JPH0376970B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Technical Field] The present invention relates to a hollow fibrous porous membrane having a new and specified structure. More specifically, the present invention relates to a hollow fibrous porous membrane having a unique structure in which the outer shell layer is substantially two-layered and denser than the inner shell layer. The present invention provides a hollow fibrous porous membrane particularly suitable for treating body fluids.

[Prior art]

In recent years, plasma exchange therapy has been used to treat nephritis, myasthenia gravis, collagen disease, acute hepatitis, and the like.

Plasma exchange therapy involves separating plasma from blood taken from a patient and exchanging approximately the same amount of plasma from a healthy person.Recently, a simple method using porous hollow fibers has become popular.

Generally, to separate plasma from blood, hollow fibers with pores of 0.1μ to 0.5μ and uniform porosity in the cross-sectional direction are used; Furthermore, due to its high porosity, it is extremely fragile and prone to leaks, and there are many problems such as a decrease in filtration efficiency during use.

[Purpose of the invention]

The present invention eliminates the above-mentioned drawbacks, particularly improves the fragility of hollow fibers, eliminates the occurrence of leaks during the manufacturing process and during use, and further improves plasma separation efficiency.

[Structure of the invention]

The present inventors have conducted extensive research to achieve this objective, and by improving the fine structure of hollow fibers into a special structure, the fragility of hollow fibers has been improved, and the plasma separation efficiency has been high and excellent properties have been achieved. A hollow fibrous porous membrane was obtained.

That is, the present invention provides a hollow fibrous porous membrane spun from a mixture of two or more organic polymers, in which the wall membrane of the porous membrane substantially consists of two layers: an inner shell layer and an outer shell layer. has a layered structure, the inner shell layer and the outer shell layer have a substantially network-like porous structure, the outer shell layer has a porous structure denser than the inner shell layer, and the average pore diameter of the inner shell layer is D ₁ is larger than the average pore diameter D ₂ of the outer surface,
The ratio D ₁ /D ₂ is 3 or less, D ₂ is in the range of 0.05 to 1μ, the average porosity of the entire wall membrane is 60% or more, and the water permeability of the porous membrane is 1000~10000
The present invention provides a hollow fibrous porous membrane characterized by ml/ ^mm2 ·hr·mmHg.

The present invention will be explained in more detail below.
Examples of scanning electron micrographs (hereinafter simply referred to as electron micrographs) of the cross section and outer surface of the hollow fibrous porous membrane of the present invention are shown in FIGS. 1 to 6. That is, FIG. 1 is an electron micrograph of a cross section of a hollow fiber, which is an example of the present invention, cut in a direction substantially perpendicular to the axial direction, and FIG. 2 is an electron micrograph of the outer surface of the hollow fiber. . Moreover, FIGS. 3 to 6 relate to hollow fibers which are other examples of the present invention. That is, FIG. 3 is an electron micrograph of a cross section of the hollow fiber cut in a direction substantially perpendicular to the axial direction, FIG. 4 is an electron micrograph of the outer surface of the hollow fiber, and FIG.
The figure is an electron micrograph of the cross section near the outer surface of the hollow fiber, and FIG. 6 is an electron micrograph of the cross section at the center of the wall of the hollow fiber.

As shown in FIGS. 1 and 3, in the hollow fibrous porous membrane of the present invention, the wall membrane is substantially composed of an outer shell layer (the area indicated as A in the figure) and an inner shell layer (the area indicated as A in the figure). It has a two-layer structure (region indicated as B). Further, the inner shell layer and the outer shell layer of the wall membrane have a substantially network-like porous structure, and the outer shell layer has a denser porous structure than the inner shell layer. The difference in density between the inner and outer shell layers can be determined by electron microscopic observation as shown in FIGS. 1 and 3.

The hollow fibers of the present invention are preferably those in which the average porosity of the outer shell layer is smaller than the average porosity of the inner shell layer. The average porosity of the outer shell layer referred to here is
Electron micrograph of the outer surface of the hollow fiber (magnification is approx.
The average porosity of the inner shell layer is the average value of the area occupied by the pores per unit area of the outer surface obtained by 4000) is the average value of the area occupied by the pores per unit area of the inner shell layer, expressed as a percentage.

Further, in the hollow fibrous porous membrane of the present invention, the average pore diameter D ₁ of the inner shell layer is larger than the average pore diameter D ₂ of the outer surface, and the ratio D ₁ /D ₂ is in the range of 3 or less, preferably 2 or less. The film shown in 1. has superior film properties. The average pore diameter D ₁ of the inner shell layer referred to here is calculated as the average pore diameter of the pores from the cross-sectional photograph of the hollow fiber as shown in FIG. 6, and the average pore diameter D ₂ of the outer surface is calculated as the average pore diameter from the outer surface photographs of the hollow fibers as shown in FIGS. 2 and 4. Such D ₂ is preferably 0.05 to 1 μ, and more preferably in the range of 0.1 to 0.5 μ, which is excellent in terms of separation characteristics and membrane strength characteristics. Further, D ₁ is preferably 0.05 to 3μ, particularly preferably 0.1 to 1μ. It is more preferable that the network porous structure of the inner shell layer has a substantially homogeneous pore distribution throughout the layer. Substantive here means
This means that there is some unevenness in homogeneity. Or, it is considered that these adjacent pores are in communication in most cases.

Further, the hollow fibrous porous membrane of the present invention has an average porosity of 60% or more over the entire wall membrane, preferably
70-95%, especially 80-90% is excellent. The average porosity of the entire wall film may be determined by any method, but is usually determined by (1-Pb/Pa)×100. Here, Pa is the density of the polymer itself, and Pb is the weight of the wall film divided by the total volume.

Furthermore, the hollow fibrous porous membrane of the present invention has a water permeability of UFR of 1000 to 10000 ml/m ²・hr・mm.
Hg, preferably a very large value of 3000 to 7000 ml/m ² ·hr·mmHg.

In addition, it is preferable that the thickness of the outer shell layer of the hollow fiber is 30% or less of the total thickness of the wall membrane, and in particular, when the thickness is in the range of 3 to 15%, membrane strength is maintained and separation properties are maintained. is also good.

As described above, the hollow fibers of the present invention are thought to have relatively few pores on the outer surface or shell layer, but the average pore diameter of the entire wall of the hollow fibers was measured by the water permeation method as follows. can. That is, the flow rate and pressure loss when a certain amount of water permeates through the wall membrane of the hollow fibers are measured, and from the results, the average pore diameter of the entire wall membrane is calculated using the following equation.

D=(32η・t・J/Pr・△P) ^1/2 (where, D is the average pore diameter of the entire wall membrane, t is the membrane thickness, J is the water permeation rate, η is the viscosity of the water, Pr is the porosity of the membrane, and ΔP is the pressure drop.) When measured by this method, the pore diameter of the hollow fibers obtained was 0.05 to 1μ, preferably 0.1 to 0.5μ.

The hollow fiber porous membrane having the novel and unique structure of the present invention can be obtained by, for example, phase separation formation during wet membrane formation proceeding in different forms in the outer shell layer and inner shell layer of the hollow system. It is considered that the That is, as seen in FIG. 5, it can be seen that the direction of the holes is different between the outer shell layer and the inner shell layer. This is because during film production, pores tend to be formed in the radial direction of the fibers due to rapid phase separation in the outer shell layer due to rapid contact with the coagulating liquid, whereas pores in the inner shell layer tend to form in the radial direction of the fibers. As phase separation progresses in the layer due to the slow intrusion of the coagulating liquid, for example, many pores are formed adjacent to each other in a direction parallel to the axis, and these pores communicate with each other, resulting in no limited directionality. It is thought that a network-like porous structure with many pores is formed. It is considered that the phase separation rate on the inner surface side of the hollow fiber is not fast because a small amount of the coagulating liquid is supplied to the inner surface side.

The organic polymer used as the material for the hollow fibrous porous membrane of the present invention may be any polymer that can be formed by wet or semi-dry and semi-wet spinning. The combined mixed yarn (ie, polymer alloy) has a higher phase separation ability during coagulation and the phase separation rate can be easily controlled, and therefore is suitable for obtaining the hollow fiber of the present invention.

There are various methods for producing the hollow fibers of the present invention, and for example, the following method can be used easily. That is, as polymers, cellulose acetate, polymethyl methacrylate, and cellulose nitrate are dissolved in a solvent in a ratio of 80:15:5, respectively. A mixed solvent of acetone/methanol (3/1) can dissolve the above three. To this, cyclohexane, cyclohexanol, N-methylpyrrolidone, etc. are mixed within 30 wt% as a swelling agent, and inorganic salts are further mixed within 5 wt%, and 16 to 20% of the polymer mixture is added. When warmly dissolved, a spinning dope is prepared.

This is discharged from the annular spinning hole and immediately introduced into the coagulation bath, and at the same time, a liquid having the same composition as the coagulation bath is also introduced from inside the annular spinning hole. The coagulation bath composition includes, for example, acetone-methanol-water (10:40:
50). In addition, the above-mentioned swelling agents such as cyclohexane, cyclohexanol, and N-methylpyrrolidone may also be added.

In this way, in a mixed system of two or more organic polymers, by making the liquid composition of the coagulation bath and the composition of the hollow internal coagulation liquid substantially the same, the coagulation rate on the outer surface side of the hollow fiber can be increased. The solidification rate can be made appropriately faster than the solidification rate on the inner surface of the hollow part, and the desired membrane wall structure can be easily obtained. In addition, in such a mixed polymer system, since it coagulates more easily than in the case of a single polymer, a dense layer of fibers, which is the shell layer as described above, is generated near the outer surface. This dense layer, which is the outer shell layer, has only a small pore density, and the pore size is
It is easy to get something that is not much different from the inside. That is, in this case, it has a microstructure that is different from the so-called conventional anisotropic membrane, which has a very small surface pore size. These hollow fibers have an inner diameter of 300μ and an outer diameter of 450μ, for example.
Therefore, it is usually preferable to attach glycerin in a dry state.

The hollow fibrous porous membrane of the present invention is excellent in membrane strength and separation performance and can be used for various purposes. Although it can be used for all types of ultrafiltration, it is particularly suitable for separation membranes in body fluid treatment devices for separating and removing specific components from body fluids. Furthermore, the hollow fibers of the present invention have particularly excellent properties as a plasma separation membrane for separating plasma from blood.

〔Effect of the invention〕

Since the hollow fibrous porous membrane of the present invention has a dense layer near the outer surface, it has excellent mechanical strength such as shape retention and abrasion resistance. Therefore,
The hollow fibers are extremely stable without leakage, damage, flattening, etc. during manufacture, transportation, storage, assembly into separation modules, use, etc.

Furthermore, since the hollow fibers have a porous structure having pores with relatively similar pore diameters throughout the wall membrane, they also have extremely excellent separation properties. That is, the permeation rate of substances that permeate is high, and the permeation rejection rate of substances whose permeation is blocked is high. For example, when the plasma separation module incorporating the hollow fibers of the present invention was applied to an animal experiment using dogs and its plasma separation ability was measured, it was found that plasma separation of 30% or more was possible at a blood flow rate of 100 ml/min. Very excellent separation properties are obtained, with a permeability of plasma proteins of over 90%.

EXAMPLES The present invention will be described in more detail below with reference to Examples, but the present invention is not limited to these Examples in any way. In the examples, "parts" means parts by weight.

Example 1 The spinning stock solution was prepared by mixing 1200 parts of cellulose acetate with a degree of axification of 52%, a degree of polymerization of 180, 255 parts of polymethyl methacrylate with a degree of polymerization of 300, and 45 parts of cellulose nitrate with a degree of nitrification of 11.5% and a degree of polymerization of 160, and 3000 parts of N-methylpyrrolidone. parts, 500 parts of magnesium chloride, acetone
It was dissolved in a mixed solvent of 3,500 parts of methanol and 1,500 parts of methanol at 50°C.

After filtering this, it is spun through an annular spinning hole with 8 holes and introduced into a coagulation bath of acetone-methanol-water (10:40:50wt%). A hollow fiber with an inner diameter of 300 μm and an outer diameter of 450 μm was obtained by flowing.

The hollow fibers were fixed in liquid nitrogen and cut, and the cross-section was observed using an electron microscope. That is, at a magnification of 1000 times, a dense layer called an outer shell layer was observed in the cross-sectional direction with a thickness of 8% from the surface. Further, when observed at a magnification of 4000 times, the inner shell layer was porous with a network structure, and the average pore diameter was approximately 0.3μ. Also on the outer surface, 4000
Approximately 5 pores/ ^μ2 with an average value of approximately 0.2μ were observed by double observation. The pore diameter determined by the water permeation method was 0.18μ, and the overall average porosity was 85%. These hollow fibers were bundled and filled into a cylindrical module (1,500 fibers), and both ends were bonded with urethane resin so that the inner diameter was 0.3 m ² . The water permeability was 5000ml/m ² ·hr ·mmHg. No leaks were observed with this product during normal transportation. In addition, it has demonstrated sufficient plasma separation performance in animal experiments and clinical evaluations.

It was used 179 times in 53 cases including fulminant hepatitis, malignant rheumatoid arthritis, and systemic lupus erythematosus, but no leaks were observed and efficacy was observed in 34 cases (64%).

In addition, the permeability of plasma proteins in clinical evaluation was as follows.

Total protein 94% Albumin 98% IgA 95% IgM 90% C ₃ 95% C ₄ 97% Example 2 Cellulose acetate with an axification degree of 52%, a polymerization degree of 180, 80%, polymethyl methacrylate with a polymerization degree of 300
Spinning yarn consisting of 18% polymer with a composition of 15% cellulose nitrate with a degree of nitrification of 11.5% and a degree of polymerization of 160, 30% cyclohexanol, 3% calcium chloride, and 49% acetone/methanol (3/1) mixed solvent. A stock solution was prepared.

The fibers were spun through eight annular spinning holes and immediately introduced into a coagulation bath of acetone-methanol-water (10:40:50 wt%), and at the same time a coagulating liquid was flowed from inside the spinning holes to create hollow fibers. The hollow fiber had an inner diameter of 320μ and an outer diameter of 480μ. Its overall average porosity is 87%,
The water permeability was 4800ml/m ² hr mmHg. We also performed electron microscopy, and cross-sectional observation revealed that 1000
At magnification, almost no porosity was observed in the outer surface layer within a thickness range of 6% from the outside, but network-like porosity was observed in the inner shell layer. Furthermore, when observed at a magnification of 4000 times, pores with an average pore diameter of approximately 0.6μ were observed in the inner shell layer. However, when the surface was observed at a magnification of 4000, approximately circular or elliptical pores were observed, and the average diameter of the pores was approximately 0.3 μ. No leaks were observed during the manufacturing process or during transportation tests.

Comparative Example 1 18% cellulose acetate with a degree of dilution of 52% and a degree of polymerization of 180, 30% cyclohexal, 3% calcium chloride, 49% acetone/methanol (3/1) mixed solvent
A spinning dope having the composition was prepared and spun under the same conditions. The porosity of the obtained hollow system is 70% or less,
The water permeability was also 2000ml/ ^m2・hr・mmHg. Even when observed under an electron microscope, the porosity was almost uniform, no particular surface layer was observed, the fibers were brittle and leaked frequently, and module processing was extremely difficult.

Reference example Polyvinylidene fluoride (Penwall Kynar301
F) 16%, polyvinylpyrrolidone 10%, cyclohexanone 30%, N-methyl-2-pyrrolidone 54
% spinning dope was prepared and spun into a coagulation bath of methanol/water (1:1) through an annular spinning hole, and at the same time a coagulating solution having the same composition was flowed from inside the spinning hole. The overall average porosity of the obtained hollow fibers was 80%, and cross-sectional electron microscopy (1000x magnification) showed that almost no porosity was observed in the 5% thickness range from the surface, but the inner shell Network-like porosity was observed in the layer. 4000 again
Cross-sectional observation at high magnification shows that the average pore size in the inner shell layer is approximately
Pores of 0.2μ were observed. Further, when the outer surface was observed at 4000x magnification, porosity with an average value of approximately 0.15μ was observed.

The water permeability was 4000 ml/m ² ·hr · mmHg, indicating that the hollow fiber had sufficient strength.

[Brief explanation of drawings]

FIGS. 1 and 2 are electron micrographs of an example of the hollow fibrous porous membrane of the present invention, with FIG. 1 being a sectional view and FIG. 2 being an external surface view. FIG. 3 is an electron micrograph of a hollow fiber according to another example of the present invention,
3, 5, and 6 are cross-sectional views, and FIG. 4 is an external surface view.

Claims (1)

[Scope of Claims] 1. A hollow fibrous porous membrane spun from a mixture of two or more organic polymers, in which the wall membrane of the porous membrane substantially consists of an inner shell layer and an outer shell layer. It has a two-layer structure, the inner shell layer and the outer shell layer have a substantially network-like porous structure, the outer shell layer has a porous structure denser than the inner shell layer, and the average of the inner shell layer is The pore diameter D ₁ is larger than the average pore diameter D ₂ of the outer surface, and the ratio D ₁ /D ₂
is 3 or less, _D2 is in the range of 0.05 to 1μ, the average porosity of the entire wall membrane is 60% or more, and the water permeability of the porous membrane is 1000 to 10000ml/ ^m2 . hr・mm
A hollow fibrous porous membrane characterized by being Hg. 2. The hollow fibrous porous membrane according to item 1, wherein the thickness of the outer shell layer is 30% or less of the thickness of the entire wall membrane. 3. The hollow fibrous porous membrane according to item 1, wherein the porous membrane is for treating body fluids.