JPS6352923B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a porous membrane made of a blend of cellulose acetate and a (meth)acrylic acid ester polymer (copolymer). Various porous membranes have already been developed. Porous membranes are also used in medical applications.
Artificial kidneys, artificial livers, plasma exchange methods, and the like require porous membranes that are permeable to substances with molecular weights of several thousand to several million. Furthermore, in such medical applications, since blood and the porous membrane come into contact, a biocompatible material that is unlikely to cause blood coagulation is required as the multiphotonic membrane. However, it has been thought that there is no porous membrane that has both permeability for medium-high molecular weight substances and biocompatibility. The present inventor obtained a blend by dissolving two different polymers in the same solvent, and formed a porous membrane made of the blend by forming a solution of this blend into a membrane in a coagulating bath. In the course of conducting research to obtain the desired results, the present invention was achieved by discovering a composition that is permeable to substances and biocompatible. According to previous research, even in the case of two types of polymers that are soluble in the same solvent, phase separation is likely to occur, resulting in poor mechanical properties and impractical use except in special cases as a polymer material. The reality is that its use has been limited due to its functionality. However, when manufacturing porous membranes using a wet method, the membrane forming stock solution is prepared by adding an auxiliary agent or non-solvent that promotes phase separation to a good solvent. Depending on the degree, gender may be advantageous. In addition, recent research results regarding the interaction between blood and polymeric materials include:
It has been discovered that microheterogeneous structures made of mixtures of styrene and hydroxyethyl methacrylate polymers are less susceptible to blood coagulation (thrombus). However, this mixture composition has low mechanical strength and cannot be formed into a practical porous membrane. An object of the present invention is to provide a porous membrane having the mechanical strength, substance permeability, and biocompatibility of the membrane material. The composition of the present invention is a porous membrane consisting of a blend of cellulose acetate and a polymer or copolymer of methacrylate ester. The present invention will be explained below. As the cellulose acetate used in the present invention, those having an acetylation degree of 50% to 62% can be used. Further, cellulose acetate having a degree of polymerization of about 80 to 400 can be used. As the methacrylate ester polymer, each polymer of methyl methacrylate, ethyl methacrylate, propyl methacrylate (n or iso), butyl methacrylate (n, iso or tert) and copolymers thereof can be used. be. Examples of the copolymer component used include methyl acrylate, ethyl acrylate, butyl acrylate, but are not limited thereto. The composition of complex acid cellulose and methacrylic acid ester polymer or its copolymer is such that complex acid cellulose is
Although 50% to 90% can be said to be a preferable condition in terms of mechanical strength, it is not limited to this depending on the film forming method. The solvent may be any solvent as long as it dissolves both the cellulose acetate and the methacrylic acid ester (co)polymer. Examples of commonly used ones include methylene chloride, acetone, methyl ethyl ketone, ethyl acetate, N-methylpyrrolidone, and dimethyl sulfoxide. When it is desired to increase the pore diameter of the porous membrane to 0.1 μ or more, a non-solvent is mixed and used as a pore-forming agent. The non-solvent may be any organic liquid that does not dissolve both polymers. Examples include hexane, cyclohexane, cyclohexanol, methanol, ethanol, propanol, butanol, and the like. It is advantageous to add inorganic salts to increase the rate of phase separation and increase the pore size of the membrane. As the inorganic salt, ammonium salt, calcium salt, magnesium salt, etc. can be used. As described above, it is a necessary condition for the film-forming stock solution that the cellulose acetate, the methacrylate ester polymer or its copolymer, the solvent, the non-solvent and the inorganic salt are almost completely dissolved. Before forming a film, it is necessary to remove foreign substances through multiple steps. The polymer concentration is determined based on technical judgment in consideration of the viscosity that facilitates film formation, but is preferably in the range of 5 to 20%. The concentration of non-solvents ranges from 10 to 50%, the salts range from 5 to 10%, and the remainder is the concentration of solvent. If salts are used, it is advantageous to use methanol in concentrations up to 20%. Although these dissolution methods are technically not difficult, first both polymers are completely dissolved in a solvent. In some cases, if the temperature is raised from room temperature to 50°C, it will dissolve in 5 hours. Next, the remaining non-solvent and salt methanol solution are added and stirred for an additional 5 hours to obtain a transparent stock solution. The method for forming a porous membrane from this stock solution is no different from general wet membrane forming, but it differs slightly depending on the form of the porous membrane, such as a flat membrane or a hollow fiber membrane. First, to explain the flat membrane, the above-mentioned stock solution may be cast into water or a water/methanol mixture as a coagulation bath. It is preferable to take care to keep the temperature at 20°C or lower so that the solvent does not easily evaporate. Recently, a method of using a porous membrane as a thin hollow fiber membrane has become popular, so this method will be explained. The polymer stock solution is discharged from the annular spinning hole, and is allowed to fall onto the coagulating liquid surface several cm to several tens of centimeters below the spinning hole.
In this case, the difference from a flat membrane is that the coagulating liquid also flows inside the hollow fiber membrane. As the coagulation bath, water,
Methanol etc. can be used. The temperature of both the stock solution and the coagulation bath is preferably 30°C or lower. Further, it is advantageous to provide a spinning tube below the spinning hole for suppressing solvent evaporation. As mentioned above, the manufacturing method of porous membranes is not particularly different from conventional methods, but by blending cellulose acetate and methacrylic acid ester polymer or copolymer, porous membranes with good material permeability and biocompatibility are created. There is an advantage that a membrane can be obtained. Examples will be described below. Example 1 The stock solution was prepared by adding 120 g and 30 g of cellulose acetate with a degree of axification of 55% and a degree of polymerization of 180 and polymethyl methacrylate with a degree of polymerization of 800, respectively, to 350 g of acetone.
It took 5 hours to dissolve at 50°C. Add 300g of cyclohexanol and add 50g of ammonium chloride.
g and 150 g of methanol were added and stirred. This stock solution was maintained at 20°C, cast onto a glass plate, and solidified in a water:methanol (1:1) coagulation bath. The permeability of this membrane to a 0.2% aqueous solution of bovine serum globulin was measured. As a comparison membrane, a membrane made only of cellulose acetate obtained under similar conditions was used.

[Table] In addition, when the above membrane was immersed in Japanese Pharmacopoeia saline and rabbit blood was dropped onto it to measure the blood coagulation time, it was found that the coagulation time was longer than that of the porous acetate membrane. Example 2 Using the stock solution of Example 1, it was spun from an annular spinning hole, and the coagulation bath was water/methanol (1:1).
Polyethylene glycol (molecular weight 200) inside
It flowed out, was allowed to fall 5 cm downward, was introduced into a coagulation bath, and was wound up at 10 m/min. A hollow fiber with an inner diameter of 300μ and a membrane thickness of 85μ was obtained. The performance of the hollow fiber was as follows.

[Table] Example 3 The stock solution is cellulose acetate with an axification degree of 54.5% and a polymerization degree of 190, and methyl methacrylate with a polymerization degree of 900.
80 each of copolymers of methyl acrylate (90:10)
Add g and 20 g to 450 g of acetone and dissolve at 50°C for 5 hours. Add 300 g of cyclohexane, then add 50 g of magnesium chloride and 150 g of methanol and dissolve with stirring. Keep this stock solution at 20℃,
Spinning from an annular spinning hole, the coagulating liquid is mixed inside and outside with water/
It is made into a hollow fiber using methanol (1:1). Since a hollow fiber with an inner diameter of 330 μm and a membrane thickness of 75 μm was obtained, it was evaluated as in Example 1.

[Table] Example 4 40 g and 10 g of cellulose acetate with an axification degree of 61% and a polymerization degree of 240 and isobutyl methacrylate polymer with a polymerization degree of 500, respectively, and 250 g of methylene chloride.
75g of methanol, calcium chloride
25 g and 100 g of cyclohexanol were added and stirred to prepare a stock solution. This stock solution is kept at 20°C or lower and cast onto a glass substrate in a methanol coagulation bath to form a film. Using this membrane, the permeability of a 0.2% aqueous solution of bovine serum γ-globulin was measured, and the following results were obtained.

[Table] Example 5 135 g and 15 g of cellulose acetate with an axification degree of 55% and a polymerization degree of 180 and a methyl methacrylate-vinyl pyrrolidone (95:5) copolymer with a polymerization degree of 500 were dissolved in 250 g of acetone, respectively. Additionally, 75g methanol, 25g borax and 100g cyclohexanone.
was added and stirred to prepare a stock solution. This stock solution was maintained at 20° C. or lower and cast into a coagulating solution of water/methanol (1:1) to form a film, and the following evaluation results were obtained.

【table】

Claims (1)

[Claims] 1. A porous membrane comprising a blend of cellulose acetate and a methacrylic acid ester polymer or a copolymer thereof. 2. The porous membrane according to claim 1, which is a blend containing 50 to 90% by weight of cellulose acetate with a degree of acetylation of 50 to 62%. 3. The porous membrane according to claim 1, wherein the methacrylate ester polymer is a blend containing a polymer consisting of any one of methyl methacrylate, ethyl methacrylate, propyl methacrylate, and butyl methacrylate. .