JP2006124714A - Contamination resistant material and contamination resistant semipermeable membrane - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a contamination resistant material which is made of a hydrophilic material that is dissolved in a solvent, is molded easily, and is excellent in thrombus resistance and contamination resistance, and further a thrombus resistant material and a contamination resistant semipermeable membrane. <P>SOLUTION: The contamination resistant material is made of a hydrophilic material which is a copolymer of a monomer (A) having polyalkylene oxide units and polymerizable carbon-carbon double bonds in a molecule, a methacrylate monomer or an acrylate monomer (B), and another monomer (C) having polymerizable carbon-carbon double bonds other than (A) and (B), wherein the polymer contains the monomer (A) at a rate of 10% by weight or more and the monomer (C) at a rate of 5% by weight or more. The contamination resistant semipermeable membrane comprises the copolymer and a methacrylate polymer or an acrylate polymer. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a novel stain resistant material and a stain resistant semipermeable membrane. As an antithrombotic material, etc., it is suitably used in the medical field, and as a water-absorbing material, a stain-resistant member, etc.

  In recent years, application of polymer materials to industrial and medical fields has progressed, and many hydrophilic polymer materials have been used. In particular, polymer materials that are insoluble in water and absorbable water, various membranes that are permeable to substances, catheters, cannulae, sanitary materials, contact lenses, blood storage containers, blood circuits, cell culture substrates, or enzymes It has come to be used as inclusion materials such as pharmaceuticals or immobilization substrates. Furthermore, the material 1 is not limited to the medical field, and can be applied to various coating materials and food-related materials such as a carrier for electrophoresis and liquid chromatography, antifouling and antifogging.

  When used in such applications, contamination resistance is often an important factor in determining material durability and performance. In particular, when these membranes are used for medical purposes and come into contact with blood, body fluids, etc., adhesion of formed components such as platelets, leukocytes, erythrocytes, fibroblasts is inevitable, and these are in contact with blood. Possible effects on the surface of thrombus formation and the complement system. As a result, it is presumed to cause the formation of thrombus and a decrease in immune function.

As a method for solving these problems, a copolymer containing a hydrophilic polyethylene oxide chain has been invented (Patent Document 1), and a selectively permeable hollow fiber comprising a copolymer containing an ethylene oxide chain has also been invented. (Patent Document 2). It has also been found that a semipermeable membrane comprising an acrylonitrile copolymer containing a hydrophilic polyethylene oxide chain and acrylonitrile is excellent in solute permeability and contamination resistance (Patent Document 3). Furthermore, a plasma separation membrane excellent in blood compatibility, which consists of a mixture of a copolymer containing an ethylene oxide chain and an isotactic methyl methacrylate polymer, was also invented.
Japanese Unexamined Patent Publication No. 57-164064 JP 60-22901 A JP 63-130103 A

  However, when synthesizing a copolymer containing a hydrophilic polyalkylene oxide chain, when copolymerized with acrylic acid or methacrylic acid ester, when the content of polyalkylene oxide in the copolymer component is large, Regardless of the type of acrylic acid or methacrylic acid ester, the produced copolymer is in a gel state and has a problem that it is difficult to dissolve in a solvent. In such a case, it cannot be used as a coating material or formed into a thread or film.

  Even when the content of polyalkylene oxide is low, the water content of the copolymer with acrylic ester or methacrylic ester is lower than that of the copolymer with, for example, polyacrylonitrile, and as a result, sufficient contamination resistance Sex and antithrombotic properties could not be obtained. As a result of diligent research to improve this gel structure, we can easily dissolve it in a solvent by copolymerizing acrylic ester or methacrylic ester, polyalkylene oxide and other copolymerizable components. Thus, a polymer having a high water content and a high affinity with acrylic acid ester or methacrylic acid ester has been obtained.

  An object of the present invention is to provide a stain-resistant material comprising a hydrophilic material that dissolves in a solvent, is easy to mold, and is excellent in anti-thrombotic stain resistance. And providing a stain-resistant semipermeable membrane.

In order to achieve the above object, the present invention has the following configuration.
That is, a monomer (A) having a polyalkylene oxide unit and a polymerizable carbon-carbon double bond in the same molecule, a methacrylic acid ester monomer or an acrylic acid ester monomer (B), and the (A ), A copolymer having a monomer (C) having a polymerizable carbon-carbon double bond other than (B) as a constituent monomer, wherein the content ratio of the monomer (A) is The present invention relates to a contamination-resistant material comprising a hydrophilic material, characterized in that it is 10% by weight or more and the content ratio of the monomer (C) is 5% by weight or more.

  Furthermore, a monomer (A) having a polyalkylene oxide unit and a polymerizable carbon-carbon double bond in the same molecule, a methacrylic acid ester monomer or an acrylic acid ester monomer (B), and ( A) a copolymer comprising a monomer (C) having a polymerizable carbon-carbon double bond other than (B) as a constituent monomer, wherein the copolymer of the monomer (A) A copolymer having a content of 10% by weight or more in the polymer and a content of the monomer (C) in the copolymer of 5% by weight or more, a methacrylic acid ester polymer or The present invention relates to a stain-resistant semipermeable membrane comprising an acrylate polymer.

  According to the present invention, a material and a semipermeable membrane excellent in contamination resistance can be obtained. In particular, the contamination resistant semipermeable membrane can be usefully used as a medical material in direct contact with blood, body fluid, or biological tissue. For example, a particularly excellent performance can be exhibited as an artificial kidney, an artificial lung, an artificial liver, or the like.

In the following, the present invention will be described in detail along with preferred embodiments.
In the present invention, the monomer (A) having a polyalkylene oxide unit and a polymerizable carbon-carbon double bond in the same molecule is not particularly limited. For example, the following general formula (1) ( It consists of a monomer represented by Chemical formula 1).

In the above formula, n is an integer of 5 or more, R ₁ is H or CH ₃ , R ₂ is a hydroxyl group, a C ₁ -C ₄ alkoxy group, and OCHφ ₂ (φ is a phenyl group), and R ₃ represents alkylene.

  A known method can be used for the production of these addition-polymerizable compounds. The polymerizable carbon-carbon double bond can be easily polymerized without using a special apparatus or method. Alternatively, it can be copolymerized with a macromonomer, and a polymer composition having a polyalkylene oxide unit can be formed efficiently and reproducibly.

  In order to express the effect of the polyalkylene oxide unit more strongly, the average degree of polymerization of the polyalkylene oxide unit in this monomer is preferably 5 or more, more preferably 15 or more. Among the polyalkylene oxide units, polyethylene oxide units, polypropylene oxide units, and polyisopropylene units are preferable. Moreover, the chain part which consists of a polyalkylene oxide unit in a monomer may be a mixture of a plurality of different types of alkylene oxide units. In this case, a chain in which polyethylene oxide units and polypropylene oxide units are alternately polymerized can be exemplified.

  The polyalkylene oxide content in the monomer and the average degree of polymerization of the polyalkylene oxide unit can be confirmed by ordinary techniques such as elemental analysis, infrared absorption spectrum, nuclear magnetic resonance spectrum, and gel permeation chromatography.

  Among the monomers (A) having a polyalkylene oxide unit and a polymerizable carbon-carbon double bond in the same molecule, the monomer represented by the formula (1) is preferably used because it is easily available. It is done. Of these, methoxypolyethylene glycol methacrylate is particularly preferred for industrial use and has high hydrophilicity.

  The content of the monomer (A) in the copolymer is preferably 10% by weight or more, and more preferably 20% by weight or more, in order to develop stain resistance.

  Examples of the methacrylic acid ester monomer or the acrylate monomer (B) include, for example, methyl acrylate, ethyl acrylate, propyl acrylate, butyl acrylate, lauryl acrylate, 2-ethylhexyl acrylate, and cyclohexyl acrylate. , Acrylate esters such as benzylid acrylate, methacrylate esters such as methyl methacrylate, ethyl methacrylate, propyl methacrylate, butyl methacrylate, lauryl methacrylate, 2-ethylhexyl methacrylate, cyclohexyl methacrylate, benzylid methacrylate Can be illustrated. The monomer (B) may be a mixture of these esters.

  This monomer (B) is used for the purpose of synthesizing a copolymer insoluble in water by copolymerizing with the monomer (A). Moreover, by using this monomer (B), it becomes possible to satisfactorily blend or coat a material having a high affinity with the monomer (B).

  As the monomer (C) having a polymerizable carbon-carbon double bond other than the above (A) and (B), addition having a carbon-carbon double bond other than a methacrylic acid ester or an acrylate monomer. Any polymerizable compound may be used, olefins such as ethylene and propylene, vinyl halides such as vinyl chloride and vinyl fluoride, vinyl esters such as vinyl formate and vinyl acetate, aromatic vinyls such as vinyl ketone, maleimide, styrene, and methylstyrene. Examples thereof include addition polymerizable compounds having a carbon-carbon double bond, such as a compound, acrylonitrile, methacrylonitrile, vinyl pyrrolidone, vinyl alcohol, and acrylamide.

  Among these, vinyl esters such as vinyl formate and vinyl acetate, vinyl ketone, maleimide, styrene, acrylonitrile, and methacrylonitrile are preferable because they are easily polymerized and have a high effect of preventing gelation.

  This monomer (C) suppresses the gelation that occurs when the monomer (A) and the monomer (B) are copolymerized, and has a high water content that is insoluble in water and soluble in other solvents. It is used for the purpose of synthesizing the copolymer. Moreover, by having this monomer (C), gelatinization is suppressed and it becomes possible to have high stain resistance. In the case of containing the same amount of monomer (A), the water content increases according to the content of monomer (C), and the effect of stain resistance, which is a feature of the present invention, is also enhanced. The moisture content mentioned here is the weight moisture content in the saturated hydrous polymer at 30 ° C. For this purpose, it is necessary for the monomer (C) to be contained in the copolymer in an amount exceeding 5% by weight on average. In order to obtain high stain resistance, the copolymer preferably contains 10% by weight or more. On the other hand, when the content of the monomer (C) is too high, the effects of the monomer (A) and the monomer (B) are lost, so that the contamination resistance and affinity with other materials are lowered. For this reason, the content of the monomer (C) needs to be less than 90% by weight on average. Preferably it is 50 weight% or less.

  Moreover, monomers other than the monomer (A), the monomer (B), and the monomer (C) can also be used as a copolymerization component depending on the purpose of use. Since the copolymer tends to dissolve in water, such as when the monomer (A) content is high and the molecular weight is low, a crosslinking monomer may be added as necessary in such cases. And a moderately crosslinked polymer may be obtained. Such a crosslinking monomer is not particularly limited, but a monomer containing at least two polymerizable carbon-carbon double bonds in the molecule, for example, ethylene glycol dimethacrylate, diethylene glycol dimethacrylate, Polyethylene glycol dimethacrylate, divinylbenzene, methylenebisacrylamide and the like are preferably used. The amount of the crosslinking monomer is determined by the type of monomer component, the crosslinking state, and the purpose of use, and is not limited, but is preferably 10% by weight or less in order not to change the characteristics of the present invention.

  The method for synthesizing the copolymer of the present invention is not particularly limited, and copolymerization is carried out in a solvent using an ordinary radical initiator such as azobisisobutyronitrile, azobisdimethylvaleronitrile, benzoyl peroxide, or the like. The method is simple and preferred.

  The molecular weight of the copolymer may be appropriately adjusted according to the purpose of use, and is not particularly limited. When copolymerization is performed using a radical initiator, the temperature, initiator concentration, monomer concentration in the solution, and the like can be arbitrarily adjusted.

  These reaction products can be confirmed by extracting the produced polymer from the reaction solution during the reaction and confirming by ordinary techniques such as elemental analysis, infrared absorption spectrum and nuclear magnetic resonance spectrum (NMR). The copolymer composition can also be confirmed by quantifying the unreacted monomer in the reaction solution by gas chromatography or high performance liquid chromatography. The molecular weight of the copolymer can be easily confirmed by techniques such as gel permeation chromatography and viscosity method since the copolymer is soluble in a solvent.

  In addition to molding by casting polymerization, melt molding, solvent casting or dipping method, polymer molding is blended with various synthetic resins such as soft polyvinyl chloride, polyurethane, polydimethylsiloxane, etc., coating on the surface, etc. It is appropriately selected according to the desired property and shape.

  As the solvent when used as a solution, any solvent capable of dissolving the copolymer can be used. For example, dimethylformamide, dimethyl sulfoxide, dimethylacetamide, N-methylpyrrolidone, tetrahydrofuran and the like are preferably used. It is also possible to use an alternating mixture of these.

  Copolymers dissolved using these solvents can be used by coating, cloth-making and film-forming. 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 under an atmosphere controlled in temperature and humidity, and after the film is formed to a required film thickness using a commercially available applicator, the film is solidified. Immerse in the bath and perform the coagulation film solvent to obtain the target film. Also in this case, it is preferable to select appropriate conditions since the film forming stock solution, the coagulation bath, the post-treatment, etc. affect the film forming performance.

  Contamination resistance, which is a feature of the hydrophilic material in the present invention, means that concentration of various protein solutions, sterilization of liquid foods, or suppression of adhesion of solute components to the membrane surface during ultrafiltration separation in wastewater treatment processes. It is a property to do. In addition, when used for medical purposes, contamination resistance includes suppression of adhesion of formed components such as platelets, white blood cells, red blood cells, fibroblasts due to contact with blood or body fluids. On the other hand, the property of suppressing thrombus formation that occurs when the material and blood are in direct contact is said to be antithrombotic. Thrombus formation is often used as an index for evaluating the antithrombogenicity of materials. Further, in the evaluation of biocompatibility of a material that comes into contact with blood, thrombus formation is a typical characteristic evaluation point. On the other hand, as a means to evaluate only antithrombogenicity, scanning electron microscope observation of extracorporeal circulation time, blood flow volume, and the amount of platelets, white blood cells, red blood cells on the material surface after contact with blood, and deformation state A method of observing with (SEM) is well known. These biocomponent non-adhesive materials can be usefully used particularly as medical materials, such as wound protection materials, membrane materials such as artificial kidneys or artificial lungs, drug-immobilized or sustained-release base materials, eyes, and the like. It exhibits particularly excellent performance as an inner lens, a blood vessel endoscope, various catheters that require blood compatibility, cannula, blood vessel indwelling needle, blood storage container, blood pumping chamber, carrier for affinity adsorption, and the like.

Hereinafter, the contamination-resistant semipermeable membrane of the present invention will be described in detail.
The semipermeable membrane of the present invention is obtained by forming a film by mixing the above-mentioned copolymer and a methacrylic acid ester polymer or an acrylic acid ester polymer. Examples of the methacrylic acid ester or acrylic acid ester polymer that can be used in this case include methyl acrylate, ethyl acrylate, propyl acrylate, butyl acrylate, lauryl acrylate, 2-ethylhexyl acrylate, cyclohexyl acrylate, Polymers composed of acrylic esters such as benzil acrylate, methacrylic acid such as methyl methacrylate, ethyl methacrylate, propyl methacrylate, butyl methacrylate, lauryl methacrylate, 2-ethylhexyl methacrylate, cyclohexyl methacrylate, benzylid methacrylate An example of the polymer is an ester. The polymer may be a mixture of these polymers or a copolymer thereof. Further, it may be a copolymer containing a small amount of copolymerizable components other than methacrylic acid esters and acrylic acid esters, but in order to have transparency as a semipermeable membrane, methacrylic acid esters and acrylic acid esters. The content of is preferably 70% by weight or more. Examples of copolymerizable components other than methacrylic acid esters and acrylic acid esters include monomers or polymers having an anionic group such as parastyrene sulfonic acid soda. In this case, copolymerization of a monomer or polymer having an anionic group with methacrylic acid ester or acrylic acid ester increases the permeability of low molecular weight substances, and the transmission of large molecular weight substances due to finer pores. We can expect to be able to prevent it. The methacrylic acid ester or acrylic acid ester polymer is mainly used by mixing with the above-mentioned copolymer having stain resistance in order to reinforce the strength of the film. In order to further increase the film strength, in this polymer, it is also preferable to use a polymer having an isotactic structure and a polymer having a syndiotactic structure at the same time to form a stereocomplex. The structure of the polymer can be confirmed by NMR.

  When blending and molding different types of polymers, they are often incompatible, and even when both are dissolved in a solvent, they are often phase separated. In such a state, a uniform molded body is formed. Can not. However, in the present invention, by selecting and using a methacrylic acid ester or an acrylic acid ester polymer, it is possible to form a stable molded body or mixed solution in a compatible or semi-compatible state. For this reason, it is preferable that the methacrylic acid ester or acrylic acid ester polymer has a high affinity with the copolymer having stain resistance. In particular, the polymer comprising the component (B) in the copolymer is a copolymer. It is preferable because of its excellent affinity with the component (B) in the coalescence.

  In addition, it is allowed to use components other than the copolymer and the methacrylic acid ester or acrylic acid ester polymer as long as the performance of the present invention, which is excellent in stain resistance, is not impaired. For example, a case where a polymer used as a pore forming agent at the time of film formation remains in the semipermeable membrane even after the film formation is considered.

  As a method for obtaining a semipermeable membrane, for example, a method of forming a fine membrane after performing melt spinning, or forming a film after dissolving a polymer in a solvent or mixing with a pore forming agent, and removing the solvent or pore forming agent. Is used.

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

  These film forming 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 under an atmosphere controlled in temperature and humidity, and after the film is formed to a required film thickness using a commercially available applicator, the film is solidified. Immerse in a bath and perform coagulation desolvation to obtain the target membrane. In this case, it is preferable to select appropriate conditions since the film forming stock solution, the coagulation bath, and the post-treatment affect the film forming performance.

  The hollow fiber membranes often used for artificial kidneys, artificial lungs and the like will be described in more detail. When discharging the spinning dope from the die, it is necessary to fully consider the maintenance of the hollow fiber shape as well as the smooth yarn formation. In order to discharge stably, the viscosity of the stock solution is an important factor. For this reason, the stock solution viscosity at the time of discharge can be adjusted by adjusting the die temperature. Usually, when drawing is not performed in the process, the size of the hollow fiber is almost determined by the coagulation bath. When using a hollow die having a pore size larger than the target size, a so-called dry-wet spinning method in which the spinning solution is once discharged into the air and then immersed in a coagulation bath and solidified is an effective means.

  In order to maintain the hollow fiber system, a liquid is injected into the hollow fiber. Examples of the liquid to be injected include a hydrophobic solvent such as a solvent of the spinning solution and a coagulant such as water and (polyhydric) alcohol, or a mixture thereof, or a non-solvent of the copolymer or a mixture thereof. Liquids such as n-octane, aliphatic hydrocarbons such as liquid paraffin, and fatty acid esters such as isopropyl myristate can also be used. When a hydrophilic coagulant is used, a hydrophilic polymer component having a high affinity for the coagulant moves to the inner surface of the film and solidifies.

  In addition, when the discharge yarn is gelled by a temperature change in the air or a solid structure is quickly formed by solidification, an inert gas such as nitrogen gas or air can be used by self-suction or press-fitting. Such a gas injection method is a very advantageous method from the viewpoint of the process. In the case of an undiluted solution system in which gelation is caused by temperature change, gelation can be promoted by blowing cold air in the dry part.

  In this case, the length of the hollow part, the so-called dry part, is 30 mm or more. In addition, it is desirable to shorten the length of the dry part when it is intended to maintain the hollow fiber form only by coagulation with a stock solution that does not gel or undergo a sudden increase in viscosity due to temperature changes. If the length of the dry section is too long, it becomes a hollow fiber with a small hollow ratio (ratio of the inner diameter to the outer diameter), and when the injection pressure is increased, local swelling occurs before the target hollow ratio is reached. End up. If it is too short, drastic drafting will be applied and spinning will become unstable, so the length of the dry part is usually set in the range of 1 mm to 100 mm, preferably 3 mm to 50 mm.

  In the case of such a gas injection method, the polymer component does not move to the inner surface during solidification, unlike the liquid injection method, but a non-uniform structure is formed near the surface of several tens of nanometers by the polymer blend technique of the present invention. It is formed. The measurement of the surface component can be confirmed by X-ray photomolecular spectroscopy (XPS) and secondary ion mass spectrometry (SIMS).

  The coagulation bath usually consists of a mixture with a coagulant such as water or (polyhydric) alcohol, or a solvent constituting the spinning dope. The composition of the coagulation bath has a great influence on the spinning stability and the membrane structure of the hollow fiber depending on the coagulation property. When the coagulation property is high with respect to the spinning dope, huge voids are generated in the membrane portion of the hollow fiber. Moreover, since it becomes difficult to maintain the hollow fiber form when the coagulation property is lowered, it must be combined with the stock solution characteristics to have an appropriate composition. The temperature of the coagulation bath largely dominates the coagulation property and is a significant factor in the permeability of the membrane. That is, the permeability increases as the bath temperature increases. For this reason, it combines with the said coagulation bath composition on suitable conditions with respect to the target permeation | transmission performance. After coagulation, after sufficient washing with water, water in the membrane structure is replaced with glycerin or ethylene glycol to prevent the water-containing hollow fiber from being damaged by drying. Furthermore, if necessary, heat treatment can be performed using a glycerin aqueous solution or the like to impart dimensional stability.

  Such a contamination-resistant semipermeable membrane can be usefully used as a medical material that is in direct contact with blood, body fluid, or biological tissue, and is particularly excellent as an artificial kidney, an artificial lung, an artificial liver, or the like. It demonstrates performance.

  Hereinafter, although an Example demonstrates in more detail, this invention is not determined by these Examples.

Example 1 and Comparative Example 1
Methoxypolyethylene glycol methacrylate "M900G" (average degree of polymerization of ethylene oxide part 90, weight average molecular weight 4060, manufactured by Shin-Nakamura Chemical Co., Ltd., hereinafter abbreviated as M900G) 20 parts by weight, methyl methacrylate (hereinafter abbreviated as MMA) 20 parts by weight After dissolving 10 parts by weight of styrene (hereinafter abbreviated as St) and 50 parts by weight of methanol, 0.1 part by weight of 2,2′-azobis-2,4-dimethylvaleronitrile (hereinafter abbreviated as ADVN) was added. Then, radical polymerization was carried out in a sealed container under a nitrogen atmosphere at 55 ° C. for 24 hours. After the polymerization, residual monomers were extracted in 4 liters of water and methanol, and this was repeated 6 times, followed by drying in a vacuum state at 30 ° C. for 48 hours to obtain a hydrophilic component-containing copolymer.

  At this time, the amount of unreacted MMA, St, and M900G during polymerization was quantitatively determined by high performance liquid chromatography over time, and the amount of unreacted monomer decreased from the time when all three components had a low polymerization rate. I confirmed that

  The yield of the obtained polymer was 97% by weight, and it was confirmed that the polymerization was almost completed. Here, since the polymer of M900G alone is water-soluble and this yield is high, it can be demonstrated that M900G, MMA, and St are copolymerized.

  The obtained copolymer could be dissolved in tetrahydrofuran, dimethyl sulfoxide (hereinafter abbreviated as DMSO) and the like. This solution was transparent even when confirmed with a 400 × phase contrast microscope. In the PMMA, PSt, and M900G polymer mixture having the same composition, sea-island-like phase separation is confirmed from the incompatibility of single polymers, indicating that a copolymer is synthesized in this example.

  The composition of the hydrophilic component-containing copolymer could be measured by NMR analysis. FIG. 1 shows the NMR data. The composition ratio of the copolymer calculated from this result is almost equal to the charged weight composition. From this, it was confirmed that the polymer obtained by this polymerization method was equal to the composition obtained in order to polymerize to a high polymerization rate in a closed container. Moreover, it was also confirmed by magnifying analysis of the carboxyl group part of PMMA that MMA and St unit were randomly copolymerized. The water content of the polymer was 50% by weight. These analyzes confirmed that the hydrophilic component-containing copolymer of the present invention could be synthesized.

The antithrombogenicity of this composition was confirmed by the following method.
A glass plate in which 15 parts by weight of the obtained copolymer was dissolved in 85 parts by weight of dimethyl sulfoxide at 105 ° C. was attached with a spacer having a thickness of 100 μm (two tapes manufactured by Scotch Corporation) and kept at 105 ° C. The solution was dropped into a flat film and stretched with a stainless steel rod. Before the solvent evaporated, this glass plate was placed in water at 30 ° C. to form a porous film. The produced porous film was sufficiently washed with water.

  This porous membrane was immersed in platelet-rich platelet plasma (hereinafter abbreviated as PRP) at 37 ° C. for 3 hours, and the platelets adhering to the membrane surface were observed with a scanning electron microscope. Here, PRP is collected from the carotid artery using a syringe containing 1/10 volume of 3.8% sodium citrate solution for whole blood, and then immediately transferred to a siliconized test tube. The one obtained by centrifuging at 800 to 1000 rpm for 8 to 15 minutes was used. The platelet count was adjusted to 200,000 / μl or more. As a comparison and control material, a glass plate showing the most stable platelet adhesion was used. The platelet adhesion state in the present invention was relatively evaluated using the criteria shown in Table 1. In SEM photographs, materials with less platelet adhesion and deformation than PMMA and glass plates can be said to have excellent antithrombogenic properties, but for practical application as antithrombogenic membranes, coating materials, and molding materials. Antithrombogenicity at levels 3 and 4 in the figure is preferred. The results obtained in Example 1 are shown in FIG. 2, and the results of Comparative Example 1 are shown in FIG. As a result, it was found that platelet adhesion to the membrane using the polymer of the present invention was remarkably reduced.

Example 2
The same conditions as in Example 1, except that 20 parts by weight of M900G, 20 parts by weight of MMA, 10 parts by weight of vinyl acetate and 50 parts by weight of methanol were dissolved and 0.1 part by weight of azobisdimethylvaleronitrile (hereinafter abbreviated as ADVN) was added. Then, polymerization and purification were performed to obtain a hydrophilic component-containing copolymer. As in Example 1, it was confirmed that a copolymer having the same composition as the charged weight was obtained. The antithrombogenic level of the membrane formed by the same method as in Example 1 was 3. The water content of the polymer was 60% by weight.

Example 3
After dissolving 20 parts by weight of M900G, 20 parts by weight of MMA and 10 parts by weight of vinyl acetate, 0.1 part by weight of azobisdimethylvaleronitrile (hereinafter abbreviated as ADVN) was added, and polymerization was started under the same conditions as in Example 1. When the overall polymerization rate reached 40 wt%, the polymer solution was precipitated in water and purified to obtain a hydrophilic component-containing copolymer.

  The composition of this composition was measured by NMR (the chart is shown in FIG. 4) and confirmed to be M900G 38% by weight, MMA 36% by weight, and vinyl acetate 28% by weight. The water content was 71% by weight.

  A solution prepared by dissolving 1.5 parts by weight of the obtained copolymer and 13.5 parts by weight of polymethyl methacrylate (hereinafter abbreviated as PMMA) in 85 parts by weight of dimethyl sulfoxide at 105 ° C. was formed in the same manner as in the example. . In this example, a film was formed from a blend of two types of polymers, but the film forming property was good because an appropriate amount of the PMMA component was contained in both polymers. The antithrombogenic level of the membrane using this polymer was 4.

Comparative Example 2
After dissolving 20 parts by weight of M900G, 30 parts by weight of MMA, and 50 parts by weight of methanol, 0.1 part by weight of ADVN was added, and polymerization and purification were performed under the same conditions as in Example 1 to obtain a hydrophilic component-containing copolymer. The moisture content of the polymer was lower than the examples of the present invention containing the same amount of M900G as 43% by weight. Since this polymer did not contain the monomer (C) referred to in the present invention, it was not completely dissolved in the solvent. When a film was formed by removing the undissolved portion from the solution, the amount of platelet adhesion in the case of using a glass plate in Comparative Example 1 was the same.

Examples 4-12, Comparative Example 3
M900G, MMA and acrylonitrile (hereinafter abbreviated as AN) were each dissolved in 50 parts by weight of methanol and 50 parts by weight of methanol, and then 0.1 part by weight of ADVN was added. Purification was performed to obtain a hydrophilic component-containing copolymer.

  The water content of these compositions was measured in the same manner as in Example 1 after confirming that a copolymer equivalent to the charged weight composition was obtained. It can be seen that the moisture content increases as the AN content increases for the same M900G amount.

  A film was formed in the same manner as in Example 3, and antithrombogenicity was evaluated. As the amount of AN increased, the holes in the membrane increased and the film-forming property tended to deteriorate, but the film-forming property was sufficiently practical. In Examples 4 to 12, all exhibited excellent antithrombogenicity.

  The polymer obtained in Comparative Example 3 had a low monomer (C) content and was gel-like, but almost dissolved in the solvent. And although the platelet adhesion to a film | membrane decreased slightly compared with the comparative example 2, compared with an Example, platelet adhesion was many and it was not the level which can be put into practical use as an antithrombotic material.

Comparative Example 4
12 parts by weight of M900G, 18 parts by weight of PAN and 70 parts by weight of methanol were dissolved, 0.1 part by weight of ADVN was added, and polymerization and purification were performed under the same conditions as in Example 1 to obtain a hydrophilic component-containing copolymer. . As in Example 1, it was confirmed that a copolymer equivalent to the charged weight composition was obtained. The water content was 65% by weight. A film was formed in the same manner as in Example 3. However, since the copolymer and PMMA caused phase separation, the film forming property was remarkably poor and the film became brittle.

Example 13
After dissolving 20 parts by weight of M900G, 20 parts by weight of MMA, 10 parts by weight of ethyl vinyl ketone and 50 parts by weight of methanol, 0.1 part by weight of ADVN was added, and polymerization and purification were carried out under the same conditions as in Example 1 to obtain a hydrophilic component. A containing copolymer was obtained. As in Example 1, it was confirmed that a copolymer equivalent to the charged weight composition was obtained. The water content was 66% by weight. The amount of platelet adhesion on this membrane using this polymer was also significantly reduced.

Example 14, Comparative Example 5
100 parts by weight of the copolymer obtained in Example 1, 100 parts by weight of MMA in DMSO, 67 parts by weight of syndiotactic PMMA having a weight average molecular weight of 600,000 by polystyrene conversion GPC method and 600,000 in weight average molecular weight 33 parts by weight of isotactic PMMA and 570 parts by weight of dimethyl sulfoxide were mixed and stirred at 110 ° C. for 8 hours to prepare a spinning dope.

The obtained spinning dope was discharged into the air at a rate of 1.2 g / min from an annular slit-type hollow die having an outer diameter / inner diameter = 1.0 / 0.7 mmφ kept at 99 ° C. At the same time, nitrogen gas was injected into the hollow interior at a pressure of 47 mmAq. The length of the dry part was 60 mm, and water at 30 ° C. was used for the coagulation bath. After washing with water, 5% relaxation heat treatment was performed at 75 ° C. with 73% glycerin aqueous solution, and sampling was performed at 30 m / min. The amount of polyethylene oxide units contained in the obtained hollow fiber polymer was 15% by weight. Inner diameter / thickness of the hollow fiber membrane at 230/28 .mu.m, water permeability ^{54ml / hr · mmHg · m 2} , permeability of 5% albumin solution is ^{8.2ml / hr · mmHg · m 2} , rejection of 99%.

  This hollow fiber membrane was cut into a length of 10 cm, bundled 30 pieces, put into an 8 mmφ glass tube, and both ends were fixed with a resin to prepare a module. The whole blood of sputum was circulated on the inner surface of the hollow fiber of this module at 37 ° C. for 3 hours, and the amount of platelets adhering to the inner surface of the membrane was observed with a scanning electron microscope. As Comparative Example 5, a PMMA hollow fiber membrane manufactured by Toray Industries, Inc. was used. The results are shown in FIG. The platelet adhesion amount of the membrane using the polymer of the present invention was remarkably reduced compared to the PMMA hollow fiber membrane (FIG. 6) used as a standard substance.

Example 15
20 parts by weight of M900G, 15 parts by weight of MMA, 15 parts by weight of acrylonitrile (hereinafter abbreviated as AN) and 50 parts by weight of methanol were added and 0.1 part by weight of ADVN was added, and polymerization and purification were carried out under the same conditions as in Example 1. A hydrophilic component-containing copolymer was obtained. As in Example 1, it was confirmed that a copolymer equivalent to the charged weight composition was obtained.

  This hydrophilic-containing copolymer, 100 parts by weight, 67 parts by weight of syndiotactic PMMA having a weight average molecular weight of 600,000 by polystyrene GPC obtained by polymerizing MMA 100% in DMSO, and isotactic having a weight average molecular weight of 600,000 33 parts by weight of tic PMMA and 570 parts by weight of dimethyl sulfoxide were mixed and stirred at 110 ° C. for 8 hours to prepare a spinning dope.

The obtained spinning dope was discharged into the air at a rate of 1.2 g / min from an annular slit-type hollow die having an outer diameter / inner diameter = 1.0 / 0.7 mmφ kept at 99 ° C. At the same time, nitrogen gas was injected into the hollow interior at a pressure of 47 mmAq. The length of the dry part was 60 mm, and water at 30 ° C. was used for the coagulation bath. After washing with water, 5% relaxation heat treatment was performed at 75 ° C. with 73% glycerin aqueous solution, and sampling was performed at 30 m / min. The amount of PEO units contained in the obtained hollow fiber polymer was 15 wt%. Inner diameter / thickness of the hollow fiber membrane at 230/28 .mu.m, water permeability ^{54ml / hr · mmHg · m 2} , permeability of 5% albumin solution is ^{8.2ml / hr · mmHg · m 2} , rejection of 99%.

  A module was produced from this hollow fiber membrane in the same manner as in Example 14. Whole blood was circulated at 37 ° C. for 3 hours on the inner surface of the hollow fiber membrane of this module, and the amount of platelets adhering to the membrane surface was observed with a scanning electron microscope. The results are shown in FIG. The amount of platelet adhesion of this membrane using the polymer of the present invention was significantly reduced compared to the PMMA hollow fiber membrane used as a comparison.

Example 16
21 parts by weight of the hydrophilic component-containing copolymer of Example 3, 27 parts by weight of syndiotactic PMMA, 126 parts by weight of p-styrene sulfonate 1.5 mol 1% copolymerized PMMA, 36 parts by weight of isotactic PMMA and 790 parts by weight of dimethyl sulfoxide Were mixed and stirred at 110 ° C. for 12 hours to prepare a spinning dope.

The obtained spinning dope was discharged into air at a rate of 2.07 g / min from an annular slit-type hollow metal having an outer diameter / inner diameter = 2.0 / 1.8 mmφ kept at 95 ° C. At the same time, nitrogen gas was injected into the hollow interior at a pressure of 34 mmAq. The length of the dry part was 190 mm, and water at 50 ° C. was used for the coagulation bath. After washing with water, heat treatment was performed with a glycerin aqueous solution at 81 ° C. and 77%, and sampling was performed at 49 m / min. The resulting hollow fiber membrane had an inner diameter / film thickness of 210/32 μm and a water permeability of 73 ml / hr / mmHg / m ² .

With this hollow fiber membrane, a minimodule having 2300 yarns, an effective length of 13.5 cm, and an effective membrane area of 0.2 was prepared, and the diffusion transmittance of a low molecular weight substance was measured. As a result, the diffuse transmittance of urea was 1.8 × 10 ⁻³ cm / sec, and the diffuse transmittance of vitamin B12 was 3.8 × 10 ⁻⁴ cm / sec.

  The hollow fiber membrane was treated in the same manner as in Example 14, and the state of platelet adhesion was observed. The platelet adhesion amount of the membrane using the polymer of the present invention was remarkably reduced as compared with the PMMA hollow fiber membrane used as the standard substance in the same manner as in Example 14.

Example 17
21 parts by weight of the hydrophilic component-containing copolymer of Example 3, 153 parts by weight of syndiotactic PMMA, 36 parts by weight of isotactic PMMA, and 790 parts by weight of dimethyl sulfoxide were mixed and stirred at 110 ° C. for 12 hours, and the spinning dope Was prepared.

The obtained spinning dope was discharged into the air at a rate of 1.46 g / min from an annular slit-type hollow die having an outer diameter / inner diameter = 2.0 / 1.8 mmφ kept at 100 ° C. At the same time, nitrogen gas was injected into the hollow interior at a pressure of 22 mmAq. The length of the dry part was 190 mm, and water at 10 ° C. was used for the coagulation bath. After washing with water, heat treatment was performed with an aqueous glycerin solution at 83 ° C. and 81%, and sampling was performed at 30 m / min. The resulting hollow fiber membrane had an inner diameter / film thickness of 210/30 μm and a water permeability of 56 ml / hr · mmHg / m ² .

With this hollow fiber membrane, a minimodule having 2300 yarns, an effective length of 13.5 cm, and an effective membrane area of 0.2 was prepared, and the diffusion transmittance of a low molecular weight substance was measured. As a result, the diffuse transmittance of urea was 7.9 × 10 ⁻⁴ cm / second, and the diffuse transmittance of vitamin B12 was 1.6 × 10 ⁻⁴ cm / second.

  The hollow fiber membrane was treated in the same manner as in Example 14, and the state of platelet adhesion was observed. The platelet adhesion amount of the membrane using the polymer of the present invention was remarkably reduced as compared with the PMMA hollow fiber membrane used as the standard substance in the same manner as in Example 14.

  According to the present invention, it is possible to provide a copolymer composition which is easily dissolved in a solvent and can be molded, and has excellent antifouling properties such as antithrombotic properties. The stain-resistant semipermeable membrane can be suitably used particularly in the medical field as an antithrombogenic material.

1 is a diagram showing an NMR chart for a copolymer in Example 1. FIG. FIG. 3 is a diagram showing the observation result of the film surface obtained in Example 1 with a microscope. It is a figure which shows the observation result by the microscope of the film | membrane surface obtained by the comparative example 1. FIG. FIG. 6 is a diagram showing an NMR chart for the copolymer in Example 3. It is a figure which shows the observation result by the microscope of the film | membrane surface obtained in Example 14. FIG. It is a figure which shows the observation result by the microscope of the film | membrane surface obtained in the comparative example 5. FIG. It is a figure which shows the observation result by the microscope of the film | membrane surface obtained in Example 15. FIG.

Claims (12)

  A monomer (A) having a polyalkylene oxide unit and a polymerizable carbon-carbon double bond in the same molecule, a methacrylic acid ester monomer or an acrylic acid ester monomer (B), and (A), A copolymer comprising a monomer (C) having a polymerizable carbon-carbon double bond other than (B) as a constituent monomer, wherein the content of the monomer (A) is 10% by weight %, And the content ratio of the monomer (C) is 5% by weight or more.   2. The contamination-resistant material according to claim 1, wherein the content ratio of the monomer (C) is 10% by weight or more and 50% by weight or less. The contamination-resistant material according to claim 1, wherein the monomer (A) is a monomer represented by the following general formula (1) (Chemical formula 1).

Wherein n is an integer of 5 or more, R ₁ is selected from H or CH ₃ , R ₂ is a hydroxyl group, a C ₁ -C ₄ alkoxy group, and OCHφ ₂ (φ is a phenyl group), and R ₃ is an alkylene Represents.)   Monomer (B) is methyl acrylate, ethyl acrylate, propyl acrylate, butyl acrylate, lauryl acrylate, 2-ethylhexyl acrylate, cyclohexyl acrylate, benzylid acrylate, methyl methacrylate, ethyl methacrylate, The contamination-resistant material according to claim 1, wherein the material is selected from propyl methacrylate, butyl methacrylate, lauryl methacrylate, 2-ethylhexyl methacrylate, cyclohexyl methacrylate and benzylid methacrylate.   2. The contamination resistance according to claim 1, wherein the monomer (C) is selected from olefins, vinyl halides, vinyl esters, aromatic vinyl compounds, acrylonitrile, methacrylonitrile, vinyl pyrrolidone, vinyl alcohol and acrylamide. Sex material.   The contamination-resistant material according to any one of claims 1 to 5, which is used as an antithrombogenic material.   A monomer (A) having a polyalkylene oxide unit and a polymerizable carbon-carbon double bond in the same molecule, a methacrylic acid ester monomer or an acrylic acid ester monomer (B), and (A), A copolymer comprising a monomer (C) having a polymerizable carbon-carbon double bond other than (B) as a constituent monomer, wherein the monomer of (A) is in the copolymer A copolymer having a content ratio of 10% by weight or more and a content ratio of the monomer (C) in the copolymer of 5% by weight or more, and a methacrylic ester polymer or an acrylate ester A contamination-resistant semipermeable membrane comprising a polymer.   The contamination-resistant semipermeable membrane according to claim 7, wherein the content ratio of the monomer (C) is 10 wt% or more and 50 wt% or less. The contamination-resistant semipermeable membrane according to claim 7, wherein the monomer (A) is a monomer represented by the following general formula (1) (Chemical formula 2).

Wherein n is an integer of 5 or more, R ₁ is selected from H or CH ₃ , R ₂ is a hydroxyl group, a C ₁ -C ₄ alkoxy group, and OCHφ ₂ (φ is a phenyl group), and R ₃ is an alkylene Represents.)   Monomer (B) is methyl acrylate, ethyl acrylate, propyl acrylate, butyl acrylate, lauryl acrylate, 2-ethylhexyl acrylate, cyclohexyl acrylate, benzylid acrylate, methyl methacrylate, ethyl methacrylate, The contamination-resistant semipermeable membrane according to claim 7, which is selected from propyl methacrylate, butyl methacrylate, lauryl methacrylate, 2-ethylhexyl methacrylate, cyclohexyl methacrylate and benzidyl methacrylate.   The contamination resistance according to claim 7, wherein the monomer (C) is selected from olefin, vinyl halide, vinyl ester, aromatic vinyl compound, acrylonitrile, methacrylonitrile, vinyl pyrrolidone, vinyl alcohol and acrylamide. Semipermeable membrane.   The antifouling semipermeable membrane according to any one of claims 7 to 11, which has antithrombogenicity.

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