overall productivity.
Japanese Patent Laid-Open No. 10-263375 Japanese Patent Laid-Open No. 10-165775

When producing a module using a hollow fiber membrane comprising a polysulfone-based polymer and polyvinyl pyrrolidone, the polyvinyl pyrrolidone is viscous, so that the hollow fiber membranes are likely to stick to each other, and the resin for end sealing is a hollow fiber membrane. There was a problem in that a portion that did not go in between occurred, resulting in poor adhesion. For example, Patent Documents 6 and 7 propose one solution to this problem. This is a technique for avoiding sticking by optimizing the hole area ratio of the outer surface of the hollow fiber membrane and reducing the contact area between the hollow fiber membranes. However, there is no mention of the aspect in which the yarn strength is lowered by increasing the porosity of the support layer, and there remains room for improvement in handling.
JP 2000-140589 A JP 2001-38170 A

  The present invention aims to solve such problems of the prior art, specifically using a cellulose acetate polymer, giving a dense structure in the thickness direction of the hollow fiber membrane, It imparts high water permeability, molecular weight fractionation characteristics, and solute permeability. In particular, in hemodialysis and hemofiltration dialysis, a selectively permeable hollow fiber membrane capable of enhancing the removal of harmful substances having a molecular weight of about 30,000 and the outflow prevention of useful substances such as albumin is provided. It is. Another object of the present invention is to provide a selectively permeable hollow fiber membrane that improves the productivity of a hollow fiber membrane that is difficult to handle and improves module productivity, and has improved safety without any effluent from the membrane. Is.

The present invention has the following configuration.
The present invention is a hollow fiber membrane having an asymmetric structure mainly comprising a cellulose acetate-based polymer and having a dense layer at least on the inner surface of the hollow fiber membrane, wherein the hollow fiber membrane has an inner diameter of 150 μm to 250 μm and a film thickness of 10 μm. less 30μm or more, 30% or less open porosity more than 15% of the outer surface of the hollow fiber membrane, cellulose, characterized in that the average opening area is one 0.01 [mu] m per ² or 0.05μm less than ² holes This is an acetate-based asymmetric hollow fiber membrane.
In the present invention, it is preferable that the Young's modulus per single yarn of the hollow fiber membrane is 5000 kg / cm ² or more and the yield strength is 25 g or more.
Further, the cellulose acetate polymer is preferably dissolved in methylene chloride / methanol = 91/9 so as to be 6% by weight, and the viscosity when measured at a temperature of 25 ° C. is preferably more than 140 mPa · s and less than 200 mPa · s. .
The cellulose acetate polymer is preferably cellulose diacetate and / or cellulose triacetate.

  A selectively permeable hollow fiber membrane made of a cellulose acetate polymer was given a dense structure and high molecular weight fractionation characteristics could be imparted. In addition, a permselective hollow fiber membrane capable of enhancing the removal of harmful substances with a molecular weight of about 30,000 and the leakage of useful substances such as albumin, particularly in hemodialysis and hemofiltration dialysis. I was able to. In addition, the productivity and module assembly of hollow fiber membranes that are difficult to handle were improved, and a selectively permeable hollow fiber membrane with improved safety and no effluent from the membrane could be obtained.

  In order to obtain the asymmetric hollow fiber membrane of the present invention, a spinning stock solution composed of a cellulose acetate polymer, a solvent, a non-solvent, and a core liquid is used as a coagulable liquid. After passing, it is led to a coagulation bath and the hollow fiber membrane shape is fixed. Excess solvent and non-solvent are removed from the resulting hollow fiber membrane in a washing bath, the membrane pore retainer is impregnated in the hollow portion and pores, and then dried and wound up.

  In the present invention, it is preferable to mainly use a cellulose acetate polymer as a material constituting the asymmetric hollow fiber membrane. Cellulose acetate-based polymers include cellulose diacetate and cellulose triacetate capped to some extent from the viewpoint of blood compatibility such as the balance between hydrophobicity and hydrophilicity, suppression of complement activity, and good blood return without blood clotting. Is easily available and is particularly preferable.

  In the conventional method for obtaining a cellulose acetate-based asymmetric membrane, the polymer concentration in the spinning dope needs to be 15% or less in order to ensure the fluidity of the spinning dope and obtain the desired performance. However, lowering the polymer concentration in the spinning dope results in a lower polymer density in the formed hollow fiber membrane, leading to a decrease in the strength of the hollow fiber membrane. In particular, there is a problem that the breaking strength, which is important in module production or the like, tends to be insufficient. When a module is manufactured using a hollow fiber membrane having such a low breaking strength, when the hollow fiber membrane bundle is loaded into the module case, the hollow fiber membrane may not be able to withstand friction, or a resin may be applied to the module end. When filling or removing the core liquid in the hollow portion, there arises a problem that causes a decrease in module productivity such that the hollow fiber membrane breaks or breaks without being able to withstand centrifugal force.

Therefore, in order to ensure module productivity while expressing the performance required for hollow fiber membranes for artificial kidneys, the hollow fiber obtained by setting the polymer concentration in the spinning dope to a relatively high value of 15% to less than 30% The film strength was ensured. Furthermore, the water permeability (UFR) is 200 ml / (hr · mmHg · m ² ) or more, β2MG clearance is 50 ml / min. (1.5 m ² ) or more, and the leakage of useful proteins such as albumin is 3 g / (3 L We examined to develop the following performance (at the time of water removal).

Generally, when the polymer concentration is increased, the viscosity of the spinning dope increases and the fluidity decreases, so it is necessary to set the nozzle temperature relatively high to ensure the fluidity of the spinning dope. In particular, in the case of a cellulose acetate polymer, the spinning dope viscosity is much higher even at the same polymer concentration as compared to a polysulfone polymer. In the case of a spinning stock solution using a polysulfone-based polymer, the viscosity of the spinning stock solution is relatively low, so even if the polymer concentration is increased, it can be sufficiently discharged from the nozzle. However, in the case of a cellulose acetate-based polymer, the polymer concentration is at most However, it is necessary to raise the nozzle temperature to 100 ° C or higher even if it is about 15%. Although there is no particular difficulty in setting the nozzle temperature to 100 ° C. or higher, it is necessary to use an aqueous solution as a core liquid in order to form a dense layer on the inner surface of the hollow fiber membrane, and the nozzle is used to prevent boiling of the aqueous solution. The temperature should be at least 90 ° C or lower.
In order to obtain a high-strength cellulose acetate asymmetric hollow fiber membrane, the above technical problems must be solved. Therefore, as a result of intensive investigations to prevent the core liquid from boiling while ensuring the fluidity of the spinning raw liquid, the present inventors separately control the temperature until immediately before discharging the spinning raw liquid and the core liquid from the nozzle. Found a means. Specifically, by using the means as described later, the fluidity of the spinning dope was secured while preventing boiling of the core solution, and the present invention was finally completed.

  For example, in order to produce a hollow fiber membrane for blood purification, a plurality of double tube nozzles having a slit outer diameter of 300 to 1000 μm, a slit inner diameter of 200 to 900 μm, and a core liquid discharge port diameter of 100 to 600 μm are generally provided in the nozzle block. Set and use. As described above, since the width of the spinning raw solution discharge hole and the diameter of the core liquid discharging hole are only several hundred μm, it is very difficult to precisely control the temperature until the spinning raw solution and the core liquid are discharged from the nozzle. The present inventors solved this problem by using a structure in which a heat medium (refrigerant) can be circulated in the nozzle block so that the temperature of the spinning dope and the core solution can be controlled separately until immediately before discharge. did. In general, several tens of nozzles are incorporated in one nozzle block, and it is necessary to consider temperature control for them uniformly. This technical difficulty has been cleared and the present invention has been achieved.

  Conventional cellulose acetate polymers include various cellulose acetate polymers with different degrees of acetylation and polymerization such as L-20, 30, 40, 50, 70, LT-35, 55, 105 from Daicel Chemical Industries. A cellulose triacetate having a 6% viscosity of 250 mPa · s to 300 mPa · s has been conventionally used. By processing the nozzle block, it is possible to perform spinning even when the polymer concentration exceeds 15% using such a high viscosity polymer, and it is possible to ensure the strength of the hollow fiber membrane. However, in order to achieve further improvements in hollow fiber membrane performance, spinning stability and module productivity, a relatively low viscosity cellulose acetate polymer with a 6% viscosity of over 140 mPa · s and less than 200 mPa · s is used. I examined that. Finally, by using a relatively low viscosity polymer and further increasing the polymer concentration in the spinning dope, it became possible to secure the strength of the hollow fiber membrane, improve the membrane performance, and optimize the balance between them. .

In the present invention, the acetylation degree of the cellulose acetate polymer is preferably 53 to 62. Here, the degree of acetylation represents the degree of acetate group substitution of hydroxyl groups in cellulose. If the degree of acetylation is too low, the number of hydroxyl groups in the polymer chain increases, which may be disadvantageous in terms of biocompatibility such that complements are easily activated when the polymer comes into contact with blood. The theoretical upper limit of the degree of acetylation is 62.5%, but if the degree of acetylation is too high, the solubility and moldability may be reduced. Therefore, the acetylation degree of the cellulose acetate polymer is more preferably 61.5% or less.
The lower the degree of acetylation, the better the solubility and moldability of the polymer, but the blood compatibility represented by complement activity tends to decrease as the number of hydroxyl groups increases. Therefore, the acetylation degree is more preferably 55% or more, and further preferably 58% or more.

  A hollow fiber membrane with an asymmetric structure that has a thin dense layer on the inner surface and the pore diameter increases toward the outside. The thin dense layer has a fractionation characteristic (β2 microglobulin permeates and albumin does not permeate). In other words, the portion (support layer) other than the dense layer has a large pore diameter, so that it does not have resistance to substance permeation, and it is possible to improve the removability of low molecular weight proteins typified by β2 microglobulin. The support layer mainly plays a role of maintaining the strength of the film. Usually, when the polymer concentration in the spinning dope is lowered or the viscosity of the spinning dope is lowered, the pore diameter of the resulting hollow fiber membrane tends to increase, so in order to strictly control the pore diameter of the thin dense layer The polymer concentration and the spinning dope viscosity are preferably high to some extent because the pore diameter and the density structure can be easily controlled.

In order to balance the performance of the hollow fiber membrane and the strength of the membrane, it is more preferable to set the cellulose acetate polymer concentration in the spinning dope to 16% by mass or more and 25% by mass or less, and 17% by mass or more and 23% by mass or less. Is more preferable.
The viscosity of the spinning dope when discharged from the nozzle is N-methylpyrrolidone (NMP) as a solvent, triethylene glycol (TEG) as a non-solvent, and cellulose acetate polymer / NMP / TEG = 16-25 / It is preferable that the viscosity when measured at 49 to 77/7 to 26 is 50 to 9000 mPa · s (50 ° C.).

  As described above, the structure of the hollow fiber membrane is a two-layer structure comprising an ultrathin dense layer that governs the separation and permeation characteristics of a substance and a support layer that retains mechanical strength and hardly affects the permeation of the substance. Or a multilayer structure is preferable. In particular, when blood is allowed to flow through the hollow portion of the hollow fiber membrane and the substance permeates from the inside to the outside of the hollow fiber membrane, it is desirable that there is a dense layer at least on the inner surface side of the hollow fiber membrane. If there is no dense layer on the inner surface side, blood protein tends to adhere to the portion, or it tends to enter into the pores, which may impede substance permeation.

  In the present invention, in order to ensure blood flow stability, the inner diameter of the hollow fiber membrane is preferably 150 μm or more and 300 μm or less. If the inner diameter of the hollow fiber membrane is too small, the blood flow linear velocity increases, and the blood cell component may be damaged. If the hollow fiber membrane is too large in diameter, the blood shear rate and pressure loss will not increase, the filtration effect contributing to the permeation of medium high molecular weight substances will be reduced, and a module (blood purifier) to compensate for the lack of membrane performance There is a possibility that the convenience of use may be impaired, such as having to increase the size. Therefore, the inner diameter of the hollow fiber membrane is more preferably 160 μm or more and 280 μm or less, and further preferably 170 μm or more and 260 μm or less.

  In the present invention, the thickness of the hollow fiber membrane is preferably 10 μm or more and less than 30 μm. If the thickness of the hollow fiber membrane is too thin, the permeation performance is improved, but it may be difficult to maintain the required strength. On the other hand, if the film thickness is too large, the permeation resistance of the substance increases and the permeability of the removed substance may be insufficient. In addition, there is a possibility that the convenience of use may be impaired because the size of the module needs to be increased. Therefore, the thickness of the hollow fiber membrane is more preferably 12 μm or more and 28 μm or less, and further preferably 13 μm or more and 26 μm or less.

  In the present invention, it is preferable to use N-methylpyrrolidone, dimethylformamide, dimethylacetamide, dimethylsulfoxide and the like as the solvent for the cellulose acetate polymer. These solvents have good compatibility with water and exhibit coagulability with respect to the cellulose acetate polymer. Non-solvents include ethylene glycol, triethylene glycol, polyethylene glycol, glycerin, propylene glycol, and alcohols.

  In the present invention, as the core liquid, an aqueous solution composed of the above-mentioned solvent, non-solvent and water can be generally used, but may further contain a swelling agent and other additives. Examples of swelling agents include formamide, urea, triethyl phosphate, glyoxal, butanol, isopropanol and the like.

  When a relatively high viscosity cellulose acetate polymer is used as a raw material, if the water content of the core liquid is too low, the coagulation property of the polymer is lowered. The formation and porosity of the ultrathin dense layer to be determined tends to be non-uniform. Therefore, the water content in the core liquid is preferably 10% by mass or more. It is more preferably 30% by mass or more, further preferably 50% by mass or more, still more preferably 70% by mass or more, and particularly preferably water alone. On the other hand, if the water content of the core liquid becomes too high, the spinning dope discharged from the nozzle is rapidly solidified, so that the spinnability is deteriorated and yarn breakage or deformation of the hollow fiber membrane occurs. Is likely to occur. Here, when the low-viscosity cellulose acetate-based polymer described above is used, the reason is not well understood, but it is found that even if the water content of the core liquid is increased, good spinning stability without occurrence of yarn breakage can be obtained. It was.

  It should be noted that, even when the core liquid is water, good productivity is ensured without affecting the stringiness. The fact that the water content of the core liquid can be increased means that it is easy to have a difference in solvent concentration between the core liquid and the spinning dope, that is, the thickness and structure of the dense layer on the inner surface of the hollow fiber membrane. This leads to a wider range of control. Moreover, since the core liquid can be easily washed and removed after the production of the hollow fiber membrane, there are secondary effects such as reduction of work man-hours, cost reduction for washing treatment, and wastewater treatment.

  As described above, it is possible to increase the discharge temperature of the spinning dope by separately controlling the temperature of the spinning dope and the core solution, and the polymer concentration in the spinning dope can be increased by using a relatively low viscosity polymer. As an effect that can be enhanced, the strength of the obtained hollow fiber membrane was improved. Another effect of using a relatively low-viscosity polymer is that a hollow fiber membrane with a high Young's modulus, which is an index of hardness, improves the polymer density (packing property) per unit volume of the hollow fiber membrane. It became possible to get.

  Further effects could be confirmed by using a spinning dope comprising a low viscosity cellulose acetate polymer. By improving the fluidity of the spinning dope, the setting range of the nozzle temperature, which is one of the means for adjusting the performance of the hollow fiber membrane, has been widened, and it has become easier to control the balance between coagulation and phase separation of the spinning dope. Controlling the balance between coagulation and phase separation means balancing the pore diameter and thickness of the dense layer of the hollow fiber membrane and the porosity of the support layer, specifically while enhancing the removability of β2 microglobulin. It leads to suppressing leakage of useful proteins represented by albumin as much as possible. Moreover, it leads also to the ensuring of the intensity | strength of the hollow fiber membrane which contributes to the improvement of the washing | cleaning removal property of a solvent and a non-solvent in the hollow fiber membrane manufacture mentioned later, and module assembly property. With conventional spinning stock solutions consisting of high-viscosity polymers, the nozzle temperature could only be lowered to around 100 ° C even if the following measures were taken, but by using low-viscosity polymers, the nozzle temperature was reduced to around 40 ° C. However, the spinning dope can be discharged uniformly and stably.

In the present invention, the outer surface porosity of the hollow fiber membrane is preferably 15% or more and 30% or less. Further, the average pore area per hole on the outer surface of the hollow fiber membrane is preferably 0.01 μm ² or more and 0.05 μm ² or less. If the outer surface open area ratio or average pore area is too large, the porosity of the entire support layer generally increases, so that the strength required for the hollow fiber membrane cannot be ensured, or the retainability of the membrane pore retainer may be reduced. There is. On the other hand, if the outer surface open area ratio or average pore area of the hollow fiber membrane is too small, the asymmetry of the pores is lost and the structure approaches a homogeneous structure, so that the permeability and filtration stability of the substance are reduced. Sometimes. Moreover, since the permeation | diffusion characteristic of a hollow fiber membrane falls, online washing | cleaning efficiency may fall. Therefore, the outer surface open area ratio of the hollow fiber membrane is more preferably 16% or more and 28% or less, and further preferably 17% or more and 26% or less. The average pore area is more preferably 0.01 [mu] m ² or more 0.04 .mu.m ² or less, more preferably 0.02 [mu] m ² or more 0.04 .mu.m ² or less.
Here, the membrane pore-retaining agent refers to pores that are temporarily removed when an air leak test is performed to prevent the pores from shrinking when the hollow fiber membrane is dried or to test the integrity of a module such as a blood purifier. It plays the role of blocking the Specific examples of the membrane pore retainer include glycerin, glycerin derivatives, polyethylene glycol, and the like. In the present invention, it is preferable to use glycerin.

  Conventionally, some hollow fiber membranes having a uniform structure have been filled with a membrane pore retainer in the pores in order to prevent shrinkage of the pores. However, in hollow fiber membranes having a so-called asymmetric structure, the pore diameter and porosity are too high, so there is a problem that the membrane pore retainer leaks from the pores, and the membrane pore retainer cannot be used. It was. In particular, a hollow fiber membrane made of a cellulose acetate-based polymer is likely to shrink due to heat during drying or storage, and a membrane design that assumes shrinkage in advance is required. In the hollow fiber membrane of the present invention, by preparing a relatively high concentration spinning stock solution using a relatively low viscosity polymer, it is possible to obtain a hollow fiber membrane having higher strength than conventional membranes. Leakage from the pores of the membrane pore retainer due to shrinkage is suppressed. In addition, when the porosity and the average pore area are reduced, the permeation resistance of the substance is increased, and thus the permeability of the substance in the low molecular protein region is lowered, but the thickness of the hollow fiber membrane of the present invention can be reduced. Therefore, the transmission performance can be improved accordingly.

In order to make the outer surface open area ratio and average pore area within the scope of the present invention, the polymer concentration in the spinning dope and the nozzle temperature are affected, but in addition, the spinning dope discharged from the nozzle is immersed in the coagulation bath. It is preferable that the length of the aerial traveling portion until the distance is 10 mm or more and 600 mm or less. Moreover, it is preferable to block the aerial travel part from the outside air and set the interior to 0 ° C. or more and 50 ° C. or less. By setting the length and temperature of the aerial traveling portion within the above ranges, the growth of polymer nuclei on the outer surface side of the spinning dope discharged from the nozzle can be promoted. On the other hand, on the inner surface side of the spinning dope, it is possible to complete the coagulation of the polymer with the core solution and form a dense layer before being affected by the solvent removal from the outer surface side.
In order to improve the stability of the spinning film formation, the length of the aerial traveling portion is more preferably 10 mm or more and 300 mm or less, and 10 mm or more and 150 mm or less is more preferable in order to offset the influence of the spinning spot discharged from the spinneret. The temperature of the aerial traveling section is preferably 3 ° C. or higher and 45 ° C. or lower in terms of easy control, and in view of performance, it is more preferably 5 ° C. or higher and 40 ° C. or lower in order to suppress the amount of useful protein leak.
The appropriate range for the length and temperature of the aerial running section varies depending on the nozzle draft and spinning speed. The scope of the present invention assumes that the nozzle draft is about 1 to 5 and the spinning speed is 30 to 90 m / min. is doing.

  In the present invention, in order to obtain an appropriate outer surface of the hollow fiber membrane, it is also an important requirement to optimize the conditions of the coagulation bath. In order to increase the porosity of the outer surface, it is effective to increase the solvent concentration in the coagulation bath and increase the temperature. By increasing the solvent concentration and temperature, it is possible to grow polymer nuclei generated in the aerial traveling section, and it is possible to expand the hole area ratio and the hole diameter. In order to set the open area ratio to 15% or more and 30% or less, the solvent concentration in the coagulation bath is preferably 50% by weight to 80% by weight and the coagulation bath temperature is preferably 20 ° C. or more and 70 ° C. or less. The solvent concentration should be 55% to 77% by weight and the coagulation bath temperature should be 30 ° C or more and 50 ° C or less, in order to ensure the hollow fiber membrane from the coagulation bath and the ease of temperature control of the running part in the air. More preferably, the solvent concentration is 60 wt% or more and 75 wt% or less, and the coagulation bath temperature is 35 ° C. or more and 45 ° C. or less.

In the present invention, the Young's modulus per single yarn of the hollow fiber membrane is preferably 5000 kg / cm ² or more and the yield strength is preferably 25 g or more. A high Young's modulus and yield strength mean that the polymer constituting the hollow fiber membrane has a high density or a strong entanglement of polymer chains. In the assembly of a module such as a blood purifier, the end portion of the hollow fiber membrane and the end portion of the module case are bonded with an adhesive resin, and at that time, the adhesive resin is filled using centrifugal force. At this time, if the Young's modulus of the hollow fiber membrane is low, the hollow fiber membrane may bend or bend due to centrifugal force. A module in which such a phenomenon has occurred can cause non-passage or residual blood when blood flows through the hollow fiber membrane, and can no longer be shipped as a product. Since the centrifugal force (RCF) used for filling the adhesive resin is about 40 × g, the Young's modulus and yield strength of the hollow fiber membrane are set to 5000 kg / cm ² or more and 25 g or more, respectively, in anticipation of the safety factor. For the above reasons, it is preferable that the Young's modulus and the yield strength are higher. However, in the case of a hollow fiber membrane for blood purification, depending on the relationship with the performance and the void ratio, about 7000 kg / cm ² per single yarn, About 40g seems to be the upper limit.

In the present invention, in order to make the Young's modulus and yield strength of the hollow fiber membrane within the above ranges, it is important to optimize the coagulation conditions in addition to the polymer concentration and nozzle temperature in the spinning dope. .
As the composition of the coagulation bath, it is preferable to use a mixed solution composed of a solvent, a non-solvent and water. As the solvent, it is preferable to use the same solvent used for the preparation of the spinning dope. As the non-solvent, it is preferable to use the same solvent used for the preparation of the spinning dope.
The solvent concentration and temperature in the coagulation bath have the most significant influence on the structure on the outer surface side of the hollow fiber membrane. In order to make the outer surface open area ratio and average pore area of the hollow fiber membrane within the scope of the present invention, it is preferable that the solvent concentration in the coagulation bath is 40 to 80% by weight and the temperature is 20 to 60 ° C.
Although addition of a non-solvent to the coagulation bath is not particularly required, it is preferable to match the solvent / non-solvent ratio in the spinning dope from the viewpoint of suppressing changes in the coagulation bath composition.

  By improving the Young's modulus and yield strength of the hollow fiber membrane, it can be sufficiently applied to hemofiltration dialysis having a higher operating pressure than ordinary hemodialysis. Since Young's modulus and strength are higher than those of conventional asymmetric membranes, blood flow is stable from the beginning of blood purification, and it is possible to stabilize the transmembrane pressure difference (TMP) by suppressing the shape change in the film thickness direction as much as possible. became.

  For example, in an experiment using bovine blood, when the filtration flux at a point where the initial TMP is 100 mmHg is measured, the filtration flux is about 30 mL / min in the uniform membrane, whereas the TMP reaches 100 mmHg. In the asymmetric membrane of the present invention, TMP is almost 100 mmHg or less even at a filtration flux of about 60 mL / min. This test concerns the initial pressure of the dialysis operation and reflects the initial performance and membrane fouling status. The absolute value of TMP can be set individually depending on the operating conditions, but the TMP increases over time when the initial TMP is higher than the filtration flux, making it difficult to continue dialysis due to performance degradation and fouling. Therefore, it is necessary to confirm that the transition of TMP is stable over time under dialysis conditions.

  In the blood reflux test of post-dilution type 10L water removal (filtration flux (Qf = 45 mL / min., 4 hours)), which is a general condition for hemofiltration dialysis, using the hollow fiber membrane of the present invention, It was confirmed that the difference between TMP 5 minutes after the start and TMP after 4 hours was 10 mmHg or less. Normally, when TMP changes over time due to performance degradation or membrane fouling, the increase in TMP difference is not linear but changes exponentially, so if the change in 4 hours is less than 10 mmHg It is considered to be sufficiently low and the filtration stability is high. In addition, when calculating the actual filtration flux / TMP for each time, if the value after 4 hours is maintained at 80% or more of the 5-minute value, it is considered that the permeation performance can be sufficiently maintained. . More preferably, it is 85% or more, and further preferably 90% or more. These findings are considered to indicate that a stable blood filtration dialysis prescription can be applied for a long time without clogging of blood components in the membrane.

  In addition, since the asymmetric membrane of the present invention has optimized pores on the outer surface and the strength of the membrane, glycerin is used as a pore size retaining agent in the dense layer portion in the same manner as a conventional cellulose acetate membrane having a uniform structure. be able to. Since the pore size retaining agent is filled in the pores, an air leak test is possible, and defects in product inspection can be easily found. Furthermore, there is concern about the formation of by-products (urethane oligomers) due to the reaction between glycerin and the urethane resin that is the sealing member of the module, but since the Young's modulus is high and the dimensional stability is high, the outer surface of the hollow fiber membrane In the urethane oligomer test, it was possible to suppress the glycerin exudation of glycerin to a region close to 0.02 or less and the detection sensitivity or less.

  EXAMPLES Hereinafter, although an Example is given and this invention is demonstrated more concretely, this invention is not limited at all by these Examples.

(Measurement of film thickness of hollow fiber membrane)
The cross section of the hollow fiber membrane is projected with a projector with a magnification of 200 times, and the inside diameter (A) and the outside diameter (B) of the hollow fiber having the maximum, minimum, and medium sizes are measured in each field of view. The film thickness of
Film thickness = (B−A) / 2
Calculate the average of 15 hollow fiber membranes per field of view.

(Calculation of membrane area)
The membrane area of the dialyzer is determined as a reference for the inner diameter of the hollow fiber membrane.
A = n × π × d × L
Here, n is the number of hollow fiber membranes in the dialyzer, π is the circumference, d is the inner diameter (m) of the hollow fiber membrane, and L is the effective length (m) of the hollow fiber membrane in the dialyzer.

(Hole ratio of hollow fiber membrane outer surface)
Observe the outer surface of the hollow fiber membrane with a 10,000x electron microscope and take a photograph (SEM photograph). The image is processed with image analysis software to determine the porosity of the outer surface of the hollow fiber membrane. The image analysis software is measured using, for example, Image Pro Plus (Media Cybernetics, Inc.). The emphasis / filtering operation is performed on the captured image so that the hole and the blockage are identified. Thereafter, the holes are counted, and when the lower polymer chain can be seen inside the holes, the holes are combined and counted as one hole. The area (A) of the measurement range and the total area (B) of the holes in the measurement range are obtained to obtain the hole area ratio (%) = B / A × 100. This is carried out 10 views and the average is obtained. Scale setting is performed as an initial operation, and holes on the measurement range boundary are not excluded during counting.

(Average pore area of the hole on the outer surface of the hollow fiber membrane)
Count as in the previous section to determine the area of each hole. Also, holes on the measurement range boundary are excluded during counting. This is carried out for 10 fields of view and the average of all the hole areas is obtained.

(Young's modulus (kg / cm ² ))
The breaking strength and yield strength are measured using a yarn tensile tester (Instron (Model No. TM) manufactured by Instron Engineering Corporation). A single yarn with a total length of about 15 cm is fixed to a chuck (10 cm between chucks), and a full-scale 100 g cell connected to the chuck is raised at a speed of 20 mm / min. The breaking elongation and breaking strength at which the hollow fiber is cut from the chart paper are read and taken as SS curve. If there is no maximum point, an auxiliary line with an extended initial slope is provided. The point where two auxiliary lines intersect is defined as the yield point, and the strength at that point is the yield strength and the elongation is the yield elongation. In addition, if there is a maximum point, the point where the auxiliary line with an extended initial slope and the auxiliary line with zero slope at the maximum point intersect is defined as the yield point, the strength at that point is the yield strength, and the elongation is the yield elongation. And Using these values, the Young's modulus is calculated by the following formula: Young's modulus = yield strength / yarn cross-sectional area / yield elongation.

(Measurement of water permeability (UFR))
The blood outlet circuit of the dialyzer (the outlet side from the pressure measurement point) is sealed with forceps. Purified water kept at 37 ° C is put into a pressurized tank, the pressure is controlled by a regulator, pure water is sent to the dialyzer kept at 37 ° C constant temperature bath, and the flow rate of the filtrate flowing out from the dialysate side is measured. The transmembrane pressure difference (TMP) is
TMP = (Pi + Po) / 2
And Here, Pi is the dialyzer inlet side pressure, and Po is the dialyzer outlet side pressure. Change the TMP at four points, measure the filtration flow rate, and calculate the water permeability (mL / hr / mmHg) from the slope of the relationship. At this time, the correlation coefficient between TMP and filtration flow rate should be 0.999 or more. In order to reduce the pressure loss error due to the circuit, TMP is measured in the range of 100mmHg or less. The water permeability of the hollow fiber membrane is calculated from the membrane area and the water permeability of the dialyzer.
UFR (H) = UFR (D) / A
Where UFR (H) is the water permeability of the hollow fiber membrane (mL / m ² / hr / mmHg), UFR (D) is the water permeability of the dialyzer (mL / hr / mmHg), and A is the membrane area of the dialyzer ( m ² ).

(Measurement of permeation performance of β2 microglobulin)
Implemented in accordance with the blood purifier evaluation method in the “Blood Purifier Performance Evaluation Method and Functional Classification” established by the Japan Dialysis Medical Association. The permeation performance is evaluated by the clearance of β2 microglobulin. (Refer nonpatent literature 1).
Journal of Japanese Society for Dialysis 29 (8) 1231-1245 (1996)

(Albumin leakage)
Use 37 ° C bovine blood to which citrate was added and coagulation was suppressed. Dilute with bovine plasma and adjust hematocrit to 30%. The blood is fed to a blood purifier at 200 mL / min., And the blood is filtered at a rate of 15 mL / min. At this time, the filtrate is returned to blood to be a circulatory system. In order to prevent hemolysis, the blood purifier is sufficiently replaced with physiological saline in advance. Confirm that the specified filtration flow rate is obtained 5 minutes after the start of circulation, and sample about 1 cc of the filtrate every 15 minutes from 15 minutes after the start. In addition, after 15 minutes, 60 minutes and 120 minutes after the start, blood at the inlet side and the outlet side of the blood purifier is sampled, and plasma is obtained by centrifugation, which is used as a test solution. The collected samples are subjected to bromcresol green (BCG method) using A / GB-Test Wako (manufactured by Wako Pure Chemical Industries, Ltd.) to calculate the albumin concentrations in the filtrate, blood and plasma. The amount of albumin leak in terms of 3L water removal can be determined as follows. Sampling is performed at 30 minutes, 45 minutes, 60 minutes, 75 minutes, 90 minutes, 105 minutes, and 120 minutes, and the albumin concentration in the filtrate is calculated. Using these data, albumin leak (TAL [mg / dl]) on the vertical axis and ln (time [min.]) (LnT) on the horizontal axis, spreadsheet software (ex. Microsoft Excel-XP) Is used to draw a fitting curve by linear approximation, and constants a and b in the relational expression TAL = a × lnT + b are obtained (correlation coefficient is preferably 0.95 or more, more preferably 0.97 or more, and more preferably 0.99 or more). The average albumin leak concentration [mg / dl] is calculated by integrating from T = 0 to T = 240 using this equation TAL = a × lnT + b and dividing this by 240 [min.]. By multiplying the obtained average albumin leak concentration by 30 dl, the amount of albumin leak in terms of 3L water removal in the present application can be obtained. However, when the albumin leak changes little over time, the average albumin leak concentration [mg / dl] is obtained by simply performing a primary fitting of TAL and time and dividing the total area by 240 [min.]. ] And multiplying the calculated average albumin leak concentration by 30 dl, the albumin leak amount in terms of 3L water removal in the present application can be obtained.

(Filtration stability evaluation)
Use 37 ° C bovine blood to which citrate was added and coagulation was suppressed. Dilute with bovine plasma and adjust hematocrit to 30%. The blood is fed to a blood purifier at 200 mL / min., And the blood is filtered at a rate of 45 mL / min. At this time, the filtrate is returned to blood to be a circulatory system. In order to prevent hemolysis, the blood purifier is sufficiently replaced with physiological saline in advance. Five minutes after the start of circulation, it is confirmed by collecting the filtrate in the graduated cylinder that the specified filtration flow rate has been obtained. At the same time, the blood inlet (Pi), blood outlet (Po), and filtrate at the pressure chamber part of the dialysis circuit, respectively. Measure the pressure at the outlet (Pf)
TMP = Pf-(Pi + Po) / 2
Calculate with Similarly, measure TMP after 240 minutes,
△ TMP = │TMP240 − TMP5│
Calculated by
Similarly, Qfmax (TMP = 100 mmHg) uses bovine blood at 37 ° C. in which citric acid is added and coagulation is suppressed. Dilute with bovine plasma and adjust hematocrit to 30%. The blood is fed to the blood purifier at 200 mL / min., And the filtration rate is increased at a rate of 15 mL / min. Every 30 minutes. At this time, the filtrate is returned to blood to be a circulatory system. In order to prevent hemolysis, the blood purifier is sufficiently replaced with physiological saline in advance. 20 minutes after changing the filtration rate, TMP is obtained by the above formula, and Qf and TMP are plotted. Appropriate fitting such as a quadratic function is performed on this relationship, and Qf at TMP = 100 mmHg is calculated as Qfmax.

(Module productivity)
For module productivity, 1000 modules with a membrane area of 1.5m ² are manufactured, ◯ when 950 or more non-defective products are obtained, △ when 900 or more and 949 or less non-defective products are obtained, △, and less than × . Causes of failure include breakage, bending, and bending of the hollow fiber membrane (when an inclined bending of 15 degrees or more with respect to the length direction of the hollow fiber is observed), crushing, leakage, and poor filling of the sealant.

(Measurement of polymer viscosity)
Dissolve each desired spinning dope for 4 hours at 180 ° C. in a nitrogen atmosphere. After confirming that the solution was uniformly dissolved visually, a sample was taken and a B-type viscometer (B-8H-HH) [ Measure the viscosity at a temperature of 50 ° C with Tokyo Keiki].

(Measurement of urethane oligomer)
An effective membrane area 1.5 m ² (on the basis of the liquid contact surface to be treated) in which both ends of the hollow fiber membrane are fixed with resin is cut into a size of about 1 cm square at both ends. The obtained sample is immersed in warm water of 40 cc and 200 cc for 2 hours to extract the eluate from the end bonded portion. The absorbance at 245 nm of a diluted solution obtained by diluting the obtained extract by 50 times is measured.

(Example 1)
Cellulose triacetate (6% viscosity = 162 mPa · s, Daicel Chemical Industries) 21% by weight of N-methyl-2-pyrrolidone (NMP, Mitsubishi Chemical) and triethylene glycol (TEG, Mitsui Chemicals) A solution uniformly dissolved in the mixed solution 2 was discharged as a spinning stock solution from the outer annular portion of the double tube nozzle, and at the same time, water was discharged as a core solution. At that time, the core liquid was cooled by flowing a 5 ° C. refrigerant through a block in which the nozzle was set. The spinning dope was kept warm by circulating a heating medium at 80 ° C. in the block.
The spinning dope discharged from the nozzle is passed through a free running part of 50mm and 30 ° C, and then diluted in water at 40 ° C by diluting a mixed solution of NMP / TEG = 8/2 with water to 70% by weight. And solidified, washed with water, adhered to glycerin, dried and wound up. The hollow fiber membrane had an inner diameter of 200 μm and a film thickness of 20 μm. The obtained hollow fiber membranes are bundled and inserted into a blood purification container, and both ends are bonded and fixed with polyurethane, and a hemodialyzer having a hollow fiber membrane inner diameter standard effective area of 1.5 m ² is prepared for various evaluations. Provided. The evaluation results are summarized in Table 1.

(Example 2)
Cellulose triacetate (6% viscosity = 154 mPa · s, Daicel Chemical Industries) 18% by weight of N-methyl-2-pyrrolidone (NMP, Mitsubishi Chemical) and triethylene glycol (TEG, Mitsui Chemicals) A solution uniformly dissolved in the mixed solution 2 was discharged as a spinning stock solution from the outer annular portion of the double tube nozzle, and at the same time, water was discharged as a core solution. At that time, the core liquid was cooled by flowing a 0 ° C. refrigerant through a block in which the nozzle was set. The spinning dope was kept warm by circulating a heating medium at 80 ° C. in the block.
The spinning dope discharged from the nozzle is passed through an idling part at 80 ° C and 30 ° C, and then in a coagulating solution at 45 ° C where NMP / TEG = 8/2 mixed solution is diluted to 72% by weight with water. And solidified, washed with water, adhered to glycerin, dried and wound up. The hollow fiber membrane had an inner diameter of 200 μm and a film thickness of 20 μm. The obtained hollow fiber membranes are bundled and inserted into a blood purification container, and both ends are bonded and fixed with polyurethane, and a hemodialyzer having a hollow fiber membrane inner diameter standard effective area of 1.5 m ² is prepared for various evaluations. Provided. The evaluation results are summarized in Table 1.

(Example 3)
Cellulose triacetate (6% viscosity = 172 mPa · s, Daicel Chemical Industries) 23 wt% N-methyl-2-pyrrolidone (NMP, Mitsubishi Chemical) and triethylene glycol (TEG, Mitsui Chemicals) 8 ratio A solution uniformly dissolved in the mixed solution 2 was discharged as a spinning stock solution from the outer annular portion of the double tube nozzle, and at the same time, water was discharged as a core solution. At that time, the core liquid was cooled by flowing a 10 ° C. refrigerant through a block in which the nozzle was set. The spinning dope was kept warm by circulating a heating medium at 80 ° C. in the block.
The spinning dope discharged from the nozzle was passed through a 20mm, 30 ° C idle running part, and then the NMP / TEG = 8/2 mixed solution was diluted with water to 60% by weight in a 35 ° C coagulation solution. And solidified, washed with water, adhered to glycerin, dried and wound up. The hollow fiber membrane had an inner diameter of 200 μm and a film thickness of 20 μm. The obtained hollow fiber membranes are bundled and inserted into a blood purification container, and both ends are bonded and fixed with polyurethane, and a hemodialyzer having a hollow fiber membrane inner diameter standard effective area of 1.5 m ² is prepared for various evaluations. Provided. The evaluation results are summarized in Table 1.

(Comparative Example 1)
Cellulose triacetate (6% viscosity = 162 mPa · s, Daicel Chemical Industries) 21% by weight of N-methyl-2-pyrrolidone (NMP, Mitsubishi Chemical) and triethylene glycol (TEG, Mitsui Chemicals) A solution uniformly dissolved in the mixed solution 2 was discharged as a spinning stock solution from the outer annular portion of the double tube nozzle, and at the same time, water was discharged as a core solution. The spinning dope was kept warm by circulating a heating medium at 80 ° C. in the block. The core liquid was not kept cold.
The spinning dope discharged from the nozzle is passed through a free running section of 50 mm and 30 ° C, and then diluted in water at 40 ° C by diluting a mixed solution of NMP / TEG = 8/2 with water to 70% by weight. And solidified, washed with water, adhered to glycerin, dried and wound up. The hollow fiber membrane had an inner diameter of 200 μm and a film thickness of 20 μm. The obtained hollow fiber membranes were bundled and inserted into a container, and both ends were bonded and fixed with polyurethane, and hemodialyzers having an effective area of 1.5 m ² were prepared for various evaluations. The evaluation results are summarized in Table 1.

(Comparative Example 2)
Cellulose triacetate (6% viscosity = 154 mPa · s, Daicel Chemical Industries) 18% by weight of N-methyl-2-pyrrolidone (NMP, Mitsubishi Chemical) and triethylene glycol (TEG, Mitsui Chemicals) The solution uniformly dissolved in the mixed solution 2 was discharged as a spinning stock solution from the outer annular portion of the double tube nozzle, and at the same time, water was discharged as a core solution. At that time, the core liquid was cooled by flowing a 0 ° C. refrigerant through a block in which the nozzle was set. The spinning dope was kept warm by circulating a heating medium at 80 ° C. in the block.
The spinning dope discharged from the nozzle was passed through air at 80 ° C and 30 ° C, and then the NMP / TEG = 8/2 mixed solution was diluted with water and introduced into a 75 ° C coagulation solution at 72% by weight. After solidifying, washing with water and glycerin adhesion treatment, it was dried and wound up. The hollow fiber membrane had an inner diameter of 195 μm and a film thickness of 25 μm. The obtained hollow fiber membranes are bundled and inserted into a blood purification container, and both ends are bonded and fixed with polyurethane, and hemodialyzers having an effective area of 1.5 m ^{2 based} on the hollow fiber membrane inner diameter standard are prepared and evaluated in various ways. It was used for. The evaluation results are summarized in Table 1.

(Comparative Example 3)
Cellulose triacetate (6% viscosity = 266mPa · s, Daicel Chemical Industries, Ltd.) 21% by weight N-methyl-2-pyrrolidone (NMP, Mitsubishi Chemical) and triethylene glycol (TEG, Mitsui Chemicals) ratio of 8 A solution uniformly dissolved in the mixed solution 2 was discharged as a spinning stock solution from the outer annular portion of the double tube nozzle, and at the same time, water was discharged as a core solution. At that time, the core liquid was cooled by flowing a 20 ° C. refrigerant through a block in which the nozzle was set. The spinning dope was kept warm by circulating a 110 ° C. heating medium in the block. The spinning dope discharged from the nozzle was passed through a free running section of 50 mm and 35 ° C, and then diluted in water at 40 ° C by diluting a mixed solution of NMP / TEG = 8/2 with water to 70% by weight. And solidified, washed with water, adhered to glycerin, dried and wound up. The hollow fiber membrane had an inner diameter of 200 μm and a film thickness of 20 μm. The obtained hollow fiber membranes are bundled and inserted into a blood purification container, and both ends are bonded and fixed with polyurethane, and a hemodialyzer having a hollow fiber membrane inner diameter standard effective area of 1.5 m ² is prepared for various evaluations. Provided. The evaluation results are summarized in Table 1.

(Reference Example 1)
Cellulose triacetate (6% viscosity = 266mPa · s, Daicel Chemical Industries) 21% by weight N-methyl-2-pyrrolidone (NMP, Mitsubishi Chemical) and triethylene glycol (TEG, Mitsui Chemicals) ratio of 8 to A solution that was uniformly dissolved in the mixed solution 2 was used as a spinning stock solution, and water was used as a core solution from a double tube nozzle. At that time, the core liquid was kept cold by flowing a 5 ° C. refrigerant around the nozzle setting block. In addition, the spinning dope was kept warm by flowing an 80 ° C heating medium around in the block. These were insulated in the block and kept warm until just before discharge.
Because the viscosity of cellulose triacetate was too high, the spinning stock solution was clogged in the nozzle and could not be discharged.

(Reference Example 2)
Cellulose triacetate (6% viscosity = 162 mPa · s, Daicel Chemical Industries) 13% by weight N-methyl-2-pyrrolidone (NMP, Mitsubishi Chemical) and triethylene glycol (TEG, Mitsui Chemicals) ratio of 8 A solution that was uniformly dissolved in the mixed solution 2 was used as a spinning stock solution, and water was used as a core solution from a double tube nozzle. At that time, the core liquid was kept cold by flowing a 5 ° C. refrigerant around the nozzle setting block. In addition, the spinning dope was kept warm by flowing an 80 ° C heating medium around in the block. These were insulated in the block and kept warm until just before discharge.
After discharging from a nozzle into air at 50 ° C and 30 ° C, the mixed solution of NMP / TEG = 8/2 was introduced into a coagulation liquid made up to 70 wt% with water, solidified at 40 ° C, solidified, washed with water, and glycerin adhered After the treatment, it was scheduled to be dried and wound up. However, since the strength of the membrane formed in the coagulation bath is very weak, the hollow fiber membrane could not be spun out from the coagulation bath to the next step.

In the present invention, a cellulose acetate-based polymer was used to give a close-packed structure close to that of a conventional synthetic polymer, and high molecular weight fractionation characteristics could be imparted. Especially in hemodialysis and hemofiltration dialysis, it has become possible to provide a selectively permeable hollow fiber membrane capable of removing harmful substances in the medium high molecular weight region such as β2-MG and enhancing the outflow prevention of useful substances such as albumin. . In addition, the productivity of hollow fiber membranes that are difficult to handle has been improved, and it has become possible to provide a selectively permeable hollow fiber membrane with improved safety and no effluent from the membrane.

Claims (4)

A hollow fiber membrane having an asymmetric structure mainly composed of a cellulose acetate-based polymer and having a dense layer on at least the inner surface thereof, wherein the hollow fiber membrane has an inner diameter of 150 μm to 250 μm and a film thickness of 10 μm to less than 30 μm, cellulose acetate-based asymmetric hollow fiber membrane of 30% or less and an average opening area aperture ratio is more than 15% of the outer surface is characterized by a per 0.01 [mu] m ² or more 0.05μm under ² holes of. The cellulose acetate asymmetric hollow fiber membrane according to claim 1, wherein the hollow fiber membrane has a Young's modulus per single yarn of 5000 kg / cm ² or more and a yield strength of 25 g or more.   The cellulose acetate polymer is dissolved in methylene chloride / methanol = 91/9 so as to be 6% by weight, and has a viscosity of more than 140 mPa · s and less than 200 mPa · s when measured at a temperature of 25 ° C. The cellulose acetate type asymmetric hollow fiber membrane according to claim 1 or 2. The cellulose acetate asymmetric hollow fiber membrane according to any one of claims 1 to 3, wherein the cellulose acetate polymer is cellulose diacetate and / or cellulose triacetate.