JP2005054023A - Method for producing polymer particles - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a new method for producing polymer particles having a small particle size but a sharp particle size distribution.
A method for producing polymer particles includes:
A method for producing polymer particles from a polymer solution comprising a polymer and a polymer-soluble solvent, comprising:
Supplying a polymer solution and a polymer poorly soluble solvent to the micromixer, and mixing the polymer solution and the poorly soluble solvent in the micromixer to phase-separate the polymer particles.
[Selection figure] None

Description

  The present invention relates to a method for producing polymer particles from a polymer solution comprising a polymer and a polymer-soluble solvent using a micromixer.

  Polymer particles such as polystyrene particles are used for calibration / performance evaluation of particle size distribution counters, foreign substance inspection devices, blood cell counters, and the like. There are various properties required for such polymer particles. For example, it is required that the particle size is small and the particle size is uniform (that is, the particle size distribution is sharp). There is a case. For example, such properties are particularly important when polystyrene particles are used in a particle size counter.

  The polymer particles are produced by various methods. For example, there is a method of obtaining a granular polymer during polymerization by emulsion polymerization or suspension polymerization. When polymer particles are continuously produced by such a method, in order to obtain polymer particles having a small particle size, polymerization is performed by rotating a stirrer at a high speed for a long time. However, even if various parameters such as the flow rate, ratio, temperature, and stirring speed of the liquid to be supplied are properly selected, it is not easy to achieve uniform mixing and has a satisfactorily controlled particle size distribution. Polymer particles cannot always be obtained.

In order to solve such a problem, a method for producing fine particles by press-fitting a liquid as a dispersed phase into a continuous phase through a microporous film body has been disclosed (see Patent Document 1). In this method, a porous film having a predetermined pore size distribution, for example, a glass porous film is used. In such a method, it is necessary to prepare in advance a porous membrane having a predetermined pore size distribution according to the dimensions of the target polymer particles. Therefore, when the size of the target polymer particle changes, it is necessary to prepare another porous film, which causes a problem that flexibility is lacking.
JP-A-2-095433

  An object of the present invention is to provide a new method for producing polymer particles having a small particle size but a sharp particle size distribution, and preferably a method having flexibility as compared with the above-described method for producing polymer particles. It is an issue to provide.

  It has been found that the above problems are solved by using a micromixer when producing polymer particles by a phase separation method. In this specification, the “phase separation method” means that a polymer constituting polymer particles is dissolved in a solvent capable of dissolving the polymer (hereinafter, such a solvent is also referred to as “polymer readily soluble solvent” or simply “easily soluble solvent”). Once dissolved completely to obtain a polymer solution, and such a polymer solution is a solvent in which the polymer is difficult to dissolve or substantially insoluble, and is compatible with a readily soluble solvent (such a solvent). Are hereinafter referred to as “polymer poorly soluble solvent” or simply “hardly soluble solvent”) to dissolve the solvents with each other to supersaturate the polymer in the solvent to generate polymer nuclei, and , Meaning the process of growing the polymer core to obtain polymer particles. Such a phase separation method can be carried out by mixing a polymer solution and a hardly soluble solvent.

Therefore, the present invention
A method for producing polymer particles from a polymer solution comprising a polymer and a polymer-soluble solvent, comprising:
Provided is a method for producing polymer particles, comprising the steps of: supplying a polymer solution and a hardly polymer-soluble solvent to a micromixer; and mixing the polymer solution and the hardly soluble solvent in the micromixer to phase-separate the polymer particles. . The polymer solution is prepared by dissolving the polymer in a polymer-soluble solvent.

  The method for producing polymer particles of the present invention using phase separation using a micromixer can easily produce polymer particles having a sharp particle size distribution.

  In the present specification, the micromixer is used to divide two fluids to be mixed into minute parts, and hold the divided minute amounts of fluids in an adjacent state, thereby allowing the two fluids to interdiffuse. Means a mixer that can achieve the same effect as mixing them. The flow path of the fluid of such a micromixer usually has an equivalent diameter of 500 μm or less, preferably 100 μm or less. The microparts of one fluid so divided are diffusively mixed (or micromixed) as described above adjacent to the microparts of the other fluid so divided. In addition to diffusive mixing, mechanical mixing (or macro mixing) can also occur, but in micromixers, diffusive mixing is dominant. The micromixer in this specification is preferably such that the representative length of a microsegment, which will be described later, as a minute portion that is theoretically considered to be formed by structural characteristics unique to the micromixer is smaller than a specific value.

  Micromixers such as those described above have been attracting attention in recent years, for example, “Microreactors New Technology for Modern Chemistry” (Wolfang Ehrfeld, Volker Hessel, published by Holger Loewe, company WILY-CH, 43, WILY-V These mixers can be used as micromixers in the method of the present invention. An example of the micromixer described here (a mode in which two types of fluids A and B are mixed) is shown in FIGS. Such a micromixer can be manufactured by, for example, a fine processing technique using microtechnology on a solid substrate.

  The micromixer shown in FIG. 1 causes a fluid to collide in a flow path, and here, a T-shaped flow path is used. When two kinds of fluids A and B collide, each of them is divided into minute portions, and these are held adjacent to each other. A micromixer as shown is useful for mixing when the volume of the flow path is small.

  The micromixer shown in FIG. 2 is one in which microdroplets of fluids A and B, which are microparts formed by a technique such as atomization, are diffused from each other so as to be adjacent to each other and contact the fluid. In this case, since a very small minute part can be obtained, a large contact interface area can be obtained.

  The micromixer shown in FIG. 3 supplies fluids A and B to a divided flow path having a minute width, and a large number of mutually adjacent subflows having a minute width flowing in the vertical direction from the flow paths (a and b respectively). Is formed as a minute portion, and these are brought into contact with each other, thereby performing differential contact diffusion mixing of two kinds of fluids. As shown in the figure, the divided flow paths of the fluid A are comb-shaped, are alternately positioned with the divided flow paths of the comb-like fluid B, and the flow path of the fluid B is positioned adjacent to the flow path of the fluid A. It has become.

  A plate having a slit extending in a minute width in a direction perpendicular to the extending direction of the divided flow path is disposed immediately above the divided flow path shown in the figure. As a result, as shown in FIG. Sidestreams a and b having a width (m) are elongated in the vertical direction and formed as microsegments. Note that the minute width of the slit is shown as n. In such a differential contact type micromixer, as shown in FIG. 3B, the width m of the micro segment is considered as the representative length. In addition, since the thickness of the wall which forms each division | segmentation flow path is small compared with the width | variety of a flow path, you may consider the width | variety of a flow path as the representative length m of a micro segment.

  FIG. 4 schematically shows the mechanism of the split / union type micromixer in a cross section perpendicular to the flow direction of the fluid in the mixer. Fluids A and B are supplied as a stream so as to be adjacent to each other (see FIG. 4 (a)), which is divided up and down into a stream containing half the amount of fluid A and fluid B (FIG. 4 (b)). After that, the shape of the divided stream is changed as necessary (see FIG. 4C), and the divided streams are merged together so as to be adjacent to each other (see FIG. 4D). Next, this is divided up and down in the same manner as before (see FIG. 4 (e)), then the shape of the divided stream is changed as necessary (see FIG. 4 (f)), and the divided streams are integrated. So that they are adjacent to each other (see FIG. 4 (g)), and so on. Many are formed in the state adjacent to. This type of micromixer is a split / union (or merging) type mixer, and forms microsegments by repeating liquid division → union → repartition → reunion →...

  The micromixer shown in FIG. 5 schematically shows a part of a specific micromixer having the mechanism shown in FIG. The illustrated micromixer is disclosed in Japanese Patent Application Laid-Open No. 20002-346353. As shown in the figure, a split section 54 having two opposing openings 50 and a partition 51 positioned therebetween, and a channel 53 extending at an equal distance in a direction perpendicular to the direction connecting the two openings. A plurality of perforation plates 52-1 to 5-4 having a plurality of holes (four in the illustrated embodiment) are overlapped in a liquid-tight state so that the positions of the openings 50 do not overlap immediately above and below, as shown in FIG. It has been. That is, the fluid does not flow through any part of the perforated plate other than the divided section 54 and does not leak between the plates.

  In the illustrated embodiment, the perforated plate 52 is omitted in thickness, but actually has a certain thickness. As a result, the opening 50 is located on the lower surface of the plate, and the partition 51 exists across the thickness direction between the opening 51 and the plate above it. The fluid flowing into the plate through the opposed openings 50 flows in two channel portions (or groove portions) 53 without contact directly due to the presence of the partition portion 51 (at this time, in contact with each other). And flows into the split section of the perforated plate through the upper perforated plate opening 50 located above the end of the channel portion.

  FIG. 6 shows a portion of the perforation plate 52-1 of FIG. 5 and the perforation plate 52-2 thereon. The function of the dividing section 54 is that two streams (X and Y) flowing from below through openings 50-1 and 50-2 of the perforated plate 52-1 are divided into two by a partition 51 and a channel 53, respectively. (X / 2 and X / 2 and Y / 2 and Y / 2), and the divided half streams (X / 2 and Y / 2) are joined together above the end of each channel. It has the function to send out to the space on the perforation plate located upwards through the opening parts 50-1 and 50-2 of the perforation plate 52-2 located in this. That is, each divided section 54 has a function of dividing the fluid flowing into it, and in the embodiment shown in the figure, the function of dividing the two kinds of fluid flowing in half and joining the divided halves to the next divided section. Have

  As shown in FIG. 5, a plate 56 is disposed below the perforated plate 52-1 located at the bottom. The plate 56 has a partition wall (not shown for simplicity, but extending vertically from the portion 57) that extends substantially vertically from the perforated plate 52-1 directly above to the fluid supplied to the mixer. A (the flow is shown by a solid line in the drawing) indicates that the space between the plate 56 and the perforated plate 52-1 is directed to the opening 50-1 (opening on the near side in the drawing) of the plate 52-1. The fluid B supplied (flow is indicated by a dotted line in the drawing) flows toward the opening 50-2 (the opening on the other side in the drawing) of the plate 52-1, and is perforated through each opening. Enter the split section 54 of the plate 52-1.

The fluids A and B flowing into the divided section 54 of the perforated plate 52-1 are each divided into two streams by the divided section 54, and the divided fluids are located above the end of each channel 53. -2 through the perforated plate 52-2 into the split section 54 and again split again. Hereinafter, the concept of the representative length of the micro segment in the split / unified micro mixer will be described. As described above, in the micromixer shown in FIG. 5, the fluid is divided into 1 / ^N by stacking N perforated plates. The fluid divided in the micromixer flows out from the outlet of the micromixer from above the stacked perforated plates. In this case, the segment divided as described above flows out of the cross section of the outlet (that is, the plane perpendicular to the fluid flow direction). Therefore, the area occupied by each segment is a value obtained by dividing the cross-sectional area of the outlet by the number of segments, that is, [cross-sectional area] / ^2N . Since each segment is adjacent to each other in a finely divided state, it can be assumed that each segment has a substantially square cross section. The length of one side of such a segment is referred to as the representative length of the micro-segment of the division / unification type micromixer, and its value is ([cross-sectional area] / 2 ^N ) ^1/2 .

  In the method of the present invention, it is necessary to mix a minute amount of the polymer solution and the hardly soluble solvent in the micromixer. For that purpose, it is preferable that the representative length of the formed micro-segment is small. For example, in the case of the differential contact type micromixer shown in FIG. 3, the typical length of the microsegment represented by the width of the divided flow path in the micromixer through which these liquids pass is generally 1 to 150 μm, For example, it is about 40 μm. The same applies to the representative length of the microsegment in the split / unified micromixer. The liquid flow in the micromixer (eg, the side flow in FIG. 3 and the flow in the split section in FIG. 5) is preferably in a laminar flow state.

Particularly preferred micromixers for use in the method of the present invention include the following:
Micro-mixer, Cellular Process Chemistry GmbH / ur Trade Select (trademark) of Cellular Process Chemistry (Fr.) ), Sold as Cytos ™;
WO96 / 12540, WO96 / 12541, JP-T-2001-521816, JP-A-2002-18271, JP-A-2002-58470, JP-A-2002-90357, JP-A-2002-102681 and the like Micro mixer.

  In addition to the above, there is a caterpillar type micromixer manufactured by the Institute, Fur, Microtechnics, Mainz, Inc., which has a flow path width of about 1 mm, but has two continuous patterns in the flow path. This is also known and can be used in the method of the present invention. The materials of these micromixers can be appropriately selected from materials that are stable with respect to substances present during phase separation, particularly solvents and polymers used.

  The micromixer that can be used in the production method of the present invention is not particularly limited as long as the fluid portion can be divided into minute portions as described above, and preferably as long as the microsegment having the representative length as described above can be formed. Absent.

  FIG. 7 is used to describe the case of using the Standard Slit Interdigital Micro Mixer, which is easily available among the above-mentioned Institute, Fleet, Microtechnique, and Mainz micromixers and is generally called an IMM mixer. Explained. FIG. 7 illustrates this IMM mixer. This micromixer embodies the mixer shown in FIG. The micromixer shown in FIG. 7 includes a mixing element 1, a micromixer upper part 2, and a micromixer lower part 3. In FIG. 7, these components are described in an exploded state. However, in actual use, these components are assembled and used in an integrated manner.

  The mixing element 1 in FIG. 7 has a flow path divided on the surface by fine processing. An example of the mixing element 1 is shown in FIG. The mixing element of FIG. 8 is formed with a comb-like flow path divided from both sides of the mixing element by a groove having the shape shown in FIG. Here, by introducing the polymer solution A and the poorly soluble solvent B, a large number of substreams (a and b, respectively) are obtained.

  The width of each of the divided flow paths (corresponding to the width of the comb teeth in FIG. 3 and corresponding to the representative length of the microsegment) is preferably 100 μm or less, and 50 μm or less from the viewpoint of mixing. More preferably. The lower limit is not particularly limited, but is on the order of several μm in production. Moreover, the depth of the flow path is not particularly limited, but may be several tens to about 500 μm, for example.

  The divided flow path of the mixing element 1 can be formed by applying a microfabrication technique used in the electronics technology. The method of forming the flow path is not particularly limited. For example, the flow path is formed by using a method called soft lithography using silicone rubber as a material, or by wet etching using hydrofluoric acid or the like using glass as a material. The method etc. can be mentioned.

  The mixer upper part 2 in FIG. 7 is provided with two inlets 4 and one outlet 5. The injection port 4 continues to the injection channel 7, and the terminal end of the injection channel 7 is connected to the mixing element channel end 9. Moreover, the said discharge port 5 is following the discharge flow path 8, and the termination | terminus part of the discharge flow path 8 forms the slit 6 provided in the approximate center part of the bottom face of the said mixer upper part. When the micromixer is assembled, the slit 6 is in contact with the approximate center of the mixing element 1. As a result, a flow path in which the flow path on the mixing element 1 and the slit 6 are connected is formed.

  The microreactor lower part 3 has a recess for fixing the mixing element 1. By fixing the mixing element 1 in the recess, a flow path divided without a gap is formed, and phase separation can be performed satisfactorily.

  When the mixing element 1, the micromixer upper part 2 and the micromixer lower part 3 are assembled, the inlet 4, the injection channel 7, the mixing element channel end 9, the divided channel on the mixing element 1, and the slit 6 are sequentially arranged. A flow path connected by a path of the discharge flow path 8 and the discharge port 5 is formed. Here, the slit 6 becomes a minute space serving as a mixing field.

  When the phase separation is performed by the IMM mixer shown in FIG. 7, it can be performed according to the following method. First, a polymer solution A and a hardly soluble solvent B, which will be described later, are injected at a constant pressure from separate injection ports 4. If pulsation occurs during injection, the polymer particles generated by phase separation may accumulate in the fine flow path, causing clogging and hindering continuous phase separation. It is preferable to use a non-pulsating pump such as a pump used in chromatography.

  The polymer solution fed from the inlet 4 is sent to the mixing element channel end 9 through the injection channel 7. The polymer solution A sent to the mixing element flow path end 9 flows in the divided flow paths on the mixing element 1 from the both ends of the mixing element to the central direction by the injection pressure. Ascending side stream a is obtained. Similarly, a large number of ascending substreams b are obtained from the hardly soluble solvent B fed from the other inlet 4. These substreams rise with adjacent substreams of different liquids.

  The large number of substreams come into contact with each other in the minute space of the slit 6, so that mixing proceeds and phase separation occurs. Since phase separation occurs in a minute space, it is easy to control conditions such as the phase separation temperature, and since many sidestreams are in contact almost simultaneously, the polymer solution and the hardly soluble solvent Is sufficiently mixed and energy efficient. Further, since phase separation is performed by continuously injecting these liquids at a constant rate, phase separation is performed by continuous operation, and it is easy to keep the phase separation conditions constant.

  The volume of the minute space in which phase separation occurs in this way can be, for example, 10 μL on the order of microliters, but is not particularly limited. The two solutions in contact with each other in the minute space flow into the slit 6. Further mixing occurs as it flows into the slit. In consideration of mixing efficiency, the width of the slit is preferably 500 μm or less, more preferably 100 μm or less, and particularly preferably 70 μm or less. The lower limit value of the width is determined by other constraints, for example, a method of forming a slit.

  The rate at which the liquid is injected depends on the volume of deposition in the minute space, the width of the flow path, the type of liquid to be supplied, the temperature, and the like, but can be a flow rate of 10 mL / min to 1.5 L / min, for example. If it is less than 10 mL / min, the phase separation rate may be slow, and efficient phase separation may not be performed. Moreover, there is a possibility that the polymer particles to be deposited accumulate and obstruct liquid flow. If it exceeds 1.5 L / min, it may be difficult to control the flow rate at a constant level, which may be undesirable because a high pressure is applied to the micromixer.

  The temperature at which the phase separation is performed is not particularly limited as long as the material used does not adversely affect the phase separation such as freezing, boiling, and decomposition. For example, the phase separation temperature can be set to the melting point of the solvent used to 85 ° C. The reaction solution that has passed through the slit 6 is discharged out of the microreactor from the discharge port 5 through the discharge path 8 and collected in an appropriate container. The polymer particles obtained in this way can be subjected to post-treatment (for example, mechanical separation of polymer particles) described later, if necessary.

  The polymer used in the present invention is not particularly limited as long as both a readily soluble solvent and a hardly soluble solvent are present and a phase separation method can be carried out. It is generally well known that polymer particles are obtained by adding a poorly soluble solvent to a solution in which a polymer is dissolved in a readily soluble solvent and causing phase separation. On the other hand, it is possible to select a readily soluble solvent and a hardly soluble solvent, and appropriately set operation conditions for phase separation for the polymer to precipitate in a mixed state. For example, in the case of polystyrene, tetrahydrofuran, N, N-dimethylacetamide, N, N-dimethylformamide or the like can be used as a readily soluble solvent, and water can be used as a hardly soluble solvent.

  Incidentally, it may be preferable that the hardly soluble solvent and / or the polymer solution, particularly the hardly soluble solvent, contain a dispersion stabilizer. This can prevent secondary aggregation of the polymer particles produced by phase separation and help achieve a uniform particle size distribution. Specifically, a dispersion stabilizer such as diisooctyl sodium sulfosuccinate can be used.

  The solvent containing the polymer particles obtained by phase separation in the micromixer can be post-treated as necessary. This post-treatment may be a treatment for separating the produced polymer particles from the solvent, a treatment for replacing the dispersion medium with the polymer particles, or the like. Specifically, operations such as centrifugation, filtration, drying and solvent replacement can be used.

By the method of the present invention, polymer particles having an average particle size smaller than that produced by a conventional method and a sharp particle size distribution can be obtained. For example, the particle diameter is on the order of several nanometers to several tens of micrometers. Therefore, the polymer particles obtained by the method of the present invention are suitable for use in, for example, a particle size distribution counter.

  EXAMPLES Hereinafter, although an Example is hung up and demonstrated in more detail, this invention is not limited only to these Examples.

Example 1
0.7 part by weight of diisooctyl sodium sulfosuccinate (trade name: AOT, manufactured by Wako Pure Chemical Industries, Ltd.) was dissolved in 99.3 parts by weight of deionized water to obtain an AOT solution. A polymer solution was obtained by dissolving 0.4 parts by weight of polystyrene (PS) (trade name: Polystyrene, manufactured by Ardrich) in 99.6 parts by weight of tetrahydrofuran (THF) (also referred to as “PS solution”). Using a microsyringe pump (trade name: IC3220, manufactured by KD Scientific) with a micromixer (trade name: YM-1, manufactured by Yamatake Corporation, type shown in FIG. 5), a total flow rate of 30 mL / It supplied by min (AOT solution flow rate: PS solution flow rate = 88: 12), phase-separated at 20 degreeC, and the polymer particle was obtained.

The mixer used is a micromixer of the type shown in FIG. 5, which is a stack of 11 perforated plates 52 shown in FIG. 6, and the outlet area of the micromixer is 5 × 10 ⁶ μm ² . Therefore, the representative length of the microsegment is 22 μm. Each perforated plate has a thickness of 0.8 mm, and the uppermost plate has one divided section 54. Hereinafter, the number of divided sections increases by one for each step down. The lowermost perforated plate 52-1 has 11 divided sections, and each fluid enters each divided section 54 through the opening 50 of the perforated plate as 11 fractions. In each divided section, it is further divided into two fractions. In the divided section, the opening 50 has a diameter of 0.4 mm, the distance (k1) between the outermost portions of both channel portions 53 is 2.0 mm, and the distance (k2) between the outermost portions of the openings is 1. The depth of the channel portion is 0.4 mm.

  The particle size distribution of the obtained polymer particles was measured using a particle size measuring device (LA-920, manufactured by Horiba, Ltd.). The average particle diameter of the polymer particles was 0.14 μm, and the coefficient of variation was 28.9%.

Comparative Example 1
An AOT solution and a PS solution were prepared in the same manner as in Example 1. Next, 26 parts by weight of the AOT solution was placed in a glass beaker, stirred at a rotational speed of 100 rpm using a magnetic stirrer, 4 parts by weight of the PS solution was added in 2 seconds, and phase separation was performed to obtain polymer particles. Similar to Example 1, the particle size distribution of the polymer particles was measured. As a result, the average particle size of the polymer particles was 17.8 μm, and the coefficient of variation was 57.1%.

Example 2
Example 1 was repeated except that the total flow rate was 50 mL / min. The average particle diameter of the polymer particles was 0.16 μm, and the coefficient of variation was 34.9%.

Example 3
As a micromixer, a differential contact type micromixer: IMM mixer (manufactured by Institute, Futur, Microtechnique, Mainz) shown in FIG. Example 1 was repeated, feeding in 3). The width of the divided flow path (substantially corresponding to m) corresponding to the representative length of the microsegment formed by this mixer is 40 μm, and the width n of the slit is 60 μm. The average particle size of the polymer particles was 0.16 μm, and the coefficient of variation was 26.0%.

Example 4
Example 3 was repeated except that the total flow rate was 10 mL / min. The average particle diameter of the polymer particles was 0.11 μm, and the coefficient of variation was 23.4%.

  The present invention can easily produce polymer particles having a sharp particle size distribution. Therefore, by using such polymer particles, calibration / performance evaluation of a particle size distribution counter, a foreign substance inspection device, a blood cell counter, etc. can be performed with high accuracy.

It is a figure which shows the schematic of an example of the mixing mechanism by a micro mixer. It is a figure which shows the schematic of an example of the mixing mechanism by a micro mixer. It is a figure which shows the schematic of an example of the mixing mechanism by a differential contact type micromixer. It is a figure which shows the schematic of an example of the mixing mechanism by a division | segmentation and uniting type | mold micromixer. FIG. 5 schematically shows how the fluid in the micromixer having the mixing mechanism of FIG. 4 is divided and united. Fig. 6 schematically shows a part of the micromixer of Fig. 5. It is a figure which shows the state which decomposed | disassembled an example of the IMM mixer which can be used with the method of this invention, the micromixer upper part 2 shows the state seen from the bottom part, and the mixing element 1 and the micromixer lower part 3 show the state from the upper part. Indicates the state. It is a figure which shows an example of the mixing element of a micro mixer.

Explanation of symbols

1 ... mixing element, 2 ... micro mixer upper part, 3 ... micro mixer lower part,
4 ... injection port, 5 ... discharge port, 6 ... slit, 7 ... injection channel, 8 ... discharge channel,
9 ... end of mixing element flow path, 50 ... opening, 51 ... partition, 52 ... perforated plate,
53 ... channel part, 54 ... divided section, 56 ... bottom plate,
57: Position of the partition wall.

Claims (6)

A method for producing polymer particles from a polymer solution comprising a polymer and a polymer-soluble solvent, comprising:
A method for producing polymer particles, comprising: a step of supplying a polymer solution and a hardly polymer-soluble solvent to a micromixer; and a step of mixing the polymer solution and the hardly soluble solvent with a micromixer to cause phase separation of the polymer particles.   The manufacturing method according to claim 1, further comprising preparing a polymer solution by dissolving the polymer in a polymer-soluble solvent.   The production method according to claim 1 or 2, wherein at least one of the easily soluble solvent and the hardly soluble solvent comprises a dispersion stabilizer that keeps the polymer particles to be phase-separated in a dispersed state.   The manufacturing method according to claim 1, wherein the micromixer forms a microsegment having a representative length of 150 μm or less.   The manufacturing method according to claim 1, wherein the micromixer is a differential contact type. The manufacturing method according to any one of claims 1 to 4, wherein the micromixer is a split / unified type.

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