JP2009280753A - Method for producing dry powder of porous polymer particle - Google Patents

Abstract

Provided is a method for efficiently removing a solvent remaining in a particle without damaging the porous structure on the surface and obtaining a dry powder of the porous polymer particle from a suspension of the porous polymer particle. .
In a method for producing a dry powder of porous polymer particles, a porous polymer particle cake is obtained by filtering a dispersion of porous polymer particles and filtering the dispersion. A dispersion of porous polymer particles is put into the container 1 and filtered to obtain the porous polymer particles as a cake, and then dried while heating the porous polymer particles under reduced pressure in the filtration container 1. A method for producing a dry powder of porous polymer particles, characterized in that a gas is supplied from the bottom of the container and the porous polymer particles are dried while flowing.
[Selection] Figure 1

Description

  The present invention is, for example, from a dispersion of porous polymer particles obtained by suspension polymerization using an organic solvent as a porous agent in water, resulting in a small amount of residual solvent and damage to the surface porous structure. The present invention relates to a method for producing a dry powder of porous polymer particles having a low content.

  Conventionally, porous polymer particles are used in ion exchange resins, adsorbents for various applications, carriers for protein synthesis, and the like. In recent years, porous polymer particles are used for synthesis of antisense oligo DNA and siRNA used as pharmaceuticals. As a carrier (see, for example, Patent Document 1), there is a need for a method for more efficiently producing porous polymer particles with fewer impurities. In particular, in the carrier for synthesis such as antisense oligo DNA or siRNA, the solvent remaining as an impurity in the porous polymer particles inhibits the synthesis of antisense oligo DNA or siRNA, so that a very low residual solvent amount is required. The

  In general, since the porous polymer particles are relatively easy to operate and are low in cost, an organic solvent (for example, 2-ethylhexanol, decanol) is used as a porous agent for the monomer and the polymerization initiator. In a relatively high-boiling organic solvent, etc.), which is then dispersed in water containing a dispersant, and subjected to suspension polymerization.

  Thus, when producing porous polymer particles by suspension polymerization using an organic solvent as a porosifying agent, the reaction mixture containing the porous polymer particles obtained by suspension polymerization is filtered and obtained. The obtained porous polymer particles are washed with water, and then washed with a relatively low boiling point organic solvent (for example, methanol, acetone, etc.) as a washing solvent, and contain the organic solvent used as the porous agent. After removing various impurities, filtration is performed to obtain a cake of porous polymer particles, which is dried to obtain a dry powder of porous polymer particles with a small amount of residual solvent. Therefore, in the case of producing porous polymer particles in this way, the residual solvent is an organic solvent used as a cleaning solvent.

  Conventionally, such a dry powder of porous polymer particles is obtained by transferring a reaction mixture obtained by suspension polymerization to a filtration device, and obtaining porous polymer particles as a cake by centrifugation, filtration treatment, etc. The cake is manufactured by transferring it to a drying device and drying it. However, according to such a method, the reaction mixture obtained by suspension polymerization is transferred to a filtration device, and loss and impurities are removed while the obtained porous polymer particle cake is transferred to a drying device. In addition to the risk of contamination, there are problems of poor production efficiency.

  In order to solve such problems, recently, an apparatus capable of performing drying in a single container along with cleaning and filtration of porous polymer particles has been developed. As a drying method in such an apparatus, hot air / air blowing drying, heating drying, freeze drying, vacuum / vacuum drying, and the like are possible. In order to efficiently reduce the residual solvent in the porous polymer particles. Among them, a heating vacuum drying method combining heating and vacuum is advantageous. However, when the production scale of the porous polymer particles is large, the heating vacuum drying method increases the volume of the porous polymer particles, and the heat transfer efficiency into the cake of the porous polymer particles is deteriorated. For this reason, there is a problem that it takes time to dry and the manufacturing cost increases.

  In order to increase the drying efficiency of the cake of porous polymer particles, a stirrer is provided in the apparatus, the cake is stirred and crushed and dried, the entire apparatus is rotated, and the cake is stirred and crushed and dried. There have been proposed devices in which the porous particles are dried while being mechanically stirred and crushed, such as a method of applying the vibration to the inside of the device and drying the cake while stirring and pulverizing the cake.

However, as described above, since the porous polymer particles obtained by suspension polymerization still contain the organic solvent used as the porosifying agent in the voids, the weight is increased. In addition, since the porous polymer particles are also swollen by the solvent, the strength of the porous polymer particles is reduced. As described above, the cake of the porous polymer particles is mechanically When drying while stirring and crushing, the porous structure on the surface of the porous polymer particles is crushed and the quality of the product is degraded.
Japanese Patent Laid-Open No. 03-068593

  The present invention has been made to solve the above-described problems in the production of dry powder of porous polymer particles, and efficiently removes impurities including residual solvent without damaging the porous structure of the surface. An object of the present invention is to provide a method for obtaining a dry powder of porous polymer particles from a suspension of porous polymer particles.

  According to the present invention, the dispersion of the porous polymer particles is filtered to obtain a cake of the porous polymer particles, and the method for producing a dry powder of the porous polymer particles for drying the cake comprises a filter medium. The dispersion liquid of the porous polymer particles is charged into the filtered container and filtered to obtain the porous polymer particles as a cake, and then dried while heating the porous polymer particles under reduced pressure in the filtration container. There is provided a method for producing a dry powder of porous polymer particles, characterized in that a gas is supplied from the bottom of the container and the porous polymer particles are dried while flowing.

  According to the method of the present invention, for example, from a dispersion of porous polymer particles obtained by suspension polymerization, the amount of residual solvent is small, and the porous polymer particles with little damage to the multi-surface porous structure are obtained. A dry powder can be obtained.

  In the present invention, the porous polymer particles are not particularly limited, but as a preferred example, an aromatic vinyl monomer such as styrene and an aromatic divinyl monomer such as divinylbenzene and, if necessary, Other monomers are dissolved in an organic solvent as a porosifying agent together with a polymerization initiator, dispersed in water containing a dispersant, and subjected to suspension polymerization.

  In the present invention, the particle diameter of such porous polymer particles is not particularly limited. However, the ion exchange resin as described above, an adsorbent in various applications, a carrier for protein synthesis, oligo DNA, When used as a carrier for synthesizing siRNA, etc., the median particle diameter is usually in the range of 2 to 3000 μm, preferably in the range of 10 to 1000 μm, and most preferably in the range of 40 to 200 μm.

  In the present invention, examples of the dispersion of the porous polymer particles include a dispersion containing the porous polymer particles obtained by suspension polymerization as described above, but are not limited thereto. For example, the dispersion containing the porous polymer particles obtained by the above suspension polymerization is filtered and washed, and the dispersion obtained by dispersing the obtained porous polymer particles in a solvent is also used in the present invention. It is a dispersion of porous polymer particles. In short, in the present invention, the dispersion of porous polymer particles refers to a dispersion of porous polymer particles in a solvent. Here, the solvent may be water or an organic solvent.

  According to the present invention, the dispersion of the porous polymer particles is filtered to obtain a cake of the porous polymer particles, and the method for producing a dry powder of the porous polymer particles for drying the cake comprises a filter medium. The dispersion liquid of the porous polymer particles is charged into the filtered container and filtered to obtain the porous polymer particles as a cake, and then dried while heating the porous polymer particles under reduced pressure in the filtration container. A dry powder of porous polymer particles is obtained by supplying gas from the bottom of the container and drying while flowing the porous polymer particles.

  A preferred example of a filtration device that can be suitably used to carry out such a method according to the invention is shown in FIG. This filtration device has a lower opening 2 at the bottom of a cylindrical container 1 and an upper opening 3 at the top. The lower opening is used as an opening for draining the filtrate when the dispersion is filtered, and as an opening for feeding dry air into the container.

  An annular filter medium support frame 4 is provided along the peripheral wall at the lower part of the container, and a filter medium support 5 through which a solvent can pass is placed on the support frame. The filter medium support is, for example, a metal plate or a metal net having a large number of through holes, but is not limited thereto. The filter medium 6 is placed on this filter medium support.

  The container further includes a stirring device 7, which supports the shaft body 8 at the top of the container so as to be rotatable and movable up and down in the axial direction in the container. A stirring blade 9 extending in the radial direction of the container is provided at the lower end of the shaft. Further, the container has a jacket 10 along the peripheral wall, and also has a jacket 11 at the bottom, and a dispersion medium or cake in the container is circulated by circulating a heating medium such as hot water in the jacket. Can be heated to a predetermined temperature.

  The filter medium is not limited in any way. For example, filter paper, stainless sintered filter, glass fiber filter paper, glass sintered filter, polypropylene or polyethylene filter cloth, nylon mesh, or the like is used. Among these, a single-layer nylon mesh has chemical resistance, strength, and good filterability, is thin and lightweight, is easy to handle, and is preferably used. The opening of the nylon mesh is not particularly limited, and may be appropriately selected according to the particle diameter of the porous polymer particles to be filtered. The thing of an opening is preferable.

  In particular, as compared with a filter medium having a multilayer structure, a single layer nylon mesh is less likely to be clogged when filtering porous polymer particles, and in the subsequent drying step, it is introduced into the container from the lower opening at the bottom of the container. It is preferably used because of high air permeability when dry air is fed. Furthermore, even if some clogging occurs during filtration, the single-layer filter medium is naturally freed from clogging during ventilation in the subsequent drying process, and air permeability is ensured. The coalesced particles can be dried.

  The production of the dry powder of the porous polymer particles according to the present invention will be described in detail with reference to such a filtration device. For example, a reaction mixture containing porous polymer particles obtained by suspension polymerization is charged into a container of a filtration device as a dispersion, and first, preferably filtered under pressure or reduced pressure, to obtain a porous polymer Get a cake of particles. If necessary, water or an organic solvent is added to the container as a washing liquid, stirred and redispersed, washed, and then filtered preferably under pressure or under reduced pressure to form porous polymer particles. Get a cake. In this way, the porous polymer particles are sufficiently washed to obtain a cake of porous polymer particles from which impurities are sufficiently removed.

  When using water for washing, those with less impurities are preferred, ion-exchanged water, purified water, distilled water, ultrapure water, etc. are used, and when using an organic solvent, it is not particularly limited, A solvent having a relatively low boiling point such as methyl alcohol, ethyl alcohol, propyl alcohol, hexane, toluene, and acetone is used. These organic solvents are used alone or in combination of two or more.

  When the reaction mixture containing the porous polymer particles obtained by suspension polymerization is used as a dispersion and is filtered and washed as described above, the reaction mixture is first washed with water, It is preferred to filter to remove the aqueous phase containing the dispersant, then wash and filter using an organic solvent as the washing solvent to remove the organic solvent used as the porosifying agent in the suspension polymerization. .

  Thus, according to the present invention, the cake of porous polymer particles obtained by filtering and washing the dispersion of porous polymer particles is then dried in the same filtration apparatus. That is, a heating medium adjusted to a temperature at which the porous polymer particles are not melted or fused between the particles is circulated in the jacket to heat the cake in the container to a predetermined temperature, and at the same time, the upper opening is vacuumed. The pressure inside the container is reduced so that the degree of vacuum is −0.05 MPa or less, preferably −0.08 MPa or less by connecting to a pump, and the atmospheric pressure dew point is passed through the filter medium from the lower opening of the container. While supplying dry air of −5 ° C. or lower, preferably −15 ° C. or lower, and thus pulverizing the cake of porous polymer particles with dry air under reduced pressure, the porous polymer particles are flowing. ,dry. In this case, if necessary, a bag filter may be provided between the upper opening and the vacuum pump to prevent the outflow of the porous polymer particles, and a cooling condenser for recovering the volatilized solvent. A trap such as the above may be provided.

  The amount of dry air flowing into the container may be set according to the size of the apparatus, the capacity of the porous polymer particle cake to be dried, the capacity of the vacuum pump, and the like. If the air flow rate is excessive, depending on the capacity of the vacuum pump, the inside of the container cannot be maintained at a predetermined degree of vacuum, so that the drying efficiency is lowered. On the other hand, if the air flow rate is too low, the porous particles Cannot be made to flow well, resulting in “unevenness” in the drying of the porous polymer particles, and the drying efficiency decreases.

Example 1
(Washing and filtration process)
In the filtration apparatus shown in FIG. 1 in which the inner diameter of the container is 550 mm, a 3 mm-thick stainless steel plate having a number of through-holes having a diameter of 6 mm is used as a filter medium support, and a filter medium (made by NRK, nylon mesh) is used thereon. , 45 μm openings).

  56 kg of acetone was added to 12 kg of dried porous polymer particles having a median particle diameter of 90 μm (product name: NittoPhase, manufactured by Nitto Denko Corporation), and the mixture was stirred to disperse the porous polymer particles in acetone. After this dispersion was charged into the container of the filtration device, air was supplied into the container through the upper opening and filtration was performed under a pressure of 0.01 MPa to obtain a cake of porous polymer particles. The position of the stirring blade during the filtration is indicated by a solid line in FIG.

  Next, 42 kg of methanol was added to the container, stirred with the cake of porous polymer particles, pulverized, the porous polymer particles were dispersed in methanol, stirred and washed, and then added again as described above. Filtration was performed under pressure. This operation was performed twice to obtain a cake of porous polymer particles in which the pores of the porous polymer particles were replaced with methanol. The position of the stirring blade at the time of stirring is indicated by a broken line in FIG.

(Drying process)
While circulating hot water at a temperature of 85 ° C. through the peripheral wall and bottom jacket of the filtration device and heating the cake of porous polymer particles in the container, the top opening is connected to a vacuum pump to reduce the pressure in the container, Dry air having an atmospheric pressure dew point of −17 ° C. is supplied into the container through the filter medium at a rate of 6 L / min from the lower opening at the bottom of the container to break up the cake, and thus the inside of the container has a gauge pressure of −0.09 MPa. The porous polymer particles were dried under fluidization for 24 hours while maintaining the reduced pressure to obtain a dry powder of porous polymer particles having a residual methanol amount of almost zero.

  Further, when the surface of the dry powder of the porous polymer particles obtained in this way was observed with a scanning electron microscope, the surface porous structure was not crushed as shown in FIG. It was.

Comparative Example 1
When drying the cake of porous polymer particles obtained in the washing and filtering step of Example 1 with a filtration device, hot water of 85 ° C. was supplied to the jacket without supplying dry air from the bottom into the container. While circulating, the inside of the container was evacuated to a gauge pressure of -0.1 MPa, and the cake was dried to obtain a dry powder of porous polymer particles.

  According to such a method, even after the cake was dried for 40 hours, the amount of residual methanol in the obtained powder was 240 μg / g. However, when the surface was observed with a scanning electron microscope, the porous structure on the surface was not crushed.

Comparative Example 2
When drying the porous polymer particle cake obtained in the washing and filtering step of Example 1 with a filtration device, 85 ° C. hot water is circulated through the jacket without supplying dry air from the bottom into the container. While making the inside of the container a vacuum of gauge pressure -0.1 MPa, the cake was stirred and pulverized at a speed of 5 rpm with a stirrer, and dried to obtain a dry powder of porous polymer particles. .

  According to such a method, it was possible to obtain a dry powder of porous polymer particles having a residual methanol amount of 20 μg / g by drying for 24 hours. When the surface was observed, as shown in FIG. 3, the porous structure of the surface was significantly crushed.

1 is a cross-sectional view illustrating an example of a filtration device that can be suitably used to carry out the method of the present invention. It is a scanning electron micrograph (20000 times) of the surface of an example of the dry powder of the porous polymer particle obtained according to the method of this invention. It is a scanning electron micrograph (20000 times) of the surface of the dry powder of the porous polymer particle obtained as a comparative example.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 ... Container 2 ... Lower opening 3 ... Upper opening 4 ... Filter medium support frame 5 ... Filter medium support body 6 ... Filter medium 7 ... Agitation apparatus 8 ... Shaft body 9 ... Agitation blade

Claims (1)

In a method for producing a dry powder of porous polymer particles, a porous polymer particle cake is obtained by filtering a dispersion of porous polymer particles to obtain a cake of the porous polymer particles. A dispersion of polymer particles is charged and filtered to obtain porous polymer particles as a cake.Then, while the porous polymer particles are heated under reduced pressure in a filtration container, a dry gas is introduced from the bottom of the container. A method for producing a dry powder of porous polymer particles, characterized by supplying and drying while allowing the porous polymer particles to flow.