JPH0470939B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to a method for producing a microporous membrane made of a thermoplastic polyester containing 3-hydroxybutyric acid units as a main component. In recent years, research and development of porous membranes made of polymeric materials has been actively conducted, and porous membranes formed in the form of flat membranes, hollow fiber membranes, etc. are widely applied to dialysis, filtration, gas exchange, etc. In particular, in the medical field, its use as artificial kidneys, artificial livers, plasma exchange therapy, and artificial lungs is rapidly expanding. The typical performance of membranes required for these medical applications is as follows:
biocompatibility and anticoagulant properties. Biocompatibility is an indispensable factor, for example, when developing artificial organs to be implanted in the body, and anticoagulability makes it possible to minimize the use of anticoagulants such as heparin. Therefore, it is currently biocompatible;
In addition, there is an urgent need to search for materials with excellent anticoagulant properties. On the other hand, another important characteristic required of microporous membranes in medical fields such as artificial kidneys and plasma exchange therapy is the uniformity of the membrane's average pore diameter and pore size distribution, as well as control of the pore shape. . for example,
In plasma exchange therapy, it is necessary to efficiently separate blood cells and γ-globulin in blood, and for this purpose, control of average pore size, pore size distribution, and pore shape is essential. Problems to be Solved by the Invention In view of the above-mentioned circumstances, the present inventors have developed a material whose main component is 3-hydroxybutyric acid, which is biocompatible and has excellent pore coagulability. Upon making the membrane porous, we were able to successfully obtain a membrane with a uniform average pore size and pore size distribution, as well as a controlled pore shape, thereby completing the present invention. Means for solving the problems That is, the method for producing a microporous membrane according to the present invention is as follows:
- It is characterized in that at least one substance in the second component is removed from a mixture of a thermoplastic polyester containing 80 mol% or more of hydroxybutyric acid units and a second component consisting of at least one substance. Hereinafter, the method for producing a microporous membrane of the present invention will be explained in detail. The component used as a membrane material in the production method of the present invention is a 3-hydroxybutyric acid unit. aliphatic polyester whose basic repeating unit is
That is, polyhydroxybutyrate (hereinafter referred to as
(abbreviated as “PHB”). PHB used in the present invention
80 mol% or more of its repeating units are 3-hydroxybutyric acid units. PHB is mainly synthesized by microorganisms, is a crystalline polymer with isotactic optical activity, and exhibits a clear crystalline melting point around 178°C. When PHB is manufactured by a microbial culture method,
For example, when microorganisms such as Alcaligenes eutrophus and Azotobacter vinellandii are cultured with glucose, PHB is produced within the organisms for a certain period of time. Furthermore, along with this glucose, propionic acid, 3-hydroxypropionic acid, 3-ethoxypropionic acid, 2-hydroxybutyric acid, isobutyric acid,
By using acrylic acid or the like, a thermoplastic fatty acid polyester containing the following repeating unit () in addition to the 3-hydroxybutyric acid unit () can be obtained. () −O・CH(CH ₃ )・CH ₂ CO− () −O・CR ¹ R ²・(CR ³ R ⁴ ) _o・CO− In the above formula, n is 0 or an integer of 1 or more, R ¹ ,
R ² , R ³ , and R ⁴ are each hydrogen, a hydrocarbon group, a hydroxy-substituted hydrocarbon group, or a hydroxy group.
However, when n=1 and R ² =R ³ =R ⁴ =H, R ¹ is not a methyl group. The molecular weight of PHB varies depending on the microbial culture conditions, and can be obtained in the range of 1 to 2 million. When choosing an organic polymer as the second component to mix with the PHB,
The molecular weight of PHB is a factor that influences the pore size of the membrane.
If PHB with a large molecular weight is used, a membrane with a finer pore size can be obtained. Generally, a molecular weight of 1 to 2 million is preferred. Examples of the second component include various organic polymers, oligomers, and inorganic salts with uniform particle size, but are not particularly limited to these. However, it must be possible to easily remove only the second component after mixing with the first component. Examples of organic polymers include polystyrene, polyvinyl acetate, polymethyl methacrylate,
Examples include polyvinyl chloride, polycarbonate, polyvinylidene chloride, polyvinyl acetate, ethyl cellulose, polyethylene terephthalate, nitrocellulose, cellulose acetate, polyvinyl alcohol, polyamide, polyacrylonitrile, and the like. These oligomers can also be used, and examples of inorganic salts include sodium chloride, calcium chloride, sodium sulfate, ammonium sulfate, sodium carbonate, sodium nitrate,
Examples include ammonium oxalate and potassium tartrate. If it is desired that the microporous membrane has two or more types of pore size distribution, two or more types of the second component can be used. When an organic polymer is used as the second component, its molecular weight is a factor that influences the pore size of the membrane, with higher molecular weights providing membranes with larger pore sizes. Usually, 10 to 2 million is preferable. When using an organic polymer as the second component, it is not preferable to use an organic polymer that is highly miscible with PHB, which is the first component. In particular, it is preferable to use an amorphous polymer or a polymer with low crystallinity as the second component. The form of the membrane is film-like, hollow fiber-like,
The shape of a tube or the like differs depending on its use, but in the present invention, any shape can be produced. Membranes intended for medical applications for blood filtering and dialysis are preferably in the form of hollow fibers. To obtain a porous membrane from a polymer material, there are two methods: dissolve the polymer in a solvent to prepare a film-forming stock solution, form it, remove the solvent (wet method, dry method), and heat the polymer to a temperature higher than its crystal melting point. There is a melting method in which the material is heated and melted, extruded through an appropriate die or nozzle, and cooled and solidified, but any method can be used in the present invention. In any of the above wet methods, dry methods, and melting methods, it is preferable to mix the first component and the second component in a dissolved or molten state. If the second component cannot be dissolved, only the first component is dissolved and mixed. If the second component is an organic polymer, the first component
It is preferable to dissolve it in the same solvent as PHB,
Examples of good solvents include chloroform and trifluoroethanol. The mixing ratio of the first component and the second component is a factor that influences the porosity of the membrane, and normally the membrane with a large amount of the second component has a large porosity. When forming into a film or hollow fiber, when an organic polymer is used as the second component group, the desolvation rate is a factor that affects the pore size of the membrane in the wet method or dry method, and the cooling rate in the melt method. Become. Generally, the faster the speed, the smaller the pore size. Although PHB, which is the first component, crystallizes in the shaping step, it is preferable to further promote crystallization by heat treatment and stretching. The crystallization temperature is preferably 50°C or higher and lower than the melting point. Next, the second component is removed from the homogeneous mixture of the first component and the second component, but any method can be used as long as it has little effect on the first component and can remove at least one of the second components. But it's okay. For example, in the case of an inorganic salt, an appropriate method should be selected depending on the nature of the second component, such as extraction with water, acid, base, or organic solvent, or heating if the second component is volatile. I can do it. In particular, a method using a solvent that does not dissolve the first component is effective. When using an organic polymer for the second component, it is easy to find a solvent that removes the second component, since PHB, the first component, is only easily soluble in a specific solvent such as chloroform. It is preferable to further heat-treat and stretch the microporous membrane obtained by removing the second component to improve shape stability and mechanical performance. The microporous membrane thus obtained has a water permeation rate of 0.01
The value of ~50/m ² hrmmHg indicates that the pores are interconnected and exhibits performance as a membrane. Since PHB is easily decomposed by microorganisms, the microporous membrane obtained by the present invention can be used not only as an ultrafiltration membrane but also as an artificial blood vessel or trachea by shaping it into a tube. By shaping it into a film, it can be used as a burn covering material, and by shaping it into a sphere containing a medicinal material, it can be used as a medicine with slow-release properties. Examples Hereinafter, the present invention will be described in more detail with reference to Examples. Example 1 Azotobacter vinelandii
vinelandi) IFO 13581 and 7 volumes of medium with the following composition per 1 part of deionized water:
Aerobic culture was performed for 72 hours at PH7.7 and 30°C to proliferate. Glucose 3% by weight/volume K ₂ HPO ₄ 0.1 CaCl ₂ 0.11 MgSo ₄・7H ₂ O 0.4 FeSO ₄・7H ₂ O 0.012 (HH ₄ ) ₆ Mo ₇ O ₂₄ 4H ₂ O 0.01 NaCl 0.4 CaCO ₃ 0.01 ZnO 0.002 MnCl・4H ₂ O 0.01 CuCl ₄・4H ₂ O 0.001 CaCl ₂・6H ₂ O 0.001 After culturing, the bacterial cells were separated from the culture medium by centrifugation (6000 rpm), further washed with deionized water and acetone, and centrifuged. The operation was repeated to obtain 80 g of bacterial cells. This bacterial body was suspended in chloroform from step 3,
Boiled for 4 hours. Strain the bacterial cells and pour the liquid into 6
of n-hexane, the coagulum was separated and dried to obtain 32 g of white powder. This powder was confirmed to be pure PHB by elemental analysis, NMR, and IR analysis. PHB synthesized as described above was dissolved in chloroform to prepare a 2.5% by weight solution. Meanwhile, polymethyl methacrylate (PMMA) as the second component
The weight average molecular weight (M _w ) of M _w =
5000, 28,000, 95,000, 270,000, and 1 million were dissolved in chloroform to create a 2.5% by weight solution.
After mixing and stirring the first component (PHB) and the second component (PMMA) at a mixing ratio of 1:1, they were cast onto a glass plate, and chloroform was evaporated at a constant rate to obtain a film with a thickness of approximately 60 μm. Ta. This film was immersed in dimethylformamide (DMF),
After removing only PMMA, it was washed with running water and dried. During drying, the film obtained from PMMA with _Mw = 28,000 was heat treated at 150°C for 30 minutes. All of the obtained films exhibited a uniform white color. As Figures 1 and 2, PHB and the second component
Each of the membranes obtained from PMMA (M _w = 28,000)
3000x and 7000x scanning electron microscopy (SEM)
Show photos. The effects of the present invention can be easily understood from these photographs. That is, it can be observed that the microporous membrane obtained by the method of the present invention has a high degree of uniformity in average pore size and pore size distribution, and has a well-controlled pore shape. Also, substantially circular pores of uniform diameter have been obtained. Table 1 shows the average pore diameter and its fluctuation rate, as well as the water permeation rate of the membrane, as determined from the SEM photograph of the membrane thus obtained. However, the rate of variation in pore diameter was calculated according to the following formula. R _i is the individual pore diameter read from the SEM photograph, is the arithmetic mean value thereof, and n is the number of pores, which is 100. This shows that if PMMA with a large molecular weight is used, a membrane with a large pore size can be obtained, and the pore size is also well arranged. Furthermore, since these water permeation rates show values of 0.01 to 50/m ² ·hr · mmHg, it is clear that the pores are interconnected and exhibit performance as a membrane. Example 2 PHB prepared in the same manner as Example 1 and molecular weight 2.8
1,000 of PMMA powder were mixed at a mixing ratio of 1:1, and melted and mixed on a hot plate with a surface temperature of 185°C. Thereafter, it was naturally cooled, immersed in dimethylformamide, and then washed with running water. Table 1 shows the pore diameter, its fluctuation rate, and water permeation rate of the membrane thus obtained. As in Example 1, a membrane with uniform pore diameter and interconnected pores was obtained. Example 3 PHB synthesized in the same manner as in Example 1 was dissolved in chloroform to create a 2.5% by weight solution. As a second component group, anhydrous calcium chloride (CaCl ₂ ) was dissolved in an 8/2 mixed solvent of chloroform/ethyl alcohol to prepare a 2.5% by weight solution. Furthermore, this solution was filtered using a glass filter G-2. The mixing ratio of these first and second components is 1:1.
After mixing and stirring and casting on a glass plate, the solvent was evaporated to obtain a film with a thickness of about 40 μm. Next, this film was immersed in ethyl alcohol to remove only CaCl ₂ and obtain a uniformly whitened film. Table 1 shows the average pore diameter and its fluctuation rate as read from the SEM photograph of this membrane, as well as the water permeation rate of the membrane. 【table】

[Brief explanation of the drawing]

Figure 1 is a scanning electron microscope (SEM) photograph (3000x) of a microporous membrane obtained from a mixture of PHB and PMMA, and Figure 2 is a SEM photograph (5000x) of the same membrane.

Claims (1)

[Scope of Claims] 1. A homogeneous mixture of a thermoplastic polyester containing 80 mol% or more of 3-hydroxybutyric acid units and a second component consisting of at least one substance is shaped, and then at least one of the second components A method for producing a microporous membrane characterized by removing one type of substance. 2. The manufacturing method according to claim 1, wherein at least one substance in the second component is dissolved and removed using a solvent that does not dissolve the first component. 3. The manufacturing method according to claim 1 or 2, wherein the second component consists of at least one type of organic polymer. 4. Claim 1, which produces a microporous membrane having a water permeation rate of 0.01 to 50/m ² ·hr · mmHg;
The manufacturing method according to item 2 or 3.