JPS618107A - Production of microporous membrane - Google Patents

Abstract

PURPOSE:To obtain a microporous membrane having living body compatibility, excellent in anti-coagulation property and uniform in an average pore size and pore size distribution, by using thermoplastic polyester containing 80mol% or more of a 3-hydroxybutyric acid unit. CONSTITUTION:Polyhydroxybutyrate containing 80mol% or more of a 3-hydroxybutyric acid unit as a fundamental repeating unit is used as a microporous membrane material and pref. has MW of 10,000-2,000,000. A non-crystalline or low- crystalline polymer or oligomer with MW of 1,000-2,000,000 or an inorg. salt with a uniform particle size is mixed with this aliphatic polyester and the resulting mixture is molded into a membrane to crystallize polyhydroxybutyrate. Subsequently, the org. polymer, oligomer or inorg. salt mixed is removed.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of Industrial Application The present invention relates to a method for producing a microporous membrane made of 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. %, and in the medical field, its use is rapidly expanding as artificial kidneys, artificial livers, plasma exchange therapy, and artificial lungs.

Typical membrane performance requirements for these medical applications include biocompatibility and anticoagulability. Biocompatibility is an essential 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, there is currently an urgent need to search for materials that are highly biocompatible and have 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 equalization of the membrane's average pore diameter and pore diameter distribution, as well as control of pore shape. It will be done. For example, in plasma exchange therapy, it is necessary to efficiently separate blood cells and γ-globulin.
For this purpose, control of the average pore diameter, pore diameter 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 anticoagulant properties. 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.

A means for solving the problem, that is, a method for producing a microporous membrane according to the present invention, consists of a thermoplastic polyester containing 80 or more moles of 3-hydroxybutyric acid units, and a thermoplastic polyester containing at least one type of substance. It is characterized by removing at least one type of substance in the second component from a mixture with the two components.

Hereinafter, the method for producing a microporous membrane of the present invention will be explained in detail.

The components used as the membrane material in the production method of the present invention are 3
-Aliphatic polyester having hydroxybutyric acid units H30 as basic edge-turning units, i.e.
= x hydroxybutyrate (hereinafter abbreviated as rp■BJ). 8 of the PHB repeating unit used in the present invention
One in which 0 or more moles are 3-hydroxybutyric acid units is used. P) fB is a crystalline polymer that is mainly synthesized by microorganisms and has isotactic optical activity.
It shows a clear crystalline melting point around 8°C.

When PHB is produced by a microbial culture method, for example, microorganisms such as Alkalidanes eutrophus and Azotobacter
・When cultivating a species such as pinellandii on glucose, PHB is produced within the organism for a certain period of time. Furthermore, along with this glucose, globioyli, 3-hydroxyglobionic acid, 3-ethoxyzolopionic acid, 2-hydroxybutyric acid,
By using isobutyric acid, acrylic acid, etc., 3-
In addition to the hydroxybutyric acid unit, the following repeating units (I) and (
If) a thermoplastic fatty acid polyester can be obtained.

(1) -o@cH(cHρ・CH2C0-(I[)
-0・CR'R2・(OR'R')・co-n is O or an integer of 1 or more, and R', R2, and R3JR' are each hydrogen, a hydrocarbon group, a hydroxy-substituted hydrocarbon group, or a hydroxy group. . However, n-1 and R2=R3=
When R' = H, R1 is not a methyl group.

The molecular weight of PHH varies depending on the microbial culture conditions, and ranges from 1 to
You can get 2 million. When an organic polymer is selected as the second component to be mixed with PHB, a membrane with a fine pore size can be obtained by using PHB with a large molecular weight (PI (the molecular weight of B is a factor that influences the pore size of the membrane)). Generally, those having a molecular weight of 1 to 2 million are preferred.

Examples of the second component include, but are not limited to, various organic salts, d IJ mom-oligomers, and inorganic salts with uniform particle size.

However, it must be possible to easily remove only the second component after mixing with the first component.

Examples of organic polymers include polystyrene, lulose, polyethylene terephthalate, nitrocellulose,
Cellulose acetate, polyvinyl alcohol, polyamide,
Examples include polyacrylonitrile. These oligomers can also be used, and examples of inorganic salts include sodium chloride, calcium chloride, sodium sulfate, ammonium sulfate, sodium carbonate, sodium nitrate, ammonium oxalate, potassium tartrate, and the like.

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 not a factor that influences the pore size of the membrane; the larger the molecular weight, the larger the pore size of the membrane.

Generally, 1,000 to 2,000,000 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 may be film-like, hollow fiber-like, or tube-like depending on its use, but any form can be produced in the present invention.

Membranes for medical applications such as blood filtration and dialysis are
Preferably, it is in the form of hollow fibers.

To obtain a porous membrane from a polymer material, the polymer is dissolved in a solvent to prepare a film-forming stock solution, and after shaping, the solvent is removed (wet method, dry method), and the polymer is heated 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. When the second component is an organic polymer, it is preferable to dissolve it in the same solvent as PHB, which is the first component, and 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 determines the pore diameter of the membrane in the wet method or dry method, and the cooling rate in the melt method. 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.

In order to remove the second component from a homogeneous mixture of the first and second components, what 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? Any method is fine. 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, since PHB, the first component, is difficult to dissolve only in specific solvents such as chloroform,
One can easily find a solvent that removes the second component.

The microporous membrane obtained by removing the second component is further heat-treated,
It is preferable to stretch the film to improve shape stability and mechanical performance.

The microporous membrane thus obtained has a water permeation rate of 0.01 to 5.
Since it has a value of 0 J%/m2hrx+xHg,
It can be seen that the pores are interconnected and exhibit performance as a lacrimal membrane. Since PHB is easily decomposed by microorganisms,
In addition to applications such as ultrafiltration membranes, the microporous membrane obtained by the present invention can be used as an artificial blood vessel or trachea by forming it into a tube shape, and as a burn covering material by forming it into a film form. In addition, by shaping it into a spherical shape containing aggregated wood, it can be used as a drug with sustained release properties.Examples The present invention will be explained in more detail with reference to Examples.

Example 1 Azotobacter vinelandii (Azotobacter vinellandii)
rvinelandl) IFOI 3581 and deionized water 1! Culture medium 7 with the following composition! Including 10! Aerobic culture was performed for 72 hours at pH 7, 7, and 30°C in a voluminous fermenter for growth.

Glucose 3wt/volume 2HPO
40,I CaC120,11 MgSO4・7H200,4 FeSO4''7H200,012 (dish,)6MO,0244H200,01NaCt0.
4 CaCO20,Of ZnOO,002 MnC4H200,01 CuC4''4H20o, OOl CaCl2'6H200,001 After culturing, the bacterial cells were separated from the culture solution by centrifugation (6000 rpm), and further washed with deionized water and acetone. The centrifugation operation was repeated to obtain soybean cells.

3 of these bacteria! The suspension was suspended in chloroform and boiled for 4 hours. The bacterial cells were filtered, and the F solution was poured into 61 n-hexane, and the coagulated product was separated and dried to obtain 3219 as a white powder.

This powder was confirmed to be pure PHB as a result of elemental analysis, (1) and IR analysis.

PHB synthesized as described above was dissolved in chloroform to prepare a 2.5% by weight solution. On the other hand, as a second component? The weight average molecular weight (MY) of methyl remethacrylate (PMMA) is MW=5000°28,000, respectively.
95,000, 270,000, and 1,000,000 were dissolved in chloroform to create a 2.5% by weight solution.

The first component (PHB) and the second component (PMMA) were mixed and stirred at a mixing ratio of 1:1, then cast onto a glass plate, and chloroform was evaporated at a constant rate to give a film thickness of 60 μm.
A film of m was obtained. This film was immersed in dimethylformamide (DMF) to remove only PMMA, and then washed with running water and dried. During drying, M of PMMA
The film obtained from W=2,8000 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 PMMA
(MW = 28,000) each of the membranes obtained from 3.
000 times and 7. ooox scanning electron microscope (SFM)
) Show photos. A substantially circular and uniform pore size is obtained. Table 1 shows the average pore diameter and its fluctuation rate as read from the 88M photograph of the membrane thus obtained, as well as the water permeation rate of the membrane. However, the rate of variation in pore diameter was calculated according to the following formula.

Ri is the individual pore diameter read from the 88M photograph, R
is the arithmetic mean value, and n is the number of 100 pieces.

This is it! 7 It can be seen that if PMMA with a high molecular weight is used, a membrane with a large pore size can be obtained, and the pore size is also well-regulated. Furthermore, these water permeation rates are 0.0
1~5017m *h? It is clear from the ymHg value that the pores are interconnected and exhibits performance as a filtration membrane. PMMA/4 powder was prepared at a mixing ratio of 1:1, and melt-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. The pore size of the membrane thus obtained,
The fluctuation rate and water permeation rate are shown in Table 1. 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 prepare a 2.5% by weight solution. As a second component group, anhydrous calcium chloride (cacz2) 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 glass filter 0-2. The first component and the second component were mixed and stirred at a mixing ratio of 1:1, cast on a glass plate, and the solvent was evaporated to obtain a film having a thickness of 40 μm.

Next, this film was immersed in ethyl alcohol, and C
A uniformly whitened film was obtained by removing only aCl-2. Table 1 shows the average pore diameter and its rate of variation as read from an 88M photograph of this membrane, as well as the water permeation rate of the membrane.

Table 1

[Brief explanation of drawings]

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

Claims (1)

[Scope of Claims] A homogeneous mixture of a thermoplastic polyester containing 80 mol% or more of 1,3-hydroxybutyric acid units and a second component consisting of at least one substance is shaped, and then the second component is A method for producing a microporous membrane, characterized by removing at least one type of substance. 2. The manufacturing method according to claim 1, characterized in that 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. Water permeation rate is 0.01-50l/m^2・hr・mm
Claim 1 for producing a microporous membrane containing Hg
2. The manufacturing method according to item 2, item 3, or item 3.