JP4180551B2 - Freeze vacuum drying apparatus and freeze vacuum drying method - Google Patents

Description

  The present invention relates to a freeze vacuum drying apparatus and a freeze vacuum drying method, and more particularly to a freeze vacuum drying apparatus and a freeze vacuum drying method in which a raw material liquid is ejected from a nozzle into a vacuum space to self-freeze.

  Conventionally, a hot air drying method, a spray drying method, a freeze vacuum drying method and the like are known as a method for drying a substance dissolved in a raw material liquid or a dispersed substance and taking it out as a fine powder. However, some pharmaceuticals and foods are denatured by heating and lose their physiological activity, and others lose their flavor. For these, the freeze-drying method is adopted. The micro raw material liquid particles obtained by spraying from the nozzle to the vacuum space are self-frozen to form micro frozen particles, and the micro frozen particles are heated at a low temperature under vacuum to sublimate the frozen solvent or dispersion medium and dry. Thus, a freeze vacuum drying method for taking out as a fine powder is adopted. The nozzle used in this method has a structure in which the raw material liquid is immediately ejected in the form of a mist from the nozzle outlet.

  FIG. 3 is a diagram showing vertical and horizontal schematic cross sections of a commonly used nozzle and a schematic shape of a spray formed. That is, FIG. 3-A is a fan-shaped nozzle, which is a nozzle that ejects liquid in a fan shape by utilizing the repulsive force when the liquid collides at the outlet and repels and spreads, and FIG. 3-B is a full-cone nozzle. In this nozzle, the liquid is rotated inside the nozzle so that the liquid comes into contact with the liquid and is divided, and sprayed by centrifugal force. FIG. 3C shows an empty conical nozzle, which is a nozzle that rotates liquid inside the nozzle, contacts and divides the liquid, and sprays by centrifugal force, like a full cone nozzle. Use one that does not have a hole in the center.

  Freeze-vacuum drying method using the above-mentioned nozzle, that is, the raw material liquid is sprayed from the nozzle into the vacuum space, the solvent or dispersion medium evaporates from the formed fine raw material liquid particles, and the latent heat of evaporation is taken away, thereby the fine raw material liquid A problem that exists in the method of self-freezing particles is that self-freezing tends to occur at the tip of the nozzle or in the vicinity of the nozzle. Thus, when self-freezing occurs around the nozzle, the nozzle is blocked and the operation is forced to be interrupted.

  As a method for preventing the self-freezing around the nozzle as described above, the nozzle of the raw material liquid supply device is enclosed in the liquid supply chamber and separated from the freezing section, and a valve is provided between the liquid supply chamber and the freezing section. At the start of spraying, the valve is closed and the freezing part is maintained at a high vacuum level at which the raw material liquid self-freezes, but the liquid supply chamber is kept at a high degree of vacuum that does not cause self-freezing, i.e., at a higher pressure than the freezing part. There is disclosed a method of supplying a raw material liquid in which a fine raw material liquid particle in a liquid supply chamber is caused to flow into a freezing section by spraying and obtaining a state where the nozzle does not self-freeze around the nozzle (see, for example, Patent Document 1). .

JP 2004-093078 A

However, in the method of the above-mentioned Patent Document 1, a liquid supply chamber and a valve are required in the raw material liquid supply device, and the valve is a portion that becomes a passage for atomized fine raw material liquid particles when the valve is opened. A large size equivalent to the inner diameter of is required. Although the feed liquid chamber is vacuumed so that the raw material liquid does not self-freeze, spraying of the raw material liquid is started, but the feed liquid chamber is evacuated independently of the freezing section, and the vacuum level in the feed liquid chamber is controlled. If the evacuating means that can be used is not provided, it is difficult to control the degree of vacuum in the liquid supply chamber, and there is a problem that self-freezing occurs similarly in the liquid supply chamber.
The present invention has been made in view of the above-mentioned problems. A freeze vacuum drying apparatus and a freeze vacuum drying method that do not cause self-freezing around a nozzle when a raw material liquid is ejected from a nozzle into a vacuum freeze drying tower and freeze vacuum dried. The issue is to provide.

The above problem is solved by the configuration of claim 1 or claim 5, but the freeze vacuum drying apparatus according to claim 1 is configured such that the raw material liquid is supplied from the nozzle provided at the upper end of the vacuum freeze drying tower under vacuum. The micro raw material liquid particles formed by supplying into the vacuum freeze-drying tower are self-frozen to form micro-freeze particles, and then the micro-freeze particles are captured on the trapping surface in the vacuum freeze-drying tower and heated to be sublimated and dried. In the freeze vacuum drying device
The nozzle has at least one fine hole at the tip as the raw material liquid ejection hole, and the raw material liquid is ejected downward from the fine pore as a liquid column, depending on the ejection condition of the raw material liquid. It is an apparatus configured such that the mist-like fine raw material liquid particles formed by diverging the liquid column at a fixed fixed length position are self-frozen to become the fine frozen particles.
In such a freeze-drying apparatus, the raw material liquid does not immediately form a mist from the tip of the fine pores, which are the nozzle ejection holes, and the raw material liquid is first ejected as a liquid column. Of course, the self-freezing of the fine raw material liquid particles does not occur even in the vicinity of the pores.

The freeze vacuum drying apparatus according to claim 2 dependent on claim 1, wherein the raw material liquid is housed in the raw material liquid supply container, a supply pressure applied to the raw material liquid in the raw material liquid supply container, and the vacuum freeze drying tower It is a device in which the internal pressure can be controlled independently.
In such a freeze-drying apparatus, by adjusting the pressure relationship between them, the raw material liquid is ejected as a liquid column from the pores into the vacuum freeze-drying tower, and the liquid column is positioned at a certain length determined by the ejection conditions. In order to ensure that it is emitted as atomized fine raw material liquid particles.

The freeze-drying apparatus according to claim 3 that is dependent on claim 1 is an apparatus in which the distance from the lower end of the pore to the capture surface is mechanically variable.
Such an apparatus can adjust the distance from the lower end of the liquid column to the capture surface of the micro frozen particles according to the length of the liquid column to be formed, and the micro raw material liquid particles whose capture surface is not yet self-frozen Can be used for freeze-drying with different types of raw material liquids or different required ejection conditions.

The freeze-drying apparatus according to claim 4 that is dependent on claim 1 is an apparatus in which the inner diameter of the pores is set in a range of 50 μm to 500 μm.
Such a freeze vacuum drying device makes it easy to set conditions for ejecting the raw material liquid from the pores as a liquid column.

The freeze-drying method according to claim 5 is a method in which a raw material liquid is self-frozen by forming fine raw material liquid particles formed by jetting a raw material liquid into a vacuum freeze-drying tower under vacuum from a nozzle provided at an upper end of the vacuum freeze-drying tower In the freeze-drying method in which the fine frozen particles are captured by a trapping surface in the vacuum freeze-drying tower and then heated and sublimated and dried, at least one formed on the tip of the nozzle. The raw material liquid is ejected downward from the pores as a liquid column, and the mist-like fine raw material liquid particles formed by the liquid column diverging at a fixed length position determined by the ejection condition of the raw material liquid are self-freezing. And making the fine frozen particles.
In such a freeze vacuum drying method, the raw material liquid is not immediately atomized from the pores of the nozzle, and the raw material liquid is first ejected as a liquid column. Does not cause the self-freezing of the fine raw material liquid particles.

  According to the freeze vacuum drying apparatus of the first aspect, the raw material liquid is ejected as a liquid column from the fine pores which are the ejection holes of the nozzle. Since freezing does not occur, work is not interrupted due to nozzle clogging.

  According to the freeze vacuum drying apparatus of claim 2, since the supply pressure applied to the raw material liquid in the raw material liquid supply container and the pressure in the vacuum lyophilization tower can be controlled independently, the raw material liquid can be controlled from the pores. After being ejected as a liquid column into the vacuum freeze-drying tower, it is ensured that it becomes a mist-like fine raw material liquid particle and diverges, and it is possible to follow some pressure fluctuations during freeze-drying. Enables stable operation of vacuum drying equipment over a long period of time. The liquid formed can also be formed by controlling the pressure in the vacuum freeze-drying tower with a constant supply pressure of the raw material liquid, and by controlling the supply pressure of the raw material liquid with a constant pressure in the vacuum freeze-drying tower. The length of the column, the divergence angle of the fine raw material liquid particles that diverge from the lower end of the liquid column, the particle diameter of the fine raw material liquid particles, and the freezing temperature can be changed.

  According to the freeze vacuum drying apparatus of claim 3, since the distance from the lower end of the liquid column to the capture surface of the fine frozen particles can be mechanically adjusted according to the length of the liquid column to be formed, Of the raw material liquid that diverges from the lower end of the liquid and reaches the capture surface without being self-frozen. It can be used for different freeze-drying and the equipment cost is reduced.

  According to the freeze-drying apparatus of claim 4, the raw material liquid is ejected as a liquid column from the pores only by changing the inner diameter of the pores in the range of 50 μm to 500 μm. It is possible to easily set conditions for generating fine frozen particles due to self-freezing of the formed fine raw material liquid particles, thereby facilitating stable operation of the freeze vacuum drying apparatus.

  According to the freeze-drying method of claim 5, the raw material liquid is ejected as a liquid column from the pores formed in the nozzle, and the self-freezing of the fine raw material liquid particles is performed not only at the tip of the pore but also in the vicinity of the pore. Therefore, the operation is not interrupted due to nozzle clogging.

  As described above, the raw material liquid is supplied from the nozzle provided at the upper end of the vacuum freeze-drying tower into the vacuum freeze-drying tower under vacuum, and the fine raw material liquid particles formed are self-frozen to form fine frozen particles. Subsequently, in the case where fine frozen particles are captured by a trapping surface in a vacuum freeze-drying tower and heated to be sublimated and dried, the freeze-drying apparatus of the present invention has at least one nozzle at its tip as a raw material liquid ejection hole. A mist that is formed by diverging the liquid column at a fixed length determined by the raw material liquid ejection conditions by ejecting the raw material liquid as a liquid column downward from the pores. This is a device configured such that the micro raw material liquid particles self-freeze to become micro frozen particles.

  In addition, the raw material liquid is supplied from the nozzle provided at the upper end of the vacuum freeze-drying tower into the vacuum freeze-drying tower under vacuum, and the fine raw material liquid particles formed are self-frozen to form fine frozen particles, In the case where fine frozen particles are captured by a trapping surface in a vacuum freeze-drying tower and heated and sublimated to dry, the freeze-vacuum drying method of the present invention uses the raw material downward from at least one pore formed at the tip of the nozzle. This is a method in which liquid is ejected as a liquid column, and mist-like micro raw material liquid particles formed by diverging the liquid column at a fixed length position determined by the raw material liquid ejection conditions are self-frozen to form micro frozen particles.

  In the freeze vacuum drying apparatus and freeze vacuum drying method of the present invention, the nozzle ejection holes for ejecting the raw material liquid are pores formed in a flat plate, and may be a single pore or a plurality of pores. There may be. That is, by attaching a nozzle having two pores, it is necessary to increase the drying capacity, but the processing capacity can be doubled. The inner diameter of the fine pores of the nozzle is, for example, 150 μm, but may be smaller or larger. In short, any material liquid can be used as long as it is ejected from the pores as a liquid column. The formation of the liquid column is governed by the supply pressure of the raw material liquid and the pressure of the vacuum freeze-drying tower. A plurality of nozzles having pores with different inner diameters may be provided on the turret plate, and a nozzle having pores with an appropriate inner diameter may be selected by rotating the turret plate.

  When the raw material liquid stored in the raw material liquid supply container is pressurized and ejected from the pores of the nozzle into the vacuum freeze-drying tower under vacuum, a liquid column of a certain length determined by the ejection conditions is formed, and the lower end of the liquid column The raw material liquid diverges and fine raw material liquid particles are formed in a mist form. That is, the ejected raw material liquid forms a liquid column for a short time although the solvent or dispersion medium evaporates from the surface, and after that time, the evaporation of the solvent or dispersion medium proceeds rapidly from the inside, and the liquid column This is because the volume of the liquid rapidly expands and the liquid column becomes mist-like fine raw material liquid particles and diverges in a substantially conical shape. In addition to the length of the liquid column at that time, the angle of divergence, the particle diameter of the fine raw material liquid particles formed and the freezing temperature are the same as the inner diameter of the pores, the supply pressure of the raw material liquid, and the vacuum Dominated by the pressure in the freeze-drying tower. Therefore, it is desirable that the supply pressure of the raw material liquid and the pressure in the vacuum freeze-drying tower can be controlled independently. The fine raw material liquid particles thus produced are evaporated while the solvent or dispersion medium evaporates while falling in the vacuum freeze-drying tower, thereby depriving latent heat of vaporization and lowering the temperature.

  Then, the fine frozen particles are dried by sublimating a solvent or dispersion medium having a temperature equal to or lower than the freezing temperature from the fine frozen particles. At the time of drying, although depending on the type of substance to be dried, sublimation is promoted by heating to a temperature at which the substance is not denatured, for example, 30 ° C. As the heating means, one that can be heated uniformly without generating a local high temperature part is desirable. When heating to 30 ° C., for example, heating by a jacket using hot water of 30 ° C. or a planar heater Etc. are used.

  When the solvent or dispersion medium of the raw material liquid is water, the frozen particles are dried by sublimating ice that is self-freezing and having a temperature of 0 ° C. or lower. Accordingly, the pressure of the vacuum freeze-drying tower is maintained at 100 Pa or less, for example, about 50 Pa or 5 Pa, although it depends on the temperature of the micro frozen particles, that is, the temperature of ice. Of course, it may be 5 Pa or less. Needless to say, when the solvent or dispersion medium is other than water, an appropriate pressure is selected for the vacuum freeze-drying tower depending on the type of the solvent or dispersion medium.

  For the vacuum freeze-drying tower having the pressure as described above, the raw material liquid is applied with a supply pressure of, for example, a high pressure (≈0.1 MPa) or more using, for example, nitrogen gas, for example, a supply pressure of 0.3 MPa. As described above, the raw material liquid is ejected as a liquid column having a fixed length from the lower end of the pore having an appropriately selected inner diameter, and then diverged as atomized fine raw material liquid particles. Freezes into micro frozen particles.

  Hereinafter, the freeze vacuum drying apparatus and freeze vacuum drying method of the present invention will be described in detail with reference to the drawings. FIG. 1 is a schematic sectional view of a freeze vacuum drying apparatus 1 used in Example 1. That is, the freeze-drying apparatus 1 is an apparatus for producing a fine powder P of mannitol using a 5% aqueous solution of mannitol as a raw material liquid L. The freeze vacuum drying apparatus 1 diverts the raw material liquid L into the fine raw material liquid particles R in the cylindrical vacuum freeze drying tower 11. The minute raw material liquid particles R are self-frozen in the middle of dropping and become minute frozen particles Q. The falling micro frozen particles Q are captured, collected, heated at a low temperature, and the ice contained in the micro frozen particles Q is sublimated and dried.

  That is, a nozzle 12 is provided at the upper end of the vacuum freeze-drying tower 11 in order to eject a raw material liquid L supplied from a raw material liquid supply container 41 described later as a liquid column K. The figure is shown in FIG. That is, the nozzle 12 has a single pore 14 formed at the center of a flat plate 13. This flat plate 13 is airtightly fixed to the upper flange 10 of the vacuum freeze-drying tower 11 through an O-ring 12c by a nozzle fixing member 12b. In the present embodiment, the nozzle 12 in which the inner diameter of the pore 14 is 50 μm, 100 μm, 150 μm, and 200 μm is used.

  The liquid column K is formed to have a certain length determined by the conditions under which the raw material liquid L is ejected, and diverges at the lower end to form the fine raw material liquid particles R in the form of mist. Then, the minute raw material liquid particles R are self-frozen in the middle of dropping and become minute frozen particles Q. At the bottom of the vacuum freeze-drying tower 11, the falling fine frozen particles Q are received and captured by a slope, and heated at a low temperature to sublimate the ice contained in the fine frozen particles Q and dry. A conical-shaped collecting / heating device 15 with an open top that slides down the surface and drops downward from the opening 16 at the bottom and a minute frozen particle Q that falls from the opening 16 are received and heated while being transferred to the left in FIG. A transfer machine 18 such as a vibration feeder is provided which is dried to obtain a fine powder P of mannitol.

  On the lower surface side of the conical collecting / heating device 15, a jacket 17 is provided as a circulation path of hot water that is introduced from the outside of the vacuum freeze-drying tower 11 and returned to the outside, not shown. The micro frozen particles Q are received while the micro frozen particles Q slide down the trapping surface 15s, which is the inclined surface of the collecting / heating device 15, and fall downward from the opening 16 in the central portion. Is heated at a low temperature to sublimate the contained ice. In addition, in order to make the fine frozen particles Q slide down smoothly, the surface may be processed with a fluororesin, or minute vibrations may be given to the collection / heating device 15. Of course, instead of the hot water jacket 17, a heater may be embedded under the capturing surface 15 s of the collecting / heating device 15 to heat it.

  Below the opening 16, a bottom portion of the vacuum freeze-drying tower 11 is formed with an extending portion 11 </ b> E leftward in FIG. 1, and a transfer machine 18 is installed from the bottom portion to the extending portion 11 </ b> E. That is, the transfer machine 18 receives the minute frozen particles Q with reduced ice content falling from the opening 16 at the bottom of the collection / heating device 15 and heats and dries while transporting to the left in FIG. At the downstream end, dry fine powder P of mannitol is obtained. Note that a planar heater is attached as a heating means, not shown. And the said extension part 11E of the vacuum freeze-drying tower 11 becomes the drooping path 11F where the mannitol fine powder P falls after being bent directly under the downstream end of the transfer machine 18, and the lower part of the drooping path 11F is It is inserted into a collection / weighing chamber 21 which will be described later, and its lower end is throttled and an automatic opening / closing valve 19 is attached.

  The collection / weighing chamber 21 into which the above-described drooping path 11F is inserted is provided integrally with the vacuum freeze-drying tower 11, and the mannitol fine powder P falling through the drooping path 11F is stored in the container 22 and weighed. . The recovery / weighing chamber 21 is provided with a sealing / extraction chamber 31 via a gate valve 29. In the sealing / removal chamber 31, after the stopper 23 is plugged into the container 22 by a stopper 32 provided on the ceiling surface side, the gate valve 39 that opens and closes to the atmosphere side is opened and taken out to the atmosphere side. It is. The sealing / extraction chamber 31 can be evacuated independently, not shown. In addition, in order to transfer the container 22 between the collection / weighing chamber 21, the capping / removal chamber 31, and the atmosphere side, each is provided with a conveyor 30. In particular, the conveyor of the collection / weighing chamber 21 is provided. Although 30 is not shown, a load cell type weight measuring device is attached.

  In FIG. 1, a supply container 41 for the raw material liquid L is installed above the left side of the vacuum freeze-drying tower 11. A raw material liquid supply pipe 42 that connects the bottom of the raw material liquid supply container 41 and the nozzle 12 at the upper end of the vacuum freeze-drying tower 11 is attached. The raw material liquid supply container 41 and the nozzle 12 are opened and closed. A valve 43 is provided. In addition, a nitrogen gas pipe 44 for applying supply pressure to the upper space of the raw material liquid L stored in the raw material liquid supply container 41 is disposed together with the on-off valve 45. The supply of the raw material liquid L may be pumped using a pump.

  Further, a vacuum exhaust system for exhausting the inside of the vacuum freeze-drying tower 11 is provided on the right side of the bottom of the vacuum freeze-drying tower 11 in FIG. That is, a root pump 52 and a rotary pump 51 are connected to a vacuum exhaust pipe 57 connected to the bottom of the vacuum freeze-drying tower 11 through a cold trap 53 having a liquid nitrogen pipe 54 for cooling. An exhaust valve 55 is provided between the trap 53 and the roots pump 52, and an open / close valve 56 is provided between the vacuum freeze-drying tower 11 and the cold trap 53.

  The spray-type vacuum freeze-drying apparatus 1 of the present embodiment is configured as described above. Next, the operation will be described. Referring to FIG. 1, a nozzle 12 having a fine hole 14 having an inner diameter of 150 μm as an injection hole for raw material liquid L is attached to the upper end of vacuum freeze-drying tower 11. The raw material liquid supply container 41 stores a 5% aqueous solution of mannitol as the raw material liquid L. Then, the automatic open / close valve 19 in the collection / weighing chamber 21 is opened, the open / close valve 56 and the exhaust valve 55 of the vacuum exhaust pipe 57 are opened, and the vacuum lyophilization tower 11 is evacuated by the rotary pump 51 and the roots pump 52. The internal pressure was maintained at 50 Pa, and the cold trap 53 was operated. Further, hot water having a temperature of 30 ° C. is circulated through the jacket 17 on the lower surface side of the collecting / heating device 15 at the bottom of the vacuum freeze-drying tower 11, and the transfer machine 18 is also energized with a planar heater (not shown) to keep the temperature at 30 ° C. It was. At that time, all other valves are closed.

  From the above state, the opening / closing valve 45 of the nitrogen gas pipe 44 of the raw material liquid supply container 41 is opened to replace the upper space of the raw material liquid L with nitrogen gas, and then the raw material liquid L is pressurized with nitrogen gas and is always 0.3 MPa. When the on-off valve 43 of the raw material liquid supply pipe 42 is opened so that the supply pressure is applied to the vacuum freeze-drying tower 11 from the fine holes 14 of the nozzle 12, the raw material is directed downward from the fine holes 14 of the nozzle 12. A liquid column K having a length of 400 mm of the liquid L was formed, the raw material liquid L was diverged from the lower end of the liquid column K, and the formed fine raw material liquid particles R dropped downward. At this time, the self-freezing of the fine raw material liquid particles R did not occur at the tip portions of the pores 14 or in the vicinity thereof. Incidentally, the flow velocity of the raw material liquid L in the pores 14 of the nozzle 12 at this time was calculated as 18.2 m / sec.

  Then, the formed fine raw material liquid particles R are self-frozen due to evaporation of moisture and deprivation of latent heat of vaporization in the middle of dropping in the vacuum freeze-drying tower 11 under vacuum, and fall as fine frozen particles Q. The trapping surface 15s on the upper side of the collecting / heating device 15 was trapped. The micro frozen particles Q are heated by the trapping surface 15s of the collecting / heating device 15, and the ice contained therein is sublimated and dried, and slides down the inclined surface to move downward from the opening 16 at the bottom. It fell down.

  The fine frozen particles Q dropped from the opening 16 are conveyed leftward in FIG. 1 by the transfer device 18 and heated by a planar heater (not shown), and a dried mannitol powder P is obtained at the downstream end of the transfer device 18. It was. Then, the fine powder P of mannitol discharged from the downstream end of the transfer machine 18 was stored and weighed in the container 22 in the collection / weighing chamber 21 via the hanging path 11F. When the weighing value reaches a predetermined value, the automatic open / close valve 19 is closed, the gate valve 29 is opened, the container 22 is carried out to the capping extraction chamber 31, and a new container 22 is collected in the collection / weighing chamber 21 for replacement. After loading into the position, the gate valve 29 was closed, the automatic opening / closing valve 19 was opened, and the storage of the mannitol fine powder P was resumed.

  On the other hand, the container 22 containing the mannitol fine powder P transported to the sealing / extraction chamber 31 was stoppered by the stopper 32 and then opened to the atmosphere side by opening the gate valve 39. In exchange for this, a new container 22 was carried in, and then the gate valve 39 was closed and evacuated to obtain a vacuum level equivalent to that of the collection / weighing chamber 21. The above operation was repeated in the collection / weighing chamber 21 and the capping / removal chamber 31.

  In the above description, the supply pressure applied to the raw material liquid L is 0.3 MPa. However, when the supply pressure is changed to 0.1 MPa, 0.2 MPa, and 0.5 MPa, the smaller the supply pressure, the more the nozzle 12 Although the liquid column K of the raw material liquid L formed below is shortened, the self-freezing of the fine raw material liquid particles R did not occur around the pores 14 of the nozzle 12. Incidentally, the length of the liquid column K when the supply pressure of the raw material liquid L was 0.1 MPa was 300 mm.

  The same freeze-drying apparatus 1 as in Example 1 was used, and the nozzle 12 having a pore 14 with an inner diameter of 100 μm was attached. The pressure in the vacuum freeze-drying tower 11 was 50 Pa, and the supply pressure applied to the raw material liquid L In the same manner as in Example 1 at 0.3 MPa, a 5% aqueous solution of mannitol as the raw material liquid L was freeze-dried. As a result, a liquid column K having a length of 200 mm of the raw material liquid L is formed below the pores 14 of the nozzle 12, and the self-freezing of the fine raw material liquid particles R at the tips of the pores 14 or in the vicinity of the pores 14. The raw material liquid L was recovered as mannitol fine powder P in the same manner as in Example 1.

  The nozzle 12 having an inner diameter of 100 μm used in the above was replaced with the nozzle 12 having an inner diameter of the pore 14 of 200 μm, and otherwise, a 5% aqueous solution of mannitol as the raw material liquid L was similarly frozen. Dried. Also in this case, a liquid column K of the raw material liquid L is formed below the pores 14 of the nozzle 12, and the self-freezing of the fine raw material liquid particles R occurs at the tips of the pores 14 or in the vicinity of the pores 14. Without doing so, the raw material liquid L was recovered as fine powder P of mannitol.

  The same freeze-drying apparatus 1 as in Example 1 was used, the nozzle 12 was attached with an inner diameter of the pore 14 of 50 μm, the pressure in the vacuum freeze-drying tower 11 was 50 Pa, and the supply pressure applied to the raw material liquid L was 0. Although it was set to 0.1 MPa, 0.2 MPa, 0.3 MPa, and 0.5 MPa, in any case, the raw material liquid L was frozen at the tips of the pores 14 and the raw material liquid L could not be ejected. This is considered to be because the raw material liquid L immediately self-frozen without forming a liquid column because the flow rate of the raw material liquid L in the pores 14 is small.

  The freeze vacuum drying apparatus and freeze vacuum drying method of the present invention have been described above with reference to the embodiments. Of course, the present invention is not limited thereto, and various modifications can be made based on the technical idea of the present invention. .

  For example, in this embodiment, the nozzle 12 uses a flat plate 13 with pores 14 and is fixed to the upper flange 10 of the vacuum freeze-drying tower 11 with the nozzle fixing member 12b. The nozzle 12 may have any structure.

  In this embodiment, the nozzle 12 is fixed to the upper end of the vacuum freeze-drying tower 11. For example, the nozzle 12 is moved up and down by a lifting mechanism via a bellows at the upper end of the vacuum freeze-drying tower 11. The distance between the pore 14 of the nozzle 12 and the lower collecting / heating device 15 may be variable. If it does in this way, it will become an apparatus which can change the height position of the nozzle 12 in the vacuum freeze-drying tower 11, and freeze-vacuum drying with which the length of the liquid column formed at the time of the ejection of the raw material liquid L is large, or minute This is a freeze vacuum drying apparatus that can also be used for freeze vacuum drying in which the type of raw material liquid and the injection conditions are different, such as freeze vacuum drying that takes time until the raw material liquid particles R become micro frozen particles Q.

  Further, in this example, a case where a 5% aqueous solution of mannitol is used as a raw material liquid and freeze-vacuum drying to produce a fine powder of mannitol has been described. The freeze-vacuum drying apparatus and freeze-vacuum drying method of the present invention are It is not limited to raw material liquids. For example, the same applies to the case where microcapsules containing active ingredients of pharmaceuticals and foods are dispersed in a dispersion medium and freeze-dried to obtain dried microcapsules. Is done.

1 is a schematic cross-sectional view of a freeze vacuum drying apparatus according to an embodiment of the present invention. It is a schematic sectional drawing of the nozzle used in the Example. It is a figure which shows the vertical and horizontal schematic cross section of the spray nozzle generally used, and the schematic shape of the spray formed.

Explanation of symbols

1 ・ Freeze vacuum drying equipment 10 ・ Upper flange,
11 ・ Vacuum freeze-drying tower, 12 ・ Nozzle,
14-pores, 15-collection and heating equipment,
18 ・ Transfer machine ・ 21 ・ Collection / weighing room,
22 ・ Container, 31 ・ Sealing and removal room,
41 ・ Raw material liquid supply container 42 ・ Raw material liquid supply pipe 44 ・ Nitrogen gas pipe 51 ・ Rotary pump
52 · Roots pump, 53 · Cold trap,
L ・ Raw material liquid, K ・ Liquid column,
P ・ Fine powder of mannitol, Q ・ Fine raw material liquid particles,
R ・ Micro frozen particles

Claims (5)

The fine raw material liquid particles formed by spraying the raw material liquid from the nozzle provided at the upper end of the vacuum freeze drying tower into the vacuum freeze drying tower under vacuum are self-frozen to form fine frozen particles, and then In a freeze vacuum drying apparatus that captures fine frozen particles at a trapping surface in the vacuum freeze drying tower and heats and sublimates and dries,
The nozzle has at least one fine hole as an ejection hole for the raw material liquid,
By spraying the raw material liquid downward from the pores as a liquid column, the mist-shaped fine raw material liquid particles formed by the liquid column diverging at a fixed length position determined by the injection condition of the raw material liquid The freeze-drying apparatus is characterized in that is self-frozen to become the above-mentioned minute frozen particles.   The said raw material liquid is accommodated in the raw material liquid supply container, The supply pressure applied to the said raw material liquid in the said raw material liquid supply container and the pressure in the said vacuum freeze-drying tower are made controllable independently. The freeze vacuum drying apparatus as described.   The freeze-drying apparatus according to claim 1, wherein a distance from the pore to the capturing surface is mechanically variable.   The freeze-drying apparatus according to claim 1, wherein an inner diameter of the pore is set in a range of 50 µm to 500 µm. The fine raw material liquid particles formed by spraying the raw material liquid from the nozzle provided at the upper end of the vacuum freeze drying tower into the vacuum freeze drying tower under vacuum are self-frozen to form fine frozen particles, and then In the freeze-drying method in which fine frozen particles are captured by a trapping surface in the vacuum freeze-drying tower, heated and sublimated and dried,
The raw material liquid is ejected downward as a liquid column from at least one fine hole formed at the tip of the nozzle, and the liquid column is diverged and formed at a fixed position determined by the ejection condition of the raw material liquid. The freeze-drying method characterized by self-freezing the mist-like fine raw material liquid particles to form the fine frozen particles.

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