JPH05111624A - Semipermeable membrane - Google Patents

Abstract

PURPOSE:To obtain a semipermeable membrane comprising a polymer compsn. excellent in contamination resistance obtd. by mixing a contamination-resistant polymers comprising a hydrophilic component and a hydrophobic component, by specifying the difference between the max. and the min. proprotions of the hydrophilic component in the semipermeable memberane. CONSTITUTION:This semipermeable membrane contains a compsn. prepared by mixing two or more kinds of contamination-resistant polymers comprising a hydrophilic component and hydrophobic component as the structural component. It is specified that the difference between the max. and the min. proportion of the hydrophobic component is >=5wt.%. By this method, affinity between a polymer having high hydrophobic content and a noncontaminant material can be increased even when the average hydrophilic component is same, so that a stable molded body or a mixture soln. can be obtd. in a compatible or semicompatible state. Thereby, the obtd. membrane is excellent stability and contamination resistance.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a semipermeable membrane having excellent stain resistance.

[0002]

2. Description of the Related Art In recent years, application of polymer materials to industrial and medical fields has progressed, and a selective permeable membrane, so-called semipermeable membrane, has been actively used especially for separating substances. For example, in the fields of reverse osmosis, dialysis, ultrafiltration and gas separation, many technical reports have been made on the application of membranes.
However, in these operations, there are problems that the membrane is contaminated by the treatment substance, the treatment capacity is lowered, and the separation performance of the membrane itself is not always sufficient. As a material for such a semipermeable membrane, a cellulose derivative, a polyacrylonitrile-based polymer, a polyvinyl alcohol-based polymer, a polymethylmethacrylate-based polymer, a polysulfone-based polymer and the like have been conventionally taken up.
Further, for the purpose of enhancing the stain resistance, a semipermeable membrane made of a polymer containing 2-hydroxyethyl methacrylate, N-vinylpyrrolidone, acrylamide, methacrylic acid containing a hydrophilic component or acrylic acid has been studied. ..

However, these membranes have insufficient permeability to substances such as water and solute, or introduce a larger amount of copolymerization component to achieve their performance, but on the other hand, have lower mechanical strength. However, the function as a practical membrane has been impaired. Furthermore, using these membranes, when performing concentration of various protein solutions, sterilization of liquid foods or ultrafiltration separation in the wastewater treatment process, adhesion of solute components to the membrane surface, causing a clogging phenomenon due to deposition, The intended operation was hindered. Furthermore, when these membranes are used for medical purposes and come into contact with blood or body fluids, platelets, white blood cells, red blood cells,
It was presumed that adherence of tangible substances such as fibroblasts was unavoidable, and these would lead to the formation of thrombus on the membrane surface and the deterioration of immune function due to activation of the complement system.

In either case, it is important to impart a stain resistance developing function to the liquid contact surface of the membrane in order to develop the stain resistance, and a composite membrane composed of multi-component layers has been developed. However, in the medical field, it is difficult to manufacture this multilayer film with hollow fiber membranes, which occupy most of the medical membrane, or it is used as a medical device without chemical bonding between the contaminant resistant substance and the substrate. In such a case, the problem arises that an eluate is generated and the film cannot be used, which delays the development of a film having a stain resistant surface. Recently, as a method of imparting an antithrombotic function to the surface by surface chemical modification, attempts have been made to ester bond polyethylene glycol carboxylic acid anhydride to a polymer membrane made of regenerated cellulose (Japanese Patent Laid-Open No. 1-297103). However, a film that does not require a complicated film forming process, retains sufficient mechanical strength, and has high-performance stain resistance has not been developed yet.

A member of the present inventor made an attempt to form a membrane with a stain resistant substance, and invented a permselective hollow fiber composed of a copolymer containing a hydrophilic polyethylene oxide chain (Japanese Patent Laid-Open No. 60-22901). Publication). Further, a semipermeable membrane made of acrylonitrile copolymer containing a hydrophilic polyethylene oxide chain and acrylonitrile is solute permeable,
It was found that the stain resistance is excellent (Japanese Patent Laid-Open No. 63-
130103).

However, at this time, the acrylonitrile copolymer and acrylonitrile contained an acrylonitrile component in both of them, but the stock solution for film formation was in an incompatible phase-separated state and was unstable. For this reason, the structure of the inner surface of the film was rough and the stain resistance was insufficient.

As a result of intensive studies, the inventors have found a method for concentrating a high-concentration stain resistant component on a liquid contact surface with a smooth film surface structure, and arrived at the present invention.

[0008]

The object of the present invention is to concentrate the stain resistant component on the liquid contact surface so as to suppress the deterioration of the mechanical strength of the membrane due to the introduction of a large amount of the hydrophilic component and to obtain the high stain resistant property. To provide a semipermeable membrane having.

[0009]

The above-mentioned object of the present invention is to provide a "semi-permeable membrane comprising at least one constituent of a composition obtained by mixing two or more kinds of stain resistant polymers comprising a hydrophilic component and a hydrophobic component. And a difference between the maximum value and the minimum value of the content ratio of the hydrophobic component in the two or more stain resistant polymers is 5% by weight or more. The present invention will be described in detail.

Contamination resistance refers to the property of suppressing the adhesion of solute components to the membrane surface during the concentration of various protein solutions, sterilization of liquid foods, or ultrafiltration separation in the wastewater treatment process. Contamination resistance includes suppression of adhesion of tangible components such as platelets, leukocytes, erythrocytes, and fibroblasts when used for medical purposes and in contact with blood or body fluid.
The fouling state of the membrane is evaluated by quantitatively analyzing the amount of the attached substances or by observing the attached state with a microscope. Membrane entrance caused by clogging of the flow path,
Contamination resistance can be evaluated by measuring the time until the differential pressure at the outlet rises or the liquid stops flowing. Whether or not a polymer composed of a hydrophilic component and a hydrophobic component has stain resistance is judged by comparison with the stain resistance of a polymer composed of only the hydrophobic component constituting the polymer.

The stain resistant polymer of the present invention comprises a hydrophilic component,
Any stain-resistant polymer made of a hydrophobic component may be used, and it may be a synthetic polymer or a natural polymer.
Further, the hydrophilic component and the hydrophobic component may each be a single component or a plurality of components. The hydrophobic component referred to in the present invention is 25 in its homopolymer.
Those having a solubility in water at 0 ° C of less than 50% by weight are applicable. Examples of the hydrophobic component include olefins such as ethylene and propylene, vinyl halides such as vinyl chloride and vinyl fluoride, vinyl esters such as vinyl formate and vinyl acetate, acrylic acid, acrylic acid such as methyl acrylate and ethyl acrylate. Acid ester, methacrylic acid, methacrylic acid ester such as methyl methacrylate and ethyl methacrylate, addition polymerizable compound having carbon-carbon double bond such as vinyl ketone, maleimide, styrene and acrylonitrile, natural high content such as chitin, chitosan and cellulose. Molecules are included. The hydrophilic component referred to in the present invention is a homopolymer having a solubility in water at 25 ° C. of 50% by weight or more. As the hydrophilic component,
For example, heparin, vinyl alcohol, vinylpyrrolidone, alkylene glycols such as ethylene glycol and propylene glycol, hydroxyethyl methacrylate,
Acrylamide, hydroxyethyl acrylate, etc. are applicable, but not limited to these.
It should be noted that the homopolymer used as the criteria for determining hydrophilicity and hydrophobicity is an uncrosslinked polymer having a weight average molecular weight of 10,000 by the GPC method in terms of polystyrene.

The stain-resistant polymer is composed of a hydrophilic component and a hydrophobic component as described above and may have stain-resistant property. Specific stain-resistant polymers include, for example, heparin. -Polyvinyl chloride, heparin-polystyrene, heparin-polymethyl methacrylate, heparin-polyacrylonitrile, heparin-silicone, heparin-cellulose, polyhydroxymethyl methacrylate-polyvinyl chloride, polyhydroxymethyl methacrylate-polystyrene, polyvinylpyrrolidone-polyvinyl chloride , Polyvinylpyrrolidone-polystyrene, polyvinylpyrrolidone-polymethylmethacrylate, polyvinylpyrrolidone-polyacrylonitrile, polyvinylpyrrolidone-silicone, polyvinylpyrrolidone-cellulose, polyvinylpyrrolidone Pyrrolidone - polysulfone, polyalkylene oxide - polyvinyl chloride, polyalkylene oxide - polystyrene, polyalkylene oxide - polymethylmethacrylate, polyalkylene oxide -
There are combinations of polyacrylonitrile, polyalkylene oxide-silicone, polyalkylene oxide-cellulose, etc., which are preferable because excellent stain resistance can be obtained.

As a method for synthesizing a stain resistant polymer comprising a hydrophilic component and a hydrophobic component, a method of copolymerizing a hydrophilic monomer or a hydrophobic monomer as a polymerization component, and a polymer such as cellulose or a synthetic polymer are used. Although there is a method of synthesizing a polymer or a monomer by reacting it, it is usually preferred because the method of copolymerizing the monomer is simple. The copolymerization method is not particularly limited, and the method of polymerizing in a solvent using a usual radical initiator such as azobisisobutyronitrile or benzoyl peroxide is simple and is preferably used.

Among the hydrophilic components, alkylene glycol is particularly preferable, and a macromonomer having a polyethylene oxide unit bonded to a reactive double bond chain is preferable because it has a high stain resistance and a copolymer can be easily obtained. Used.

In the present invention, a macromonomer having a polyethylene oxide unit having a degree of polymerization of 5 or more and a polymerizable carbon-carbon double bond in the same molecule is preferably used. Examples of such a monomer include those represented by the general formula: (1)

[0016]

[Chemical 1]

(Where n ≧ 5, R ₁ is H or C
H ₃ and R ₂ are a hydroxyl group, an alkoxy group having 1 to 4 carbon atoms, or acrylic acid or methacrylic acid ester represented by OCHφ ₂ (φ is a phenyl group), or the general formula (2).

[0018]

[Chemical 2]

(Where n ≧ 5, R ₁ is H or C
It is a vinyl monomer represented by H ₃ ).

Methods for producing these addition-polymerizable compounds are known, and the polymerizable carbon-carbon double bond allows easy polymerization without using any special equipment or technique, and further, other monomers or macromonomers. It is also possible to copolymerize with
A polymer composition having a polyethylene oxide unit can be formed efficiently and reproducibly. In particular, the component represented by the formula (1) is preferably used because it is easily available. The content of polyethylene oxide in the copolymer can be confirmed by a usual method such as elemental analysis, infrared absorption spectrum and nuclear magnetic resonance spectrum.

The non-contamination resistant material referred to in the present invention is a material made of a hydrophobic material and has a function as a strength retaining material when a film is formed. 5 as impurities
The hydrophilic component may be contained in an amount of 1% by weight or less, but preferably 1% by weight or less.

Non-stain resistant hydrophobic materials are preferably used as blend materials with the stain resistant composition for the purpose of the present invention to concentrate the stain resistant components on the liquid contact surface.
This is because by utilizing the phase separation phenomenon between polymers,
This is because the stain resistant component can be made to exist at a high concentration on the liquid contact surface. Further, the non-contamination-resistant hydrophobic material also functions as a strength-retaining material, and is preferable also in the sense of maintaining the strength of the film.

In the present invention, "a composition obtained by mixing two or more kinds of stain resistant polymers comprising a hydrophilic component and a hydrophobic component" means a mixture of two or more kinds of polymers having different contents of the hydrophobic component in the polymer. In this composition, the compounds constituting the hydrophilic component and the hydrophobic component may be the same or different. Further, by devising the synthesis method, it is possible to obtain the composition of the present invention by synthesizing once without mixing two or more kinds of polymers, but the maximum content of the hydrophobic component is And polymers having a minimum value difference of 5% by weight or more correspond to the composition of the present invention. "The difference between the maximum value and the minimum value of the content ratio of the hydrophobic component is 5% by weight or more."
Means that the weight content ratio of the hydrophobic component in each of the two or more polymers is measured, and the difference between the maximum value and the minimum value in the content ratio is 5% by weight or more.
However, for polymers in which the difference in the weight content of the hydrophobic components in the polymers to be mixed is less than 1% by weight, the total weight of the polymers is less than 1% by weight in the total polymer composition after mixing, the maximum here. It is not included in the target polymer that is the value or the minimum value.

When a conventional polymer having no difference in the content ratio of the hydrophobic component is used, when the polymer is blended with a hydrophobic non-staining material and molded, the same component as the polymer blended in the stain-resistant polymer is used. In many cases, they are not compatible with each other even when they are contained, and in many cases they are phase-separated even when both are dissolved in a solvent and used. In such a state, a uniform molded product could not be formed. However, as described above, by using the composition of the present invention having a difference in the content of the hydrophobic component of 5% by weight or more, even if the average amount of the hydrophilic component is the same, the content of the hydrophobic component is Since the difference can be appropriately selected, the affinity between the polymer having a high content of hydrophobic components in the stain-resistant polymer composition and the non-stain-resistant material is increased, and the polymer is stable in a compatible or semi-compatible state. It is possible to form a molded body or a mixed solution. Among them, the non-stain-resistant material and the stain-resistant polymer composition of the present invention, when the average value of the hydrophobic component content is the same, the compatibility is particularly excellent, a stable and stain-resistant film Is obtained.

The composition of the present invention may be a mixture of only two kinds of polymers having different contents of the hydrophobic component,
If the compositions of the polymers to be mixed are too far apart, the compatibility in the composition tends to deteriorate, so it is preferable to mix as much of the composition as possible, and the content of the hydrophobic component is continuously different. Preferably.

As described above, the stain-resistant polymer composition of the present invention having a difference in the content of the hydrophobic component has a composition having a high affinity with the non-stain-resistant material and a high hydrophilicity exhibiting a higher stain resistance. It is a polymer composition that has stain resistance because it has the same composition and has excellent compatibility with non-stain resistance materials.
Above all, it is preferable that at least a part thereof contains a stain resistant polymer having a content of the hydrophobic component of 50% by weight or more, since the affinity for the non-stain resistant material is excellent. Furthermore, the content of the hydrophobic component is at least 70% by weight.
It is more preferable to include the above polymers.

A mixture of polymers can be obtained by mixing several kinds of polymers having different compositions, but it can be conveniently prepared by changing the feeding rate of the monomers for polymerization or by utilizing the difference in the reactivity of the monomers. A mixture having a uniform composition distribution is obtained. Next, the method will be described.

First, the method of polymerizing by changing the monomer supply rate is a method of polymerizing by continuously or intermittently supplying at least one component of the monomer into the polymerization solution. For example, in the case of obtaining a copolymerized polymer composed of A and B2 components, a method may be mentioned in which only the A component is initially charged in the polymerization liquid and then the B component is continuously or intermittently supplied. Further, even when both components A and B are continuously fed, the intended copolymer polymer composition can be obtained by appropriately changing the feeding rate of both components.

Further, when the reactivity of the copolymerization component is different, it is possible to give the composition distribution without supplying the monomer during the polymerization. Assuming that the reaction rate of each component is the rate at which the monomer of each component is converted into a copolymer, the copolymer having a composition twice as much as B at the initial stage of polymerization in a system in which A is twice as fast as B. Although a polymer can be obtained, when the overall polymerization rate is near 100%, almost no A monomer remains, so a B homopolymer is obtained.

The composition of these reaction products can be calculated from the reactivity of each monomer by theoretical calculation of copolymerization, or the produced polymer is extracted with time from the reaction solution during the reaction, elemental analysis, infrared It can also be confirmed by analyzing the polymer composition obtained with time by a usual method such as an absorption spectrum or a nuclear magnetic resonance spectrum.
It is also possible to confirm the composition of the polymer obtained over time by quantifying the unreacted monomer in the reaction liquid during the reaction by gas chromatography and high performance liquid chromatography, and calculating the amount polymerized from this. .

The semipermeable membrane of the present invention can be preferably used for medical purposes by using an antithrombogenic polymer as the stain resistant polymer.

The antithrombotic property is a property of suppressing thrombus formation which occurs when the surface of the material is in direct contact with blood. The antithrombotic material is a material which suppresses adhesion of protein or platelets, that is, contamination. That is. As such an antithrombogenic material, the hydrophilic and hydrophobic stain resistant polymer composition of the present invention is preferably used. In this case, the blood-contacting surface after film formation has less adhesion of platelets to the glass plate corresponds to the “antithrombotic polymer” in the present invention. A Matsunami cover glass was used as the reference glass plate here. As a method for evaluating antithrombogenicity, a method of observing the amount of platelets, white blood cells, red blood cells and the deformed state on the material surface after contact with blood by scanning electron microscope (SEM) is well known.

When blood is flown into the hollow fiber in the form of a hollow fiber membrane, the time until the differential pressure at the membrane inlet or outlet increases due to clogging of the channel due to blood coagulation, or until the blood stops flowing, It can be evaluated by measuring. Whether or not the membrane has antithrombotic property is judged by comparison with the antithrombotic property of the membrane composed only of the hydrophobic component constituting the membrane.

As the solvent for the stock solution for film formation, any solvent capable of dissolving the polymer composition can be used, and for example, dimethylformamide, dimethylsulfoxide, dimethylacetamide, N-methylpyrrolidone and the like are preferably used. It is also possible to use an alternating mixture of these.

The copolymer dissolved in these solvents can be used by forming a film. These molding methods can be performed using known methods. For example, in the case of a flat film, the film-forming stock solution is cast on a glass plate in an atmosphere where the temperature and humidity are controlled, and a commercially available applicator is used to form a film having a required film thickness, followed by coagulation. Immersion in a bath and solidification desolvation can be performed to obtain the target membrane.

In hollow fiber membranes often used for artificial kidneys, artificial lungs, etc., an antithrombogenic surface without anticoagulant is especially required. Next, the hollow fiber membrane will be described in detail.

When the spinning dope is discharged from the spinneret, it is necessary to sufficiently consider not only the formation of a smooth thread but also the shape retention of the hollow fiber. The viscosity of the undiluted solution is an important factor for stable ejection, and therefore, the viscosity of the undiluted solution at the time of ejection can be adjusted by adjusting the die temperature. Usually, in the process, if no drawing is carried out, the coagulation bath determines the dimensions of the hollow fibers. When a hollow spinneret having a pore size larger than the target size is used, the so-called dry-wet spinning method, in which the spinning solution is once discharged into the air and then immersed in the coagulation desire and coagulated, is an effective means.

In order to retain the hollow fiber system, a liquid is injected into the hollow fiber. Examples of the liquid to be injected include a solvent of the spinning dope and a coagulant such as water or (polyhydric) alcohol or a mixture thereof.
Alternatively, a hydrophobic liquid such as a non-solvent for the copolymer or a mixture thereof, for example, an aliphatic hydrocarbon such as n-octane or liquid paraffin, or a fatty acid ester such as isopropyl myristate can be used.

When the discharged yarn is gelled due to temperature change in the air or rapidly solidified by solidification, an inert gas such as nitrogen gas or air is used by self-suction or press fitting. You can Such a gas injection method is a very advantageous method from the viewpoint of the process. In the case of a stock solution system that causes gelation due to temperature change, cold air can be blown in the dry portion to promote gelation.

The coagulation bath is usually composed of a coagulant such as water or (polyhydric) alcohol, or a mixture with a solvent constituting the spinning dope. The composition of the coagulation bath affects the spinning stability and the membrane structure of the hollow fiber depending on its coagulability. When the coagulation property with respect to the spinning dope is high, huge voids are generated in the membrane portion of the hollow fiber. Further, if the coagulability becomes low, it becomes difficult to maintain the hollow fiber form, so it is preferable to have an appropriate composition together with the characteristics of the stock solution. The temperature of the coagulation bath largely controls the coagulability of the coagulation bath, and is a significant factor in the permeability of the membrane. That is, the higher the bath temperature, the greater the permeability. Therefore, it is combined with the above coagulation bath composition under appropriate conditions for the target permeation performance.

After coagulation, after sufficient washing with water, the water inside the membrane structure is replaced with glycerin or ethylene glycol in order to prevent the membrane structure from being destroyed by drying the hydrated hollow fiber. Further, if necessary, a glycerin aqueous solution or the like may be used for heat treatment to impart dimensional stability.

The surface morphology of the hollow fiber membrane can be changed by appropriately selecting such spinning operation conditions, but if the polymer stock solution used is non-uniform, coagulation will be non-uniform and the membrane structure will be different. Also becomes uneven. In particular, when a stain resistant polymer composed of a hydrophilic component and a hydrophobic component and a hydrophobic non-stain resistant polymer are used in the spinning dope, the compatibility is usually poor and the film surface also has a non-uniform structure. However, a stain-resistant semipermeable membrane using a stain-resistant polymer and a non-stain-resistant polymer comprising the polymer composition of the present invention has a good compatibility with the stain-resistant polymer and the non-stain-resistant polymer, and thus is uniform. A simple surface structure can be easily obtained. The morphology of the surface structure can be observed with a scanning electron microscope (SEM). However, when discussing the surface state of a size of several hundred angstroms, if the kind of metal for the film and the deposition conditions are not sufficiently considered, the deposition material You will observe the structure of itself. In the observation of the present invention, platinum-palladium was used as the vapor deposition material, and the vapor deposition thickness was set to 100 angstroms or less.

When a film is prepared by blending incompatible polymers, either component can be selectively concentrated on the liquid contact surface depending on the film forming conditions. However, when a stain-resistant polymer that is usually composed of a hydrophilic component and a hydrophobic component and a hydrophobic non-stain-resistant polymer are used, the phase separation is too large, and there is a risk that the stain-resistant substance will elute. However, such a thing cannot be used for medical purposes, but the stain-resistant semipermeable membrane of the present invention has a high affinity between a highly hydrophobic stain-resistant polymer and a hydrophobic non-stain-resistant polymer. Therefore, there is no such problem.

The liquid contact surface in the present invention is a region of 20 nm or less from the surface in contact with the liquid, and the concentration of the stain resistant component in this region is measured by X-ray photoelectron spectroscopy (XPS) and secondary It can be confirmed by ion mass spectrometry (SIMS).

Such a material is used for a filter separation membrane for protein concentration, liquid sterilization, wastewater treatment, etc., and is particularly useful as a medical material that is in direct contact with blood, body fluid or living tissue. For example, it exhibits particularly excellent properties as a wound protection material, a membrane material such as an artificial kidney or an artificial lung, and a drug-immobilized or sustained-release base membrane.

Hereinafter, the present invention will be described in more detail by way of examples, but the present invention is not limited to these examples.

[0047]

【Example】

Example 1 Methoxy polyethylene glycol methacrylate "M9"
00G "(average degree of polymerization of ethylene oxide portion is 90,
After dissolving 48.5 parts by weight of a weight average molecular weight of 4060, manufactured by Shin-Nakamura Chemical Co., Ltd., hereinafter abbreviated as M900G) in 343 parts by weight of dimethyl sulfoxide (hereinafter abbreviated as DMSO), 113 parts of acrylonitrile (hereinafter abbreviated as AN). When
0.248 parts by weight of 2,2′-azobis-2,4-dimethylvaleronitrile (hereinafter abbreviated as ADVN) was added, and radical polymerization was carried out in a closed container under a nitrogen atmosphere at 41 ° C. for 48 hours. It was After polymerization, the residual monomer was extracted in 4 liters of methanol, and this was repeated 6 times, and then 3
It was dried under vacuum at 0 ° C. for 48 hours to obtain a stain resistant polymer composition.

This composition was confirmed to have an average M900G content of 30% by weight by elemental analysis of carbon, nitrogen and hydrogen. Also, by high performance liquid chromatography, the reactivity of each monomer during the polymerization was measured, and
The composition of a polymer mixture having a distribution of at least 50% by weight to 95% by weight in the content ratio of the PAN component is synthesized by measuring the composition of the polymer component during polymerization with time by elemental analysis. It was confirmed.

100 parts of this copolymer polymer composition and 66 parts of polyacrylonitrile having a weight average molecular weight of 600,000 by polystyrene-converted GPC method in which AN was polymerized in DMSO by a known method and dimethyl sulfoxide 94.
0 parts were mixed and stirred at 103 ° C. for 16 hours to prepare a spinning dope. The spinning solution was transparent to the naked eye.

Outer diameter / inner diameter = 0.6 /
From an annular slit type hollow base of 0.3 mmφ, 1.16
It was discharged into the air at a rate of g / min. At the same time, nitrogen gas was injected into the hollow at a pressure of 68 mmAq. Water at 31 ° C. was used for the coagulation bath. The amount of M900G units contained in the polymer of the obtained hollow fiber was 18% by weight.
The inner diameter / membrane thickness of the hollow fiber membrane was 306/34 μm, the water permeability was 100 ml / hr · mmHg · m ² , the water permeability in bovine plasma was 9.4 ml / hr · mmHg · m ² , and albumin leakage was observed. I couldn't do it.

Using the inner surface of the hollow fiber as a blood contact surface, the contents of oxygen, carbon and nitrogen at a depth of about 5 nm estimated from the surface were analyzed by X-ray photoelectron spectroscopy (XPS). From this result,
From the chemical structure of this example, the content of the hydrophilic component M900G component in the surface stain resistant composition was calculated to be 4
It was 5% by weight, which was a very high value compared to the average concentration of 18% by weight.

Secondary ion mass spectrometry (SIMS)
By measuring the concentration of carbon and oxygen ions in the depth direction from the surface, the M900G as shown in FIG.
Was obtained. At around 40 nm, the M900G concentration was lower than the lower concentration, but at a region closer to the inner surface than 20 nm, the M900G concentration was remarkably high, and the stain resistant composition was concentrated in the vicinity.

When the surface morphology in the film was observed by SEM, the size of the particulate structural unit was about 400 Å on average, and the surface was very smooth.

Using the membrane of this example, a blood filtration membrane module having a membrane area of 0.25 m ² was prepared by a known method, and an extracorporeal blood circulation test was carried out in dogs. In addition, the membrane was not blocked due to blood coagulation during the experimental time of 8 hours, and stable circulation was possible. When the membrane surface after the experiment was observed by SEM, no platelet adhesion was observed on the membrane surface, indicating excellent antithrombotic properties.

Example 2 29 parts of M900G was dissolved in 343 parts of DMSO and then A
N132.5 parts and ADVN 0.248 parts were added to obtain a polymer composition having an M900G content of 18% by weight in the same manner as in Example 1.

150 parts of this polymer composition and 850 parts of dimethylsulfoxide were mixed and stirred at 95 ° C. for 16 hours to prepare a spinning dope. The spinning solution was transparent to the naked eye.

Outer diameter / inner diameter = 0.6 /
1.2g from 0.3mmφ annular slit type hollow base
It was discharged into the air at a rate of / min. At the same time, nitrogen gas was injected into the hollow at a pressure of 74 mmAq. The inner diameter / thickness of the hollow fiber membrane is 328/127 μm, and the water permeability is 5
^{0ml / hr · mmHg · m 2} , permeability of bovine plasma is ^{8.2ml / hr · mmHg · m 2} , leakage of albumin was not observed.

When the change in the M900G concentration from the inner surface was examined by SIMS in the same manner as in Example 1, it was found that the structure was not such that M900G was remarkably aggregated on the inner surface as in Example 1, but the M900G concentration was gradually increased on the surface. High components were agglomerated. FIG. 2 shows the result of the concentration change of M900G by SIMS.

Comparative Example 1 A copolymerized polymer having a uniform composition was synthesized and compared. This polymer is polymerized by adding 27 parts by weight of M900G to D
After dissolving in 838 parts by weight of MSO, 143 parts by weight of AN and 0.3 part by weight of ADVN were added, and radical polymerization was carried out in a closed container under a nitrogen atmosphere at 41 ° C. for 4 hours. After polymerization, reprecipitation was carried out in 4 liters of water, and then residual monomer components were extracted 5 times with 4 liters of methanol and then 3
It was dried under vacuum at 0 ° C. for 48 hours to obtain an antithrombotic polymer composition.

100 parts of this copolymer polymer composition and 66 parts of polyacrylonitrile having a weight average molecular weight of 600,000 by polystyrene-converted GPC method in which AN was polymerized in DMSO by a known method and dimethyl sulfoxide 94
0 parts were mixed and stirred at 103 ° C. for 16 hours to prepare a spinning dope. In the spinning dope, unevenness that could be visually recognized as phase separation was observed.

Outer diameter / inner diameter = 0.6 /
1.2g from 0.3mmφ annular slit type hollow base
It was discharged into the air at a rate of / min. At the same time, nitrogen gas was injected into the hollow at a pressure of 74 mmAq. The hollow fiber membrane had an inner diameter / thickness of 318/30 μm and a water permeability of 51.
ml / hr · mmHg · m ² , water permeability in bovine plasma is 12
It was ml / hr · mmHg · m ² , and albumin leakage was not observed.

When the surface morphology of the film was observed by SEM,
The size of the particulate structural units averaged about 2000 angstroms and was a very rough surface.

Using the membrane of this example, a blood filtration membrane module having a membrane area of 0.25 m ² was prepared by a known method, and an extracorporeal blood circulation test was conducted in dogs without using an anticoagulant. However, within 4 hours, membrane occlusion due to blood coagulation occurred, and circulation became impossible.

[0064]

According to the present invention, the affinity between the stain resistant material and the non-stain resistant material such as the film strength holding material is improved, and the stain resistant component is concentrated on the liquid contact surface. It was possible to provide a semipermeable membrane composed of a polymer composition excellent in

[Brief description of drawings]

FIG. 1 is the M of the film surface obtained in Example 1 of the present invention.
It is drawing which shows the density | concentration change of 900G.

FIG. 2 is the M of the film surface obtained in Example 2 of the present invention.
It is drawing which shows the density | concentration change of 900G.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Ryozo Terada 1111 Tehiro, Kamakura City, Kanagawa Prefecture

Claims (3)

[Claims] 1. A semi-permeable membrane comprising at least one composition comprising a mixture of two or more stain resistant polymers comprising a hydrophilic component and a hydrophobic component, said two or more stain resistant polymers. In the semipermeable membrane, the difference between the maximum value and the minimum value of the content ratio of the hydrophobic component is 5% by weight or more. 2. A semipermeable membrane according to claim 1, which contains a non-staining resistant polymer as one constituent. 3. As a constituent monomer of a stain resistant polymer,
The semipermeable membrane according to claim 1 or 2, wherein a monomer having a polyalkylene oxide unit having a degree of polymerization of 5 or more and a polymerizable carbon-carbon double bond in the same molecule is contained.