WO2017195457A1 - Polyethylene resin porous hollow fiber membrane, separation membrane, and method for manufacturing said membranes - Google Patents

Abstract

A polyethylene resin porous hollow fiber membrane having a plurality of microfibrils which include a polyethylene resin and which are aligned in the fiber longitudinal direction, and nodular parts comprising a lamellar laminate connected to both ends of the microfibrils, wherein the mass fraction of components having a molecular weight of 10,000 or less is 17.5 mass% or above, and the mass fraction of components having a molecular weight of 1,000,000 or higher is less than 1.5 mass%.

Description

Polyethylene resin porous hollow fiber membrane, separation membrane, and production method thereof

The present invention relates to a porous hollow fiber membrane containing a polyethylene-based resin, and in particular, a separation membrane used for separating and eliminating a specific substance (particularly suitable for separating plasma from blood in plasma exchange therapy). The present invention relates to a porous hollow fiber membrane that can be suitably used as a base material for a separation membrane used in the above and a production method thereof.

In recent years, as one of the extracorporeal circulation blood purification therapy, blood cell components and plasma components containing a pathogenic substance are separated from a patient's blood using a separation membrane comprising a porous hollow fiber membrane, and an alternative plasma component is obtained. Plasma exchange therapy, which returns the purified blood to the patient's body, has attracted attention.

As a method for producing a porous hollow fiber membrane, a non-solvent induced phase separation method, a thermally induced phase separation method, a melt stretch opening method and the like are known. Among them, the melt-stretching and opening method is a method in which a crystalline polymer compound is melted and spun into a hollow fiber shape, and the wound hollow fiber is made porous by stretching to obtain a porous hollow fiber membrane. Since the porous hollow fiber membrane obtained by this method does not use a liquid component such as a solvent or a plasticizer in the production process, there is no fear of elution of the liquid component during use, and it is suitable for plasma separation.
When applying to plasma separation, if the porous hollow fiber membrane is made of a hydrophobic polymer, the porous surface is covered with a hydrophilic substance, etc., imparting hydrophilicity / low protein adsorption, and blood compatibility Sexuality is enhanced. The pore diameter of the porous hollow fiber membrane is controlled in the range of 0.01 to 2 μm from the viewpoint of separation of blood cell components and plasma components from blood. Further, the porous hollow fiber membrane is sterilized from the viewpoint of safety before plasma separation.
By the way, the porous structure formed by the melt-stretching hole-opening method is such that a lamellar laminate of hollow fibers before stretching (hereinafter referred to as “hollow fibers before stretching”) is cleaved by cold stretching, and the resulting micropores are further expanded by hot stretching. Can be obtained.
However, if the hollow fiber before stretching contains an insufficiently grown lamellar laminate, the porous hollow fiber membrane after stretching is not perforated by about 0.1 to 50 mm in the yarn length direction. A portion (hereinafter referred to as “unstretched portion”) is generated. Since the unstretched portion is not porous, it does not have a separation function, but it only constitutes a part of the porous hollow fiber membrane, so that it does not reach the original separation / permeability of the separation membrane. Absent. That is, the porous hollow fiber membrane including the unstretched portion does not cause a problem in terms of function as a separation membrane.
However, when a porous hollow fiber membrane containing an unstretched part is used for plasma separation, there are therapeutic problems in the following points. That is, the hollow fiber before stretching has a translucent appearance, but the porous hollow fiber membrane after stretching is whitened due to irregular reflection of light by the pores. On the other hand, the unstretched portion having no pores reflects the appearance of the hollow fiber before stretching and remains translucent. In plasma exchange therapy, blood is passed through the hollow portion of the porous hollow fiber membrane. At this time, if there is an unstretched portion that is translucent in the porous hollow fiber membrane, blood passing through the hollow portion appears to permeate. Therefore, the practitioner misunderstands that blood has leaked from the unstretched part. If a blood leak is detected in plasma exchange therapy, the treatment is interrupted, so that the so-called pseudo-leakage of blood due to the unstretched part is difficult to distinguish from the actual blood leak. The treatment will also be interrupted and the patient's opportunity for treatment will be lost. In view of the above, in plasma exchange therapy, there is a demand for a porous hollow fiber membrane excellent in homogeneity having no unstretched part in addition to good separation and permeability.

In Patent Document 1, as a means for improving the homogeneity of a porous hollow fiber membrane obtained by a melt-stretching hole-opening method, a metal compound having a crystallization nucleation ability is formed on a crystalline polymer constituting the porous hollow fiber membrane. A method of adding 0.01% by weight or more is disclosed. However, the porous hollow fiber membrane disclosed in Patent Document 1 is intended to improve the fine pore distribution spots in the hollow fiber length direction and the hollow fiber cross-sectional direction, which leads to the elimination of the unstretched portion. Not.

JP 54-77729 A

An object of the present invention is to provide a polyethylene resin porous hollow fiber membrane having few unstretched parts and excellent in homogeneity, which can be used as a base material for a separation membrane for plasma separation. It is to provide a separation membrane with less pseudo-leakage of blood using a porous hollow fiber membrane.

As a result of intensive studies, the present inventors have found that the ratio of the component having a molecular weight of 10,000 or less and the component having a molecular weight of 1,000,000 or more contained in the porous hollow fiber membrane is in a specific range, or a polyethylene resin used as a raw material. When the resin composition containing a polyethylene-based resin contains 1.0% by mass or more of a component having a molecular weight of 1000 or less, the melt flow rate measured by JIS K7210 (Code D) (hereinafter, “MFR / D”) And when the melt flow rate (hereinafter referred to as “MFR / G”) measured in accordance with JIS K7210 (Code G) is within a specific range, the above-described problems can be solved. It came to be completed.

That is, the present invention is as follows.
[1] A porous hollow fiber membrane comprising a polyethylene resin and having a plurality of microfibrils oriented in the yarn length direction, and a knot portion composed of a lamellar laminate connected to both ends of the microfibrils, having a molecular weight of 10,000 A polyethylene resin porous hollow fiber membrane having a mass fraction of the following components of 17.5% by mass or more and a mass fraction of a component having a molecular weight of 1 million or more of less than 1.5% by mass.
[2] The polyethylene resin porous hollow fiber membrane according to [1], wherein the polyethylene resin contains an olefin wax. [3] The olefin wax is a high density low molecular weight ethylene polymer having a density of 960 kg / m ³ or more, a low density low molecular weight ethylene polymer having a density of less than 940 kg / m ³ , a low molecular weight ethylene-propylene copolymer, and The polyethylene resin porous hollow fiber membrane according to [2], which is at least one selected from the group consisting of a low molecular weight ethylene-butene copolymer.
[4] The polyethylene resin porous hollow fiber membrane according to any one of [1] to [3], wherein the polyethylene resin is high-density polyethylene.
[5] A polyethylene resin porous hollow fiber membrane according to any one of [1] to [4], and a hydrophilic polymer provided on at least a part of the surface of the polyethylene resin porous hollow fiber membrane. And a hydrophilic layer.
[6] The separation membrane according to [5], wherein the hydrophilic polymer is an ethylene-vinyl alcohol copolymer.
[7] The separation membrane according to [5] or [6], wherein a melt flow rate (MFR / D) measured by JIS K7210 (Code D) is 0.03 or more.
[8] The separation membrane according to any one of [5] to [7], which is for plasma separation.
[9] A polyethylene resin porous material comprising a step of producing a hollow fiber from a polyethylene resin or a resin composition containing a polyethylene resin, and a step of forming a porous hollow fiber membrane by stretching the hollow fiber. A method for producing a hollow fiber membrane, wherein the polyethylene resin or the resin composition contains 1.0% by mass or more of a component having a molecular weight of 1000 or less.
[10] The production of a polyethylene resin porous hollow fiber membrane according to [9], wherein the polyethylene resin contains 0.1 to 10.0% by mass of an olefin wax having a viscosity average molecular weight of 700 to 8000. Method.
[11] The method for producing a polyethylene resin porous hollow fiber membrane according to [9] or [10], wherein the polyethylene resin is high-density polyethylene.
[12] The melt flow rate (MFR / D) measured by JIS K7210 (Code D) of the polyethylene resin or the resin composition containing the polyethylene resin is 3.0 to 10.0, and JIS K7210 ( The method for producing a polyethylene resin porous hollow fiber membrane according to any one of [9] to [11], wherein the melt flow rate (MFR / G) measured in Code G) is 150 to 300.
[13] The olefin wax is a high density low molecular weight ethylene polymer having a density of 960 kg / m ³ or more, a low density low molecular weight ethylene polymer having a density of less than 940 kg / m ³ , a low molecular weight ethylene-propylene copolymer, and The method for producing a polyethylene resin porous hollow fiber membrane according to any one of [10] to [12], which is at least one selected from the group consisting of a low molecular weight ethylene-butene copolymer.
[14] The method for producing a polyethylene resin porous hollow fiber membrane according to [13], wherein the olefin wax is a high density low molecular weight ethylene polymer having a density of 960 kg / m ³ or more.
[15] A step of obtaining a polyethylene resin porous hollow fiber membrane by the production method according to any one of [9] to [14], and a hydrophilic polymer on at least a part of the surface of the porous hollow fiber membrane The manufacturing method of the separation membrane including the process of providing the hydrophilic layer containing.
[16] The method for producing a separation membrane according to [15], wherein the hydrophilic polymer is an ethylene-vinyl alcohol copolymer.
[17]
The method for producing a separation membrane according to [15] or [16], further comprising a step of sterilizing the porous hollow fiber membrane with radiation.

According to the present invention, it is possible to provide a polyethylene resin porous hollow fiber membrane having a high degree of homogeneity with few unstretched portions that can be used as a base material for a separation membrane for plasma separation with less pseudo blood leakage. it can.

It is a model figure which shows the specific example of the structure of the porous hollow fiber membrane of this invention.

Hereinafter, a mode for carrying out the present invention (hereinafter referred to as “the present embodiment”) will be described in detail. In addition, this invention is not limited to the following embodiment, It can implement by changing variously within the range of the summary.

The porous hollow fiber membrane of this embodiment contains a polyethylene resin. The porous hollow fiber membrane can be used as a separation membrane as it is, but it is more suitable for plasma separation if at least a part of its surface is covered with a hydrophilic layer containing a hydrophilic polymer. It becomes. In addition, by performing sterilization treatment with radiation or the like, a separation membrane more suitable for plasma separation is obtained.
In the porous hollow fiber membrane, the mass fraction of the component having a molecular weight of 10,000 or less is 17.5% by mass or more, and the mass fraction of the component having a molecular weight of 1,000,000 or more is less than 1.5% by mass. .

The porous hollow fiber membrane of the present embodiment is composed of a plurality of microfibrils oriented in the yarn length direction (short fibrous bodies composed of an assembly of molecular chains (however, the length is not limited)), and the microfibrils of the microfibrils It has a nodule part (a nodal connection part connecting the ends of microfibrils) made of a lamellar laminate connected to both ends, and has a plurality of slit-like pores formed between adjacent microfibrils ing. The bundling portion connects, for example, end portions of oriented (or substantially parallel) microfibrils. The structure composed of the knot part-the plurality of microfibrils-knot parts may be repeated in the yarn length direction to constitute a substantially mesh structure. Such a structure is generally a structure found in a porous hollow fiber membrane obtained by a melt-stretch opening method, and is confirmed by observing the surface of the inner wall or outer wall of the hollow fiber with a scanning electron microscope or the like. Can do. A specific example of this structure is shown in FIG.
According to the melt stretch opening method, since there is no elution of the liquid additive remaining in the membrane and a porous hollow fiber membrane suitable for plasma separation is obtained, in this embodiment, the porous hollow fiber membrane is It is preferable to manufacture by the melt stretch opening method.

The porous hollow fiber membrane of this embodiment contains a polyethylene resin. The content of the polyethylene resin in the porous hollow fiber membrane is not limited, but is preferably 70% by mass or more, more preferably 80% by mass or more, and further preferably 90% by mass or more. 95% by mass or more is particularly preferable. Moreover, 100 mass% may be sufficient.
The mass fraction of the component having a molecular weight of 10,000 or less in the porous hollow fiber membrane is 17.5% by mass or more, preferably 18.0% by mass or more, and particularly preferably 18% by mass or more and 20.0%. It is less than mass%. Further, the mass fraction of the component having a molecular weight of 1,000,000 or more of the porous hollow fiber membrane may be less than 1.5 mass%, may be 1.45 mass% or less, or is 1.35 mass% or less. May be. The porous hollow fiber membrane is porous hollow so that the mass fraction of the component having a molecular weight of 10,000 or less is 17.5% by mass or more and the mass fraction of the component having a molecular weight of 1,000,000 or more is less than 1.5% by mass. When the raw material of the yarn membrane was adjusted, it was found that a porous hollow fiber membrane with few unstretched parts could be produced by the melt stretch pore opening method. However, when the component having a molecular weight of 10,000 or less is too much, the pressure resistance of the porous hollow fiber membrane is lowered, and the hollow fiber membrane may be broken or ruptured during use. Therefore, the mass fraction of the component having a molecular weight of 10,000 or less. Is preferably less than 20.0% by mass. In addition, when the component having a molecular weight of 1 million or more is too small, the elastic recovery rate of the hollow fiber before stretching is lowered, so that appropriate stretch opening is not performed, and a porous hollow fiber membrane having a desired pore diameter range cannot be obtained. Therefore, the component having a molecular weight of 1 million or more is preferably 1% by mass or more.

In this embodiment, the mass fraction of the component having a molecular weight of 10,000 or less and the mass fraction of the component having a molecular weight of 1,000,000 or more of the porous hollow fiber membrane are the polyethylene resin or polyethylene resin that is the raw material of the porous hollow fiber membrane. Can be adjusted by appropriately adjusting the molecular weight distribution of the resin composition containing, particularly, because it is affected by the mass fraction of the component having a molecular weight of 1000 or less, the melt flow rate, etc. The mass fraction of the component having a molecular weight of 10,000 or less in the porous hollow fiber membrane can be easily made 17.5 mass% or more, and the mass fraction of the component having a molecular weight of 1,000,000 or more can be easily made less than 1.5 mass%. I understood. Here, the “resin composition containing a polyethylene resin” means a material other than a single type of polyethylene resin among the polyethylene resin-containing materials constituting the porous hollow fiber membrane of the present embodiment. For example, a mixture of a plurality of polyethylene resins (for example, a mixture of a polyethylene resin and an olefin wax, which are main raw materials described later), a mixture of a polyethylene resin and other resins, and additives other than resins. And the like added.
That is, in order to set the mass fraction of the component having a molecular weight of 10,000 or less of the porous hollow fiber membrane to 17.5% by mass or more and the mass fraction of the component having a molecular weight of 1,000,000 or more to less than 1.5% by mass, A porous hollow fiber membrane may be produced while appropriately adjusting the molecular weight distribution, but the component having a molecular weight of 1000 or less as a raw material is generally in the range of 1.0% by mass or more without finely adjusting the molecular weight distribution of the raw material. When the adjusted polyethylene resin or polyethylene resin-containing resin composition is used, the mass fraction of the component having a molecular weight of 10,000 or less of the porous hollow fiber membrane is easily 17.5% by mass or more and the component having a molecular weight of 1,000,000 or more. The mass fraction can be less than 1.5% by mass.
In particular, the MFR / D (melt flow rate measured by JIS K7210 (code D)) is 3.0 to 10.0, and the MFR / G (melt flow rate measured by JIS K7210 (code G)) is 150 to 300. In the polyethylene resin or polyethylene resin-containing resin composition having a molecular weight distribution such that the component having a molecular weight of 1000 or less is in the range of 1.0% by mass or more, the molecular weight of the porous hollow fiber membrane obtained therefrom is 10,000. The mass fraction of the following components tends to be 17.5% by mass or more, and the mass fraction of a component having a molecular weight of 1 million or more tends to be less than 1.5% by mass.
The mass fraction of the component having a molecular weight of 10,000 or less in the porous hollow fiber membrane tends to increase as the proportion of the component having a molecular weight of 1000 or less in the raw material increases. Since such a low molecular weight component has a problem of elution and desorption from the porous hollow fiber membrane, the component having a molecular weight of 1000 or less in the raw polyethylene resin or resin composition is preferably 3% by mass or less. It is more preferably at most mass%, further preferably at most 1.5 mass%.

Further, when the polyethylene resin-containing porous hollow fiber membrane was produced, a raw material polyethylene resin or resin composition having a mass fraction of a component having a molecular weight of 1000 or less of 1.0% by mass or more was used. In this case, it was found that the growth of the lamella laminate of the raw yarn before drawing was promoted, and thereby the lamella laminate was made uniform in the yarn length direction and the film thickness direction. Although the mechanism of action is not clear, the component having a molecular weight of 1000 or less in the polyethylene resin or the resin composition acts as a plasticizer, and the crystallization rate of the polyethylene resin is reduced, thereby promoting the growth of the lamellar laminate. This is thought to lead to uniformization.
Therefore, also from such a viewpoint, it is preferable to use a polyethylene resin or resin composition having a mass fraction of a component having a molecular weight of 1000 or less in a range of 1.0% by mass or more.

As described above, when the MFR / D of the raw material polyethylene resin or resin composition is 3.0 to 10.0 and the MFR / G is 150 to 300, the component having a molecular weight of 10,000 or less in the porous hollow fiber membrane It becomes easy to make the mass fraction of the component having a mass fraction of 17.5% by mass or more and the molecular weight of 1 million or more less than 1.5% by mass. It tends to be more facilitated to make the lamellar laminate uniform in the yarn length direction and the film thickness direction, which is seen when a material having a mass fraction of 1.0% by mass or more is used. This is presumably because, when the melt viscosity is in an appropriate range, the component having a molecular weight of 1000 or less acts like a plasticizer, and the effect of reducing the crystallization speed of the polyethylene resin is more easily exhibited.
The MFR / D of the polyethylene resin or the resin composition is more preferably 3.5 to 6.0, still more preferably 3.8 to 5.8, and the MFR / G is more preferably 160 to 270, and further Preferably, it is 170-200.

Here, the polyethylene resin is an ethylene homopolymer or a copolymer of ethylene and other monomer components (the content of other monomer components is preferably 5 mol% or less). A preferred specific example in this embodiment is high density polyethylene with high density and few branches. The density of the high density polyethylene (according to JIS K7112: 1999) is preferably 950 kg / m ³ or more, more preferably 960 kg / m ³ or more.
In general, a pre-stretch raw yarn obtained from high-density polyethylene having a density of less than 950 kg / m ³ has a low crystallinity, so that the pore size of the porous hollow fiber membrane obtained by stretching is desired (for example, suitable for plasma separation). D) It is difficult to adjust the stretching conditions for the range.

In this embodiment, when used for plasma separation, the porous hollow fiber membrane preferably has a pore size of 0.01 to 2 μm, more preferably 0.1 to 0.6 μm.
Here, the pore diameter refers to the maximum pore diameter measured by the bubble point method (JIS K3832: 1990).

In this embodiment, there is no limitation on the method for adjusting the mass fraction of the component having a molecular weight of 1000 or less of the polyethylene resin or resin composition that is the raw material of the porous hollow fiber membrane. The component having a molecular weight of 1000 or less may have a mass fraction of 1.0% by mass or more. For example, a component having a molecular weight of 1000 or less can be obtained by blending an olefin wax with a polyethylene resin as a main raw material. The resin composition having a mass fraction of 1.0% by mass or less can be obtained.
Specifically, the olefinic wax is generally within a range of 0.1 to 10.0% by mass with respect to the total amount of the main raw material polyethylene resin and the olefinic wax (the content of the main raw material polyethylene resin is It may be blended with the polyethylene resin so that it falls within the range of 90.0 to 99.9% by mass. However, the actual blending amount of the olefin-based wax can be determined according to the respective properties with the above as a guide.
The olefin wax preferably has a viscosity average molecular weight of 700 to 8000, more preferably in the range of 2000 to 6000. The olefin wax having a viscosity average molecular weight of less than 700 has a molecular weight that is too low and may be eluted from the porous hollow fiber membrane. On the other hand, an olefin wax having a viscosity average molecular weight of more than 10,000 loses its plasticizer effect due to its too high molecular weight and cannot be expected to promote the growth and uniformity of the lamellar laminate.
In this embodiment, the viscosity average molecular weight (Mv) is determined by dissolving the sample in decalin solution at different concentrations, and the intrinsic viscosity [η] (dl / g) obtained by extrapolating the reduced viscosity obtained at 135 ° C. to the concentration 0. ) From the following formula A.
Mv = (5.34 × 10 ⁴ ) × [η] ^1.49

In the present embodiment, the olefin wax is a high density low molecular weight ethylene polymer having a density of 960 kg / m ³ or more, a low density low molecular weight ethylene polymer having a density of less than 940 kg / m ³ , a low molecular weight ethylene-propylene copolymer, And at least one selected from the group consisting of low molecular weight ethylene-butene copolymers.
Here, the high density low molecular weight ethylene polymer means a polymer having an ethylene group as a basic skeleton having a density of 950 kg / m ³ or more and a viscosity average molecular weight of 10,000 or less. The coalescence refers to a polymer having an ethylene group as a basic skeleton having a density of less than 950 kg / m ³ and a viscosity average molecular weight of 10,000 or less.
The low molecular weight ethylene-propylene copolymer means a copolymer having an ethylene-propylene group as a basic skeleton having a viscosity average molecular weight of 10,000 or less, and the low molecular weight ethylene-butene copolymer means a viscosity average A copolymer having a molecular weight of 10,000 or less and having an ethylene-butene group as a basic skeleton.
In the present embodiment, the olefin wax is preferably a high density low molecular weight ethylene polymer having a density of 960 kg / m ³ or more, more preferably a density of 970 kg / m ^{3 in view of} compatibility with the main raw material polyethylene resin. It is the above high-density low molecular weight ethylene polymer.
In the present embodiment, the MFR / D of the resin composition containing a polyolefin wax is preferably 3.0 to 10.0, more preferably 3.5 to 6.0, and still more preferably 3. 8 to 5.8. The MFR / G of the polyethylene resin mixed with the polyolefin wax is preferably 150 to 300, more preferably 160 to 270, and still more preferably 170 to 200.

In this embodiment, the porous hollow fiber membrane may contain any additive in addition to the polyethylene resin and the olefin wax. Examples of such additives include antioxidants, lubricants, ultraviolet absorbers, light stabilizers, and the like. Examples of the antioxidant include trade names “Irganox 1010”, “Irganox 1076”, and Irgafos 168 ”. Examples of the lubricant include calcium montanate, calcium stearate, magnesium stearate and the like. The total content of such optional additives is preferably 5% by mass or less, more preferably 2% by mass or less, and further preferably 1% by mass or less of the porous hollow fiber membrane. .

The porous hollow fiber membrane of this embodiment contains a polyethylene resin that is a hydrophobic polymer. Hydrophobic polymers interact with blood, so when they are used for plasma separation membranes, etc., the surface of the porous hollow fiber membrane is covered with a hydrophilic layer containing a hydrophilic polymer. It is preferable to do.
Examples of the hydrophilic polymer include polyhydroxyethyl methacrylate, polyhydroxypropyl methacrylate, polyvinyl pyrrolidone, and an ethylene-vinyl alcohol copolymer. These may be used alone or in combination of two or more. Among these, an ethylene-vinyl alcohol copolymer having good adhesion to a polyethylene resin and less peeling from the pore surface of the porous structure is preferable.
The ethylene-vinyl alcohol copolymer may be any type such as a random polymer, block polymer, or graft polymer, but the ethylene content of the copolymer is within the range of 20 to 70 mol%. Preferably, it is more preferably in the range of 25 to 50 mol% from the viewpoint of the balance between hydrophilicity and adhesiveness.
When the ethylene content is 20 mol% or more, the adhesiveness of the ethylene-vinyl alcohol copolymer to the polyethylene resin is better, and it is possible to prevent the peeling of the pore surface of the porous structure from the hydrophilic layer. it can.
Further, when the ethylene content is 70 mol% or less, the interaction between the hydrophilic layer containing the ethylene-vinyl alcohol copolymer and blood can be reduced.
In the present embodiment, when the polyethylene resin contained in the porous hollow fiber membrane is high density polyethylene, since the adhesiveness increases because the ethylene chain is shared, the hydrophilic polymer may be ethylene-vinyl alcohol. It is preferable to use a copolymer.

The hydrophilic layer may be composed of only a hydrophilic polymer or may contain additives other than the hydrophilic polymer. In that case, the content of the hydrophilic polymer is preferably 70% by mass or more, more preferably 80% by mass or more, and further preferably 90% by mass or more.
Here, the degree of hydrophilicity of the porous hollow fiber membrane covered with the hydrophilic layer can be evaluated by the contact angle of water. There are two types of contact angle measurement methods, the static contact angle method and the dynamic contact angle method, but the dynamic contact angle method reflecting the morphology of the porous membrane surface is preferred. Of the dynamic contact angle methods, the well-helmi method is more preferable because it has a high degree of freedom in the shape of the sample. As for the contact angle, the receding contact angle directly reflects the hydrophilicity of the surface of the substance in water, and is therefore an important index for judging the degree of hydrophilicity of the porous hollow fiber membrane.
In the present embodiment, the receding contact angle of water of the porous hollow fiber membrane covered with the hydrophilic layer is preferably 0 to 15 degrees, more preferably 0 to 10 degrees, and further preferably 0 to 5 degrees. When the receding contact angle of water exceeds 15 degrees, there is a risk of causing plasma protein adsorption, hemolysis, thrombus formation, etc. when used as a separation membrane for plasma separation.
In addition, the measurement of the receding contact angle with respect to the water of the porous hollow fiber membrane by a well Helmi method can be implemented as follows, for example.
Water for injection (Japanese Pharmacopoeia manufactured by Fuso Pharmaceutical Co., Ltd.) is used as the test water, and a dynamic contact angle measuring device (DCAT11 manufactured by DataPysics Instrument GmbH) is used as the measuring device. The porous hollow fiber membrane is cut to about 2 cm and attached to the measuring device. The motor speed at the time of measurement is 0.10 mm / second, the immersion depth is 10 mm, the forward and backward movements are one cycle, and five cycles are measured. The average value of the values obtained by the five measurements is defined as the receding contact angle.

The method for producing a porous hollow fiber membrane according to the present embodiment includes a step of producing a porous hollow fiber membrane by a melt stretch opening method or the like, and further when the porous hollow fiber membrane is used as a separation membrane for plasma separation. It is preferable to include a step of forming a hydrophilic layer containing a hydrophilic polymer on the surface of the porous hollow fiber membrane by a coating method or the like.
In the melt-stretch opening method, the main raw material polyethylene resin and, if necessary, a resin composition containing an olefin wax are melt-spun into a hollow fiber shape, and the wound hollow fiber (original yarn before drawing) is made porous by drawing. To obtain a porous hollow fiber membrane.
In the coating method, for example, the porous hollow fiber membrane is dipped in an organic solvent or the like (coating liquid) containing a hydrophilic polymer, and then taken out, and then the solvent is dried by heat to form a porous hollow fiber. The surface of the membrane is coated with a hydrophilic polymer.
The production of the porous hollow fiber membrane by the melt drawing / opening method can be performed, for example, based on the procedure shown in Japanese Patent Publication No. 6-91945.

Hereinafter, an example of a procedure for creating a porous hollow fiber membrane in the method for producing a porous hollow fiber membrane / separation membrane of the present embodiment will be described.
(1) A main raw material polyethylene resin or a resin composition containing a main raw material polyethylene resin and an olefin wax is melt-kneaded by an extruder.
(2) A molten polyethylene-based resin (or resin composition) is extruded into a hollow fiber into a spinning cylinder by a circular double nozzle and wound up with a high draft (for example, a draft ratio of 1000 to 8000). It winds up as the formed hollow fiber (original yarn before drawing).
(3) The raw yarn before drawing is heat-treated in two stages in an oven.
(4) The pre-stretch raw yarn is stretched (for example, a stretch ratio of 10 to 50%) at a low temperature (for example, 10 to 40 ° C.), and the lamellar laminate is cleaved to form micropores.
(5) If necessary, the pores are further expanded by thermal stretching (for example, at 80 to 130 ° C. and a stretching ratio of 200 to 500%).
(6) Fix the hole structure by heat setting.
By the above procedure, a porous hollow fiber membrane having a plurality of microfibrils oriented in the yarn length direction and a knot portion composed of a lamellar laminate connected to both ends of the microfibrils can be obtained.
When the raw material of the porous hollow fiber membrane is a resin composition containing an olefinic wax, for example, a polyethylene resin (for example, 90.0 to 99.9% by mass) used as a main raw material and an olefinic wax are used. (For example, 0.1 to 10.0% by mass) may be melt-kneaded with a single screw extruder, pelletized with a pelletizer, and then subjected to melt-kneading (the above step (2)).

In the case where a porous hollow fiber membrane is produced by a melt stretch opening method using a resin composition containing a polyethylene resin having a molecular weight of 1000 or less and 1.0 mass% or more, particularly an olefin wax polyethylene, an unstretched part It has been found that it is preferable to satisfy the following two requirements in order to produce a porous hollow fiber membrane with a low content.
First, the idle running time from the formation of the unstretched raw yarn to the winding (the residence time until the raw material is extruded from the spinning nozzle (specifically, a circular double nozzle) and wound as a hollow fiber) ) For 1 second or longer, more preferably 1.1 seconds or longer. Second, prior to drawing the raw yarn before drawing, heat treatment is performed in two stages. In particular, it is preferable that the temperature of the first stage is 10 to 15 ° C. lower than that of the second stage. The heat treatment method, temperature and time are not limited. For example, the heat treatment method includes placing in a constant temperature room such as an oven. The temperature and time are about 90 to 105 ° C. for 2 to 10 hours at the first stage. The stage can be 100 to 120 ° C. for 1 to 2 hours.
Although the mechanism of action is not clear, these two requirements, combined with the properties of the polyethylene resin and resin composition as raw materials, promote the growth and homogeneity of the lamellar laminate of the raw yarn before drawing, We think that we reduce.

In producing the separation membrane of the present embodiment, a method for forming a hydrophilic layer containing a hydrophilic polymer on at least a part of the surface of the porous hollow fiber membrane is not particularly limited, When an ethylene-vinyl alcohol copolymer is used as the molecule, for example, a coating method disclosed in Japanese Patent Publication No. 4-27891 can be used.
That is, the porous hollow fiber membrane is left to stand for a predetermined time in a solution in which an ethylene-vinyl alcohol copolymer is heated and dissolved in a water-miscible organic solvent aqueous solution having a predetermined concentration, and then the excess solution is removed. By drying with hot air at a predetermined temperature, a porous hollow fiber membrane having a hydrophilic layer on the surface can be obtained.
The obtained porous hollow fiber membrane having a hydrophilic layer has few unstretched parts, so there is no pseudo-leakage of blood, is excellent in homogeneity, and is a separation membrane suitable for plasma separation.
Further surprisingly, the porous hollow fiber membrane of the present embodiment has less elution of the hydrophilic polymer even when a hydrophilic layer containing the hydrophilic polymer is provided on the porous hollow fiber membrane. A separation membrane having excellent protein adsorptivity and improved compatibility with blood can be obtained.
The reason why the elution of the hydrophilic polymer is small is not clear, but it is assumed that the porous hollow fiber membrane of the present embodiment has a large specific surface area and a large contact area with the hydrophilic polymer.

Furthermore, when using the porous hollow fiber membrane of this embodiment for the separation membrane for plasma separation, it is preferable that it is sterilized before use. Therefore, it is preferable that the manufacturing method of the separation membrane of this embodiment includes the process of sterilizing a porous hollow fiber membrane. When providing the above-mentioned hydrophilic layer, it is preferable to sterilize the porous hollow fiber membrane after forming the hydrophilic layer.
Sterilization methods include ethylene oxide gas sterilization, high pressure steam sterilization, and radiation sterilization. Among these, radiation sterilization with an electron beam, gamma ray, or the like is preferable because the object to be processed can be processed in a packaged state. In this embodiment, the porous hollow fiber membrane is particularly preferably sterilized by irradiation with gamma rays having a high sterilization effect. However, when the irradiation dose of gamma rays is too high, the performance as a separation membrane deteriorates, so the irradiation dose of gamma rays is adjusted according to the material of the separation membrane. In the present embodiment, it is preferably in the range of 20 kGy to 40 kGy.
In the present embodiment, when the porous hollow fiber membrane is sterilized with gamma rays, the MFR / D of the material constituting the porous hollow fiber membrane after sterilization with gamma rays is preferably 0.03 or more. If MFR / D is 0.03 or more, the performance as a separation membrane is not impaired.
When the porous hollow fiber membrane having many unstretched parts is sterilized with gamma rays, it does not show melt viscosity and MFR / D cannot be measured. The cause is not clear, but since the unstretched part is not made porous, the energy density of the part becomes high, and the generation of radicals causes a crosslinking reaction between the molecular chains, resulting in the formation of a network structure that melts. It is assumed that the viscosity is lost.

In this embodiment, the method for sterilizing the porous hollow fiber membrane with gamma rays is not limited, but an example of the procedure is given below.
(1) A separation membrane bundle in which 2200 separation membranes having a length of 250 mm are bundled is inserted into a plasma separation container, a potting agent such as polyurethane resin is injected into both ends, both ends are sealed, a header is attached, and plasma is added A separation module (hereinafter referred to as a module) is created.
(2) Fill the module with physiological saline, apply vibration, etc., and completely evacuate the internal air.
(3) Seal the headers at both ends.
(4) Bring the module into a gamma irradiation facility and irradiate it with a predetermined dose.

EXAMPLES Hereinafter, although this invention is demonstrated in detail by an Example and a comparative example, this invention is not limited to a following example. Evaluation and analysis in the examples were performed by the following methods.
(1) Unstretched incidence Rate Light is applied from below the traveling porous hollow fiber membrane, and the thread shadow is continuously observed from above with an image sensor for a predetermined time, and the portion where the thread shadow is interrupted by light transmission is regarded as an unstretched portion. The unstretched number n (unit: pieces) was measured. The unstretched occurrence rate E was determined from Equation 1 from the length L (unit: m) of the porous hollow fiber membrane that ran during the observation time and the unstretched number n.
The lower E, the higher the homogeneity in the yarn length direction of the porous hollow fiber membrane, preferably 0.2 pieces / m ·% or less, more preferably 0.1 pieces / m ·% or less.
Formula 1: E = (n / L) × 100 (pieces / m ·%)

(2) Blood pseudo-leakage confirmation test A separation membrane bundle in which 2200 separation membranes having an effective filtration length of 250 mm are bundled is inserted and filled into a cylindrical transparent container having one or more filtrate ports, and the end of the separation membrane bundle And the container end by potting with urethane resin, further cutting the cured urethane resin layer and opening the separation membrane at its end, and then attaching header caps with filtrate distribution ports to both ends of the container Ten hollow fiber membrane modules were molded.
These 10 modules are placed on a holder, and red ink (red ink made by Kaimei Co., Ltd.) is pumped from the filtrate outlet at the bottom of each module. Filled with red ink. The filtrate flow ports at both ends of each module were closed, the module was removed from the holder, and the outer periphery of the inner separation membrane bundle was visually observed from the side of the module to confirm the presence of vermilion spots. A vermilion spot was regarded as a simulated blood leak, and it was determined that there was no simulated blood leak when there were no vermilion spots in all 10 modules.

(3) Eluate test 1.5 g of separation membrane was put in 150 mL of hot water at 70 ° C. and kept for 1 hour while controlling the temperature. Thereafter, the mixture was allowed to cool, 5 mL of hot water was taken out, put into a test tube, and stoppered.
Hold the test tube by hand and shake vigorously for 3 minutes. After standing for 3 minutes, the state of the generated foam was confirmed. When the foam disappeared completely, the elution of the hydrophilic polymer was judged as “none”.

(4) Inner Diameter and Film Thickness Measurement The separation membrane was inserted into a polyethylene tube having an inner diameter of 5 mm, and a silicon adhesive was injected around the separation membrane in the tube. After the silicone adhesive was cured, the cross section of the polyethylene tube was cleaved with a razor. The cross section of the separation membrane exposed on the end face of the tube was observed with a microscope, and the outer diameter (DO) and inner diameter (DI) as the equivalent circle diameter were determined using image analysis software (Image-pro plus manufactured by Media Cyberbertics). .
DI was defined as the inner diameter of the separation membrane, and half of the difference between DO and DI was determined as the thickness of the separation membrane.

(5) Measurement of a mass fraction of a component having a molecular weight of 1000 or less (hereinafter referred to as “mf (1000) ratio”) of a polyethylene resin (or a resin composition in which an olefin wax is blended with a polyethylene resin) (5- 1) 1,2,4-Trichlorobenzene (TCB) was added so that the concentration of the polyethylene resin was 1.0 mg / mL.
(5-2) After standing still (160 ° C. × 0.5 hours) using a high-temperature dissolver, rocking (160 ° C. × 1 hour) was performed to dissolve the polyethylene resin in TCB.
(5-3) The sample was filtered through a 1.0 μm filter in the heated state (160 ° C.), and the filtrate was used as a GPC measurement sample.
(5-4) GPC measurement was performed under the following conditions.
・ Measuring device: High-temperature GPC device (PL-GPC220 manufactured by Agilent Technologies)
・ Column: TSKgel GMH _HR -H (20) 2 ・ Device temperature: 140 ℃ for all channels
Eluent: TCB (containing 0.05% 4,4'-thiobis (6-tert-butyl-3-methylphenol)
・ Sample injection amount: 200 μL
・ Detector: Suggested refractive index detector RI
・ Calibration curve: Calculation was carried out in the first order using a monodisperse polystyrene as a standard sample and a conversion factor (0.43).
(5-5) The mass fraction for each molecular weight was calculated from the calibration curve, and the mf (1000) rate was determined.

(6) The mass fraction of the polyethylene-based resin constituting the porous hollow fiber membrane, or the component having a molecular weight of 10,000 or less (hereinafter referred to as “mf (10000) fraction”) and the mass fraction having a molecular weight of 1,000,000 or more. Measurement of rate (hereinafter referred to as “mf (million) rate”) (6-1) 30 mg of the separation membrane was immersed in 5 mL of dimethyl sulfoxide for 50 hours to remove the hydrophilic layer on the surface, and the porous hollow fiber membrane Got. Hereinafter, this was used as a sample.
(6-2) The sample was further immersed in methanol / water = 60/40 (volume ratio) for 6 hours and then vacuum dried at room temperature.
(6-3) The dried sample was weighed and TCB was added so that the sample concentration was 1.0 mg / ml.
(6-4) After standing (160 ° C. × 0.5 hours) using a high-temperature dissolver, rocking (160 ° C. × 1 hour) was performed to dissolve the sample in TCB.
(6-5) While being heated (160 ° C.), the mixture was filtered through a 1.0 μm filter, and the filtrate was used as a GPC measurement sample.
(6-6) GPC measurement was performed under the following conditions.
・ Measuring device: High-temperature GPC device (PL-GPC220 manufactured by Agilent Technologies)
・ Column: TSKgel GMHHR-H (20) 2 ・ Device temperature: 160 ℃ for all channels
-Eluent: TCB (containing 0.05% dibutylhydroxytoluene)
Sample injection volume: 500 μL
・ Detector: Suggested refractive index detector RI
・ Calibration curve: Calculation was carried out in the first order using a monodisperse polystyrene as a standard sample and a conversion factor (0.43).
(6-7) The mass fraction for each molecular weight was calculated from the calibration curve, and the mf (10000) rate and mf million) rate were determined.

Example 1
High-density polyethylene (density 965 kg / m ³ , MFR / D: 5.1, MFR / G: 186, mf (1000) rate: 1.4 mass%) as a raw material, polymer extrusion using a hollow double nozzle Spinning was performed at an amount of 16.1 g / min, a hollow nitrogen amount of 22.5 mL / min, a spinning temperature of 150 ° C., a spinning speed of 200 m / min, a spinning draft ratio of 3400, and an idle running time of 1.2 seconds. Thread).
Next, the raw yarn before drawing was further heated in an oven at 100 ° C. for 6 hours, and further heat treated at 115 ° C. for 1 hour. Using the undrawn raw yarn after the heat treatment, cold drawing, hot drawing, and heat setting were continuously performed. Specifically, after performing cold drawing at a cold drawing ratio of 30% at room temperature, followed by two-stage hot drawing at 102 ° C. with a hot drawing ratio of 200% and 115 ° C. with a further 43%, air heating at 128 ° C. By adjusting the speed between the rolls in the tank, a two-stage heat setting was performed at a heat setting rate of 27% for the first stage and 17% for the second stage to obtain a porous hollow fiber membrane. When the inner wall of this porous hollow fiber membrane was confirmed by SEM (5000 times), it was composed of a plurality of microfibrils oriented in the yarn length direction and a knot portion composed of a lamellar laminate connected to both ends of the microfibril. It was confirmed that The unstretched incidence of the porous hollow fiber membrane was 0.07 (pieces / m ·%).
An ethylene-vinyl alcohol copolymer having an ethylene content of 38 mol% was dissolved by heating in a 75 vol% aqueous ethanol solution to give a 0.5 mass% solution. The porous hollow fiber membrane was immersed in the solution maintained at a temperature of 50 ° C. and left for 10 minutes. Next, excess ethylene-vinyl alcohol copolymer was removed, followed by drying with hot air at 50 ° C. for 3 hours to obtain a separation membrane having a hydrophilic layer made of an ethylene-vinyl alcohol copolymer on the surface. The obtained separation membrane had an inner diameter of 320 μm and a film thickness of 45 μm.
The porous hollow fiber membrane obtained by removing the ethylene-vinyl alcohol copolymer from the separation membrane had an mf (10000) ratio of 19.0 mass% and an mf (1 million) ratio of 1.4 mass%.
In the blood pseudoleakage confirmation test, no vermilion spot was confirmed, and the blood pseudoleakage was determined to be “none”. In the eluate test, the foam disappeared after standing for 3 minutes, and the elution of the hydrophilic polymer was judged as “none”.
Further, a plasma separation module was prepared using the separation membrane, and irradiated with gamma rays at a dose of 25 kGy. Thereafter, the separation membrane was taken out from the plasma separation module, and the separation membrane was immersed in dimethyl sulfoxide for 50 hours, then washed with a 50% by volume aqueous methanol solution, vacuum-dried for 5 hours, and MFR / D was measured. 03.

(Example 2)
High-density polyethylene (density 962 kg / m ³ , MFR / D: 5.2, MFR / G: 195, mf (1000) rate: 1.0 mass%) as a raw material, polymer extrusion using a hollow double nozzle Spinning was carried out at an amount of 16.0 g / min, a hollow nitrogen amount of 22.0 mL / min, a spinning temperature of 149 ° C., a spinning speed of 200 m / min, a spinning draft ratio of 3430, an idle running time of 1.2 seconds, and a hollow fiber (original before drawing) Thread).
Next, the raw yarn before drawing was further heated in an oven at 100 ° C. for 8 hours, and further heat treated at 115 ° C. for 2 hours. Using the undrawn raw yarn after the heat treatment, cold drawing, hot drawing, and heat setting were continuously performed. Specifically, cold drawing at a cold drawing ratio of 30% is performed at room temperature, followed by two-stage hot drawing at 105 ° C. with a hot drawing ratio of 200% and 115 ° C. with a further 43%, followed by air heating at 127 ° C. By adjusting the speed between the rolls in the tank, a two-stage heat setting was performed at a heat setting rate of 27% for the first stage and 17% for the second stage to obtain a porous hollow fiber membrane. When the inner wall of this porous hollow fiber membrane was confirmed by SEM (5000 times), it was composed of a plurality of microfibrils oriented in the yarn length direction and a knot portion composed of a lamellar laminate connected to both ends of the microfibril. It was. The unstretched incidence was 0.07 (pieces / m ·%).
According to the procedure described in Example 1, an ethylene-vinyl alcohol copolymer was applied to obtain a separation membrane. The obtained separation membrane had an inner diameter of 315 μm and a film thickness of 44 μm.
The porous hollow fiber membrane obtained by removing the ethylene-vinyl alcohol copolymer from the separation membrane had an mf (10000) ratio of 18.0 mass% and an mf (1 million) ratio of 1.3 mass%.
In the blood pseudoleakage confirmation test, no vermilion spot was confirmed, and the blood pseudoleakage was determined to be “none”. In the eluate test, elution of hydrophilic polymer was not observed.
According to the procedure described in Example 1, the MFR / D was measured after irradiating the separation membrane with gamma rays and found to be 0.05.

(Example 3)
High-density polyethylene (density 967 kg / m ³ , MFR / D: 2.8, MFR / G: 114, mf (1000) ratio: 0.7% by mass) as a raw material, polymer extrusion using a hollow double nozzle Spinning was performed at an amount of 16.1 g / min, a hollow nitrogen amount of 22.5 mL / min, a spinning temperature of 155 ° C., a spinning speed of 200 m / min, a spinning draft ratio of 3400, and an idle running time of 1.2 seconds. Thread).
Next, the raw yarn before drawing was further heated in an oven at 100 ° C. for 8 hours, and further heated at 115 ° C. for 1 hour. Using the undrawn raw yarn after the heat treatment, cold drawing, hot drawing, and heat setting were continuously performed. Specifically, cold drawing at a cold drawing ratio of 30% is performed at room temperature, followed by two-stage hot drawing at 102 ° C. with a hot drawing ratio of 200% and 115 ° C. with a further 43%, followed by air heating at 127 ° C. By adjusting the speed between the rolls in the tank, a two-stage heat setting was performed at a heat setting rate of 27% for the first stage and 17% for the second stage to obtain a porous hollow fiber membrane.
When the inner wall of the porous hollow fiber membrane at this time was confirmed by SEM (5000 times), a plurality of microfibrils oriented in the yarn length direction, and a knot portion composed of a lamellar laminate connected to both ends of the microfibrils It was confirmed that it was configured. The unstretched incidence of the porous hollow fiber membrane was 0.29 (pieces / m ·%).
The inner diameter of the separation membrane was 315 μm and the film thickness was 45 μm. The porous hollow fiber membrane obtained by removing the ethylene-vinyl alcohol copolymer from the separation membrane had an mf (10000) rate of 17.5% by mass and an mf (million) rate of 1.4% by mass.
In the blood pseudoleakage confirmation test, a bundle having vermilion spots in the test module was confirmed, and the blood pseudoleakage was determined to be “present”. In the eluate test, the foam disappeared after standing for 3 minutes, and the elution of the hydrophilic polymer was judged as “none”.

(Comparative Example 1)
The procedure described in Example 1 was followed except that high-density polyethylene (density 966 kg / m ³ , MFR / D: 5.1, MFR / G: 183, mf (1000) ratio: 0.8 mass%) was used as a raw material. A porous hollow fiber membrane and then a separation membrane were obtained.
When the inner wall of this porous hollow fiber membrane was confirmed by SEM (5000 times), it was composed of a plurality of microfibrils oriented in the yarn length direction and a knot portion composed of a lamellar laminate connected to both ends of the microfibril. In addition, the unstretched incidence was 1.20 (pieces / m ·%).
The inner diameter of the separation membrane was 320 μm and the film thickness was 46 μm. The porous hollow fiber membrane obtained by removing the ethylene-vinyl alcohol copolymer from the separation membrane had an mf (10000) ratio of 17.3 mass% and an mf (1 million) ratio of 1.1 mass%.
In the blood pseudoleakage confirmation test, a bundle having vermilion spots in the test module was confirmed, and the blood pseudoleakage was determined to be “present”. No elution was observed.
Example 1 After irradiating the separation membrane with gamma rays, measurement of MFR / D was attempted, but it could not be measured because it did not melt.

(Comparative Example 2)
The procedure described in Example 1 was followed except that high-density polyethylene (density 965 kg / m ³ , MFR / D: 5.0, MFR / G: 155, mf (1000) ratio: 0.8% by mass) was used as a raw material. A porous hollow fiber membrane and then a separation membrane were obtained.
When the inner wall of this porous hollow fiber membrane was confirmed by SEM (5000 times), it was composed of a plurality of microfibrils oriented in the yarn length direction and a knot portion composed of a lamellar laminate connected to both ends of the microfibril. In addition, the unstretched incidence was 0.34 (pieces / m ·%).
The inner diameter of the separation membrane was 320 μm and the film thickness was 46 μm. The porous hollow fiber membrane obtained by removing the ethylene-vinyl alcohol copolymer from the separation membrane had an mf (10000) rate of 17.5% by mass and an mf (million) rate of 1.5% by mass.
In the blood pseudoleakage confirmation test, a bundle having vermilion spots in the test module was confirmed, and the blood pseudoleakage was determined to be “present”. No elution was observed.

(Comparative Example 3)
High-density polyethylene (density 965 kg / m ³ , MFR / D: 1.4, MFR / G: 90, mf (1000) ratio: 0.6% by mass) as a raw material, polymer extrusion using a hollow double nozzle Spinning was performed at an amount of 15.5 g / min, an amount of hollow nitrogen of 22.5 mL / min, a spinning temperature of 155 ° C., a spinning speed of 200 m / min, a spinning draft ratio of 3540, and an idle running time of 1.2 seconds. Thread).
Next, the raw yarn before drawing was further heated in an oven at 100 ° C. for 6 hours, and further heat treated at 115 ° C. for 1 hour. Using the undrawn raw yarn after the heat treatment, cold drawing, hot drawing, and heat setting were continuously performed. Specifically, after performing cold drawing at a cold drawing ratio of 30% at room temperature, followed by two-stage hot drawing at 102 ° C. with a hot drawing ratio of 200% and 115 ° C. with a further 43%, air heating at 128 ° C. By adjusting the speed between the rolls in the tank, a two-stage heat setting was performed at a heat setting rate of 27% for the first stage and 17% for the second stage to obtain a porous hollow fiber membrane. When the inner wall of this porous hollow fiber membrane was confirmed by SEM (5000 times), it was composed of a plurality of microfibrils oriented in the yarn length direction and a knot portion composed of a lamellar laminate connected to both ends of the microfibril. It was. The unstretched occurrence rate was 2.75 (pieces / m ·%).
Thereafter, according to the procedure described in Example 1, a separation membrane was obtained.
The inner diameter of the separation membrane was 320 μm and the film thickness was 43 μm. The porous hollow fiber membrane obtained by removing the ethylene-vinyl alcohol copolymer from the separation membrane had an mf (10000) rate of 16.9% by mass and an mf (1 million) rate of 2.4% by mass.
In the blood pseudoleakage confirmation test, a bundle having vermilion spots in the test module was confirmed, and the blood pseudoleakage was determined to be “present”. Elution was observed.

(Comparative Example 4)
High-density polyethylene (density 944 kg / m ³ , MFR / D: 0.5, MFR / G: 33, mf (1000) rate: 0.6 mass%) as a raw material, polymer extrusion using a hollow double nozzle Spinning was performed at an amount of 15.6 g / min, a hollow nitrogen amount of 22.5 mL / min, a spinning temperature of 170 ° C., a spinning speed of 200 m / min, a spinning draft ratio of 3520, and an idle running time of 1.2 seconds. Thread).
Next, the raw yarn before drawing was further heated in an oven at 100 ° C. for 6 hours, and further heat treated at 115 ° C. for 1 hour. Using the undrawn raw yarn after the heat treatment, cold drawing, hot drawing, and heat setting were continuously performed. Specifically, after performing cold drawing at a cold drawing ratio of 30% at room temperature, followed by two-stage hot drawing at 102 ° C. with a hot drawing ratio of 200% and 115 ° C. with a further 43%, air heating at 128 ° C. By adjusting the speed between the rolls in the tank, a two-stage heat setting was performed at a heat setting rate of 27% for the first stage and 17% for the second stage to obtain a porous hollow fiber membrane. When the inner wall of this porous hollow fiber membrane was confirmed by SEM (5000 times), it was composed of a plurality of microfibrils oriented in the yarn length direction and a knot portion composed of a lamellar laminate connected to both ends of the microfibril. It was. The unstretched incidence was 13.80 (pieces / m ·%).
Thereafter, according to the procedure described in Example 1, a separation membrane was obtained.
The inner diameter of the separation membrane was 320 μm and the film thickness was 43 μm. The porous hollow fiber membrane obtained by removing the ethylene-vinyl alcohol copolymer from the separation membrane had an mf (10000) rate of 16.0% by mass and an mf (million) rate of 2.8% by mass.
In the blood pseudoleakage confirmation test, a bundle having vermilion spots in the test module was confirmed, and the blood pseudoleakage was determined to be “present”. In the dissolution test, elution of hydrophilic substances was observed, and the dissolution was judged as “present”.

(Comparative Example 5)
The procedure described in Example 3 was followed except that high-density polyethylene (density 961 kg / m ³ , MFR / D: 2.9, MFR / G: 145, mf (1000) ratio: 1.0 mass%) was used as a raw material. A porous hollow fiber membrane and then a separation membrane were obtained.
When the inner wall of this porous hollow fiber membrane was confirmed by SEM (5000 times), it was composed of a plurality of microfibrils oriented in the yarn length direction and a knot portion composed of a lamellar laminate connected to both ends of the microfibril. In addition, the unstretched incidence was 0.66 (pieces / m ·%).
The inner diameter of the separation membrane was 316 μm and the film thickness was 45 μm. The porous hollow fiber membrane obtained by removing the ethylene-vinyl alcohol copolymer from the separation membrane had an mf (10000) rate of 17.0% by mass and an mf (million) rate of 1.7% by mass.
In the blood pseudoleakage confirmation test, vermilion spots were confirmed, and the blood pseudoleakage was determined to be “present”. No elution was observed.

Example 4
A resin containing 99.0% by mass of the high-density polyethylene used in Comparative Example 1 and 1.0% by mass of a high-density low molecular weight ethylene polymer (olefin wax) (density 970 kg / m ³ , viscosity average molecular weight 4000). A composition (MFR / D: 5.1, MFR / G: 188, mf (1000) ratio: 1.1% by mass) was obtained. Using this resin composition as a raw material, a porous hollow fiber membrane was prepared according to the procedure described in Example 1, and a separation membrane was further obtained.
When the inner wall of the porous hollow fiber membrane obtained here was confirmed by SEM (5000 times), a knot portion comprising a plurality of microfibrils oriented in the yarn length direction and a lamellar laminate connected to both ends of the microfibrils. In addition, the unstretched incidence was 0.08 (pieces / m ·%).
The inner diameter of the separation membrane was 321 μm and the film thickness was 45 μm. The porous hollow fiber membrane obtained by removing the ethylene-vinyl alcohol copolymer from the separation membrane had an mf (10000) ratio of 18.5 mass% and an mf (1 million) ratio of 1.1 mass%.
In the blood pseudoleakage confirmation test, no vermilion spot was confirmed, and the blood pseudoleakage was determined to be “none”. No eluate was observed.
The MFR / D was measured after irradiating the separation membrane with gamma rays according to the procedure described in Example 1. As a result, it was 0.11.

(Example 5)
A resin containing 95.0% by mass of the high-density polyethylene used in Comparative Example 1 and 5.0% by mass of a high-density low molecular weight ethylene polymer (olefin wax) (density 980 kg / m ³ , viscosity average molecular weight 2000). A composition was obtained (MFR / D: 5.8, MFR / G: 239, mf (1000) ratio: 1.2% by mass). Using this resin composition as a raw material, a porous hollow fiber membrane was prepared according to the procedure described in Example 1, and a separation membrane was further obtained.
When the inner wall of the porous hollow fiber membrane obtained here was confirmed by SEM (5000 times), a knot portion comprising a plurality of microfibrils oriented in the yarn length direction and a lamellar laminate connected to both ends of the microfibrils. And consisted of The unstretched incidence was 0.10 (pieces / m ·%).
The inner diameter of the separation membrane was 320 μm and the film thickness was 46 μm. The porous hollow fiber membrane obtained by removing the ethylene-vinyl alcohol copolymer from the separation membrane had an mf (10000) ratio of 19.3% by mass and an mf (1 million) ratio of 1.0 mass%.
In the simulated blood leak test, no simulated blood leak was observed. In the eluate test, no eluate was observed.

(Example 6)
Resin containing 98.0% by mass of the high-density polyethylene used in Comparative Example 1 and 2.0% by mass of a low-density low-molecular-weight ethylene polymer (olefin wax) (density 935 kg / m ³ , viscosity average molecular weight 2000). A composition was obtained (MFR / D: 5.5, MFR / G: 263, mf (1000) ratio: 1.0 mass%). Using this resin composition as a raw material, a porous hollow fiber membrane and then a separation membrane were obtained according to the procedure described in Example 1, except that the second heat treatment temperature and heat treatment time were 117 ° C. and 2 hours, respectively.
When the inner wall of this porous hollow fiber membrane was confirmed by SEM (5000 times), it was composed of a plurality of microfibrils oriented in the yarn length direction and a knot portion composed of a lamellar laminate connected to both ends of the microfibril. In addition, the unstretched incidence was 0.16 (pieces / m ·%).
The inner diameter of the separation membrane was 322 μm, and the film thickness was 46 μm. The porous hollow fiber membrane obtained by removing the ethylene-vinyl alcohol copolymer from the separation membrane had an mf (10000) rate of 18.7% by mass and an mf (1 million) rate of 1.1% by mass.
No simulated blood leak or eluate was observed.

(Example 7)
98.0% by mass of the high density polyethylene used in Comparative Example 1 and 2.0% by mass of a low density low molecular weight ethylene-propylene polymer (olefin wax) (density 940 kg / m ³ , viscosity average molecular weight 2000) The obtained resin composition was obtained (MFR / D: 6.0, MFR / G: 290, mf (1000) rate: 1.1 mass%). Using this resin composition as a raw material, a porous hollow fiber membrane was prepared according to the procedure described in Example 1 except that the spinning temperature was 152 ° C., and a separation membrane was obtained.
When the inner wall of the porous hollow fiber membrane obtained here was confirmed by SEM (5000 times), a knot portion comprising a plurality of microfibrils oriented in the yarn length direction and a lamellar laminate connected to both ends of the microfibrils. And consisted of The unstretched incidence was 0.20 (pieces / m ·%).
The inner diameter of the separation membrane was 326 μm, and the film thickness was 44 μm. The porous hollow fiber membrane obtained by removing the ethylene-vinyl alcohol copolymer from the separation membrane had an mf (10000) rate of 18.0% by mass and an mf (million) rate of 1.1% by mass.
In the blood pseudoleakage confirmation test, no vermilion spot was confirmed, and the blood pseudoleakage was determined to be “none”. In the eluate test, elution of the hydrophilic polymer was judged as “none”.

(Example 8)
A resin containing 95.0% by mass of the high-density polyethylene used in Comparative Example 1 and 5.0% by mass of a high-density low molecular weight ethylene polymer (olefin wax) (density 970 kg / m ³ , viscosity average molecular weight 4000). A composition was obtained (MFR / D: 5.7, MFR / G: 191 and mf (1000) ratio: 1.5 mass%). Using this resin composition as a raw material, a porous hollow fiber membrane and a separation membrane were obtained according to the procedure described in Example 1.
When the inner wall of this porous hollow fiber membrane was confirmed by SEM (5000 times), it was composed of a plurality of microfibrils oriented in the yarn length direction and a knot portion composed of a lamellar laminate connected to both ends of the microfibril. In addition, the unstretched occurrence rate was 0.17 (pieces / m ·%).
The inner diameter of the separation membrane was 318 μm, and the film thickness was 44 μm. The porous hollow fiber membrane obtained by removing the ethylene-vinyl alcohol copolymer from the separation membrane had an mf (10000) ratio of 20.2 mass% and an mf (1 million) ratio of 1.0 mass%.
In the blood pseudoleakage confirmation test, no vermilion spot was confirmed, and the blood pseudoleakage was determined to be “none”. In the eluate test, elution of the hydrophilic polymer was determined to be “present”.

(Comparative Example 6)
99.0% by mass of high density polyethylene (density 964 kg / m ³ , MFR / D: 5.0, MFR / G: 172, mf (1000 ratio): 0.7% by mass), and high density low molecular weight ethylene weight The resin composition which mix | blended 1.0 mass% of coalesced (olefin type wax) (density 970 kg / m < ³ >, viscosity average molecular weight 4000) was obtained (MFR / D: 5.2, MFR / G: 193, mf (1000 ) Rate: 0.9. Mass%). Using this resin composition as a raw material, a porous hollow fiber membrane was prepared according to the procedure described in Example 1, and then a separation membrane was obtained.
When the inner wall of the porous hollow fiber membrane obtained here was confirmed by SEM (5000 times), a plurality of microfibrils oriented in the yarn length direction, and a knot portion composed of a lamellar laminate connected to both ends of the microfibrils, Consisted of. The unstretched incidence was 1.55 (pieces / m ·%).
The inner diameter of the separation membrane was 322 μm, and the film thickness was 43 μm. The porous hollow fiber membrane obtained by removing the ethylene-vinyl alcohol copolymer from the separation membrane had an mf (10000) rate of 17.4% by mass and an mf (million) rate of 1.5% by mass.
In the blood pseudoleakage confirmation test, a bundle having vermilion spots in the test module was confirmed, and the blood pseudoleakage was determined to be “present”. In the eluate test, elution of the hydrophilic polymer was judged as “none”.
Following the procedure described in Example 1, the separation membrane was irradiated with gamma rays, and then MFR / D measurement was attempted. However, the MFR / D could not be measured because it did not melt.

The polyethylene resin porous hollow fiber membrane of the present invention has industrial applicability in the medical field that it can be used in plasma exchange therapy.

This application is based on a Japanese patent application (Japanese Patent Application No. 2016-097423) filed with the Japan Patent Office on May 13, 2016, the contents of which are incorporated herein by reference.

Claims (17)

1. A porous hollow fiber membrane comprising a polyethylene-based resin and having a plurality of microfibrils oriented in the yarn length direction and a knot portion made of a lamellar laminate connected to both ends of the microfibrils,
   The mass fraction of the component having a molecular weight of 10,000 or less is 17.5% by mass or more, and the mass fraction of the component having a molecular weight of 1,000,000 or more is less than 1.5% by mass.
   Polyethylene resin porous hollow fiber membrane.
2. The polyethylene resin porous hollow fiber membrane according to claim 1, wherein the polyethylene resin contains an olefin wax.
3. The olefin wax is a high density low molecular weight ethylene polymer having a density of 960 kg / m ³ or more, a low density low molecular weight ethylene polymer having a density of less than 940 kg / m ³ , a low molecular weight ethylene-propylene copolymer, and a low molecular weight The polyethylene resin porous hollow fiber membrane according to claim 2, which is at least one selected from the group consisting of ethylene-butene copolymers.
4. The polyethylene resin porous hollow fiber membrane according to any one of claims 1 to 3, wherein the polyethylene resin is high-density polyethylene.
5. The polyethylene resin porous hollow fiber membrane according to any one of claims 1 to 4, and a hydrophilic layer containing a hydrophilic polymer provided on at least a part of the surface of the polyethylene resin porous hollow fiber membrane; A separation membrane.
6. The separation membrane according to claim 5, wherein the hydrophilic polymer is an ethylene-vinyl alcohol copolymer.
7. The separation membrane according to claim 5 or 6, wherein the melt flow rate (MFR / D) measured by JIS K7210 (code D) is 0.03 or more.
8. The separation membrane according to any one of claims 5 to 7, which is used for plasma separation.
9. A polyethylene resin porous hollow fiber membrane, comprising: a step of producing a hollow fiber from a polyethylene resin or a resin composition containing a polyethylene resin; and a step of drawing the hollow fiber to form a porous hollow fiber membrane. A manufacturing method of
   The polyethylene resin or the resin composition contains 1.0% by mass or more of a component having a molecular weight of 1000 or less,
   A method for producing a polyethylene resin porous hollow fiber membrane.
10. The method for producing a polyethylene resin porous hollow fiber membrane according to claim 9, wherein the polyethylene resin contains 0.1 to 10.0% by mass of an olefin wax having a viscosity average molecular weight of 700 to 8000.
11. The method for producing a polyethylene resin porous hollow fiber membrane according to claim 9 or 10, wherein the polyethylene resin is high-density polyethylene.
12. The melt flow rate (MFR / D) measured by JIS K7210 (code D) of the polyethylene resin or the resin composition containing the polyethylene resin is 3.0 to 10.0, and JIS K7210 (code G). The method for producing a polyethylene resin porous hollow fiber membrane according to any one of claims 9 to 11, wherein the melt flow rate (MFR / G) measured in 1 is 150 to 300.
13. The olefin wax is a high density low molecular weight ethylene polymer having a density of 960 kg / m ³ or more, a low density low molecular weight ethylene polymer having a density of less than 940 kg / m ³ , a low molecular weight ethylene-propylene copolymer, and a low molecular weight The method for producing a polyethylene resin porous hollow fiber membrane according to any one of claims 10 to 12, which is at least one selected from the group consisting of ethylene-butene copolymers.
14. The method for producing a polyethylene resin porous hollow fiber membrane according to claim 13, wherein the olefin wax is a high-density low molecular weight ethylene polymer having a density of 960 kg / m ³ or more.
15. A step of obtaining a polyethylene resin porous hollow fiber membrane by the production method according to any one of claims 9 to 14, and a hydrophilic property comprising a hydrophilic polymer on at least a part of the surface of the porous hollow fiber membrane. And a step of providing a layer.
16. The method for producing a separation membrane according to claim 15, wherein the hydrophilic polymer is an ethylene-vinyl alcohol copolymer.
17. The method for producing a separation membrane according to claim 15 or 16, further comprising a step of sterilizing the porous hollow fiber membrane with radiation.

Images