JPH02208332A - Production of polymeric porous material - Google Patents

Abstract

PURPOSE:To obtain a polymeric porous material having many uniformly dispersed cells having a specified diameter, separated from each other by films and interconnected to each other through the apertures in the films, having a large void volume and suited as a catalyst, an adsorbent, etc., by freezing a solution of a polymer other than cellulose and extracting the solvent from the product. CONSTITUTION:A polymer except cellulose (e.g. chitosan or sodium alginate) is dissolved in a solvent (e.g. dil. hydrochloric acid or aqueous sodium hydroxide solution). The obtained polymer solution is frozen by cooling to a temperature lower than the solidification temperature of the polymer solution. The solvent is extracted or deprived of its solvency to obtain a polymeric porous material having many cells of a diameter >= about 2mum and separated from each other by films and interconnected to each other through the apertures in the films which separate the adjacent cells to form an interconnected structure. By controlling the temperature and time in freezing, the pore diameter can be controlled.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a method for producing a porous polymer (excluding cellulose) having a novel structure. More specifically, the present invention relates to a method for producing a porous polymer having a structure suitable for catalysts, enzymes, pharmaceutical carriers, ion exchangers, raw materials for adsorbents, microcarriers for cell culture, and the like.

[Conventional technology]

Polymer microparticles can be prepared by gel filtration chromatography (Gel filtration chromatography).
It is widely used as a filler for PC). In addition, when various functional groups can be easily introduced, it has a wide range of applications as a variety of ion exchangers and as a base material for affinity chromatography. Particularly in recent years, with the development of biochemistry and genetic engineering, the demand in the field of separation and purification of trace proteins in living organisms has been significantly expanding. Some of the polymer particles currently on the market are called porous particles, but they are mainly used to create pores with extremely fine pores in order to adjust the exclusion limit molecular weight for GPC and control particle density. Since it has a structure, its pore diameter is essentially about 1 μm at most.

On the other hand, sponges are known as polymeric structures with large pores, but the pores are several hundred pm or more, usually several mm.
The unit hole is open.

Generally, to create a porous polymer body, a large amount of porous material with a particle size corresponding to the desired pore size is added to a polymer solution or melt, and the solidified or solidified solution is partially altered in quality.
Polymers may partially precipitate. moreover,
In order to significantly increase the porosity of the porous material or create a continuous pore structure, it is necessary to mix a large excess of porous material into the polymer solution or melt, which reduces fluidity and makes it extremely difficult to form fine particles. It becomes difficult. Furthermore, the strength of the porous body after removing the porous material is inevitably significantly reduced.

As a method of obtaining a porous polymer body without using such a porous material, a solution of the polymer is poured into a mold for the purpose of providing a highly water-containing molded product of water-soluble polymer gel. Or,
There is a proposal to obtain a gel molded body using the conventional method of fixing the gel structure of the solution by the so-called freeze-vacuum drying method, which involves forming a coating film, freezing it, and vacuum-drying it without thawing.
For example, a method using polyvinyl alcohol was published in Japanese Patent Application Laid-open No. 5
7130543 and JP-A-57-159826, and a method using solubilized collagen is disclosed in JP-A-56-23896).
. The product obtained by such a freeze-vacuum drying method is also sometimes referred to as porous, but this concept refers to the extremely microscopic spaces between the molecular networks of the gel, and the vacuoles or pores of the porous polymer of the present invention are The concept is completely different.

[Problem that the invention is trying to solve]

2, which is between the pore size range of conventional polymer gels and sponges.
Until now, there have been few examples of porous polymers having pore diameters of /7In or more, and production has been difficult.

In addition, using porous materials makes it difficult to perform fine molding,
The use of blowing agents has the problem that it is difficult to create continuous pores and that the dimensional stability of the product is unstable.

Furthermore, simple freeze-drying of a polymer solution does not control the growth of solvent crystals, making it difficult to control the pore size.
It's a minute. Furthermore, upon freezing, a polymer solution undergoes phase separation into solvent crystals and a concentrated polymer phase between the crystals, but when attempting to fix the structure by freeze-drying, the solvent crystal portion becomes pore-formed due to solvent sublimation. It remains. However, in the polymer-rich phase part, the retained solvent is removed by sublimation without polymer aggregation.
Traces of the solvent leaving behind become fine pores, forming a partition wall structure with the same thickness as when frozen. Therefore, in a porous body obtained by the freeze-drying method, it is difficult to thin the partition walls between the pores, and it is difficult to increase the volume ratio of relatively large openings formed by the escape of solvent crystals.

Moreover, if the solvent or certain components in the solvent are difficult to sublimate, the structure cannot be fixed by freeze-drying.
Applicable polymer solutions are limited.

SUMMARY OF THE INVENTION It is therefore an object of the present invention to solve the problems of the prior art and to
The object of the present invention is to provide a method capable of finely molding a porous polymer material in which pores larger than pores are distributed relatively uniformly and the spatial volume thereof is extremely high.

[Means to solve the problem]

First, the inventor of the present invention filed a patent application filed in 1983 to develop a manufacturing method for cellulose porous materials that achieves the same purpose as above.
2-198285) found that this method is also effective for producing other porous polymer materials.

The method for producing a porous polymer of the present invention involves forming a polymer solution into a desired shape, cooling and freezing the solution below its solidification temperature, and then extracting and removing the solvent or causing the solvent to lose its ability. This method is characterized by

The features of the method for producing a porous polymer material of the present invention can be summarized in the following three points.

First, when a polymer solution freezes and solidifies, many microcrystals of the solvent or its constituent components (hereinafter referred to as "solvent, etc.") are formed, and the dissolved polymer is concentrated and separated in the gaps between the solvent microcrystals. A type of phase separation phenomenon is used as a means of creating porosity.

Second, the pore size can be controlled by controlling the temperature and time during freezing.

Thirdly, when fixing the porous structure, unlike the freeze-drying method, the polymer-concentrated portion located in the gaps between the solvent microcrystals loses its ability to dissolve the polymer, causing shrinkage and solidification accompanied by solvent removal.

Based on the above characteristics, the porous polymer material obtained by the method of the present invention has pores separated by an extremely thin film with a diameter of 2.
It has many vacuoles larger than #I.

One of the preferred embodiments of the porous polymer obtained by the method of the present invention is one having a structure in which continuous pores of communicating vacuoles extend substantially perpendicularly into the interior from the surface.

The thickness of the membrane separating the vacuoles of the porous polymer material obtained by the method of the present invention varies depending on the concentration of the polymer solution, the vacuole diameter, etc., but is not more than 1/4, preferably not more than 1/10 of the vacuole diameter. In some cases, even 1/30 or less is possible.

Further, the diameter of the vacuoles of the porous polymer material is larger than about 2 μm, preferably the majority of the vacuoles are 57/m or more, and more preferably 10//m or more. When the diameter is smaller than this, free movement of fluids and substances within the porous polymer material is not achieved, and its uses are restricted.

The upper limit of the vacuole size is not particularly limited;
It can be selected depending on the purpose of use and the strength of the particles, but usually 50
It is often selected to be 0μ or less, preferably 20hm or less.

There are no particular restrictions on the structure of the vacuolar septum, other than that it should have an opening for connecting the winter vacuoles, but the size of the opening should be much smaller than the diameter of the vacuole. Preferably not too small, approximately 1 vacuole diameter.
/30 or more is desirable. If the opening is too large, the strength of the particle structure will be insufficient, leading to destruction during use, which is undesirable; therefore, it is desirable that the opening is about 3/4 or less, particularly about 2/3 or less, of the vacuole diameter.

In addition to the above-mentioned large-diameter openings, the diaphragm may have a finer pore structure, but this is a preferable embodiment as long as it does not particularly impede the purpose of the invention.

The membrane constituting the porous polymer body is substantially made of polymers (excluding cellulose). Here, the polymer is preferably rubber, polysaccharide, protein, water-soluble synthetic polymer, or organic solvent-soluble synthetic polymer, but is not particularly limited.
Even if it is an inorganic polymer, if it is soluble in a solvent with a freezing temperature,
Included within the scope of the present invention.

Specific examples of polymers include natural plant compounds such as gum arabic, quince seed mucilage, gum tragacanth, carrageenan, agar, guar gum, gum karaya,
Locust bean gum, pectin, galactan, pullulan or xanthan gum, natural animal compounds, e.g.
Gelatin, casein, caseinate potassium salt, caseinate sodium salt, or chondroitin sulfate sodium salt,
Collagen, elatin, fibroin, chitosan, chitin, hyaluronic acid, starch-based semi-synthetic polymer compounds such as carboxymethyl starch, methylhydroxypropyl starch, dextrin, dextran, alginic acid-based semi-synthetic polymer compounds such as alginate propylene glycol ester or alginates, synthetic polymer compounds,
For example, polyvinyl alcohol, polyvinylpyrrolidone, polyvinylethyl ether, carboxyvinyl polymer, polyacrylic acid, polyacrylamide, polystyrene, polyvinyl chloride, polyvinyl acetate, polyacrylonitrile, etc., or copolymers of their respective monomers with other vinyl monomers, etc. , polyamide, polyester polyaramid, and other condensation polymers, epoxy reactants, and polyurethane and other addition polymers. Derivatives, salts, crosslinked products, and blends thereof are also included, and the polymer is not particularly limited.

The polymer forming the porous body is obtained by dissolving these polymer raw materials and re-precipitating or regenerating them by the method described below, and the average molecular weight thereof is not particularly limited. Furthermore, the presence of metals, inorganic substances, organic substances, and gases in the polymer is permissible as long as this does not impair the purpose of the present invention.

The shape and size of the porous body are not particularly limited either.

When the porous body is a particle, the shape is usually selected from spherical, oblate spherical, or oblate spherical, but special shapes such as cylindrical, cylindrical, saddle, etc. that enhance the filling effect are also allowed. The size may be arbitrarily selected depending on the application, and it is usually 5 to 500 μm in diameter, and even 5+nm or more in diameter is possible in some cases. It can even be in the form of fibers or films.

In the method of the present invention, there is no need to add foreign matter such as a porous material to the polymer solution during production, so it is possible to easily create minute droplets with a uniform diameter, and the particle size can be controlled arbitrarily. can. The diameter and shape of the vacuole are basically determined by the size and shape of crystals of the solvent, etc. that are formed when the solvent, etc. in the solution freezes and solidifies. Therefore, the shape and pore diameter of the vacuole can be adjusted by changing the freeze-solidification conditions such as the type of polymer solution and the temperature.

The shape and size of porous polymer particles can be controlled by the type of polymer solution, polymer concentration, viscosity of the solution, etc., and the shape and size of the particles can also be controlled arbitrarily by changing the solution into droplets. .

Methods for forming droplets include, but are not limited to, a spray nozzle method in which the solution is sprayed into a gas, a method in which the solution is discharged into a fluid, and an emulsion dispersion method.

When the porous body is a thread, the cross-sectional shape is usually selected from circular, triangular, polygonal such as hexagonal, oblate polygon, oblate circular, hollow, and box-shaped, but is limited to this range. isn't it. The thread diameter may also be arbitrarily selected depending on the application, and is usually 5 to 500 mm in diameter, and even 5 mm or more in diameter is possible in some cases. Needless to say, the yarn diameter does not need to be uniform in the yarn length direction, and the yarn length can also be arbitrary.

When the porous body is a film, the film thickness may be arbitrarily selected depending on the application, and is usually 5 to 500/1 m thick, and may even be 5nr+n or more in some cases. The film thickness does not need to be uniform, and depending on the purpose of use, it may be a preferable embodiment to provide the film with unevenness. Furthermore, it will be easily understood that it is also possible to take a tubular shape, a honeycomb shape, or any other arbitrary shape.

Molding into threads, films, honeycombs, hollow fibers, tubes, etc. includes, but is not limited to, extrusion methods from ordinary nozzles or gouers, injection methods into molds, and the like. Further, it is also possible to stretch, stretch, and cut in an appropriate process.

Freezing is performed by introducing the polymer solution into a medium adjusted to an arbitrary temperature. It freezes almost uniformly in a liquid or gas that is non-reactive and immiscible with the polymer solution. Also, if it is in a liquid that is miscible with the solution, it will freeze in a distorted shape, and if it is in a reactive gas or liquid, only the surface part of the particle can be reacted and modified and then frozen. . For example, when freezing in a liquid or gas that is miscible with a polymer solution, the liquid or gas infiltrates only the contact interface before reaching the freezing temperature.
Polymers precipitate in a film that covers the surface.

As a result, a porous polymer body whose surface layer is covered with a membrane is obtained.

When performing freezing in this method, the freezing temperature is not particularly limited as long as it is lower than the temperature at which the solvent etc. freeze. However, the solvent, etc. that determines the vacuole diameter of the porous body is important from the point of view of crystal growth, and is selected based on the type of solvent, etc. and the intended vacuole diameter. Too low a temperature is often undesirable, as the polymer solution will be frozen in a state close to its solution structure without forming crystals during freezing, resulting in a gel structure similar to that of normal wet coagulation. However, by setting the freezing temperature appropriately, it is possible to make only the surface of the porous material have a gel structure and the inside to have a porous structure, and also partially cover the surface with a gel coating and partially open the connection port to the inside of the particle. You can also leave it. Porous particles with such a structure have particularly high resistance to deformation during compression. Generally, the freezing temperature is 4
It is preferable not to set the temperature at a temperature lower than 0°C, and it is usually set in a range of 0 to 20°C lower than the freezing temperature.

Furthermore, in order to adjust the pore size, first the polymer solution is heated as low as possible, preferably 40 to 200 degrees below the freezing temperature.
℃ quickly freezing at a low temperature, and then increasing the temperature to an arbitrary temperature slightly lower than the freezing temperature,
The crystal growth of the solvent can be controlled by changing the holding time at that temperature.

That is, in the method of the present invention, since the shape and size of the pores are determined by the shape and size of the solvent crystals, the key point is how to control the growth of the solvent crystals. In the present invention, by rapidly freezing at an ultralow temperature and then arbitrarily setting the temperature and time for growing solvent crystals, it is possible to control the pore diameter within a range even if the polymer solution is the same.

In the method of the present invention, the frozen polymer solution is then treated by extracting and removing the solvent in which the polymer is dissolved or by lowering its solubility (hereinafter, these treatments are collectively referred to as "solvent removal, etc."). ”), and solidified porous polymer material.

Methods such as solvent removal include displacement dilution precipitation or precipitation with a non-solvent that is normally used during wet molding of polymer solutions, solvent extraction, acid-alkali neutralization reaction, and coagulation methods such as removal of solubility by modification of the polymer. can be applied as is.

Conditions such as solvent removal are not particularly limited. Normally, it is sufficient to quickly introduce the frozen polymer solution into a coagulation bath that has been cooled to below the freezing temperature of the polymer solution. It is preferable to lower the temperature by 10°C or more.

The porous polymer material from which the solvent has been removed is then washed with water or other cleaning agents, and if necessary, subjected to drying, liquid replacement, etc., and then subjected to post-treatment. The washing and drying conditions are not particularly limited either, and conditions may be arbitrarily selected depending on the application.

〔Example〕

Hereinafter, the method of the present invention will be specifically explained with reference to Examples.

The diameter of the particles and the diameter of the thread were measured using an optical microscope at an appropriate magnification. The microparticles having a diameter of 50 mm or less and the diameter of the openings on the surface were subjected to gold sputtering treatment and then enlarged to an appropriate magnification using a scanning electron microscope (SIEM) for observation and measurement.

The undried product was rapidly cooled with liquid nitrogen to freeze while maintaining its structure, and then freeze-dried (freeze-drying treatment) in a vacuum of 0.1 torr, followed by SEM observation. The open pore diameter and film thickness inside the porous carrier were determined by freezing it with liquid nitrogen as described above, cutting it at the same temperature, drying it in a vacuum, and then observing the cross section with an SEM. I asked for it.

Regarding the particle size, pore size, etc., if they were not a true sphere or a perfect circle, they were defined as the shortest diameter.

Comparative Example 1 Polystyrene with a molecular weight of 30,000 was dissolved in benzene to obtain a 2% solution. 5 g of this solution was placed in a polyethylene bag, deaerated, sealed, placed on a flat plate, and frozen at -10°C. -10℃
After maintaining the temperature for 8 hours, the polyethylene bag was removed at the same temperature, and freeze-drying was performed in a vacuum of 0.1 torr.
A porous film with a thickness of about 1 mm was obtained.

After depositing gold on this film, it was subjected to scanning electron microscopy (SBM).
When observing the surface at
There was also /ffl.

Example 1 3 g of chitosan (manufactured by Tokyo Kasei) was dissolved in a 1.5% aqueous hydrochloric acid solution to obtain a 3% aqueous chitosan solution.

On the other hand, silicone oil (KF9 manufactured by Shin-Etsu Silicone Co., Ltd.)
6) 2β to 3! Place in a beaker and cool at -20°C.
When the chitosan solution was dropped into this oil using a syringe, the droplets of chitosan solution slowly settled in the silicone oil, became spherical, froze, turned white, and reached the bottom of the beaker. After raising the temperature of this silicone oil to 10℃ and leaving it for 30 minutes, -7℃
500 cc of 10% ammonia aqueous solution was put into a beaker.

When the material that reached the bottom of the beaker was washed with hexane and water, chitosan particles with a diameter of 5 mm were obtained. This particle is a spherical particle with a sponge function that deforms when pressure is applied with a finger and expels the water inside, but it quickly recovers its shape when the pressure is removed. It turned out to be a structure.

After freeze-drying the particles, the surface of the particles was observed using a scanning electron microscope, and it was found that 50 to 100 pores were uniformly formed on the surface. The membrane separating the pores was about 2 to 3 microns (see Figure 2).

Example 2 Silicone oil (KP96 manufactured by Shin-Etsu Silicone Co., Ltd.) cooled to 30°C was prepared, and an aqueous solution of 2% IJium concentration (alginic acid prepared by dissolving sodium alginate (manufactured by Tokyo Kasei) in a 1% aqueous sodium hydroxide solution) was prepared. Pore diameter 100
When extruded into silicone oil using a 17 m syringe, it froze in the form of a thread. The temperature of the silicone oil was raised to -12°C, and after being left for 3 hours, it was poured into a 50% aqueous sulfuric acid solution at -20°C, and after being kept at -20°C for 1 hour, the alginic acid-based product was taken out.

Separately from the syringe, an extrusion experiment of the above alginic acid solution was carried out through a goo with a slit width of 100cm and a slit length of 15cm, and an alginic acid film was obtained by the same treatment.

After washing with water, we observed the thread and film using an optical microscope.
The thread diameter is 120mm and the film thickness is 120μm, both of which are 1.
It was observed that pores with a diameter of 0 to 40 tones were uniformly opened from the surface.

In addition, when observed with SEM, the diameter of the membrane separated by 10
It was confirmed that the fibers and film had a shape of aggregates of ~40 pm vacuoles. Observation at high magnification revealed that the membrane separating the vacuoles formed a partially open continuous pore structure (see Figure 3). The thickness of the diaphragm is 1~
It was 27/ffl.

〔Effect of the invention〕

The porous polymer material produced by the method of the present invention is about 2//
It has the characteristics that vacuoles larger than m are distributed relatively uniformly, the spatial volume thereof is extremely high, and the septa that form the vacuoles are extremely thin.

This porous body is suitable for catalysts, enzymes, pharmaceutical carriers, ion exchangers, raw materials for adsorbents, microcarriers for cell culture, and the like.

[Brief explanation of the drawing]

FIG. 1 is a scanning electron microscope (SEM) photograph showing the surface of an example of a conventional porous polymer material, and FIG. 2 is an SEM photo showing the surface of an example of a porous polymer material obtained by the method of the present invention.
FIG. 3 is a SEM photograph showing the surface of another example of a porous polymer obtained by the method of the present invention.

Claims (1)

[Claims] The membrane-separated diameter is characterized in that a polymer (excluding cellulose) solution is cooled to below the solidification temperature of the polymer solution, frozen, and then the solvent is extracted away or the solubility is lost. having numerous vacuoles larger than about 2 μm;
A method for producing a porous body, wherein the blank pores form a continuous pore structure that communicates with each other through openings in a membrane that separates adjacent vacuoles.