JPS5892411A - Semi-permeable membrane and module using same - Google Patents

Abstract

PURPOSE:To obtain a semi-permeable membrane having blood compatibility, excellent in filtering and separating efficiency and improved in the lowering of a filtering and separating speed with the elapse of time, by mutually arranging plural elongated hydrophobic regions and hydrophilic regions oriented to one direction on the surface of the semipermeable membrane at random. CONSTITUTION:A hydrophobic polymer such as polyamide and a hydrophilic polymer such as polyvinyl alcohol are dissolved or melted to be mixed uniformly and the obtained mixture is formed into a hollow fiber by applying draft to the same in a film forming direction. After a solvent or a plasticizer is removed from the hollow fiber, the hydrophilic polymer is partially removed to form fine pores. Thus obtained semi-permeable membrane is accommodated in a container to be used as a module.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a semipermeable membrane having hydrophobic and hydrophilic regions.

Conventionally, semipermeable membranes have been designed with membrane structures, especially pores with a 4° shape, #, and
The arrangement status was part ■. However, in medical public funds that process body fluids, the selective separation ability of semipermeable membranes is insufficient.

Daikichi changes with processing time. For example, when blood V overoperation is started, Ffill decreases over time.

The permeability of solutes through F1 also changes and decreases. this is,
Semipermeable membrane filtration ll1vc not only causes concentration polarization.

The semipermeable membrane is incompatible with blood, resulting in changes in blood components.

This is because special ingredients cause adhesion, adsorption, and #blood.

Therefore, the development of materials with excellent body compatibility and blood compatibility has been actively researched based on the research results of living tissues, but nothing satisfactory has yet been obtained. What is on the level is just a blood passage,
For example, a pipe 1 for a flow path.

Artificial blood vessels, catheters, etc., which do not require selective separation power.

Currently, in imitating living tissues, blood compatibility.

For example, a substance that is said to have excellent antithrombotic properties (Kagaku to Kogyo 32900 (1979)) is a hydrophobic block pirimer with a complex structure that has both hydrophobic and hydrophilic properties.

It is said that the hydrophilicity is 300 to soo X and has a lamellar structure. This polymer is a block polymer of 1-lyethylene glycol and polyurethane; mer-ester;
Vol 2. m5 P2S5 (1977) ) 4
has been saved and development is progressing. However, the current situation is that these polymers have been given a selective ability as semipermeable membranes.

The inventors of the present invention have researched the development of semipermeable membranes with biocompatibility and blood compatibility, and have created a large number of elongated hydrophobic regions and hydrophilic regions oriented in one direction on the surface of the membrane that comes into contact with living organisms or blood. We have invented a semipermeable membrane in which these regions are randomly arranged with each other.

Since the present invention has blood compatibility, it is possible to
For example, the decrease in filtration over time in blood F- and the decrease in permeability of solutes to be treated are greatly improved.

The measure of the semicircular membrane itself is also 4IA.

In the present invention, what is meant by at least one surface of a polymer layer?

As mentioned above, living organisms and blood Ka! 1, blood d tree, blood r distance, plasma layering, plasma component separation.

A large number of elongated hydrophobic regions and hydrophilic regions oriented in one direction, each having a length of 0.02 to 4 μm and a width of 0.01 to 4 μm.
A long and narrow hydrophobic band with a diameter of 0.3 μm.

Most of the hydrophilic bands are arranged in the Nk direction. Therefore, the length directions of the hydrophobic region and the hydrophilic region are the same.
AK do not intersect, but are arranged in parallel. The large number means that a hydrophobic region and a hydrophilic region are present in most of the WIa surface. However, there is sufficient space for pores to exist at the bonding surface of the inner region.

Furthermore, an important feature of the present invention is that the hydrophobic region and the woody region are randomly arranged with each other.

Random means that the inner region has no regularity on the membrane surface,
It is a mixed whole.

The above two configurations are important in blood processing.

That is, by orienting in one direction, the flow direction of blood and plasma is aligned with the flow direction of blood and plasma, thereby improving the Pa efficiency and pumping efficiency in blood filtration and plasma separation. In addition, the randomly arranged mutual arrangement of hydrophobic and woody regions facilitates the adsorption of proteins on the a-liquid base.
This prevents the generation of fibrinogen, etc., and improves the reduction in filtration speed jet 1 separation speed over time.

The material for this semipermeable membrane is a known polymer, and it is easier to make it using a hydrophobic polymer or a hydrophilic polymer, but it is a Breck copolymer. Graft I! #! A polymer complex or the like may be used.

The shape can be flat, tubular, or hollow fibrous, but
To make Modinir housed in a container.

Hollow fibers are better in increasing the effective P4 area with a constant volume, but flat membranes are advantageous in terms of construction because they are inexpensive.

One method is #I waterborne polymers, such as polyamides.

Polyester, polyethylene, poly°propicine.

Polycarbonate field 1 usually has a water content of 10% or less, preferably 5% or less, and wood-loving lrimer 1, such as cellulose, melivinyl alcohol, polyvinyl pyrrolidone, which is soluble in water or has a water content of 5% or less. 10- is dissolved in a solvent, or a single agent is added and melted to form a homogeneous solution or melt in which a hydrophobic polymer and a hydrophilic polymer are completely mixed, and then S+* do. 1
When Ill@membrane, it is essential to apply one or more drafts in the -m7F direction. - After membrane, desolvent, deplasticizer, v! pores are formed by partial removal of the hydrophilic y +)mer.

For wood-philic polymers, it is necessary to take measures to prevent them from eluting during blood treatment, and the molecular weight, fx kneading at 41 degrees, heat treatment such as crosslinking, and post-treatment may be performed.

Particularly, plasma separation and elution, which is the partial removal of the polymeric dense material Kr1, is an effective filtration method, and the pores on the membrane surface and inside can be controlled by combining with the membrane forming conditions.

The present invention is a module in which the semipermeable membrane is housed in a container.

The semipermeable membrane must be a flat membrane, with the blood side facing the semipermeable membrane of the present invention, and the module must be housed in a container in the same manner as in the case of hollow fibers.

Example 1 A polyacrytetranitrile copolymer containing 916% acrylonitrile, 8.0% methyl acrylate, 0.5% methacrylsulfonic acid, and an equal amount of vinyl pyridone.
67-Dissolved in steel machine aqueous solution 16.5vt%&lj7-
Relying on soybean paste, after foaming at -10℃, 15% was added to the steel spinneret.
-/At the same time, 1.2 liters of water is pumped into the center of the annular spinneret.
tg/+m was injected. The hollow fiber containing water in the center was introduced into a coagulation bath using a screwdriver of 7) 1.5, coagulated for 1 d, and wound up at a speed of 30 m/height. The coagulation bath is 1% nitric acid in water at 30°C.

The obtained hollow embroidery has an inner diameter of 190μ and an outer diameter of 280μ.

When the inner surface of the hollow MA fiber was examined using a 7,000x magnification electron microscope, the length was 0.1 to 3.0μ, and the width was 0.05 to 0.2μ.
There is an aggregate of polyacrylonitrile copolymer consisting of μ and polyvinylpyrroli F ◇ The obtained hollow fibers were placed in a container, a module was taken, and blood was filtered. Hv was obtained. Limit Fa, i! Vomiting for up to 3 hours
l was 5%.

Example Poor polyethylene tereate and polyvinylalcohol: I-
# k 4 〘 * 1 in hexafluoreizopropanol
5wt was dissolved to a low density, and after foaming, 0.0% was deposited on the glass plate.
By casting at a high speed of 20 m/m at a thickness of 5M, the surface of the cast membrane is run in one direction. Immediately thereafter water KeltI1. #dL Bovine Permeable Membrane ObtainedO The obtained membrane surface has many lengths in one direction of 0.02 to 4μ, width o, ot~
There is an aggregate region of 0.2μ of ethylene terephthalate and vinyl alcohol.

There were pores of 0.02 to 0.05 microns with a porosity of 50 hiss.

Procedural amendment Buds June 1980 Japan Patent Office Commissioner Kazuo Wakasugi 1 Indication of the case Patent application No. 1986-190676 2 Title of the invention Semi-permeable membrane and module using the same 6 Relationship with the case to be amended/Patent Applicant Asahi Medical Co., Ltd. 4 Agent No. 2929 Tora, Nomon-chome, Minato-ku, Tokyo UF” 1 Industrial Building 5th floor Full text of amended specification 1 Name of the invention Semi-permeable membrane and module using the same 2 Patent claim Scope 1) A semipermeable membrane in which at least one surface of the polymer membrane has a large number of elongated hydrophobic regions and hydrophilic regions oriented in one direction, and these regions are randomly arranged with each other.

5. Detailed Description of the Invention The present invention relates to a semipermeable membrane having hydrophobic and hydrophilic regions. Conventionally, semipermeable membranes have been modified to improve selective separation ability by changing the membrane structure, especially the selective separation ability. Determining the size, shape, number, and arrangement of the pores was an issue, but in the medical field where body fluids are processed, the selective separation ability of semipermeable membranes changes greatly with processing time. For example, when blood filtration is started, hyperphagia decreases over time, and the permeability of solutes to be filtered also changes and decreases.

This not only causes concentration polarization on the filtration surface of the semipermeable membrane, but also
This is because the semipermeable membrane lacks compatibility with blood, resulting in changes in blood components, adhesion and adsorption of special components, and coagulation. Therefore, based on the research results of living tissues, active research has been carried out to develop various round materials with excellent biocompatibility and blood compatibility, but nothing satisfactory has yet been achieved. However, currently,
Those that are at a practical level are mere blood passages, flow path tubes, such as artificial blood vessels, catheters, etc., and these do not require selective separation ability.

Currently, among biological tissue imitators, those that are said to have excellent blood compatibility, such as antithrombotic properties (Chemistry and Engineering 'Todan 900 (1979)), have hydrophobic and hydrophilic properties. It is a block polymer with a composite structure, and is said to have a lamellar structure with hydrophobicity and hydrophilicity Fi of 300 to 500λ. This polymer is a block polymer of polyethylene glycol and polyurethane; polyester: polycarbonate, or a graft polymer of acrylonitrile, methacrylic acid, etc. to polyvinyl acetate (II Vol 2. i
s P 358 (1977)) etc. are being considered and development is progressing. However, the current situation is that these polymers cannot be given the selective separation ability of a semipermeable membrane.

The present invention has been developed by researching the development of a semipermeable membrane that is biocompatible and blood compatible, and has a large number of elongated hydrophobic regions and hydrophilic regions oriented in one direction on the membrane surface that comes into contact with living organisms or blood. They invented a semipermeable membrane in which these regions are randomly arranged with each other.

Since the present invention has blood compatibility, when processing blood,
For example, the decrease in filtration rate over time in blood filtration and the decrease in permeability of solutes that should be treated with P are greatly improved, and the strength of the semipermeable membrane itself is also strong.

In the present invention, at least one surface of the polymer membrane refers to the above-mentioned i.
! j1shi refers to the surface that comes into contact with living organisms and blood, and in vehicular dialysis, hemofiltration, plasma separation, plasma component separation, etc., refers to the surface on which blood and plasma pass through, and in particular, in plasma separation, both surfaces are the structure of the present invention. This is desirable.

A large number of elongated hydrophobic regions and hydrophilic regions oriented in one direction each have a length of about 0.02 to 4 μm and a width of 0.01 to 4 μm.
Hydrophobic bands and hydrophilic bands each having a length of approximately 0.3 μm are arranged in the lengthwise direction. Therefore, the length directions of the hydrophobic region and hydrophilic region intersect with each other)
They are not rows that match, but are lined up parallel to each other. In most cases, a hydrophobic region and a hydrophilic region exist on most of the membrane surface. However, the space in which pores exist at the joint surface of both regions exists in the era name.

Furthermore, what is important about the present invention is that the hydrophobic region and the hydrophilic region are randomly arranged with each other, and "random" means that both regions have a single regularity on the 11 surface and are mixedly integrated. The above two configurations overlap in blood processing.

In other words, by oriented in one direction, and by matching the flow direction of blood and plasma, it becomes a round product with excellent filtration efficiency and separation efficiency in blood filtration and plasma separation, and the hydrophobic and hydrophilic regions are random. The mutual arrangement is blood compatible, prevents protein adsorption and the generation of fibrinogua, and improves the deterioration of filtration rate and separation rate over time.The material of this semipermeable membrane is made of known polymers. Although it is easier to manufacture using hydrophobic polymers and hydrophilic polymers, block copolymers, grafts, polymer complexes, etc. may also be used.

The membrane shape may be flat membrane, tubular, hollow fiber, etc.
In order to make a module housed in a container, hollow fibers are better for increasing the effective filtration area while keeping the volume constant.
In terms of manufacturing method, flat membranes are advantageous because of their inexpensive surface.

The manufacturing method uses hydrophobic polymers, which are commonly referred to as hydrophobic polymers, such as polyamides, polyesters,
polyethylene, polypropylene, polycarbonate, etc.
Hydrophilic polymers are generally polymers with hydrophilic properties, such as cellulose, polyvinyl alcohol, polyvinyl pyrrolidone, etc. A homogeneous solution in which a hydrophobic polymer and a hydrophilic polymer are completely mixed can be obtained by dissolving polymers with low solubility or water content exceeding 10 cm in a solvent, or by adding a plasticizer and melting them.
After becoming a molten substance, it becomes a gland. During film formation, it is essential to apply one or more drafts in the direction of the fB film. After film formation, pores are formed by removing the solvent, removing the plasticizer, and then partially removing the hydrophilic polymer.

Hydrophilic polymers must be designed to prevent them from eluting during blood treatment, and may be subject to changes in molecular weight, degree of blending, heat treatment such as crosslinking, post-treatment, etc.

To form hollow fibers, a solution or melt in which a hydrophobic polymer and a hydrophilic polymer are completely mixed is discharged from an annular spinneret. Particularly in the case of a solution, a hollow forming agent is injected from the center of the annular spinneret to stabilize hollow forming. This hollow forming agent uses a gas or a liquid, but liquids are generally more stable and tend to keep the hollow in the shape of the spinneret, particularly circular. The hollow forming agent is not particularly limited as long as it does not react with the solution or the like. However, in order to accelerate coagulation, a liquid with high coagulation ability must be selected.

The circular fluid flowing out from the annular spindle creates a draft in the direction of the outflow.
Above, preferably 1.5 to 10 while hollow -
Linearize.

It can be made into hollow fibers using a circular spinneret, and can be produced using the usual hollow fiber method, dry or wet, except for drafting. The obtained hollow II1 fibers are treated with solvent removal, deplasticizer, etc.
In some cases, treatments such as heat treatment are also performed.

Particularly, blood plasma separation, separation of high molecular weight substances, Vctli, and elution, which is the partial removal of the hydrophilic polymer mentioned above, are effective means, and the membrane surface and internal pores can be controlled in combination with membrane forming conditions.

The semipermeable membrane of the present invention is generally used as a module by being housed in a container, and in general, when the semipermeable membrane is a flat membrane, the blood side is the II of the semipermeable membrane of the present invention, and the hollow fiber-like The module must be housed in a container so that it is the same in all cases.

A preferred module of the present invention is a module in which a semipermeable membrane is housed in a container having an inlet and an outlet for a liquid to be treated and is provided with an F liquid inlet, wherein the semipermeable membrane is a polymer membrane. has at least one surface oriented in one direction and has a large number of lIl
The module is characterized in that it has a long hydrophobic region and a hydrophilic region, and these regions are randomly arranged with each other, and the F liquid port of the container is provided through the semipermeable membrane. , Figures 1 and 2 illustrate nine modules using the semipermeable membrane of the present invention. Figure 1 shows the case where the semipermeable membrane is a flat membrane, and Figure 1 shows the case where the semipermeable membrane is a hollow fiber. In the drawing, A is a semipermeable membrane, 1 and 2 are an inlet and an outlet for the liquid to be treated, and a collection port [Fl].

The present invention can be used not only for blood processing such as blood filtration and plasma separation, but also for blood contact containers, transport pipes, blood circuits, etc. Furthermore, curlers can be used as biomaterials. Further, it can be considered to be used as a treatment membrane for treating charged solutions such as cations and anions, such as coating waste liquids and electrolytes.

Example 1 Acrylonitrile 91.59G, methyl acrylate 8.
16. Dissolve equal amounts of polyacrylonitrile copolymer containing 0.5% methacryl sulfo/sodium acid and polyvinyl pyrrolidone in an aqueous solution of 67 nitric acid. After adjusting the concentration of the polymer to VT-polymer and filtering and defoaming at -10C, add 1 to the annular opening.
．． At the same time, 1.5 m/" of water is pumped into the center of the annular spindle.
2+d/- was injected. The hollow fiber with water wrapped in the center part is introduced into a coagulation bath with a draft of 1.5 and coagulated,
0W! It was wound up with /-. The coagulation bath was 30C of nitric acid water.The obtained hollow fibers had an inner diameter of 190μ and an outer diameter of 280μ, and when the inner surface of the hollow fibers was observed with a 7,000x scanning f-type electron microscope, the length was 0.1μ. ~3.0μ, width 0.05~0.2μ
There is an aggregate of polyacrylonitrile copolymer and polyvinylpyrrolid.

The obtained medium perforated mackerel fibers were placed in a container, used as a module, and blood filtrated.
r-11Hg was obtained. The rate of decrease of the limit or overspeed up to 5 hours was Fl5ch.

Example 2 Polyethylene terephthalate topolyvinyl alcohol was dissolved in hexafluoroisopropanol to a concentration of 15 wt, and after filtration and defoaming, it was cast onto a glass die to a thickness of 0.5 m/- at a speed of 20 m/-. The cast film was cast at high speed to run in one direction on the surface of the cast film.2 Immediately thereafter, it was immersed in water and coagulated to obtain a semipermeable film.

The obtained membrane surface has many lengths of 0.02 to 4μ in one direction,
There is an aggregate region of polyethylene terephthalate and polyvinyl alcohol with a size of 0.01 to 0.2μ, and the porosity is 5.
There were 0.02-0.05μ pores.

The obtained membrane was assembled into a module, and blood f (fresh blood T P
= 7. Of/dt%at-41) As a result of filtration, the ultrafiltration rate was 24.5 wl/m'-Tk ・ll
Hg t-obtained, the rate of decrease in ultrafiltration rate up to 4 hours was 8
-It was. In addition, after returning the blood V, 1 was returned with saline, 5 was fixed with tiglutaraldehyde, and after drying, the adhesion of blood cells to the surface was observed using a scanning electron microscope. No reticular deposits such as fibrinogen were observed.

[Brief explanation of drawings]

Figures 1 and 2 are explanatory diagrams of a module using the semipermeable membrane of the present invention. Figure 1 shows the case where the semipermeable membrane is a flat membrane, and Figure 2 shows the case where the semipermeable membrane is a hollow fiber. . A... Semipermeable membrane 1... Entrance 2... Outlet 5...
Collection port Figure 1 Figure 2

Claims (1)

[Claims] 1) A semi-permeable polymer membrane in which at least one surface of the polymer membrane has a large number of elongated hydrophobic regions and hydrophilic regions oriented in one direction, and these regions are randomly arranged with each other. film. 2) A semipermeable membrane in which at least one surface of the polymer membrane has a large number of elongated hydrophobic regions and hydrophilic regions oriented in one direction, and in which these regions are randomly arranged with each other, was housed in a container. module.