JPH0579252B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to a method for producing polymer particles (porous uniform polymer particles) which are porous from the surface to the inside and have a narrow particle size distribution. More specifically, the present invention relates to a method for producing porous uniform polymer particles that can be used as base materials for ion exchange resins, fillers for chromatography, carriers for enzyme immobilization, carriers for affinity chromatography, and the like.

[Prior Art/Problems to be Solved by the Invention] Dispersion methods and spray methods are known as methods for producing spherical polymer particles.

In the dispersion method, a dilute polymer solution is dispersed into small droplets in a dispersion medium containing a surfactant, and the solvent is evaporated from the droplet-shaped polymer solution to solidify it (see Japanese Patent Application Laid-Open No. 56-24430). ) Spherical polymer particles are obtained by a method such as gradually adding small droplets of a coagulant to this dispersion and solidifying it (see Japanese Patent Application Laid-Open No. 159801/1983).

However, the particles obtained by this method have a wide particle size distribution, and washing with water alone is insufficient to remove the solvent, dispersion medium, surfactant, etc. from the solidified droplets, and washing with an organic solvent is required. It is.

As an alternative to the dispersion method, a method is also known in which polymerizable monomers are dispersed in a dispersion medium and then polymerized to obtain spherical polymer particles. When the particles obtained by this method are magnified using an electron microscope, it is observed that the fine spherical particles have aggregated into spherical particles.

The particles obtained by this method also have a wide particle size distribution, and when a suspension of the particles is stirred with a magnetic stirrer, a large amount of small polymer debris, which is thought to be due to the above structure, is generated. Occur.

On the other hand, in the spray method, spherical polymer particles are produced by spraying a polymer solution into a coagulant. These particles also have a wide particle size distribution and are relatively large (see Japanese Patent Laid-Open No. 129788/1983).

In recent years, a technology (hereinafter referred to as
A method of obtaining spherical polymer particles with a narrow particle size distribution by applying it to a method in which polymerizable monomers are dispersed in a dispersion medium and polymerized has already been proposed (Japanese Patent Application Laid-Open No. 57−
(See Publication No. 102905).

However, this particle has the same drawback as the dispersion method, in that it tends to generate polymer debris.

[Means for Solving the Problems] The present inventors have worked diligently to eliminate the various drawbacks of the conventional methods and to find a method that can easily produce spherical porous uniform polymer particles that do not generate minute polymer debris. As a result of repeated research, we have completed the present invention.

That is, in the present invention, a polymer solution having a cloud point is ejected from an opening into the gas phase in the form of uniformly sized droplets at a constant flow rate while adding a constant periodic turbulence. After being charged with an electric charge, the droplet is brought to a temperature below the clouding point, and then the droplet is allowed to penetrate into a coagulating liquid that has a surface tension such that the droplet naturally wets the droplet, and is solidified. The present invention relates to a method for producing porous uniform polymer particles.

[Example] In the present invention, a polymer solution that can have a cloud point is used.

The term "having a cloud point" means that after dissolving a polymer in a solvent, the obtained solution is cooled, or a part of the good solvent is evaporated from a solution using a good solvent and a poor solvent or a non-solvent. A cloud point occurs when a solution absorbs a poor solvent. As mentioned above, when the temperature reaches below the clouding point, the polymer solution separates into a coagulated polymer phase and a phase mainly composed of solvent, and if this state is solidified, 3
A dimensional network structure can be obtained.

the type of polymer constituting the polymer solution;
There are no particular limitations on molecular weight, etc., and any polymer can be used as long as it is a polymer from which a polymer solution having a cloud point can be prepared.

Specific examples of such polymers include cellulose-based polymers such as cellulose, cellulose derivatives, and regenerated cellulose; silk-based polymers such as silk fibroin; chitin-based polymers such as chitosan; natural polymers such as collagen, alginates, carrageenan, and starch. Polymers; vinyl polymers such as polyacrylonitrile, polymethyl methacrylate, polyhydroxyethyl methacrylate, polystyrene, polyvinyl acetate, polychloromethylstyrene, polyvinyl alcohol, polyvinyl chloride, or vinyl monomers that become these polymers, and is a copolymer with other monomers, such as ethylene-vinyl alcohol copolymer; 6-nylon, 6,6-nylon, polyethylene terephthalate, polybutylene terephthalate, polysulfone, or various polyurethanes, polyamino acids, etc. Examples include synthetic polymers such as polycondensation polymers, which can be dissolved in a solvent suitable for each polymer to prepare a polymer solution having a cloud point.

The solvent constituting the polymer solution is not particularly limited, and any solvent can be used as long as it can produce a polymer solution that can have a clouding point.

For example, when the polymer is cellulose diacetate, specific examples of solvents that produce a clouding point simply by lowering the temperature of the solution include dimethylformamide, dimethylacetamide, dimethyl sulfoxide, N-methyl-2-pyrrolidone, and other non-volatile solvents. For example, if a part of the good solvent is evaporated from the solution to a temperature below the clouding point, such as a mixed solvent of a good solvent and a refractory non-solvent such as a polyhydric alcohol such as ethylene glycol, propylene glycol, or glycerin. Specific examples of suitable solvents include volatile good solvents such as acetone, tetrahydrofuran, and dioxane, and ethanol, propanol, butanol, water, ethylene glycol,
Specific examples of solvents used when a solution absorbs a poor solvent or non-solvent to bring the temperature below the clouding point, such as mixed solvents with relatively non-volatile to non-volatile non-solvents such as propylene glycol, glycerin, and formamide. For example, in the above-mentioned refractory good solvent,
Specific examples of gaseous nonsolvents to be absorbed include mixed solvents with a nonvolatile nonsolvent added so that the cloud point is below the temperature of the gas phase, and volatile poorsolvents such as water, methanol, and ethanol. can be given.

There are no particular limitations on the concentration, viscosity, etc. of the polymer solution that can have the above-mentioned cloud point, but in the present invention, the polymer solution is heated at a constant flow rate to a uniform size while adding a constant periodic turbulence. Since the liquid must be ejected into the gas phase from the opening as small droplets, the viscosity at a temperature higher than the cloud point is preferably about 20 to 2000 cP, more preferably about 50 to 1000 cP. When the viscosity is less than about 20 cP, the concentration of the polymer in the liquid is too low, and the strength of the resulting polymer particles becomes weak.
When it exceeds about 2000 cP, it tends to become difficult to form droplets with uniform particle size.

The solution concentration that provides a polymer solution with the above-mentioned viscosity is usually about 3 to 30% (weight %, the same applies hereinafter), preferably about 5 to 20%.

The flow rate when jetting the polymer solution into the gas phase from the opening is usually about 3 to 30 m/sec, preferably about 5 to 20 m/sec, but is not limited to these ranges. , the viscosity of the polymer solution, a certain periodic turbulence added at the time of ejecting the polymer solution, which will be described later, the size of the opening, etc., and may be appropriately selected and set.

The periodic turbulence when the polymer solution is ejected from the opening into the gas phase is usually 1000~
40,000 Hz, preferably about 2,000 to 30,000 Hz is adopted, but it is not limited to these ranges, and may vary depending on the concentration of the polymer solution, the flow rate when spouting into the gas phase from the opening, the size of the opening, etc. You can select and set the settings as appropriate.

The openings are usually a plurality of holes provided in the center of the nozzle of the device as described in, for example, Japanese Patent Application Laid-Open No. 62-191033, and are generally circular in shape and have a diameter of 10 to 10 mm. The thickness is about 500 μm, preferably about 20 to 300 μm. opening size,
The shape etc. may be appropriately selected depending on the size of porous uniform polymer particles to be produced.

Examples of the gas phase include, for example, air, a non-solvent that is absorbed into the droplets to bring the droplets formed from a polymer solution, which may have a cloud point, to a temperature below the cloud point, such as when the polymer is cellulose acetate. In this case, examples include an environment containing the above-mentioned non-solvent in a gaseous state, and an environment in which a good solvent present in the droplets is evaporated to a temperature below the clouding point.

There are no particular limitations on the temperature and pressure of the gas phase, but if the temperature is to be lowered to reach the clouding point, it is preferably around room temperature, and the clouding point can be achieved by volatilizing the good solvent in the droplets. When the temperature is below the clouding point, it is preferable that the temperature and pressure be such that the good solvent evaporates easily, and when the temperature is below the clouding point by absorbing a poor solvent or non-solvent gas into the droplets, Preferably, the air is at a saturating concentration thereof.

After the droplets from the polymer solution are ejected into the gas phase, they are charged to have the same sign of charge.
When droplets have charges of the same sign, it becomes difficult for the droplets to coalesce while flying in the gas phase, making it easier to obtain particles with a uniform size (JH
Shneider and CDHendricks，Review of
Scientific Instruments, 35 1349 (1964)).

As a method of imparting charges of the same sign to droplets,
For example, there is a method in which a parallel plate-shaped electrode is installed in front of the nozzle of the apparatus described in the above-mentioned Japanese Patent Application Laid-Open No. 62-191033, and a DC voltage is applied between the electrode and the nozzle.

The droplets, which are ejected into the gas phase in a solution state and given an electric charge of the same sign, fly through the gas phase and, after reaching a temperature below the clouding point, are It is made to penetrate into a coagulating liquid that has a surface tension such that it becomes wet.

The temperature at which the polymer solution is jetted is not particularly limited as long as the polymer solution can maintain a uniform solution state, but if the polymer solution is cooled to a temperature below the cloud point, The temperature is preferably about 5 to 20 degrees Celsius higher than the cloud point of
The good solvent is evaporated from the polymer solution to a temperature below the cloud point.

Alternatively, when the droplets are made to absorb a poor solvent or non-solvent gas to bring the temperature below the clouding point, the temperature is preferably about room temperature.

The term spherical is a concept that includes not only a substantially perfect sphere but also an elliptical rotating body with a minor axis/major axis of approximately 0.8.

There is no particular limit to the distance that a droplet flies in the gas phase, and it can be any distance as long as the temperature of the droplet is below the clouding point, but a distance of about 0.3 to 5 m is usually adopted; preferable. When the distance is less than 0.2 m, many droplets are not spherical, and many droplets enter the coagulation liquid before the temperature reaches the clouding point or lower. Furthermore, when the distance exceeds 5 m, even if the droplets are charged with the same sign, they tend to coalesce more often due to flying ashes caused by air resistance.

It is very difficult to directly measure that the temperature of the droplet is below the clouding point when it enters the coagulation liquid.

Therefore, in the present invention, as described by Ratspel et al.
Lappel and CBShepherd，Industrial and
Engineering Chemistry, 32 (5) 605 (1940)), find the air resistance and droplet velocity every 1/100 seconds, calculate the flight time, and calculate the temperature drop during this flight time using the Lantz formula. (WERanz and WR
Marshall, Chemical Engineering Progress, 48
247 (1952)).

Note that the temperature determined in this way does not take into account the temperature drop due to evaporation of the solvent, and it is thought that the temperature will be lower by this amount.

The coagulating liquid used in the present invention with a surface tension high enough to naturally wet the droplets is a non-solvent or poor solvent for the polymer used that has a relatively low surface tension; An aqueous solution of , an aqueous solution of a surfactant, an aqueous solution of a good solvent, etc. can be used.

The temperature of the coagulating liquid is not particularly limited, and any temperature can be used as long as it acts as a coagulating liquid, but a temperature of about 0 to 60°C is preferred from the viewpoint of ease of handling.

As mentioned above, when the temperature of the droplets reaches below the clouding point and the polymer has separated to a certain extent, it is allowed to enter the coagulation liquid. For example, three-dimensional mesh-like particles having a porous interior as shown in FIG. 2, for example, as shown in FIG. 3, can be obtained. In addition, FIG. 4 is a photograph in which approximately 2/3 of the part from the lower left to above the right center of the photograph shows the interior of the particle, and approximately 1/3 of the part from the lower left to below the right center shows the particle surface.

Although there is no particular limitation on the diameter of the pores present on the surface of the porous polymer particles, those having a diameter in the range of about 0.01 to 1 μm can be easily produced. Also, the internal 3
Although there is no particular limitation on the diameter of the pores that form the dimensional network structure, those in the range of about 0.1 to 10 μm can usually be easily produced.

Further, there are no particular limitations on the number average particle diameter of the porous polymer particles, but those having a range of about 10 to 100 μm can be easily produced. Further, as for the particle size distribution, particles in which 95% or more of the particles are within ±10% of the number average particle size can usually be produced.

The porous uniform polymer particles thus produced by the method of the present invention have a porosity of about 50 to 95%, and are uniform and have a narrow particle size distribution, so they can be used as fillers for chromatography. It can be used for applications such as enzyme immobilization carriers, affinity chromatography carriers, and base materials for ion exchange resins, and when used in these applications, pressure drop, selectivity, and fraction sharpness It is excellent in terms of speed, adsorption and desorption speed, etc.

Next, the manufacturing method of the present invention will be explained based on Examples.

Example 1 Cellulose diacetate was dissolved in a mixed solution of dimethyl sulfoxide/propylene glycol in a weight ratio of 21/79 to a concentration of 5%. The cloud point of the resulting solution was 72°C.

Parallel plate-shaped electrodes with a width of 5 cm and a length of 5 cm in the direction of droplet flight are installed at a distance of 2 cm 5 mm in front of the nozzle, and a 500 V DC current is applied between the electrodes and the nozzle. A voltage was applied. From the circular orifice with a diameter of 50 μm provided in this nozzle, 91
The above solution kept at ℃ was heated at 25.5k at a linear speed of 25m/sec.
The solution was ejected while applying Hz vibration to form uniform droplets. After flying about 0.4 m in the gas phase at 20°C, a neutral surfactant (polyoxyethylene sorbitan monolayer) was added at 20°C. Cellulose diacetate particles were obtained by coagulating the particles into an aqueous solution containing 0.5% of cellulose diacetate. The temperature of the droplet before entering the coagulation liquid is estimated using the method described above to be 38°C, which is 34°C below the cloud point.
The temperature was low.

The number average particle size of the obtained cellulose diacetate particles was measured by the method described below and was found to be 155 μm, which was within ±5% of the number average particle size.

The resulting cellulose diacetate particles were thoroughly washed with methanol, vacuum-dried at room temperature, gold was deposited on them, and the surface and cross section were observed using a scanning electron microscope. There were many pores with similar pore diameters in the cross section, resulting in a porous three-dimensional network composition.

Figure 1 is an electron micrograph of the particle surface observed at 15,000x magnification, and Figure 2 is a cross-sectional view of the particle.
This is an electron micrograph observed at 15,000x magnification.

(Number average particle size and particle size distribution) Optical microscopic images of several hundred particles (approximately 500 to 1000 particles) are processed using an image processing device (Ruzetskus manufactured by Nireco Co., Ltd.).

Example 2 Cellulose diacetate was dissolved in a mixed solution of dimethyl sulfoxide/propylene glycol at a weight ratio of 4/6 to a concentration of 6%. The cloud point of the resulting solution was 30°C.

Parallel plate-shaped electrodes with a width of 5 cm and a length of 5 cm in the direction of droplet flight are installed at a distance of 2 cm 5 mm in front of the nozzle, and a 500V DC current is applied between the electrodes and the nozzle. A voltage was applied. From the circular orifice with a diameter of 40 μm provided in this nozzle, 68
The above solution kept at ℃ was heated at 25.5K at a linear speed of 17m/sec.
The solution was ejected while applying Hz vibration to form uniform droplets. After flying about 1.7 m in the gas phase at 20°C, a neutral surfactant (polyoxyethylene sorbitan monolayer) was added at 20°C. Cellulose diacetate particles were obtained by coagulating the particles into an aqueous solution containing 0.5% of cellulose diacetate. The temperature of the droplet before entering the coagulation liquid was estimated by the above method and was equal to the temperature of the gas phase and 10° C. lower than the cloud point.

The number average particle size of the obtained cellulose diacetate particles was measured by the method described below and was found to be 115 μm, which was within ±5% of the number average particle size.

The resulting cellulose diacetate particles were thoroughly washed with methanol, vacuum-dried at room temperature, gold was deposited on them, and their surfaces and cross-sections were observed using a scanning electron microscope. There were many pores with similar pore diameters in the cross section, resulting in a porous three-dimensional network composition.

Figure 3 is an electron micrograph of a polymer particle magnified 500 times, and Figure 4 shows the surface of the particle (from the bottom left of the photo to the area below the center right) and cross section (the area from the bottom left of the photo to the area above the center right). ) is an electron micrograph observed at 2,000 times magnification, and FIGS. 5 and 6 are electron micrographs of the particle surface observed at 4,000 times and 20,000 times, respectively.

Comparative Example 1 A cloud point of 42 was obtained in the same manner as in Example 1 except that the solvent used in Example 1 was changed to a mixed solvent of dimethyl sulfoxide/propylene glycol in a weight ratio of 32/68.
℃ solution was prepared, solution temperature 100℃, orifice diameter 120μm, linear discharge speed 4m/sec, frequency 400Hz,
Cellulose diacetate particles were produced in the same manner as in Example 1 except that the gas phase distance was 75 cm. The temperature of the droplets before entering the coagulation liquid was approximately 70°C, 28°C above the cloud point.

The number average particle size of the obtained cellulose diacetate particles was measured in the same manner as in Example 1, and was found to be 490 μm.
All particles were within ±5% of the number average particle diameter.

When the obtained cellulose diacetate particles were treated in the same manner as in Example 1 and the cross section including the surface was observed using a scanning electron microscope, it was found that a skin layer was present on the surface, which could be observed using a scanning electron microscope. Na
Although no pores with a pore diameter of 0.01 μm or more were observed, there were many pores with a pore diameter of about 0.2 μm inside the particles, forming a porous three-dimensional network structure.

Note that FIG. 7 is an electron micrograph of a cross section including the particle surface observed at a magnification of 15,000 times, and FIG. 8 is an electron micrograph of a cross section of the particle observed at a magnification of 15,000 times.

[Effects of the Invention] When polymer particles are produced by the method of the present invention, polymer particles that are porous from the surface to the inside and have a very small and uniform particle size distribution are produced.

[Brief explanation of drawings]

FIG. 1 and FIG. 2 are electron micrographs for explaining the surface structure and internal structure of polymer particles produced by the method of Example 1, which is the method of the present invention, and show the particle surface and particle cross section, respectively. Figure 3 is an electron micrograph for explaining the shape of polymer particles produced by the method of Example 2, which is the method of the present invention, and is a photo of polymer particles enlarged 500 times. ,
Figure 4 is an electron micrograph for explaining the surface structure (portion from the bottom left of the photograph to the portion below the center right) and cross-sectional structure (portion from the bottom left to the portion above the center right of the photograph) of the polymer particles selected in Example 2. 5 and 6 are electron micrographs of the surfaces of the polymer particles obtained in Example 2, magnified 4000 times and 20000 times, respectively. 7 and 8 are electron micrographs for explaining the cross-sectional structure including the surface of the polymer particles obtained in Comparative Example 1, and the cross-sectional structure, respectively, and are photographs in which each part is enlarged 15,000 times.

Claims (1)

[Claims] 1 A polymer solution that can have a cloud point is ejected from an opening into the gas phase as uniformly sized droplets at a constant flow rate and with constant periodic turbulence, and charges of the same sign are ejected into the gas phase. After being electrically charged, the droplet is brought to a temperature below its clouding point, and then the droplet is allowed to penetrate into a coagulating liquid having a surface tension sufficient to naturally wet the droplet, thereby solidifying the droplet. A method for producing polymer particles of uniform quality.