JP4972726B2 - Phase inversion temperature emulsification apparatus and emulsification method - Google Patents

Description

  The present invention relates to an apparatus and method for performing emulsification using a microreactor, in particular, phase inversion temperature emulsification, and aims to reduce the diameter of the resulting emulsion.

  Oil-in-water (O / W type) emulsions are used in the fields of paints, cosmetics, foods and the like, and are a basic dispersion system for fine particle preparation and microcapsule preparation. As a method for preparing an emulsion, mechanical stirring with a stirring blade or a homogenizer is generally used. However, since emulsions obtained by these methods are polydispersed, there is a need for classification operation after preparation and problems of stability. It is known to occur. From such a background, a method capable of preparing a monodisperse emulsion has recently attracted attention.

  As typical methods for preparing a monodisperse emulsion, for example, an SPG membrane emulsification method, a microchannel emulsification method, a microchannel branch emulsification method and the like as described in Non-Patent Documents 1 to 4 are known.

H. Yoshizawa et al., Col. Polym. Sci. 282 (2004) 965-971 Y. Hatake et al., J. Appl. Polym. Sci. 64 (1997) 1107-1113 H. Yoshizawa et al., J. Chem. Eng. Japan, 29 (1996) 1027-1029 S. Sugiura et al., J. Colloid Interface Sci. 227 (2000) 95-103

  As a method for obtaining a fine emulsion, a phase inversion emulsification method is known. In the phase inversion emulsification method, an emulsion of the opposite type to the intended type is prepared, and when the critical point is reached by operations such as increasing the dispersoid concentration, heating the temperature, and cooling, the phase inversion emulsification method is used. This type of emulsion is prepared. As a specific example of such a phase inversion emulsification method, for example, in Patent Document 1, an oil phase in which a polyglycerin ester and an alkyl polyglycoside are dissolved or dispersed in an oily agent is heated to a temperature above the phase inversion temperature and stirred. A method for producing an oil-in-water emulsion in which an aqueous phase heated to a temperature is gradually added to emulsify and cooled to a temperature below the phase inversion temperature to cause phase inversion is described.

JP-A-9-308822

  However, in the monodisperse emulsion preparation methods as described in Non-Patent Documents 1 to 4, the emulsion diameter obtained is at least about 10 μm, and a technique capable of obtaining a finer emulsion is required. Moreover, the phase inversion emulsification method as described in Patent Document 1 is generally a process in batch units, and apart from the initial emulsification step, a step of heating and cooling the emulsion after the initial emulsification is required. Since this heating and cooling takes time, there is a risk of adversely affecting the quality of the product and the stability of the emulsion due to the influence of the thermal history.

  An object of the present invention is to provide a device and a method capable of preparing a continuously stable fine emulsion, and to solve such problems of the prior art. is there.

In order to achieve the above object, a phase inversion temperature emulsifying device of the present invention includes a first inlet port for introducing a first liquid that becomes a continuous phase and a second inlet for introducing a second liquid that becomes a dispersed phase. Two inlet ports, a microchannel that communicates with these first and second inlet ports, mixes and emulsifies the two introduced liquids to prepare an initial emulsion in which the second liquid is dispersed in the first liquid, and A confluence microreactor unit having an outlet port connected to the microchannel and recovering the initial emulsion; and the initial emulsion is heated to a phase inversion temperature or higher to cause phase inversion; at least one heating microreactor unit 1 of the liquid to prepare an intermediate emulsion dispersed, cause phase inversion by cooling the heated intermediate emulsion below the phase inversion temperature, the first liquid The second liquid is dispersed, is arranged between the at least one cooling microreactor units preparing fine final emulsion than the initial emulsion, and the heating microreactor unit and the cooling microreactor unit during the heating A Peltier element having a microreactor unit side as a heat generating surface and a cooling microreactor unit side as a heat absorbing surface is laminated. By adopting such a configuration, the thermal controllability is enhanced while the installation area is reduced, and it becomes possible to quickly heat and cool the emulsion by efficiently using thermal energy.

  In this apparatus, the micro flow path is formed in a Y shape, and the angle formed by the flow path portion communicating with the first inlet port and the flow path portion communicating with the second inlet port is greater than 0 degree and 90 degrees. It is preferably smaller, and more preferably in the range of 30 to 60 degrees.

  Furthermore, it is preferable that the flow of the first and second liquids in the microchannel is a laminar flow.

  Furthermore, in the micro flow channel, the width of the flow channel portion communicating with the first inlet port is preferably larger than the width of the flow channel portion communicating with the second inlet port.

  In addition, the difference between the outlet temperature of the heating microreactor unit and the phase inversion temperature of the emulsion is preferably in the range of 10 to 30 ° C, and more preferably in the range of 15 to 25 ° C.

  The outlet temperature of the cooling microreactor unit is preferably in the range of 10 ° C. to room temperature (25 ° C.), more preferably in the range of 10 to 20 ° C.

The phase inversion temperature emulsification method according to the present invention, when forming an emulsion in which the second liquid that is the dispersed phase is dispersed in the first liquid that is the continuous phase, A heated microreactor that is introduced into a flow path, mixes and emulsifies the two liquids in the micro flow path, prepares an initial emulsion in which the second liquid is dispersed in the first liquid, and is attached to the heat generating surface of the Peltier element The emulsion was heated above the phase inversion temperature using a unit to cause phase inversion, and an intermediate emulsion in which the first liquid was dispersed in the second liquid was prepared and attached to the endothermic surface of the Peltier element using a cooling microreactor units by cooling the intermediate emulsion below the phase inversion temperature cause phase inversion, in the first liquid and the second liquid is dispersed, fine than the initial emulsion Characterized in that to obtain a final emulsion. By adopting such a configuration, the thermal controllability is enhanced, and the emulsion can be rapidly heated and cooled.

  In this method, it is preferable that the first and second liquids form a laminar flow in the microchannel.

  Furthermore, the initial emulsion is preferably heated to a temperature range 10 to 30 ° C. higher than the phase inversion temperature, and more preferably heated to a temperature range 15 to 25 ° C. higher than the phase inversion temperature.

  Furthermore, the intermediate emulsion is preferably cooled to a temperature range of 10 ° C. to room temperature (25 ° C.), more preferably to a temperature range of 10 to 20 ° C.

  In addition, the emulsion diameter of the final emulsion is preferably less than 1 μm.

  According to the present invention, since the emulsion is rapidly heated and cooled in the phase inversion emulsification, it is possible to continuously prepare an emulsion having high quality and stability and a small emulsion diameter.

  Embodiments of the present invention will be described below with reference to the drawings. FIG. 1 is an exploded perspective view of a typical phase inversion temperature emulsifying device according to the present invention, FIG. 2 is a side view showing the assembled device of FIG. 1, and FIG. 3 is a view of the device of FIG. It is a top view of a merging microreactor unit.

  A phase inversion temperature emulsification apparatus 1 shown in FIG. 1 has a confluence microreactor 5 having a first inlet port 2, a second inlet port 3, and an outlet port 4. The merging microreactor 5 is formed with a micro flow path 6 having one end communicating with the outlet port 4 and the other end branching into two branches and communicating with the first inlet port 2 and the second inlet port 3. Has been.

  The apparatus 1 also includes a heating microreactor unit 9 and a cooling microreactor unit 10 in which microchannels 7 and 8 are formed, respectively. The heating microreactor unit 9 is attached to a heat generating surface of a Peltier element 13 that is a heat source via a partition plate 11 and a copper heat transfer plate 12. The cooling microreactor unit 10 is in contact with one surface of the cooling water jacket 14, and the other surface of the cooling water jacket 14 is attached to the cooling surface of the Peltier element 13 via a copper heat transfer plate 15. ing.

  A glass plate 16 for observing the emulsified state in the microchannel 6 is attached to one surface of the confluence microreactor 5 by a presser plate 17, and the other surface flows in the microchannel 6. A precooling water jacket 18 for precooling the liquid is attached. This preliminary cooling water jacket is not essential, and can be appropriately omitted depending on the temperature of the liquid supplied to the merging microreactor 5 and the phase inversion temperature.

  In addition, a glass plate 19 for observing the emulsified state in the micro flow path 8 is attached to the cooling microreactor unit 10 by a pressing plate 20 on the side opposite to the cooling water jacket 14.

  When these members are sequentially laminated, liquid-tightly fixed by fixing means such as bolts, and the units are connected by pipes or tubes, a device with a very small installation area is configured as shown in FIG. .

  Next, a method for performing phase inversion temperature emulsification using the apparatus 1 will be described.

  First, a first liquid that becomes a continuous phase in a desired emulsion is introduced into the first inlet port 2, and a second liquid that becomes a dispersed phase is introduced into the second inlet port 3. The introduced first and second liquids pass through the microchannel 6 and merge with each other at a branching portion of the microchannel 6. At this time, the first liquid and the second liquid form a parallel two-phase flow, and the emulsification gradually proceeds at the contact interface thereof, that is, droplets of the second liquid are formed and dispersed in the first liquid. The two liquids are completely emulsified before reaching the outlet port 4 of the microchannel 6. When two liquids are mixed in the microchannel 6 in this way, an emulsion in which the diameter of the droplets of the dispersed phase is smaller than the width of the channel can be obtained. As a result, an initial emulsion in which the second liquid is dispersed in the first liquid is obtained from the outlet port 4 of the microchannel 6.

  This initial emulsion is introduced into the heated microreactor unit 9 via a pipe or tube. Heat from the heating surface of the Peltier element 13 is transmitted to the heating microreactor unit 9 via the partition plate 11 and the heat transfer plate 12, and the introduced initial emulsion passes through the microchannel 7 by this heat. When heated and the phase inversion temperature is exceeded, phase inversion occurs, resulting in an intermediate emulsion in which the first liquid is dispersed in the second liquid. At this time, the initial emulsion held in the microchannel 7 is a very small amount and has a small heat capacity, and thus is quickly and uniformly heated. For this reason, compared with the conventional phase inversion emulsification method in which batch processing has been performed, the influence on the quality of the first liquid and the second liquid and, if necessary, the emulsifier added to these liquids is extremely small, and intermediate The emulsified state of the emulsion becomes very homogeneous.

  This intermediate emulsion is then introduced into the cooled microreactor unit 10 via a pipe or tube. The cooling microreactor unit 10 is cooled by the water jacket 14, and the heat of the water jacket unit 14 is absorbed by the heat absorbing surface of the Peltier element 13 via the heat transfer plate 12. For this reason, the introduced intermediate emulsion is cooled while passing through the microchannel 8, and phase inversion occurs when the temperature falls below the phase inversion temperature, resulting in a final emulsion in which the second liquid is dispersed in the first liquid. At this time, the intermediate emulsion held in the micro flow path 8 is a very small amount, and its heat capacity is small, so that it is cooled quickly and uniformly. In this way, by rotating the initial emulsion twice, a final emulsion that is finer and uniform than the initial emulsion, that is, the emulsion diameter is smaller than that of the initial emulsion and is monodispersed is obtained.

  Thus, in the transfer temperature emulsification method according to the present invention, all steps are performed in the microreactor, so that heating and cooling can be performed quickly and uniformly, and continuous production of emulsions is possible. Further, the transfer temperature emulsification apparatus according to the present invention is very compact because it is configured by laminating the units.

  The micro flow path 6 of the confluence microreactor 5 is preferably formed in a Y shape as in the illustrated example. As a result, the diameter of the dispersed phase droplets formed in the microchannel 6 is reduced. In addition, an angle formed by the flow channel portion communicating with the first inlet port 2 and the flow channel portion communicating with the second inlet port 3 so as to allow the first liquid and the second liquid to smoothly merge (angle α in FIG. 3). Is preferably larger than 0 degree and smaller than 90 degrees. Furthermore, since this angle α affects the diameter of the droplets of the dispersed phase to be formed, it is preferable that the angle α is in the range of 30 to 60 degrees from the viewpoint of reducing the diameter of the droplets.

  Moreover, it is preferable to perform liquid feeding so that the flow of the 1st and 2nd liquid in the microchannel 6 becomes a laminar flow, respectively. The micro space has the feature that the contribution of the interfacial tension and the viscous force becomes very large compared to the normal macro space. For this reason, in order to cause turbulent flow, it is necessary to increase the flow rate of these liquids. This causes an increase in energy required for liquid transfer, and also improves the performance and / or size of the heating and cooling microreactor unit. It is forced to become. However, the inventors have conducted research on emulsification in the combined microreactor unit, and found that sufficient emulsification by the contact interface occurs in the microchannel even if the two liquids flow in parallel in laminar flow. It was. Therefore, it is advantageous to send two liquids in a laminar flow from the viewpoint of energy saving and downsizing of the apparatus.

  Further, in the micro flow channel 6, the width of the flow channel portion communicating with the first inlet port 2 is preferably larger than the width of the flow channel portion communicating with the second inlet port 3. As described above, by configuring the flow path of the second liquid serving as the dispersed phase to be relatively small, the droplet diameter of the second fluid in the initial emulsion can be reduced.

In the heating microreactor unit 9, it is preferable to heat the initial emulsion to a temperature range higher by 10 to 30 ° C. than the phase inversion temperature. In general, 100% of the initial emulsion does not invert at the phase inversion temperature, and almost 100% inversion occurs at a temperature about 20 ° C. higher than the phase inversion temperature. This is advantageous in terms of miniaturization. On the other hand, if heating is performed excessively, there is a concern about the influence on the quality of the first liquid and the second liquid and, if necessary, the emulsifier added to these liquids, and the heating microreactor unit 9 and cooling microreactor unit 10 Since it leads to an increase in size, it is advantageous to heat in a temperature range of the phase inversion temperature + 30 ° C. or less.

  In the cooling microreactor unit 10, it is preferable to cool the intermediate emulsion to room temperature (25 ° C.) or lower. In general, 100% of the intermediate emulsion does not invert at the phase inversion temperature, and almost 100% inversion occurs at a temperature below room temperature. Therefore, cooling to this temperature is necessary for the refinement of the final emulsion. It is advantageous. On the other hand, if the cooling is performed excessively, the time and energy required for cooling increase and the size of the cooling microreactor unit 10 is increased. Therefore, it is advantageous to cool in a temperature range of 10 ° C. or higher.

  Further, as in the illustrated example, a Peltier element 13 is disposed between the heating reactor unit 9 and the cooling reactor unit 10 so that the heating reactor unit 9 side becomes a heat generating surface and the cooling reactor unit 10 side becomes a heat absorbing surface. Is preferably energized. With this configuration, heating and cooling can be performed simultaneously with one unit (Peltier element), and thus the apparatus can be further downsized. In addition, the heating temperature can be controlled with high accuracy. At this time, it is preferable to measure the temperature at the outlet of the heating reactor unit 9 and control the heat generation amount of the Peltier element based on this temperature. If the desired cooling temperature is not reached by heat absorption by only the Peltier element, a cooling water jacket 14 may be further provided as shown in the figure. Of course, instead of the Peltier element, other heat sources such as a heating water jacket or a surface heater can be used.

  Furthermore, from the viewpoint of improving the stability of the final emulsion, it is preferable to set the above parameters appropriately so that the emulsion diameter is less than 1 μm, which has been difficult to achieve with the prior art.

  The above description shows only a part of the embodiment of the present invention, and these configurations can be combined alternately or various changes can be made without departing from the gist of the present invention. For example, the path length of the micro flow path can be changed or a plurality of heating and cooling microreactor units can be provided according to the phase inversion temperature and the processing amount of the liquid to be processed.

  Next, since the emulsion was actually prepared using the transfer temperature emulsification apparatus described above, the result will be described.

  The apparatus used in the experiment has the same configuration as in FIG. 1, and the micro flow path of the confluence microreactor unit has a width of 132 μm on the first liquid side, a width of 100 μm on the second liquid side, and a depth of 47 μm. there were. In addition, the microchannels of the heating microreactor unit and the cooling microreactor unit both had a width of 711 μm and a depth of 35 μm.

  Distilled water is supplied to the first inlet port as a first liquid that becomes a continuous phase at a rate of 100 μl / min, and 20% by mass of a nonionic surfactant (Brij30) and 80% as a second liquid that becomes a dispersed phase. A mixed solution of mass% dodecane was supplied to the second inlet port at a rate of 50 μl / min.

  The exit temperature of the heating microreactor unit was controlled to 60 ° C. and the exit temperature of the cooling microreactor unit was controlled to 20 ° C. to obtain the final emulsion. When this final emulsion was subjected to dynamic light scattering (DLS) measurement, the average emulsion diameter was 95.2 nm and the polydispersity index was 8.6. As a result, it has been found that the apparatus and method according to the present invention are an effective means for preparing nanoemulsions that have been difficult to achieve with conventional emulsification techniques.

  As is clear from the above description, the present invention makes it possible to prepare a continuously stable nanoemulsion, which has been actively researched in the pharmaceutical field in recent years, such as drug delivery systems (DDS), agricultural chemicals / cosmetics-related fields, Furthermore, application to food related fields can be expected.

It is a disassembled perspective view of the typical phase inversion temperature emulsification apparatus according to this invention. It is a side view shown in the state which assembled the apparatus of FIG. It is a top view of the confluence | merging microreactor unit of the apparatus of FIG.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Phase inversion temperature emulsification apparatus 2 1st inlet port 3 2nd inlet port 4 Outlet port 5 Merge microreactor 6, 7, 8 Micro flow path 9 Heating microreactor unit 10 Cooling microreactor unit 10
11 Partition plate 12, 15 Heat transfer plate 13 Peltier element 14 Water jacket for cooling 16, 19 Glass plate 17, 20 Holding plate 18 Preliminary cooling water jacket

Claims (6)

A first inlet port for introducing a first liquid that becomes a continuous phase, a second inlet port for introducing a second liquid that becomes a dispersed phase, and a first inlet port and a second inlet port that communicate with the first and second inlet ports. A microchannel for preparing an initial emulsion in which the two liquids are mixed and emulsified to disperse the second liquid in the first liquid, and an outlet port connected to the microchannel for recovering the initial emulsion. A combined microreactor unit,
At least one heated microreactor unit that heats the initial emulsion above the phase inversion temperature to cause phase inversion to prepare an intermediate emulsion in which the first liquid is dispersed in a second liquid;
The heated intermediate emulsion is cooled to a phase inversion temperature or lower to cause phase inversion, and the second liquid is dispersed in the first liquid, and at least one for preparing a final emulsion finer than the initial emulsion Two cooling microreactor units;
A phase inversion temperature emulsification device, which is disposed between the heating microreactor unit and the cooling microreactor unit, and is formed by laminating a Peltier element having the heating microreactor unit side as a heat generating surface and the cooling microreactor unit side as a heat absorbing surface. .   The microchannel is formed in a Y shape, and an angle formed by a channel portion communicating with the first inlet port and a channel portion communicating with the second inlet port is larger than 0 degree and smaller than 90 degrees. The emulsification apparatus according to claim 1.   The emulsification apparatus according to claim 1 or 2, wherein the flow of the first and second liquids in the microchannel is a laminar flow.   4. The micro flow channel according to claim 1, wherein a width of a flow channel portion communicating with the first inlet port is larger than a width of a flow channel portion communicating with the second inlet port. 5. Emulsifying device.   The emulsification apparatus according to any one of claims 1 to 4, wherein a difference between an outlet temperature of the heating microreactor unit and a phase inversion temperature of the emulsion is in a range of 10 to 30 ° C.   The emulsification apparatus according to any one of claims 1 to 5, wherein an outlet temperature of the cooling microreactor unit is in a range of 10 ° C to room temperature (25 ° C).

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