JPH0951946A - Blood processing polyolefin composite microporous film - Google Patents

Abstract

PROBLEM TO BE SOLVED: To improve a filtering characteristic of a blood plasma component by layering a microporous layer having a reinforcing function on one surface of a microporous layer having a separating function, and constituting the respective layers of a microporous layered body composed of plural microfibril bundles oriented in the drawing axis direction of a film and node parts of stacked lamellas. SOLUTION: When a composite microporous film is formed by layering (a and b) layers of microporous layers, the (a and b) layers are composed of a microporous layered body composed of plural microfibril bundles oriented in the drawing axis direction of a film and node parts of stacked lamellas. This micropore communicates with the other surface from one surface of the composite microporous film, and the microfibrile bundles and the node parts of the stacked lamellas are covered with a hydrophilic copolymer of 3 to 30wt.% to a composite microporous film precursor 100wt.%. The ratio of an average distance of Db to Da between the microfibril bundles is set in a range of (1.3<=Db/Da<=15), and Db is set in 0.2 to 1.0μm, and an average distance between the node parts in the (b) layer is set in 0.4 to 4.0μm.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to hydrophilicity for blood treatment, which is useful as a separation of blood cell components and plasma components from blood, removal of attribute organic components in ascites, removal of various infusion components, and various bacteria removal filters. Porous porous polyolefin hollow fiber membrane.

[0002]

2. Description of the Related Art Hydrophilized porous polyolefin hollow fiber membranes have high strength and are not easily damaged, and even dry membranes can be used without any special hydrophilization treatment, which makes them easy to handle. It is usefully used as a hollow fiber membrane for treatment, but the pore shape of the polyolefin hollow fiber membrane made by the stretch opening method is a strip structure formed by stack lamellae and microfibrils connecting the stack lamellae. Therefore, it is said that there is a problem that a blood cell component is deficient when a blood treatment is performed.

In order to obtain a polyolefin hollow fiber membrane used for blood treatment that is less likely to damage blood cell components, the microfibrils that compose the polyolefin porous membrane are bound with a linear polymer, and the strip-shaped micropores are oblong. The method for forming the state is disclosed in Japanese Patent Publication No. 4-1653 and Japanese Patent Publication No. 3-70539.

The invention disclosed in Japanese Examined Patent Publication No. 4-1653 discloses that a porous polyolefin hollow fiber membrane produced by a stretch opening method is treated with a solution of an ethylene-vinyl acetate copolymer to bond the stacked lamellae. The microfibrils are bound together to be converted into a hollow fiber membrane having a porous structure having elliptical micropores, and then the ethylene-vinyl acetate copolymer is hydrolyzed to be converted to ethylene-vinyl alcohol to obtain a hydrophilic polyolefin. It is a hollow fiber.

The invention disclosed in Japanese Examined Patent Publication No. 3-70539 discloses a microfibril bundle in which a plurality of microfibrils oriented in the fiber axis direction are bound by a linear polymer, and the bundle and the both ends thereof intersect each other. A network-like porous hollow fiber membrane having a cell structure membrane formed by a knotted portion composed of a stack lamella to be bonded, wherein the microfibrils and the stack lamellae are made of a crystalline polymer, and further the cell structure is formed. The film has a dimensional network structure that is almost uniform as a whole, and its space part forms elliptical through holes oriented in the fiber axis direction. The average spacing between the stacked lamellae (1s) μm, micro Average spacing of fibril bundles (d
b) μm and the ratio of both are 0.2 ≦ 1s ≦ 5 (μm) 0.1 ≦ ds ≦ 3 (μm) 1 ≦ 1s ≦ ds ≦ 5, and the average of the microfibril bundles on the inner surface is The spacing (dbi) μm, the average spacing (dbo) μm of the microfibril bundles on the outer surface portion, and the average spacing (dbc) μm of the microfibril bundles on the central portion in the film thickness direction are 0.8 ≦ dbc / dbi ≦ 1.20. The hollow fiber membrane has a relationship of 0.8 ≦ dbc / dbo ≦ 1.2.

[0006] In this porous hollow fiber membrane, a polyolefin hollow fiber membrane precursor produced by a stretch opening method is treated with an ethylene-vinyl alcohol copolymer, and the microfibrils in the precursor are treated with an ethylene-vinyl alcohol copolymer. The rectangular holes in the precursor are changed to ellipse-shaped fine holes by binding with a polymer and coating the stud lamella.

[0007]

When a porous hollow fiber membrane is used as a blood treatment membrane, the membrane is required to have the following functions and characteristics. It has a high blood cell component rejection rate and excellent plasma component filtration characteristics. It can be a small blood separation device and has low-pressure plasma separation ability. Membrane composition during blood separation treatment Having no dissolved components in blood

In plasma separation for therapeutic purposes, examples of substances to be removed from blood include immunoglobulins, immune complexes, and low-density lipoproteins. These substances to be removed generally have a molecular weight of several hundred thousand to 100,000. Millions, molecular size 300
It is a huge polymer of Å ~ 500Å.

On the other hand, in plasma separation, it is necessary to collect useful plasma components, and albumin, which constitutes plasma components, has a molecular weight of 60,000 and a molecular size of 40Å × 120Å, which is a relatively low-molecular substance. Fibrinogen has a relatively high molecular weight with a molecular weight of 340,000 and a molecular size of 30Å × 150Å. Thus, in filtration performed for treatment and plasma collection, the substance to be permeated through the membrane is a giant polymer with a molecular size of several hundred liters, and it is necessary that the fractionation characteristics of the membrane be suitable for the purpose. is there. From the viewpoint of a blood processing apparatus, it is necessary that the blood processing can be performed in the shortest possible time and that the blood processing apparatus has a small extracorporeal circulating blood volume, that is, a priming volume.

From this point of view, Japanese Patent Publication No. 4-1
The hollow fiber membrane of the invention disclosed in Japanese Patent Publication No. 653 and Japanese Patent Publication No. 3-70539 has suitability as a hollow fiber membrane for blood treatment, but its thickness is relatively large at 40 to 70μ, Moreover, since the elliptical through holes are uniformly formed in the membrane wall, it is difficult to increase the blood filtration rate, and
It is necessary to apply a considerable filtration pressure, and in order to make a blood processing device with a smaller priming volume, it is now possible to perform one step of low-pressure blood filtration and a microporous membrane for blood processing with a higher filtration rate. It is just waiting for its appearance.

[0011]

Means for Solving the Problems Accordingly, the present inventors have
The present invention has been completed as a result of studies to obtain a porous hollow fiber membrane for blood treatment, which has high fractionation characteristics, high water permeability, and is less likely to damage blood constituents when used for blood filtration.

The gist of the present invention is a polyolefin composite microporous membrane in which at least one surface of a microporous layer a layer having a separating function is laminated with a microporous layer b layer having a reinforcing function. A layered body of elliptical micropores in which each of the layers and the b layer is composed of a plurality of microfibril bundles oriented in the stretching axis direction of the membrane and a knotted portion of a stacked lamella joined at both ends of the microfibril bundles. The micropores are communicated from one surface to the other surface of the composite microporous membrane, and the microfibril bundles forming the micropores of the microporous membrane and the knotted portions of the stacked lamella are composite. An average distance Da between the microfibril bundles of the micropores present in the a layer while being covered with 3 to 30% by weight of the hydrophilic copolymer with respect to 100% by weight of the microporous membrane precursor;
A polyolefin composite microporous membrane for blood treatment, characterized in that the ratio of the average distance Db between the microfibril bundles of the micropores present in layer b is in the range 1.3 ≦ Db / Da ≦ 15. In particular, the average distance Db between the microfibril bundles of the micropores in the layer b is 0.2 to 1.0 μm,
Average distance Lb between the nodules of the stacked lamellae in layer b
Is 0.4 to 4.0 μm, which is a polyolefin composite microporous membrane for blood treatment. The polyolefin porous membrane of the present invention is also characterized in that the maximum pore diameter of the membrane measured by the bubble point method is 0.05 to 1.0 µm.

[0013]

BEST MODE FOR CARRYING OUT THE INVENTION The microporous membrane for blood treatment of the present invention has a thickness in the range of 5 to 500 .mu.m, and the microporous layer b layer having a reinforcing function is the microporous layer a layer having a separating function. It has a multi-layer structure in which it is laminated on one side. The layers a and b in the structure of the microporous membrane for blood treatment of the present invention are
Micropores, the micropores are arranged in the stretching axis direction of the membrane, and the microvoids communicate with each other in the a layer, the b layer, and the a layer b layer, It is an asymmetric structure film in which micropores are formed which are laminated and communicated from one surface to the other surface of the composite microporous film.

The micropores formed in the layer a are formed by the microfibril bundles arranged in the stretching axis direction of the membrane and the knots of the stacked lamellae arranged in the direction perpendicular to the stretching axis of the membrane. The gap between the bundle and the knot is an elliptical fine hole. As the size of the micropores in the layer a, the average distance Da between the microfibril bundles is 0.
The thickness is preferably 1 to 0.8 μm, and more preferably 0.3 to 0.5 μm. The microporous membrane of the present invention having an average distance Da between the microfibril bundles of 0.3 μm or more has a high water permeability, good blood filterability at low pressure, and has a Da of 0.5 μm or less. The film has a good ability to block fine particles, that is, a high-fractionation film.

The thickness of the layer a is preferably 0.5 to 20 μm, more preferably 3 to 12 μm. When the thickness of the a layer is less than 0.5 μm, pinhole defects tend to occur in the a layer, while when the thickness of the a layer exceeds 20 μm, the water permeability of the composite microporous membrane is increased. Is low and the blood filterability at low pressure is insufficient, making it difficult to obtain a blood processing apparatus with a small priming volume. The thickness of the a layer is 1/100 of the total thickness.
It is preferably 3 or less, and the composite microporous membrane thicker than this has a drastic decrease in water permeability, and deterioration of blood filtration characteristics at low pressure can be observed.

The microporous layer b layer has a reinforcing function of supporting the microporous layer a layer which has a separation function in the composite membrane. Like the layer a, the layer b also has a laminated structure of micropores oriented in the stretching axis direction of the film, and the micropores are formed by the microfibril bundles and the nodules of the stacked lamellae. The size of the micropores in the b layer is preferably 0.2 to 1 μm, more preferably 0.4 to 0.5 μm in terms of the average distance Db between the microfibril bundles. A composite microporous membrane having a b-layer consisting of micropores having a Db of less than 0.2 μm tends to have a low water permeation rate, while when Db exceeds 1 μm, b having micropores is present.
The mechanical strength of the composite microporous membrane provided with the layer tends to decrease.

The average distance Lb between the nodules of the stacked lamella in the layer b is preferably 0.4 to 4.0 μm, more preferably 0.7 to 2.0 μm. The water permeation rate tends to decrease in the composite microporous membrane having the b layer composed of micropores having Lb of less than 0.4 μm, and when Lb exceeds 4.0 μm, the mechanical strength of the composite microporous membrane is low. Tends to decrease.

In the present invention, the ratio of Db to Da is 1.3 ≦ D.
It is necessary that b / Da ≦ 15. Db
A composite microporous membrane having a / Da of less than 1.3 is unlikely to be a membrane having a high fraction and a high water permeability, which is the object of the present invention. Further, in the case of a composite microporous membrane having Db / Da exceeding 15, it tends to be difficult to stably manufacture the membrane.

In the composite microporous membrane of the present invention, the maximum pore size of the membrane determined by the bubble point method is 0.05 to 1.0 μm.
It is preferably in the range of m. Maximum pore size is 0.05
A composite microporous membrane having a thickness of less than μm tends to decrease the water permeation rate, and a thickness of more than 1.0 μm decreases the mechanical strength. The feature of the composite microporous membrane of the present invention is that the microporous membrane has the above-described composite structure, and thus has a high fraction and a high flux.

The polyolefins used as the material for forming the microporous membrane of the present invention are, for example, polyethylene, polypropylene, poly-3-methylbutene-1, poly-4.
-Methylpentene-1, polyvinylidene fluoride alone or a mixture of these polymers can be used. In the microporous membrane for blood treatment of the present invention, it is preferable to use, as a membrane material, a material having a small content of elution components and having blood compatibility.

The MI value (melt index value) of the polyolefin used in the present invention measured by ASTM D-1238 is in the range of 0.1 to 50, preferably in the range of 0.3 to 15. A polyolefin having an MI value of less than 0.1 has a too high melt viscosity, so that it is difficult to shape it and a desired microporous membrane cannot be produced. On the other hand, a polyolefin having an MI value of more than 50 has a too low melt viscosity and cannot be stably shaped.

The density of the polyolefin used for carrying out the present invention varies depending on the material used, but for example, in the case of polyethylene, it is preferably 0.95 g / cm ³ or more, and in the case of polypropylene, 0.91 g / cm ^3.
/ Cm ³ or more is preferable.

In producing the microporous membrane of the present invention, when the MI value MIa of the polyolefin for forming the a layer and the MI value MIb of the polyolefin for forming the b layer are selected so that MIa <MIb, the polyolefin for forming the a layer is selected. Density ρa,
The composite microporous membrane of the present invention can be obtained even if the polyolefins ρb for forming the b layer are substantially equal. Conversely, ρa <
When the respective polyolefins are selected so as to have ρb, the composite microporous membrane of the present invention can be obtained even if MIa and MIb are almost equal. Preferably MIa <M
When the respective polyolefins are selected so as to satisfy both the relations of Ib and ρa <ρb, the composite microporous membrane of the present invention can be efficiently produced.

The average distance between the microfibril bundles of micropores in the present invention is measured as follows.
A 6500-times transmission electron micrograph of a sample obtained by cutting an ultrathin section from the microporous film in the stretching direction of the film is taken into a CRT screen of an image processing apparatus from a 6500-times transmission electron micrograph. (Figure 1
Shows this image). 0.052 μm from the upper side of the captured image to the lower side in the direction perpendicular to the film stretching direction.
Draw the first to nth scanning lines at a pitch. Then, the fine hole portion whose average distance between the microfibril bundles cannot be measured is excluded, and each distance of the line segments passing through the hole portion in the first scanning line, for example, the sum of a ₁ is obtained, and then,
Similarly, for example, the sum of b ₁ to b ₆ is calculated for the second scanning line, and the sum of, for example, n ₁ to n ₆ of the nth scanning line is sequentially calculated to obtain the sum (distance sum). Next, the number of fine holes that each scanning line passed (5 in the first scanning line and 6 in the second scanning line).
, The n-th line is 6), and the sum of distances / sum of numbers is set as the average intervals Da and Db.

In order to produce the composite microporous hollow fiber membrane of the present invention, first, an intermediate composite porous hollow fiber membrane precursor is produced, and then a coating treatment with a hydrophilic copolymer is carried out. In order to make the precursor, it is preferable to select a polyolefin that satisfies the above conditions and to form a film by the composite spinning method, and it is preferable to use a nozzle having two annular discharge ports arranged concentrically. .

The spinning temperature is not less than the melting point of the polyolefin (preferably 10 to 100 ° C. higher than the melting point), and the discharged product is 0.1 to 3 m / m in an atmosphere of 10 to 40 ° C.
The multilayered body obtained by taking it off at a transaction rate of seconds was heat-treated as it was or at a temperature below the melting point of the polyolefin (preferably 5 to 50 ° C. lower than the melting point) to form a stacked lamella. After that, the multi-layer body is stretched and subjected to an opening treatment. As for stretching, it is preferable to carry out hot stretching after cold stretching. Cold stretching is a process of causing structural destruction of a multilayer body at a relatively low temperature to generate microcracks between stacked lamellas, and the cold stretching is performed in a range of 0 ° C. to 50 ° C. lower than the melting point of the polymer. It is preferable to carry out. When polyethylene is used as the polyolefin, the cold stretching temperature is in the range of 0 to 80 ° C, preferably 10 to 50 ° C. The cold stretching ratio is preferably 5 to 100%. When it is 5% or less, the generation of microcracks becomes insufficient, and it becomes difficult to obtain a target pore size. Also, 100%
In the above case, the number of microcracks is increased and the supporting layer (b
It becomes difficult to form a desired large pore size in the layer).

The subsequent hot stretching is a process of expanding the microcracks generated in the multilayer body to form microfibrils between the stacked lamellae and forming a porous film having slit-like micropores. The hot stretching temperature is preferably as high as possible within the range not exceeding the melting point of the polyolefin. The heat draw ratio may be appropriately selected depending on the target pore size, but is 50 to 2000.
%, Preferably 100 to 1000%, in terms of process stability. Furthermore, in order to obtain the dimensional stability of the obtained microporous membrane precursor, heat setting is performed under a fixed length or in a state where the membrane is slightly relaxed. In order to perform heat setting effectively, the heat setting temperature is higher than the stretching temperature,
It is preferably below the melting point temperature.

Next, permanent hydrophilicity is imparted to the obtained multilayer composite film precursor. The hydrophilic copolymer used in the present invention contains ethylene in an amount of 20 mol% or more and hydrophilic monomer in an amount of 10 mol% or more.
It is a copolymer containing at least mol%, and these copolymers may be any type of copolymers such as random copolymers, block copolymers and graft copolymers. When the ethylene content of the copolymer is less than 20 mol%, the copolymer has a weak affinity for the precursor, and the precursor is dipped in a hydrophilic copolymer solution to make it 3 to 30% based on 100% by weight of the precursor. It is not preferable because the hydrophilic copolymer cannot be coated at a weight percentage.

Examples of the hydrophilic monomer used when polymerizing the hydrophilic copolymer used in the present invention include vinyl acetate, (meth) acrylic acid and salts thereof, hydroxyethyl (meth) acrylate, polyethylene glycol (meth). Examples thereof include vinyl compounds such as acrylic acid ester, vinylpyrrolidone, and acrylamide.
Further, the hydrophilic copolymer used in the present invention may contain one or more third components other than ethylene and a hydrophilic monomer, and the third component may be, for example, vinyl acetate, (meth).
Acrylic acid ester, vinyl alcohol fatty acid ester, formal compound or butyral compound of vinyl alcohol, etc. can be mentioned.
An ethylene-vinyl alcohol copolymer, which is a hydrolyzate of a vinyl acetate copolymer, is preferred.

The coating amount of the hydrophilic copolymer on the microporous membrane precursor is in the range of 3 to 30% by weight in terms of the precursor weight. A microporous membrane having a hydrophilic copolymer coating amount of less than 3% by weight has a poor affinity for water and insufficient water permeability to the microporous membrane, while the hydrophilic copolymer coating amount is too small. If it exceeds 30% by weight, the copolymer is apt to block the pores of the microporous membrane and the water permeability thereof is likely to decrease.

The solvent of the copolymer used in the present invention is preferably a water-miscible organic solvent, and specific examples thereof include alcohols such as methanol, ethanol, N-propanol and isopropyl alcohol, dimethyl sulfoxide, Examples thereof include dimethylformamide. These solvents can be used alone, but a mixture with water is more preferable because it has a strong solubility in the hydrophilic copolymer. Further, from the viewpoint of ease of creating a vapor-containing atmosphere of a solvent used when drying a microporous membrane coated with a hydrophilic copolymer, that is, low vapor pressure of the solvent and low toxicity to humans, a boiling point of 100 ° C. It is particularly preferable to use a mixed solvent of water with alcohols of less than, for example, methanol, ethanol, isopropyl alcohol and the like.

The mixing ratio of the water-miscible organic solvent and water may be within the range that does not impair the permeability of the precursor and does not reduce the dissolution of the copolymer, and depends on the type of the copolymer used. However, when ethanol is used as the organic solvent, the ratio of ethanol / water is 90/10.
It is preferably in the range of -30/70 (vol%).

The concentration of the hydrophilic copolymer solution is 0.1 to 1
It is about 0% by weight, preferably 0.5 to 5% by weight. When the precursor is treated with a solution having a concentration of less than 0.1% by weight, it is difficult to uniformly coat the hydrophilic copolymer, and if it exceeds 10% by weight, the solution viscosity becomes too large, and the precursor is treated with the solution. Upon treatment, the micropores of the multi-layer composite membrane are blocked with the copolymer. As a method of immersing the precursor in the hydrophilic copolymer solution, the precursor solution may be dipped twice or more in the copolymer solution having the same concentration, or may be dipped twice or more in the solutions having different concentrations.

The higher the temperature of the hydrophilic copolymer solution to be subjected to the dipping treatment, the lower the viscosity thereof, and the better the permeability of the solution into the precursor, which is preferable, but from the viewpoint of safety, it is preferably not higher than the boiling point of the solution. preferable. The immersion treatment time varies depending on the thickness of the precursor used, the fine pore diameter, and the porosity, but it is preferably in the range of several seconds to several minutes.

The precursor is soaked in a hydrophilic polymer solution and before being subjected to a drying treatment, the organic solvent vapor is contained in an amount of 3 vol% or more, and the temperature is raised from room temperature to a temperature not higher than the boiling point of the solvent and the temperature is raised at least. It is necessary to stay for 30 seconds or more and perform the setting process.

The purpose of this treatment step is to prevent clogging of the micropores by forming a film of the hydrophilic copolymer on the surface of the knots between the microfibrils and the stacked lamella forming the precursor. Another object is to bind the microfibrils and increase the diameter of the slit-shaped micropores to form elliptical micropores, thereby increasing the amount of water permeation and enhancing the affinity with the treated water.

In order to prevent film formation on the precursor surface of the hydrophilic copolymer during the setting step, it is necessary to prevent rapid drying on the precursor surface. For that purpose, the precursor surface of the copolymer solution is required. It is necessary to suppress the evaporation rate at the same time and to keep the precursor surface wet with the solvent. From this viewpoint, the atmosphere of the setting process should be 3 vol% or more of the water-miscible organic solvent vapor. Will be required.

It is preferable that the evaporation rate of the solvent from the precursor in the setting step be as low as possible, and the atmosphere in the setting step should be an atmosphere close to the saturated vapor concentration of the solvent. Further, in order to slow down the evaporation of the solvent on the surface of the precursor in this step, it is better to lower the setting temperature, but if it is too low, the phenomenon that the solvent removal in the setting step does not proceed is not preferable. Therefore, the temperature of the atmosphere is preferably room temperature or higher and not higher than the boiling point of the water-miscible solvent.

The precursor after immersion is raised from the immersion bath into the atmosphere, and the angle of the rise is 45 ° to 90 °.
It is preferable to set it in the range. By starting up, a part of the copolymer solution attached to the precursor is drained from the precursor by its own weight. The amount of liquid removed depends on the speed of the precursor rising from the bath, the viscosity of the immersion solution, the height of the precursor rising from the bath surface, and the like.
As an auxiliary means for enhancing the liquid removal effect in this setting step, wiping of the solution on the surface of the precursor by means of guides, slits or the like may be used together.

This setting time is at least 30
Seconds are required, during which time the copolymer solution is concentrated as the solvent evaporates from the precursor and the membrane is homogenized by migration on the surface of microfibrils and stacked lamellae. In particular, when the precursor is continuously treated with the hydrophilic copolymer solution, this setting time needs to be at least 30 seconds or more.

If the setting is shorter than 30 seconds, the concentration due to evaporation of the solvent is insufficient, and the drying is carried out with the excess solution attached to the precursor, and the hydrophilic copolymer clogs the micropores. In addition, the uniform adhesion of the copolymer within the membrane structure becomes insufficient, and it is difficult to obtain a microporous membrane having good water permeability and fractionation performance. The amount of evaporation of the solvent from the precursor when the setting time was 30 seconds was 15 to 3 of the hydrophilic copolymer solution used.
It is preferably about 0%.

As a method of controlling the evaporation amount of the solvent from the precursor in the setting step, there may be mentioned a setting atmosphere temperature and a method of blowing a gas such as air or an inert gas into the atmosphere. After the setting, the precursor is dried in vacuum,
A known drying method such as hot air drying may be used. The drying temperature may be a temperature at which the composite microporous membrane is not deformed by heat. For example, in the case of a polyethylene composite microporous membrane, it is preferable to dry at a temperature of 120 ° C. or lower, and 40 to 7
It is particularly preferred to dry at a temperature of 0 ° C.

From the viewpoint of filtration characteristics, the amount of the hydrophilic copolymer attached to the composite microporous membrane is 1 to 30% by weight based on the weight of the composite microporous membrane precursor which is the substrate.
Preferably it is 3 to 15% by weight.

By the coating treatment with the hydrophilic copolymer, the microfibrils of the microporous membrane precursor are converged into a microfibril bundle, and the slit-like micropores are elliptical micropores.

The porous hollow fiber membrane for blood treatment of the present invention is treated with ethylene oxide gas, high pressure steam, γ
It can be sterilized by a radiation treatment.

The hollow fiber membrane for blood treatment of the present invention has good handleability such that it can be handled in a dry state, and has a high molecular weight which has been a drawback of the conventionally developed microporous membrane for blood treatment. The filterability of the components has been greatly improved, and the safety when used as a plasma separation membrane, blood cell separation membrane, plasma component separation membrane, ascites treatment membrane, etc. is extremely high. Also,
Although the hollow fiber for blood treatment of the present invention has a high fractionation, it has a high filtration rate, and thus has a small priming volume and is a membrane that is unlikely to damage blood cell components.

[0047]

The present invention will be described in more detail with reference to the following examples. In addition, various measurements and evaluations in Examples were carried out by the following methods.

1 For the ethanol concentration in the atmosphere, a gas detector tube (product name {Gastec detector tube} Gastec Co., Ltd.) was used.

2 The coating amount of the hydrophilic copolymer was calculated according to the following formula.

[Equation 1]

The amount of water permeation of 3 membranes is an effective membrane area of 70 to 90c.
A mini module of m ² was prepared, ion-exchanged water was filtered at a differential pressure of 1 kg / cm ² , and the amount of water permeation at that time was measured.

4 The particle size captured by the latex standard particles was 0.1 wt% of a surfactant (polyethylene glycol-based) in a hollow fiber membrane module having a membrane area of about 50 cm ^2.
(p-isooctylphenyl ether) aqueous solution was used to replace the air in the membrane, and then polystyrene latex particles having a single dispersed particle diameter of 0.1% of a predetermined particle diameter were filtered at a pressure of 0.7 kg / cm ² to obtain a filtrate. The concentration of latex particles was measured with a Hitachi spectrophotometer (U-3400) at a wavelength of 320 nm to obtain a capture rate.

At 5 bubble points (hereinafter abbreviated as BP), a hollow fiber membrane module having a membrane area of about 50 cm ² is immersed in ethanol having a concentration of 95% or more so that the hollow fiber membrane portion is completely immersed. . After sucking 100 ml or more of ethanol from the inside of the hollow fiber membrane so that the porous inside of the hollow fiber membrane was sufficiently wet with ethanol, nitrogen was fed into the hollow fiber membrane in the immersed state to give 0.1 kg / cm ² every 10 seconds.
Increase the air pressure in steps. The bubble point is defined as the nitrogen pressure when bubbles are generated from almost the entire surface of the hollow fiber membrane and the distance between bubble generation points is within 1 mm. In addition, B. P.
The average pore size from was calculated by the following relational expression. P = 2σ cos θ / r P: Pressure (bubble point value) σ: Surface tension of ethanol θ: Contact angle between ethanol and membrane r: Average pore radius

The porosity of the 6 film was measured using a mercury porosimeter Model 221 manufactured by Carlo Erba.

7 The average distance between the microfibril bundles of micropores was measured by the method described above. 8 The average distance La or Lb between the knots of the stacked lamella of micropores in the a layer or the b layer and the microfibril bundle is
The average distance between the microfibril bundles of the micropores was calculated by the same method (however, the scanning line was the film stretching direction and the pitch width was 0.045 μm).

Plasma filtration rate (ml / m ² .hr.mmH
g) was measured at 37 ° C. using bovine ACD (citrate-Na citrate-glucose) supplemented blood (hematocrit 35%).
Measure plasma filtration rate when high pressure of 30 mmHg is applied to the membrane.

<Example 1> Density 0.968 g / cm ³ ,
High-density polyethylene with MI value of 0.35 (BU004F,
67% by weight, density 0.962 g
/ Cm ^3, high density polyethylene MI value 0.35 (BT
004, manufactured by Mitsubishi Kasei Co., Ltd.) 33 wt% and melt-kneaded with a twin-screw extruder at a temperature of 180 ° C. to obtain a density of 0.966.
A blended polymer having a g / cm ³ and an MI value of 0.35 was obtained.

Next, using this blended polymer as a layer-forming polymer, the above-mentioned density of 0.968 g / cm ³ , M
A high-temperature polyethylene having an I value of 0.35 is used as a polymer for forming the b layer, and a discharge temperature of 180 ° C. is obtained by using a hollow fiber manufacturing nozzle having two circular tubular discharge ports concentrically arranged.
Melt spinning was performed at a winding speed of 35 m / min. At this time, the blended polymer was discharged from the outer discharge port, the high density polyethylene was discharged from the inner discharge port at a ratio of 1/5, the total discharge amount was 7.5 cc / min, the discharge port and the discharge linear velocity were 57 cm.
/ Min, and the discharge ratio was 75. Further, the yarn discharged from the nozzle was wound while a cooling air having a temperature of 20 ° C. and a wind speed of 0.5 m / sec was evenly flowed around the yarn to obtain an undrawn composite hollow fiber.

The unstretched hollow fiber thus obtained was heat-treated for 16 hours in the air heated to 125 ° C. while being wound on a bobbin.
Furthermore, this annealed yarn was cold-drawn by 16% between rollers kept at 30 ° C., and subsequently hot-rolled between rollers in a heating furnace heated at 119 ° C. so that the total drawn amount was 400%, Further, heat setting was performed in a heating furnace heated to 123 ° C. with a constant length to obtain a composite microporous hollow fiber membrane precursor composed of two layers.

Next, an ethylene-vinyl alcohol copolymer (Soarnol DC320) having an ethylene content of 32 mol% was used.
3, manufactured by Nippon Synthetic Chemical Industry Co., Ltd.) at 70 ° C in ethanol /
A hydrophilic copolymer solution having 2.0% by weight dissolved in a water / 40/60 vol% mixed solution was prepared. After dipping the above precursor in the hydrophilic copolymer solution for 30 seconds, the precursor was pulled up, and a part of the hydrophilizing agent solution excessively attached to the surface of the precursor was squeezed out by a guide. Continuing, ethanol vapor concentration 40 vol%, 60
After rising in an atmosphere of ℃ at a rising angle of 90 ° and making it stay for 80 seconds to uniformly attach the hydrophilic agent to the inner surfaces of the micropores of the composite hollow fiber, the solvent was dried with hot air at 70 ° C. At that time, the adhesion rate of the ethylene-vinyl alcohol copolymer was 10.5% by weight.

The obtained composite microporous hollow fiber membrane was observed with a scanning electron microscope. As a result, the inner and outer surfaces and the inner surfaces of the micropores of the composite microporous hollow fiber membrane were thin films of ethylene-vinyl alcohol copolymer. The average distance between the microfibril bundles of the micropores in the inner layer is 0.54 μm, and the average distance between the microfibril bundles of the micropores in the outer layer is 0.35.
μm. At this time, the pore diameter ratio is Db / Da = 1.5.
4. The film thickness of the outer layer, which is the separation functional layer, was 8 μm. The film characteristics of the obtained film are shown in Table 1.

Example 2 A composite microporous hollow was prepared under the same conditions as in Example 1 except that the outer and inner discharge ratios in spinning were 1/4, the total discharge rate was 3.0 cc / min, and the discharge port was used. A thread film was created. The membrane characteristics of the obtained composite microporous hollow fiber membrane are shown in Table 1.

<Comparative Example 1> A hollow fiber producing nozzle having a single tubular discharge port was used to obtain a density of 0.968 g / c.
Discharge amount of high density polyethylene with m ³ and MI value of 5.5 7.
It was discharged at 8 g / min. The discharge temperature at that time was 160 ° C., and the film was wound at a winding speed of 100 m / min.

The obtained undrawn yarn was heat-treated at 115 ° C. for 12 hours in the air while being wound on a bobbin. In addition, 80% of this heat treated yarn is kept between the rollers kept at 30 ° C or less.
It is cold-stretched and then hot-rolled between rollers in a heating furnace heated to 110 ° C. so that the total stretching amount becomes 400%.
Heat setting was performed in a state of being relaxed by 5% to obtain a porous film.
The hydrophilic treatment step was performed in exactly the same manner as in Example 1. The membrane characteristics of the obtained microporous hollow fiber membrane are shown in Table 1.

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[Table 1]

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[Table 2]

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EFFECT OF THE INVENTION The composite microporous polyolefin membrane for blood treatment of the present invention has good handleability such that it can be handled in a dry state, and it can be used as a microporous membrane for blood treatment which has been conventionally developed. The difficulty in filtering high molecular weight components has been greatly improved, and the safety when used as a plasma separation membrane, blood cell separation membrane, plasma component separation membrane, ascites treatment membrane, etc. is extremely high. Further, the hollow fiber for blood treatment of the present invention is a membrane having a small priming volume and being less likely to damage blood cell components because of its high filtration rate, despite its high fractionation.

[Brief description of drawings]

FIG. 1 is a schematic diagram of a CRT image used for measuring the average distance between microfibril bundles and the average distance between stacked lamellae of the composite microporous membrane for a blood treatment polyolefin of the present invention. is there.

Claims (3)

[Claims] 1. A polyolefin composite microporous membrane comprising a microporous layer a layer having a separation function and a microporous layer b layer having a reinforcing function laminated on at least one surface of the layer, wherein each of the a layer and the b layer is a layer. A plurality of microfibril bundles oriented in the stretch axis direction of the membrane and a laminated body of elliptical micropores composed of knots of a stack lamella that are bonded at both ends of the microfibril bundle, and the micropores are formed. The composite microporous membrane precursor is communicated from one surface to the other surface, and the microfibril bundles forming the micropores of the microporous membrane and the knots of the stacked lamellae are 100 weight of the composite microporous membrane precursor. %, And the average distance Da between the microfibril bundles of the micropores present in the a layer and the micropores present in the b layer while being covered with 3 to 30% by weight of the hydrophilic copolymer. Of microfibril bundles The ratio of the distance Db is 1.3 ≦ Db / Da
≦ 15, the average distance Db between the microfibril bundles of the micropores in the b layer is 0.2 to 1.0 μm,
Average distance Lb between the nodules of the stacked lamellae in layer b
Is 0.4 to 4.0 μm, a composite microporous membrane made of polyolefin for blood treatment. 2. The composite microporous polyolefin membrane for blood treatment according to claim 1, wherein the maximum pore size of the membrane measured by the bubble point method is 0.05 to 1.0 μm. 3. The polyolefin composite microporous membrane for blood treatment according to claim 1 or 2, wherein the hydrophilic copolymer is an ethylene-vinyl alcohol copolymer.