JP2018150858A - Cryotrap - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a cryotrap that allows steam sterilization treatment.SOLUTION: A cryotrap 38 comprises a refrigerator 40 including a cylinder 41 in which a reciprocating displacer 60 is housed, and a compressor 50 for helium circulation, and cools the inside of a case 30 connected to a chamber 11 that is a deaerated space in which steam sterilization treatment is performed. The displacer has a heat-resistant temperature equal to or higher than a temperature condition in the steam sterilization treatment.SELECTED DRAWING: Figure 3

Description

  The present invention relates to a cryotrap, and more particularly to a technique suitable for use in a refrigerator used in a cold trap for condensing moisture from an object to a low temperature surface at a constant exhaust speed during freeze drying or the like.

  There has been proposed a vacuum drying apparatus equipped with a cold trap for freezing and vacuum drying raw material liquids such as pharmaceuticals, foods, cosmetics, and chemicals (for example, Patent Document 1).

  According to a conventional vacuum drying apparatus, a vacuum pump is connected to a drying chamber that accommodates an object to be dried via an exhaust path, and a cold trap is provided in the middle of the exhaust path. The water to be dried can be dried by condensing the water vapor sublimated from the material to be dried in the drying chamber by condensing in a cold trap.

In addition, as a recent trend in freeze-drying equipment for pharmaceuticals, the needs for “antibody drugs” and “biopharmaceuticals” are increasing.
Since these chemicals have a higher water activity than conventional chemicals, there is a background that the water content must be lower. In Non-Patent Document 1, a heat exchanger using liquid nitrogen is added. Therefore, it is possible to produce these drugs by creating a low temperature and lowering the pressure in the freeze-drying tank.
In the case of these drugs, it is necessary to “realize the manufacturing method as it is” as to how to make the investigational drug.

  However, in the technique shown in Non-Patent Document 1, the use of liquid nitrogen makes the apparatus extremely large, and there has been a demand for miniaturization and space saving. Furthermore, the use of liquid nitrogen increases maintenance labor and running costs, and therefore an apparatus and method with good workability without such costs being required.

  For this reason, the use of a cryotrap that has been used in semiconductor and FPD manufacturing apparatuses has been studied. (Patent Document 2)

Japanese Patent No. 5574318 JP 7-189907 A

Taiyo Nippon Sanso Technical Report No. 33 (2014) p1-p2 Koya Mori Masahiro Yonekura “Liquid nitrogen vacuum freeze dryer for biopharmaceuticals” Internet (URL; https://www.tn-sanso-giho.com/pdf /33/tnscgiho33_06.pdf)

However, there are strict standards (sanitary standards) in pharmaceutical manufacturing, and sterilization and cleaning of the inside of the device is necessary. Therefore, the temperature range and pressure range assumed in the manufacture of semiconductors and FPDs assumed in conventional cryotraps. On the other hand, it was not possible to adapt to different use conditions, particularly high temperatures during sterilization cleaning.
Furthermore, since a metal such as copper cannot be used in the portion directly exposed to a pharmaceutical preparation or the like according to this sanitary standard, it is necessary to achieve compatibility with maintaining the conventional cooling capacity.
In addition, cryotraps are originally used in the manufacture of semiconductors and FPDs. Compared with this, pharmaceutical manufacturing may require a large cooling capacity, and the influence of an increase in the weight of the displacer, etc. Therefore, this could not be applied as it is.

The present invention has been made in view of the above circumstances, and intends to achieve the following object.
1. Make the cryotrap applicable to freeze-drying (vacuum drying) equipment.
2. To enable freeze-drying that can be applied to pharmaceutical production.

  When a mechanical refrigerator is used for the cold trap, the heat contact plate of the cold trap and the thermal contact part of the cylinder use materials having good thermal conductivity at low temperature, for example, oxygen-free copper, and the heat transfer plate and heat A soft material such as an indium foil is used between the contact portions to increase the contact area and improve heat transferability. However, when the object to be freeze-dried is a pharmaceutical product, the materials that can be used in the drying furnace are limited, and when the usable material SUS316L is used, the heat transfer coefficient at a low temperature is greatly impaired.

  In addition, when the object to be freeze-dried is a pharmaceutical product, it is necessary to perform steam sterilization at 121 ° C. or higher as a process before and after freeze-drying. However, since the heat resistant temperature of the displacer, adhesive, etc., which are the components inside the conventional refrigerator, is 70 ° C., it is difficult to install the refrigerator in a steam sterilization atmosphere. Therefore, it is necessary to select a displacer material that can withstand steam sterilization and a fixing method without using an adhesive. When a resin that can withstand a temperature of 121 ° C. or higher is selected, the clearance between the conventional cylinder and the displacer interferes with the inside due to thermal expansion, and on the other hand, the clearance increases at low temperatures, which affects the refrigeration performance. In consideration of thermal expansion, when stainless steel of the same material as the cylinder is used as the material of the displacer, the weight of the displacer increases and mechanical reliability is impaired. When the displacer is a resin, as a result of being exposed to a steam sterilization atmosphere, a released gas is generated and contaminates the high-purity helium gas which is a refrigerant.

The cryotrap of the present invention includes a refrigerator having a cylinder in which a reciprocating displacer is housed, and a helium circulation compressor, and is connected to a chamber that is a degassed space for performing steam sterilization processing. A cryotrap that cools
The said subject was solved by having the heat-resistant temperature more than the temperature conditions in the said steam sterilization process.
In the present invention, it is more preferable that the outer surface exposed to the deaerated space side of the cylinder is made of SUS316L.
In the cryotrap of the present invention, the inner surface on the low temperature side of the cylinder can be made of copper.
Further, the displacer of the present invention may employ a means in which a wear ring that slides on the inner surface of the cylinder is provided on the outer surface of the cold end side that is the low temperature side of the cylinder and the opposite end side thereof. it can.
Further, a wear ring provided on the outer surface on the displacer low-temperature end side may be provided at a position sliding with the inner surface on the cylinder low-temperature side made of copper.
The wear ring provided on the outer surface on the displacer low temperature end side may be narrower than the wear ring provided on the outer surface on the opposite side of the displacer low temperature end side.
Further, a wear ring provided on the outer surface opposite to the displacer low temperature end side may be provided at a position where the wear ring slides on the inner surface opposite to the cylinder low temperature side made of SUS316L. .
The wear ring that is provided on the outer surface of the displacer and slides on the inner surface of the cylinder may be provided with a thermal expansion absorption groove (step cut) that is spaced apart in the circumferential direction of the displacer.
Further, the circumferential position of the thermal expansion absorption groove may be shifted depending on the position of the displacer in the reciprocating direction.
The thermal expansion absorption groove may be provided with a sliding portion that slides in the circumferential direction and maintains a sealed state in the reciprocating direction of the displacer when the wear ring is thermally expanded.
Also, a lid that closes the end of the displacer at the low temperature end is provided, the lid is fitted to the outer peripheral side of the displacer, and the spring penetrates from the outer peripheral side of the displacer to the lid It can be locked by a pin.
Further, the inside of the displacer is a regenerator, a lid portion is provided to close the end portion on the displacer low temperature end side, and a position closer to the regenerator side than the lid portion is provided on the outer peripheral side portion of the displacer. A plurality of open helium gas jets can be provided.
The displacer may be made of a material selected from bakelite, polyetheretherketone, and polyphenylene sulfide.
In addition, the displacer may be made of SUS316L, and a thinned portion having a thickness dimension that is thinner than a portion that slides with the cylinder inner surface may be provided on an outer surface that does not slide with the cylinder inner surface.
Further, the displacer made of SUS316L may be provided with a coating portion made of resin at the thinned portion.
The cylinder may be a bottomed cylinder made of SUS316L, and the low temperature side inner surface and the low temperature side inner bottom of the cylinder may be made of copper.
The thickness of SUS316L made of copper at the outer surface position on the low temperature side of the cylinder may be 0.1 to 2 mm.
Moreover, it is preferable that an adsorber for removing decontamination of helium is provided in a circulation path from the refrigerator to the compressor.
Further, the vacuum drying apparatus of the present invention, any of the cryotrap as described above,
A chamber which is a deaerated space.

The cryotrap of the present invention includes a refrigerator having a cylinder in which a reciprocating displacer is housed, and a helium circulation compressor, and is connected to a chamber that is a degassed space for performing steam sterilization processing. A cryotrap that cools
The said subject was solved by having the heat-resistant temperature more than the temperature conditions in the said steam sterilization process.

  In the present invention, it is more preferable that the outer surface exposed to the deaerated space side of the cylinder is made of SUS316L.

  In the cryotrap of the present invention, the inner surface on the low temperature side of the cylinder can be made of copper.

  Further, the displacer of the present invention may employ a means in which a wear ring that slides on the inner surface of the cylinder is provided on the outer surface of the cold end side that is the low temperature side of the cylinder and the opposite end side thereof. it can.

  Further, a wear ring provided on the outer surface on the displacer low-temperature end side may be provided at a position sliding with the inner surface on the cylinder low-temperature side made of copper.

  The wear ring provided on the outer surface on the displacer low temperature end side may be narrower than the wear ring provided on the outer surface on the opposite side of the displacer low temperature end side.

  Further, a wear ring provided on the outer surface opposite to the displacer low temperature end side may be provided at a position where the wear ring slides on the inner surface opposite to the cylinder low temperature side made of SUS316L. .

  The wear ring that is provided on the outer surface of the displacer and slides on the inner surface of the cylinder may be provided with a thermal expansion absorption groove (step cut) that is spaced apart in the circumferential direction of the displacer.

  Further, the circumferential position of the thermal expansion absorption groove may be shifted depending on the position of the displacer in the reciprocating direction.

  The thermal expansion absorption groove may be provided with a sliding portion that slides in the circumferential direction and maintains a sealed state in the reciprocating direction of the displacer when the wear ring is thermally expanded.

  Also, a lid that closes the end of the displacer at the low temperature end is provided, the lid is fitted to the outer peripheral side of the displacer, and the spring penetrates from the outer peripheral side of the displacer to the lid It can be locked by a pin.

  Further, the inside of the displacer is a regenerator, a lid portion is provided to close the end portion on the displacer low temperature end side, and a position closer to the regenerator side than the lid portion is provided on the outer peripheral side portion of the displacer. A plurality of open helium gas jets can be provided.

  The displacer may be made of a material selected from bakelite, polyetheretherketone, and polyphenylene sulfide.

  In addition, the displacer may be made of SUS316L, and a thinned portion having a thickness dimension that is thinner than a portion that slides with the cylinder inner surface may be provided on an outer surface that does not slide with the cylinder inner surface.

  Further, the displacer made of SUS316L may be provided with a coating portion made of resin at the thinned portion.

  The cylinder may be a bottomed cylinder made of SUS316L, and the low temperature side inner surface and the low temperature side inner bottom of the cylinder may be made of copper.

  Further, the thickness of SUS316L made of copper at the outer surface position on the low temperature side of the cylinder may be 0.1 to 2 mm.

  Moreover, it is preferable that an adsorber for removing decontamination of helium is provided in a circulation path from the refrigerator to the compressor.

Further, the vacuum drying apparatus of the present invention, any of the cryotrap as described above,
A chamber which is a deaerated space.

  According to the present invention, it is possible to provide an effect that it is possible to provide a cryotrap that can be applied to a vacuum drying apparatus (freeze drying apparatus) used in pharmaceutical manufacture that requires steam sterilization. Become.

It is a schematic diagram showing a first embodiment of a vacuum drying apparatus provided with a cryotrap according to the present invention. It is a mimetic diagram showing a 1st embodiment of a cryotrap concerning the present invention. It is side sectional drawing which shows the refrigerator in 1st Embodiment of the cryotrap which concerns on this invention. It is a sectional side view which shows the cylinder of the refrigerator in 1st Embodiment of the cryotrap which concerns on this invention. It is sectional drawing which shows the cylinder of the refrigerator in 1st Embodiment of the cryotrap which concerns on this invention. It is a side view which shows the displacer of the refrigerator in 1st Embodiment of the cryotrap which concerns on this invention. It is a bottom view which shows the displacer of the refrigerator in 1st Embodiment of the cryotrap which concerns on this invention. It is a side step view which shows the displacer of the refrigerator in 1st Embodiment of the cryotrap which concerns on this invention. It is a flowchart which shows the vacuum drying process using 1st Embodiment of the cryotrap which concerns on this invention. It is a side view which shows the displacer of the refrigerator in 2nd Embodiment of the cryotrap which concerns on this invention. It is a bottom view which shows the displacer of the refrigerator in 2nd Embodiment of the cryotrap which concerns on this invention. It is a side step figure which shows the displacer of the refrigerator in 2nd Embodiment of the cryotrap which concerns on this invention. It is a schematic diagram which shows the other example of the step cut in embodiment of the cryotrap which concerns on this invention.

Hereinafter, a cryotrap according to a first embodiment of the present invention will be described with reference to the drawings.
FIG. 1 is a schematic diagram showing a vacuum drying apparatus provided with a cryotrap according to the present embodiment. In the figure, reference numeral 10 denotes a vacuum drying apparatus.

  The vacuum drying apparatus 10 according to the present embodiment is for freezing and vacuum-drying the raw material liquid in order to produce, for example, pharmaceutical products, pharmaceutical preparations, and raw materials thereof. The to-be-dried product F1 may be a pharmaceutical preparation or a material thereof, and may be in a liquid state in which the raw material liquid is contained in a container, or in a solid state (for example, a lump or powder) that has been frozen in a vacuum in the previous step. Also good. This embodiment will be described using the former example.

  As shown in FIG. 1, the vacuum drying apparatus 10 according to the present embodiment is connected to a drying chamber 11 for storing a material to be dried and the drying chamber 11, and condenses and collects moisture sublimated from the material to be dried F <b> 1. A first dehydrating unit 12 having a first collecting means 17 capable of being cooled to a first temperature that can be cooled, and connected to the drying chamber 11 independently of the first dehydrating unit 12, The second dehydrating part 30 having the collecting means 38 that can be cooled to the second temperature lower than the first temperature, and the drying chamber 11 and the first dehydrating part 12 as the switching means are selectively used. The first partition 21 that can be communicated / desorbed, the second partition 23 that can selectively communicate / desorb the drying chamber 11 and the second dehydrator 30 as switching means, and the controller 14. And.

  The drying chamber 11 is a space for vacuum-drying the raw material F1, which is an object to be dried. The degree of vacuum in the drying chamber 11 can be adjusted, for example, in the range of 5 to 300 Pa. The drying chamber 11 has a plurality of shelves 11a that support trays (not shown) on which the samples F1 are placed, respectively.

  Each of the plurality of shelves 11a in the drying chamber 11 is provided with a heater (temperature control means) 11b. The heater 11b is controlled by the control unit (control unit) 14 so that the sample F1 placed on the shelf 11a can be heated and cooled. As the heater 11b, for example, a mechanism for circulating a heating medium inside the shelf 11a, a resistance heating type heater such as a sheathed heater, or the like can be used. The set temperature of the heater 11b during heating is not particularly limited, and can be set to 20 ° C., for example.

  A temperature sensor 11c is provided on at least one of the shelves 11b. The temperature sensor 11c detects the temperature of the sample F1 placed on the shelf 3 heated by the heater 11b, and outputs this to the control unit 14 as a detection signal. The temperature sensor 11c can be an object that measures temperature from the upper side of the shelf 11a, and is preferably provided for each shelf 11a.

  A first dehydrating unit 12 and a second dehydrating unit 30 are independently connected to the drying chamber 11, and the drying chamber 11 is evacuated via the first dehydrating unit 12 and the second dehydrating unit 30. The pump (first exhaust unit) 15 and the pump (second exhaust unit) 16 communicate with each other. The vacuum pump 15 is a pump for exhausting the inside of the drying chamber 11 to a predetermined degree of vacuum. Various vacuum pumps such as a rotary pump and a dry pump can be employed as the vacuum pump 15.

  As will be described later, the drying chamber 11 is provided with a cleaning / sterilization means 19 for cleaning and sterilizing the inside of the drying chamber 11, the first dehydrating unit 12, and the second dehydrating unit 30. The drying chamber 11, the first dehydrating unit 12, and the second dehydrating unit are controlled by the unit 14 and are supplied with steam of about 121 ° C. for the sterilization process or pure water that satisfies a predetermined standard for the cleaning process. 30 can be supplied inside.

  The drying chamber 11 is provided with pressure gauges 26 and 27 for measuring the pressure inside the drying chamber 11. The pressure gauge 26 is a first vacuum gauge capable of measuring the total pressure without being affected by the measurement instruction value depending on the type of measurement gas, and is, for example, a capacitance manometer such as a Baratron vacuum gauge or a diaphragm pressure gauge. The pressure gauge 27 is a vacuum gauge capable of measuring the total pressure using heat conduction, and is a second vacuum gauge that causes a difference in measurement indication value depending on the type of measurement gas, for example, a Pirani vacuum gauge.

During the first drying step or heat drying step by the first dehydrating unit 12, the measurement instruction value in the drying chamber 11 by the first vacuum gauge 26, and the measurement instruction value in the drying chamber 11 by the second vacuum gauge 27 And the time point at which the difference between the measurement instruction values converges to the minimum is determined as the end point of the first drying process or the heat drying process. This is a discrimination process described later.
That is, when the measured values of the pressure gauges 26 and 27 change from the separated state to the coincident state, it is determined that the moisture inside the drying chamber 11 has been removed to the capacity limit of the first dehydrating unit 12, and the first It is possible to switch to the second possible process by the two dehydrating units 30. The measured values of the pressure gauges 26 and 27 are output to the control unit 14.

  The first dehydrating unit 12 serves as one exhaust path that allows the drying chamber 11 and the vacuum pump (first exhaust unit) 15 to communicate with each other. The first dehydrating unit 12 is provided with a first cold trap 17. It has been. The 1st cold trap 17 comprises the collection surface (1st collection surface) which can condense and collect water vapor | steam. The first cold trap 17 is, for example, larger than a second cold trap 38 described later, and is used as a cold trap for main drying that can collect a larger amount of water vapor.

  The first cold trap 17 in the first dewatering unit 12 is configured by winding a tube through which a cooling medium flows in a coil shape. In addition to this, the first cold trap may be configured in a flat plate shape. The first cold trap 17 has a refrigerant introduction part 17a and a lead-out part 17b at both ends of the tube. The refrigerant introduction part 17 a and the lead-out part 17 b are connected to a first cooling unit 17 c that supplies and distributes the refrigerant in the first cold trap 17.

  The first cooling unit 17 c is controlled by the control unit 14 and causes the refrigerant to flow through the first cold trap 17. The first cooling unit 17c includes a compressor that compresses the refrigerant, a condenser that liquefies the compressed high-temperature and high-pressure refrigerant, an expansion valve that adiabatically expands the liquid refrigerant, and an evaporator that vaporizes the liquid refrigerant. The first cold trap 17 corresponds to the evaporator. The refrigerant is introduced into the first cold trap 17 from the introduction part 17a, circulates through the first cold trap 17, and circulates by being led out from the lead-out part 17b. As the refrigerant, for example, Freon gas R404A, silicon oil, or the like can be used.

  The first cooling unit 17c cools the surface (first collection surface) of the first cold trap 17 to the first temperature. The first temperature is a temperature at which the first cold trap 17 can condense and collect most of the water vapor sublimated from the sample F1 in the drying chamber 11, and the value is the object to be dried. It is set according to the type of the sample F1, the ultimate pressure in the drying chamber, and the like, and in this embodiment, is in the range of about −40 ° C. and about −20 ° C. to −60 ° C.

  In the first dehydrating unit 12, a first partition 21 serving as a switching valve is provided between the drying chamber 11 and the first cold trap 17, and the first cold trap 17 and the vacuum pump (first exhaust) Means) 15 is provided with a first switching valve 22 as switching means. The first partition 21 and the first switching valve 22 are controlled to open and close by the control unit 14.

  The first partition 21 is a partition 21a that can close a portion opened on the wall surface of the drying chamber 11, and a drive unit (not shown) that moves the partition 21a between a closed state in contact with the wall surface and an open state in which the partition member 21a is detached from the wall surface. And a drive source (not shown) for driving the drive unit. When the drive source is driven and controlled by the control unit 14, opening / closing control of the first partition portion 21 is performed. As will be described later, the partition 21a and the drive unit are configured to be washable when the first dehydrating unit 12 and the drying chamber 11 are cleaned and sterilized.

By opening the first partition portion 21, the drying chamber 11 and the first dehydrating portion 12 can be communicated with each other. By opening both the first partition 21 and the first switching valve 22, the drying chamber 11 and the vacuum pump 15 can be communicated with each other. By closing the first partition 21 and opening the first switching valve 22, the inside of the first dehydrating unit 12 can be exhausted. By closing both the first partition portion 21 and the first switching valve 22, exhaust in the drying chamber 11 through the first dehydrating portion 12 can be restricted.
The vacuum pump 15 and the first switching valve 22 constitute a first exhaust means.

  In the present embodiment, a second cold trap 38 is provided in the second dehydrating unit 30 that is the other exhaust path communicating with the drying chamber 11. The second cold trap 38 constitutes a collection surface (second collection surface) capable of condensing and collecting water vapor. The second cold trap 38 is configured to be cooled to a second temperature lower than the first collection surface of the first cold trap 17.

FIG. 2 is a cross-sectional view showing the cryotrap in the present embodiment.
The cryotrap in the present embodiment is attached to the vacuum drying apparatus 10 as the second dehydrating unit 30 for finish drying, and is provided in a case 31 connected to a drying chamber (chamber) 11 that is a space to be deaerated. ing.

  In the present embodiment, the capacity required for the refrigerator 17c of the first cold trap 17 is to have a large heat capacity at a temperature in the vicinity of −50 to −60 ° C., whereas the second cold trap 30 Is secondary drying. In this case, since it is a treatment after adsorbing moisture in the primary drying, the heat capacity may be small at a lower temperature (for example, −80 ° C. to −100 ° C.). Therefore, the second cold trap 38 is made smaller than the first cold trap 17, and the amount of water vapor that can be collected is smaller than that of the first cold trap 17, and is used as a cold trap for finishing drying. It is done. For example, the last 1% of about 500 kg of moisture in the material to be dried is provided to be dried by the second cold trap 38.

  The second cold trap 38 is controlled by the control unit 14 and is installed in the case 31 as a trap panel using a low-temperature panel 38a cooled by a mechanical refrigerator (refrigerator) 40 described later. The plate surface of the low-temperature panel 38a is installed toward the degassing source (object to be dried) F1 in the chamber 11.

The low-temperature panel 38a can be cooled down to an ultra-low temperature of, for example, 80K by Simon expansion of the helium gas by the mechanical refrigerator 40, and cannot be reached by the exhaust pump 16 or the like by condensing gas molecules therein. The degree of vacuum in the drying chamber 11 can be increased to a high vacuum.
The exhaust pump 16 is configured to exhaust the inside of the deaerated space 30 in the second dehydrating unit 30 to a vacuum, and can be a turbo molecular pump.

  The second cold trap 38 has a surface (second collection surface) of the low-temperature panel 38a lower than the surface of the first cold trap 17, for example, about -70 ° C to -100 ° C or about -85 ° C. Cool down. If the surface temperature of the low temperature panel 38a is set too low, it is not preferable because the necessary capacity of the mechanical refrigerator 40 is too large, and if the surface temperature of the low temperature panel 38a is set too high, the drying object F1 This is not preferable because the moisture content cannot be reduced to a required level.

  As described above, the second cold trap 38 uses a high-performance cryotrap that can be applied to the manufacture of semiconductors and FPDs as described above. It is what is used.

  In the second dehydrating unit 30, as shown in FIG. 1, a second partition 23 serving as a switching valve is provided between the drying chamber 11 and the second cold trap 38, and the second cold trap 38. A second switching valve 24 as a switching means is provided between the exhaust pump 16 and the exhaust pump (second exhaust means) 16. The second partition 23 and the second switching valve 24 are controlled to open and close by the control unit 14.

  The second partition 23 includes a partition 23a that can close a portion opened on the wall surface of the drying chamber 11, and a drive unit (not shown) that moves the partition 23a between a closed state in contact with the wall surface and an open state in which the partition member 23a is detached from the wall surface. And a drive source (not shown) for driving the drive unit. This drive source is driven and controlled by the control unit 14 so that the opening / closing control of the second partition portion 23 is performed. As will be described later, the partition 23a and the drive unit are configured to be washable when the deaerated space of the second dehydrating unit 30 and the drying chamber 11 are cleaned and sterilized.

By opening the second partition 23, the drying chamber 11 and the space to be deaerated of the second dehydrating unit 30 can be communicated with each other. By opening both the second partition 23 and the second switching valve 24, the drying chamber 11 and the exhaust pump (second exhaust means) 16 can be communicated with each other. By closing the second partition 23 and opening the second switching valve 24, the inside of the deaerated space of the second dehydrating unit 30 can be exhausted. By closing both the second partition 23 and the second switching valve 24, the space to be deaerated in the second dehydrating unit 30 and the inside of the drying chamber 11 can be closed independently.
The exhaust pump 16 and the second switching valve 24 constitute a second exhaust means.

The vacuum drying apparatus 10 according to the present embodiment communicates the drying chamber 11 with the first dehydrating unit 12 after cleaning the drying chamber 11, the first dehydrating unit 12, and the second dehydrating unit 30. The first dehydration unit 30 is closed and the first freeze-drying process is performed. Thereafter, the drying chamber 11 and the second dehydration unit 30 are communicated with each other, and the first dehydration unit 12 is closed and the second freeze-drying is performed. The process is supposed to be performed.
Therefore, in the vacuum drying apparatus 10 according to the present embodiment, the drying chamber 11, the first dehydrating unit 12, and the degassed space of the second dehydrating unit 30 can be cleaned and sealed, respectively. .

  Specifically, in the first dehydration unit 12 and the second dehydration unit 30, the surface for heat treatment at the time of sterilization and pharmaceutical preparation production was covered with a metal selected from SUS316L, Au, and Pt. Can be configured. In addition, you may use Cu etc. with favorable electroheating in the surface which is not wash | cleaned, ie, the part which does not touch the inner surface of the dehydration parts 12 and 30.

  Similarly, both the first switching valve 22 and the first switching valve 22 are closer to the vacuum pump 15 side, and the second switching valve 24 and the second switching valve 24 are closer to the exhaust pump 16 side. In addition, the flow does not flow back to the drying chamber 11 side.

  Next, the cryotrap 38 in this embodiment will be described.

  As shown in FIG. 2, the cryotrap 38 includes a mechanical refrigerator (refrigerator) 40 and a helium circulation compressor 50 serving as a refrigerant. The refrigerator 40 and the compressor 50 are connected by circulation paths 50a to 50c, and the circulation path 50b that circulates from the refrigerator 50 to the compressor 50 has a high purity as a refrigerant when continuously exposed to a high-temperature atmosphere. An adsorber 51 filled with molecular sieve or activated carbon activated so that helium gas is not contaminated by the released gas is arranged.

  Since the adsorber 51 is disposed between the refrigerator 40 and the compressor 50 in which helium gas circulates, when the refrigerator is continuously exposed to an atmosphere of 121 ° C., a release gas is generated from each material, and the refrigerant Even when the high purity helium gas is contaminated, the helium gas passes through the adsorber 51 every cycle of the refrigerator, and the released gas is trapped each time to prevent contamination of the high purity helium gas.

  As a result, it is possible to prevent the flow of helium flowing in the expansion chamber from condensing inside the regenerator 61, which is generated when the contaminated helium gas is used for cooling, from being reduced and causing deterioration in performance. Further, when there is a large amount of pollutant condensed, the pressure loss increases, making it difficult to operate the refrigerator 40 at a constant speed, and it is possible to prevent intermittent abnormal noises from being caused and causing mechanical problems.

FIG. 3 is a cross-sectional view showing a refrigerator (refrigerator) 40 in the present embodiment.
As shown in FIG. 3, the refrigerator 40 includes a cylinder 41 and a displacer 60.

A displacer 60 that reciprocates in the axial direction by a drive source 40 a is accommodated in the cylinder 41, and a low temperature expansion chamber 42 is formed in the cylinder 41 at the tip end in the axial direction of the displacer 60.
Inside the displacer 60, a regenerator 61 made of a metal net or metal particles is provided, and helium at room temperature compressed by an external helium circulation compressor 50 can be circulated through the intake valve 44 and the discharge valve 45. It has become.

FIG. 4 is a side sectional view showing the cylinder 41 in the present embodiment, and FIG. 5 is a sectional view seen from the opening side showing the cylinder 41 in the present embodiment.
As shown in FIGS. 4 and 5, the cylinder 41 in the present embodiment has a bottomed cylindrical shape, and has, for example, a circular cross section. The closed bottom side of the cylinder 41 is a low temperature expansion chamber 42 which is the low temperature side of the refrigerator 40.

  The entire surface of the cylinder 41 is covered with SUS316L, and the expansion chamber side surface 42a and the inner bottom surface 42b that become the low temperature expansion chamber 42 are made of copper, more preferably oxygen-free copper. Further, the inner side surface 43c other than the low temperature expansion chamber 42 is made of SUS316L. The expansion chamber side surface 42a and the inner bottom surface 42b made of copper are made of an integrated cup-shaped copper, and the outer surfaces of the expansion chamber side surface 42a and the inner bottom surface 42b are entirely covered by the side outer layer 43a and the bottom outer layer 43b made of SUS316L. Is covered. Cylinder 41 can satisfy the sanitary standard for freeze-drying drugs and foods and freezing and storing foods and biological materials by covering the entire outer surface with SUS316L.

The opening end of the expansion chamber side surface 42a and the end portion of the inner surface 43c are substantially flush with each other, and an expansion portion 43 that increases in thickness toward the expansion chamber side surface 42a is provided at the position of the inner surface 43c side end portion. ing. The thicknesses of the side outer layer 43a and the bottom outer layer 43b are both 0.1 to 2 mm to prevent a decrease in thermal conductivity. Moreover, the thickness of the inner side surface 43c is set as 1.6 mm-2.2 mm as a dimension for maintaining the intensity | strength which can be enclosed with a high pressure gas, making the heat penetration from room temperature small.
A flange 41 a made of SUS316L is provided at the opening end position of the cylinder 41.

  The cylinder 41 has a bottom outer layer 43b and is open at both ends. The cylinder 41 is formed of SUS316L formed to have different inner diameters. The inner bottom surface 42b is inserted and vacuum brazed, and the bottom outer layer 43b is covered and vacuum brazed, and the entire circumference is welded and sealed.

FIG. 6 is a side view showing the displacer in the present embodiment, FIG. 7 is a bottom view of the displacer in the present embodiment as viewed from the opening side, and FIG. 8 is a side sectional view showing the displacer in the present embodiment.
The displacer 60 in the present embodiment is made of a resin material selected from bakelite, polyether ether ketone, and polyphenylene sulfide having heat resistance equal to or higher than the temperature condition in the steam sterilization treatment that is exposed to steam at 121 ° C. or higher for 20 minutes or more. Is done. Table 1 shows a comparison of these physical properties.

  As shown in Table 1, it is understood that the displacer 60 is preferably a polyether ketone or polyphenylene sulfide that can withstand continuous use in a high temperature atmosphere and has a low coefficient of thermal expansion even at a low temperature.

As shown in FIGS. 6 to 8, the displacer 60 has a substantially cylindrical outer peripheral side portion 62 closed at both ends, and a regenerator 61 made of a metal net or metal particles is provided therein.
The displacer 60 is closed at the low temperature end side, which is the low temperature expansion chamber 42 side, by the lid portion 63, and at the opposite side to the low temperature end side as a room temperature end portion 64 integrated with the outer peripheral side portion 62.

  A wear ring 65 is provided around the outer peripheral surface of the outer peripheral side portion 62 that is the low temperature end side of the displacer 60, and a wear ring 66 is provided on the outer peripheral surface of the outer peripheral side portion 62 that is opposite to the low temperature end side of the displacer 60. Is installed around.

  The displacer 60 slides on the inner surface of the cylinder 41 only on the outer periphery of the wear ring 65 and the wear ring 66, and the portions other than the wear ring 65 and the wear ring 66 are in relation to the outer diameter dimensions of the wear ring 65 and the wear ring 66. The outer diameter is set to be small.

  The wear ring 65 and the wear ring 66 have heat resistance in a temperature condition in a steam sterilization process that is exposed to, for example, steam of about 121 ° C. or more for 20 minutes or more, and the amount of released gas is extremely small. In contrast, it is made of a material selected from a fluorinated resin, a thermoplastic resin and the like having wear resistance and heat resistance.

  The wear ring 65 has an outer diameter that slides between the expansion chamber side surface 42a of the cylinder 41 and seals between the cylinder 41 and the displacer 60. The wear ring 65 is slid with the expansion chamber side surface 42a made of copper in correspondence with the reciprocating movement of the displacer 60, and is disposed at a position not in contact with the inner side surface 43c.

  The wear ring 66 has an outer diameter that can slide between the inner surface 43 c of the cylinder 41 and seal between the cylinder 41 and the displacer 60. Wear ring 66 slides on inner surface 43c made of SUS316L in response to the reciprocating motion of displacer 60, and is disposed at a position that does not contact expansion chamber side surface 42a.

  Thus, by setting the arrangement of the wear ring 65 and the wear ring 66 in the reciprocating direction of the displacer 60, the sealing performance between the cylinder 41 having the inner surface made of different materials and the displacer 60 can be maintained. .

  The width dimension t65 of the wear ring 65 is set to be smaller than the width dimension t66 of the wear ring 66. In other words, the wear ring 65 is narrower than the wear ring 66 in the reciprocating direction of the displacer 60. Thereby, the frictional heat generated from the wear ring 65 sliding with the expansion chamber side surface 42a on the low temperature side can be reduced without changing the sealing performance.

  As shown in FIG. 8, the wear ring 65 and the wear ring 66 are fitted into groove portions 62 a and 62 b provided around the outer peripheral side portion 62 of the displacer 60.

  As shown in FIG. 6, the wear ring 65 and the wear ring 66 are each provided with a step cut 67 serving as a groove that absorbs an increase in volume due to thermal expansion.

  The step cut 67 absorbs the increase in volume in the circumferential direction of the displacer when the wear rings 65 and 66 are thermally expanded, and prevents the displacer 60 from interfering with the inside of the cylinder 41. The sliding state and the sealing performance are not changed.

  As the step cut 67, the wear rings 65 and 66 are separated in the circumferential direction to form grooves that are separated from each other, and the grooves are arranged differently in the circumferential direction of the displacer 60 at the axial position of the displacer 60. It is.

  Specifically, as the step cut 67, grooves 67a and 67b formed so as to extend in the axial direction of the displacer 60 so that the ends of the wear rings 65 and 66 are separated in the circumferential direction are It is formed as a cut portion that is continuous at a cut 67c that becomes a sliding portion that connects adjacent end portions. As described above, the circumferential positions of the grooves 67a and 67b are shifted from each other by the position of the displacer 60 in the reciprocating direction.

  Displacer 60 circumferential dimension t67a of groove 67a and groove 67b can be 3 to 4 mm, depending on the diameter of displacer 60 and the material of wear rings 65 and 66.

  The cut 67c in the step cut 67 has a length t67c in which the ends of the wear rings 65 and 66 are in contact with each other in the circumferential direction of the displacer 60, considering heat shrinkage and thermal expansion, and the grooves 67a and 67b are connected during heat shrinkage. On the other hand, at the time of thermal expansion, the dimension between the groove 67a and the groove 67b disappears and does not interfere, for example, 3 to 4 mm.

The lid portion 63 closes the end portion on the low temperature end side of the regenerator 61 inside the displacer 60, and the lid portion 63 is screwed inside the outer peripheral side portion 62 of the displacer 60.
The lid 63 is locked by a spring pin 68 that penetrates the outer peripheral side 62 of the displacer.

  The spring pin 68 is a hollow cylindrical halved part having a size equal to or larger than the diameter of the hole to be inserted, and when it is press-fitted and inserted, the repulsive force within the elastic limit of the metal inside the hole. It will spread through and will not come out unless destroyed. The spring pin 68 is disposed so as to enter the center axis side of the outer peripheral surface of the outer peripheral side portion 62 and is provided so as not to contact the inner surface of the sliding cylinder 41 when the displacer 60 reciprocates. Yes. At the same time, the spring pin 68 also prevents the lid portion 63 from rotating relative to the outer peripheral side portion 62.

A plurality of helium gas jets 69 opening outward from the outer periphery are provided on the outer peripheral side portion 62 of the displacer 60 at positions closer to the regenerator 61 than the lid portion 63.
The helium gas jets 69 are arranged on the outer periphery of the displacer 60 at a uniform half angle in the circumferential direction, and are provided at 12 locations in the present embodiment. The outer peripheral side 62 on the cold end side of the helium gas outlet 69 has an outer diameter smaller than the inner diameter of the low temperature expansion chamber 42, and the displacer 60 and the inner peripheral surface of the low temperature expansion chamber 42 are in contact with each other. However, helium gas flows between the regenerator 61 and the low temperature expansion chamber 42 through this gap.

  A helium gas inlet 64 a connected to the suction valve 44 and the discharge valve 45 is provided in the room temperature end portion 64 so as to penetrate to the regenerator 61.

  In the refrigerator 40 of the present embodiment, a regenerator 61 is provided inside the displacer 60, and helium at room temperature compressed by an external helium circulation compressor 50 fills the cylinder 41 of the refrigerator 40. . This helium feeding is controlled by opening and closing the intake valve 44.

  When the displacer 60 moves so as to expand the volume of the low temperature expansion chamber 42 (toward the right in the figure), helium flows into the low temperature expansion chamber 42 while being cooled by the regenerator 61. Next, when the intake valve 44 is closed and the exhaust valve 45 is opened, helium cools the expansion chamber 42 by Simon expansion, and at the same time returns to the compressor 50 while cooling the regenerator 61.

  As a result, the inside of the refrigerator 40 has a minimum pressure, and the displacer 60 moves (to the left in the figure) so as to reduce the volume of the low temperature expansion chamber 42, and the low temperature helium cools the regenerator 61. While flowing backwards. Through the above cycle, the low temperature expansion chamber 42 becomes a very low temperature of about 77.3 K or less, and each cryopanel 38a is cooled to a corresponding temperature by heat conduction.

  Further, in the second dehydrating unit 31, in the vacuum drying method in the present embodiment to be described later, in the sterilization process, the cleaning process, the storing process, and the first drying process, the exhaust is performed more than the second switching valve 24 of the second exhaust unit. The pump 16 side is closed.

Hereinafter, a vacuum drying method using the cryotrap in the present embodiment will be described.
FIG. 9 is a flowchart showing a vacuum drying method using the cryotrap in the present embodiment.

  As shown in FIG. 9, the vacuum drying method using the cryotrap of the present embodiment includes a preparation step S01, an opening / closing step S02, a sterilization step 03, a cleaning step 04, a preliminary drying step S05, and an opening / closing step S06. A housing step S07, an opening / closing step S08, a first drying step S09, a heat drying step S10, a second exhausting step S11, a discrimination step S12, an opening / closing step S13, a second drying step S14, 1 exhaust process S15, sealing process S16, opening and closing process S17, and take-out process S18.

  The vacuum drying method of this embodiment prepares so that the necessary to-be-dried material F1 can be carried in to the shelf 11a as preparation process S01 shown in FIG. The control unit 14 prepares necessary manufacturing condition information.

Next, as an opening / closing step S02 shown in FIG. 9, the partitions and valves are opened and closed as follows under the control of the control unit 14.
Drying chamber 11 opened First partition 21 opened Second partition 23 opened First switching valve 22 closed Second switching valve 24 closed

  Next, as the sterilization step 03 shown in FIG. 9, the state set in the opening / closing step S02, that is, the first partition portion 21 and the second partition portion 23 are opened, and the drying chamber 11, the first dehydrating portion 12, and the second partition portion are opened. The inside of the drying chamber 11, the first dehydrating unit 12, and the second dehydrating unit 30 is sterilized by communicating with the dehydrating unit 30 and supplying steam from the cleaning / sterilizing unit 19 under the control of the control unit 14.

  The part to which the pharmaceutical preparation which is the material to be dried F1 is exposed must be completely sterilized, and therefore has a steam sterilization process S03 as a preceding process every time the drug production process is started. Sterilization necessary in a freeze-drying apparatus for pharmaceuticals is to kill bacteria by exposing to steam at 121 ° C. or higher for 20 minutes or longer.

  The pressure in this steam sterilization process is about 210 kPa. It is set to about 220 kPa to 240 kPa. Actually, as the steam sterilization step S03, the inside of the apparatus is maintained at a high temperature for about 3 hours.

  Next, as the cleaning step 04 shown in FIG. 9, the state set in the opening / closing step S02, that is, the first partition portion 21 and the second partition portion 23 are opened, and the drying chamber 11, the first dehydrating portion 12, and the second partition portion are opened. The dehydrating unit 30 is in communication with the drying chamber 11, the first dehydrating unit 12, and the second by supplying pure water satisfying a predetermined standard for cleaning from the cleaning / sterilizing unit 19 under the control of the control unit 14. The inside of the dehydrating unit 30 is washed. Although it is not expected in a vacuum apparatus in other manufacturing fields such as semiconductors, the inside of the apparatus is washed with water. For this reason, it is desirable that the interior of the drying chamber 11, the first dehydrating unit 12, and the second dehydrating unit 30 has a structure in which water does not accumulate as much as possible.

  Next, as the preliminary drying step 05 shown in FIG. 9, the state set in the opening / closing step S02, that is, the first partition portion 21 and the second partition portion 23 are opened, and the drying chamber 11, the first dehydrating portion 12, and the second portion are opened. The dehydrating unit 30 is communicated, and the first cold trap 17 is driven under the control of the control unit 14 to predry the drying chamber 11, the first dehydrating unit 12, and the second dehydrating unit 30, Remove wash water. At this time, the inside of the drying chamber 11 can be heated by the temperature adjusting means of the shelf 11a.

  In the preliminary drying step 05, the control unit 14 drives the first cooling unit 17c to circulate the refrigerant in the first cold trap 17, and the first partition unit 21, the second partition unit 23, and the first partition unit The switching valve 22 is opened and the second switching valve 24 is closed, and the vacuum pump 15 is driven to exhaust the drying chamber 11 through the first dehydrating unit 12 serving as the first exhaust path. Thereby, the water | moisture content inside evaporates because the pressure of the drying chamber 11, the 1st dehydration part 12, and the 2nd dehydration part 30 falls. The vacuum pump 15 pumps out the gas inside the drying chamber 11, the first dehydrating unit 12, and the second dehydrating unit 30 containing water vapor via the first exhaust path. The water vapor is collected by the first cold trap 17.

  In the preliminary drying step 05, it is preferable not to drive the second cold trap 38. However, in the case where the moisture in the second dehydrating unit 30 is exhausted in a subsequent step by a second exhaust step S11 described later, This is not the case.

Next, as an opening / closing step S06 shown in FIG. 9, each partition and valve are opened and closed under the control of the control unit 14 as follows.
Drying chamber 11 opened First partition 21 opened Second partition 23 closed First switching valve 22 closed Second switching valve 24 closed

  Next, as the housing step S07 shown in FIG. 9, the state set in the opening / closing step S06, that is, the first partition portion 21 is opened to allow the drying chamber 11 and the first dehydrating portion 12 to communicate with each other, and the second partition The object to be dried F1 is carried into the drying chamber 11 in a state where the part 23 is closed and the second dehydrating part 30 is made independent.

Next, as an opening / closing step S08 shown in FIG. 9, the gates and valves are opened / closed as follows under the control of the control unit 14.
Drying chamber 11 closed First partition 21 opened Second partition 23 closed First switching valve 22 opened Second switching valve 24 closed

  Next, as the first drying step 09 shown in FIG. 9, the state set in the opening / closing step S08, that is, the first partition portion 21 is opened to allow the drying chamber 11 and the first dehydrating portion 12 to communicate with each other. The first cold trap 17 is driven under the control of the control unit 14 in a state where the two partition portions 23 are closed and the second dehydrating unit 30 is made independent, and the drying chamber 11 and the first dehydrating unit 12 are controlled. The inside, especially the drying chamber 11 is freeze-dried. Thereby, the water | moisture content inside evaporates because the pressure of the drying chamber 11 and the 1st spin-drying | dehydration part 12 falls. The vacuum pump 15 pumps the gas in the drying chamber 11 containing water vapor through the first exhaust path. The water vapor is collected by the first cold trap 17.

Of the gas pumped out from the drying chamber 11, non-condensed gas such as nitrogen is pumped out by the vacuum pump 15 without condensing in the first cold trap 17. The sample F1 placed on the shelf 11a is frozen by removing the latent heat of evaporation from moisture.
The temperature of the first cold trap 17 in the first drying step 09 is set to about −40 ° C.

  Next, as the heating and drying step S10 shown in FIG. 9, the state set in the opening and closing step S08, that is, the first partition portion 21 is opened to allow the drying chamber 11 and the first dehydrating portion 12 to communicate with each other. The temperature control means 11b provided in each shelf 11a is driven by the control of the control unit 14 in a state where the partition 23 is closed and the second dehydrating unit 30 is made independent.

  The heater (temperature control means) 11b promotes drying of the sample F1 by heating the sample F1 placed on the shelf 11a by heating the shelf 11a in the drying chamber 11 to 20 ° C. The ice contained in the heated sample F1 takes in latent heat from the sample F1 and sublimates into water vapor.

  The vacuum pump 15 pumps the gas in the drying chamber 11 containing the water vapor through the first exhaust path. Of the gas pumped out by the vacuum pump 15, water vapor releases latent heat on the surface of the first cold trap 17, condenses into ice, and is collected by the first cold trap 17. Of the gas pumped out from the drying chamber 11, non-condensed gas such as nitrogen is pumped out by the vacuum pump 15 without condensing in the first cold trap 17.

  By continuing the exhaust operation of the drying chamber 11 by the vacuum pump 15, the drying chamber 11 reaches the ultimate pressure of the vacuum pump 15. In addition, when the condensation point of the water vapor in the drying chamber 11 is lowered, the collecting ability of the first cold trap 17 is deteriorated, and the increase in the degree of vacuum in the drying chamber 11 is stopped. When the increase in the degree of vacuum in the drying chamber 11 stops, the ice contained in the sample F1 cannot be sublimated. As a result, since the ice contained in the sample F1 does not take in latent heat from the solid raw material as long as no sublimation is performed, the temperature of the sample F1 rises due to the heating action of the heater 11b. The temperature sensor 11c provided on the shelf 11a detects the surface temperature of the sample F1 heated by the heater 11b, and outputs this to the control unit 14 as a detection signal.

  At the same time, the evacuation operation of the drying chamber 11 by the vacuum pump 15 is continued, so that the increase in the degree of vacuum in the drying chamber 11 is stopped. At this time, the measurement instruction value of the pressure gauge 26, which is the first vacuum gauge capable of measuring the total pressure without being affected by the measurement instruction value depending on the type of measurement gas, and the vacuum gauge capable of measuring the total pressure using heat conduction. In addition, the measurement instruction value of the pressure gauge 27, which is the second vacuum gauge in which the measurement instruction value varies depending on the type of measurement gas, is output to the control unit 14.

The control unit 14 compares the measurement instruction value in the drying chamber 11 by the first vacuum gauge 26 with the measurement instruction value in the drying chamber 11 by the second vacuum gauge 27, and the difference between the measurement instruction values converges to a minimum. Detecting when to do. By comparing the difference between the measurement instruction values in the first and second vacuum gauges, and determining that the time when the difference between the measurement instruction values converges to the minimum is when the drying end point is confirmed, or measurement by the second vacuum gauge The time of the inflection point of the descending curve in the instruction curve is detected as the time when the drying end point is confirmed.
At the same time, the control unit 14 detects that the surface temperature of the sample F1 is equal to the heating temperature of the heater 11b and reaches the upper limit based on the detection signal from the temperature sensor 11c.

  Next, as a discrimination step S12 shown in FIG. 9, the control unit 14 is based on the detection signal from the temperature sensor 11c and / or at the time of confirming the dry end point detected by the comparison of the measurement instruction values from the pressure gauges 26 and 27. If it is determined that the upper limit at which the detected surface temperature of the sample F1 is equal to the temperature of the heater 11b is reached, it is determined that this is the end point of the heating and drying step S10, and the first partition portion 21 is first closed, and then Then, the driving of the first cold trap 17 is stopped. In addition, as long as the 1st partition part 21 is obstruct | occluded, the open / close state of the 1st switching valve 22 may be any.

Next, as an opening / closing step S13 shown in FIG. 9, the gates and valves are opened and closed as follows under the control of the control unit 14.
Drying chamber 11 closed First partition 21 closed Second partition 23 opened First switching valve 22 closed Second switching valve 24 opened

  Next, as the second drying step S14 shown in FIG. 9, the state set in the opening / closing step S13, that is, the second partition 23 is opened to allow the drying chamber 11 and the second dehydrating unit 30 to communicate with each other. In a state where the first partition 21 is closed and the first dehydrating unit 12 is made independent, the second cold trap 38 is driven under the control of the control unit 14, and the drying chamber 11 and the second dehydrating unit 30 are driven. The inside, especially the drying chamber 11 is freeze-dried.

  Thereby, the water | moisture content inside evaporates because the pressure of the drying chamber 11 and the 2nd spin-drying | dehydration part 30 falls. The turbo molecular pump 16 pumps the gas in the drying chamber 11 containing water vapor through the second exhaust path. The water vapor is collected by a cryotrap 38 that is a second cold trap.

The heater 11b and the turbo pump 16 are continuously driven from the heat drying step S10. Further, the driving of the cryotrap 38 may be started before the second partition 23 is opened.
The cryotrap 38 is set to a temperature lower than that of the first cold trap 17, for example, about −100 ° C.

  The second cold trap 38 cooled to −100 ° C. collects the water vapor that could not be collected by the first cold trap 17. Along with this, the pressure in the drying chamber 11 decreases. Thereby, sublimation of the ice remaining in the sample F1 is resumed. The ice remaining in the sample F1 takes in latent heat from the sample F1 and sublimates, and the generated water vapor condenses on the surface of the low-temperature panel 38a of the second cold trap 38 to condense into ice to form the second cold. It is collected by the trap 38. By this finish drying, the sample F1 subjected to the heat drying step S10 can be further dried, the final dryness of the sample F1 can be increased, and the moisture content can be reduced by two orders of magnitude. Note that the moisture removed in the second drying step S14 using the second dehydrating unit 30 is 1% of the moisture removed in the first drying step S09 using the first dehydrating unit 12 and the heat drying step S10. The degree, that is, about 5 kg.

  Next, as the sealing step S16 shown in FIG. 9, the state set in the opening and closing step S13, that is, the second partition 23 is opened to allow the drying chamber 11 and the second dehydrating unit 30 to communicate with each other, and the first partition In a state where the part 21 is closed and the first dehydrating part 12 is made independent, the object to be dried F1 is sealed with an aluminum seal or the like using a sealing means (not shown) under the control of the control unit 14.

Next, as an opening / closing step S17 shown in FIG. 9, the gates and valves are opened / closed as follows under the control of the control unit 14.
Drying chamber 11 opened First partition 21 closed Second partition 23 closed First switching valve 22 closed Second switching valve 24 closed

  Next, as an extraction step S18 shown in FIG. 9, the material to be dried F1 whose moisture content has been reduced to the desired state and dried is taken out from the drying chamber 11, and the drying process in this batch is completed.

  As shown in FIG. 9, in a part or all of the first drying step 09 and the heating drying step S10, the state set in the opening / closing step S08 as the second exhaust stroke S11, that is, the first partition portion 21 is opened. Then, while the drying chamber 11 and the first dehydrating unit 12 are in communication with each other, the second switching valve 24 is opened while the second partitioning unit 23 is closed and the second dehydrating unit 30 is made independent. The second dewatering unit 30 in the independent state can be evacuated to exhaust the moisture collected by the second cold trap 38 to the outside. Thereby, it becomes possible to start the freeze-drying process of the next batch without delay.

  Similarly, in part or all of the second drying step S14 shown in FIG. 9, the state set in the opening / closing step S13 as the first exhaust stroke S15, that is, the second partition 23 is opened, and the drying chamber 11 is opened. In a state where the second dehydrating unit 30 is communicated and the first partitioning unit 21 is closed and the first dehydrating unit 12 is made independent, the first switching valve 22 is opened to be in this independent state. The first dewatering unit 12 can be exhausted, and the moisture collected by the first cold trap 17 can be exhausted to the outside. Thereby, it becomes possible to start the freeze-drying process of the next batch without delay.

In the present embodiment, by setting one of the two switchable cold traps 17 and 38 as an independent cryotrap 38, the material to be dried is freeze-dried to a moisture content that is two digits lower than previously possible. It became possible.
In addition, the running cost is lower than that of the conventionally proposed method of obtaining an extremely low temperature with liquid nitrogen, and the temperature condition can be made variable, so that it can cope with various drying conditions.

  When starting the cryotrap 38, the first partition 21 or the second partition 23 is closed, so that the first cold trap 17 whose processing temperature is lower than that of the first cold trap 17 is brought into the first cold trap 38. The possibility that ice adhering to the trap 17 is adsorbed can be prevented.

  A partition valve such as an orifice plate can be provided between the cryotrap 38 and the drying chamber 11 in addition to the second partition portion 23.

  Further, first, a cryotrap 38 can be added to the existing freeze-drying apparatus by adding a valve by drilling a hole in the same manner as the first cold trap 17. In this case, it is necessary to adopt the above-described specification or to conform to the specification so as to be compatible with the cleaning / sterilization process.

  The interior of the drying chamber 11, the first dehydrating unit 12, and the second dehydrating unit 30 to which the material to be dried F1 is exposed must be completely sterilized in the drying process, and therefore, the drug production process It is indispensable to perform a steam sterilization process and a cleaning process as a pre-process every time the process is started. Sterilization necessary for pharmaceuticals, particularly freeze-drying equipment applied to water for injection (WFI) production, etc. is to kill bacteria by exposure to steam at 121 ° C or higher for 20 minutes or longer. .

  The pressure inside the drying chamber 11 in this steam sterilization process is about 210 kPa and about 220 kpa to 240 kpa. Actually, the inside of the apparatus is maintained at a high temperature as a steam sterilization process for about 3 hours.

  In the cryotrap 38, it is necessary to set the output of the mechanical refrigerator 40 so that the cooling capacity of the mechanical refrigerator 40 is superior and the temperature of the trap panel 38a does not reach a temperature sufficient for sterilization. It is.

  Moreover, if it is an apparatus for pharmaceutical formulation manufacture like this embodiment, the foil body for improving heat transfer to the connection part of the mechanical refrigerator 40 and the low-temperature panel 38a can be made into gold plating, gold foil, etc.

  After the first drying step S09 and the heat drying step S10 for trapping water by the first cold trap 17 at −50 ° C. to −70 ° C., the cryofinishing at −90 ° C. to −100 ° C. is further performed as a total finish. The 2nd drying process S14 which squeezes the water | moisture content which remained with the trap 38 is performed. For this reason, it is preferable to install the first cold trap 17 and the cryotrap 38 in a separated room (space). Moreover, it is preferable not to use the heater 11b for melting ice in the low temperature panel 38a.

  In the refrigerator 40 of the cryotrap 38, the cylinder 41 and the displacer 60 are configured as described above, thereby having heat resistance. The material of the low temperature panel (trap panel) 38a is SUS316L, and the heat transfer portion is made of a metal having high corrosion resistance such as gold foil.

  The second drying step S14 that traps moisture at an extremely low temperature to reduce the moisture content of the material F1 to be dried is a slight amount of remaining moisture as a finishing step after the first drying step S09 in which freeze-drying is performed in a normal operation. It becomes the operation of adsorbing. Therefore, it is not necessary to increase the processing speed to shorten the processing time, and the object is to improve the degree of moisture content by about two digits.

  When freeze-drying is performed using the cryogenic refrigerator 40 of the present embodiment, the temperature is lower than that of the refrigerator using the refrigerant, and therefore, the cold trap 38 using the cryogenic refrigerator 40 is used. When the moisture content inside the product in the drying furnace is reduced by using a refrigerator that uses a refrigerant by performing subsequent drying, about 1% remains as residual moisture, but the residual moisture can be reduced as much as possible. . By performing this secondary drying, there is an effect that the medicine can be stored for a longer period of time.

  Although a cold trap using liquid nitrogen can be considered as a means of performing secondary drying, liquid nitrogen vaporizes and decreases due to condensation heat generated when moisture is condensed and radiant heat in the furnace. Replenishment of liquid nitrogen is necessary, and it is expensive and troublesome to refill liquid nitrogen. On the other hand, by using the mechanical refrigerator 40 of this embodiment, starting / stopping is only a push of the power switch, and the work process can be reduced.

  For the low-temperature expansion chamber 42 of the cylinder 41 serving as the heat transfer section of the refrigerator 40, a copper-based material having good thermal conductivity is selected in consideration of heat transfer efficiency, and a thin material 0.1-2 of SUS316L is selected. By joining 0.0mm to the outer surface of the copper material, the copper material is exposed to the surface without greatly degrading the efficiency of heat transfer without using a stainless material with low thermal conductivity at low temperature in the low temperature expansion chamber 42 part. It can be used in freeze-drying furnaces that handle pharmaceutical products.

  The conventional cryogenic mechanical refrigerator cannot be used in an environment such as a steam sterilization atmosphere at 121 ° C. because the temperature limit value in the high temperature region is 70 ° C. In the present embodiment, the displacer 60 is not used. The cover 63 that suppresses the regenerator material, for example, the wire mesh, etc., filled in the displacer 60 is made of a material having a high heat-resistant temperature, and has a structure using a spring pin 68 to prevent rotation, without using an adhesive. As a result, even in an atmosphere of 121 ° C., it can be operated without mechanical loss.

  When exposed to a steam sterilization atmosphere of about 121 ° C. as described above, if resin is used for the displacer 60, the coefficient of thermal expansion is 2 to 10 times greater than that of SUS316L of the cylinder 41. It becomes difficult to perform reciprocating motion. On the other hand, when the clearance at room temperature is increased in consideration of thermal expansion at 121 ° C., the clearance becomes too large due to thermal contraction of the displacer 60 when cooled to a low temperature, resulting in poor cooling. On the other hand, in the present embodiment, by providing the displacer 60 with grooves 62a and 62b and winding the wear rings 65 and 66 provided with step cuts 67 at one place on the circumference, thermal expansion and Displacer 60 that absorbs changes in clearance due to thermal contraction, reduces the amount of change, does not interfere with cylinder 41 when thermally expanded, and can ensure an appropriate clearance when cooled to a low temperature. Can do.

  Hereinafter, a second embodiment of the cryotrap according to the present invention will be described with reference to the drawings.

  FIG. 10 is a side view showing the displacer in the present embodiment, FIG. 11 is a bottom view seen from the opening side showing the displacer in the present embodiment, and FIG. 12 is a side sectional view showing the displacer in the present embodiment. In the present embodiment, the difference from the first embodiment described above is the point related to the outer peripheral side portion 72, the lid portion 73, and the covering portions 75 and 76 of the displacer 60, and corresponds to the other first embodiment described above. The components are denoted by the same reference numerals and the description thereof is omitted.

  In the displacer 60 in the present embodiment, the outer peripheral side portion 72 and the lid portion 73 are made of SUS316L. Since the displacer 60 reciprocates in the cylinder 41, it is preferable to reduce the weight. For this reason, as shown in FIGS. 10-12, the outer peripheral side part 72 in this embodiment is provided with the thinning parts 72c and 72d in the part where the wear rings 65 and 66 are not provided.

Specifically, a thinned portion 72 c on the low temperature end side of the helium gas ejection port 69 and a thinned portion 72 d between the wear ring 65 and the wear ring 66.
As shown in FIGS. 10 to 12, these thinned portions 72 c and 72 d make the thickness of the outer peripheral side portion 72 thinner, and a covering portion 75 and a covering portion 76 made of resin are provided on the outer sides thereof, respectively. Has been. The thinned portions 72c and 72d are formed by reducing the outer diameter of the outer peripheral side portion 72 in the same manner as the groove portions 62a and 62b. However, the degree of reduction of the outer diameter dimension is set larger than that of the groove portions 62a and 62b for weight reduction. Has been.

The outer peripheral dimensions of the covering portions 75 and 76 are set to be smaller than the wear rings 65 and 66 in the same manner as the outer diameter size of the outer peripheral side portion 72 so that they do not come into contact with the inner surface of the cylinder 41 during the reciprocating operation of the displacer 60. .
The thickness dimensions of the covering portions 75 and 76 are the same as the outer diameter size of the outer peripheral side portion 72 to compensate for the decrease in the outer diameter size of the thinned portions 72c and 72d with respect to the thickness dimension of the wear rings 65 and 66. It is set to become.

The covering portions 75 and 76 can be made of the same material as that of the wear rings 65 and 66. However, as the different materials, it is not necessary to consider the resistance to sliding, so that the weight can be further reduced.
Similarly to the step cut 67, the covering portions 75 and 76 are provided with a step cut 77 as shown in FIG. 10, and when the covering portions 75 and 76 are thermally expanded, the increase in volume is distributed in the circumferential direction of the displacer. To absorb.

  As the step cut 77, grooves that are separated from each other by separating the covering portions 75 and 76 in the circumferential direction are formed, and the grooves are arranged differently in the circumferential direction of the displacer 60 at the axial position of the displacer 60. It is.

  Specifically, as the step cut 77, grooves 77a and grooves 77b formed so as to extend in the axial direction of the displacer 60 so that the end portions of the covering portions 75 and 76 are spaced apart in the circumferential direction, It is formed as a cut portion that is continuous at a cut 77c that becomes a sliding portion that connects adjacent end portions. In this way, the circumferential positions of the grooves 77a and 77b are shifted depending on the position of the displacer 60 in the reciprocating direction.

  The circumferential direction dimension of the displacer 60 of the groove 77a and the groove 77b may be 3 to 4 mm depending on the diameter dimension of the displacer 60 and the material of the covering portions 75 and 76.

The cut 77c in the step cut 77 has a length in which the ends of the covering portions 75 and 76 are in contact with each other in the circumferential direction of the displacer 60, 2 to 5 times the circumferential dimension of the groove 77a and the groove 77b, for example, 3 to 4 mm. It can be.
it can.

  As shown in FIGS. 11 to 12, the covering portion 75 is disposed so as to cover the outer sides of the spring pins 68 and 68 that lock the lid portion 73. The spring pin 68 is disposed so as to be covered with the covering portion 75 and is provided so as not to be exposed to the inner surface side of the sliding cylinder 41 when the displacer 60 reciprocates.

  Also in the present embodiment, the same effect as that of the first embodiment described above can be obtained, and the displacer 60 is formed by the SUS316L having increased rigidity, and the displacer 60 is reduced in weight, so that the mechanical parts of the moving parts can be mechanically operated. It can prevent that reliability falls.

  When the material of the displacer 60 is made of stainless steel so that the thermal expansion coefficients of the cylinder 41 and the displacer 60 are the same, the density of the stainless steel is larger than that of the resin, so that the mass becomes large. As a result, the mechanical drive unit is overloaded, which affects long-term machine reliability. However, in this embodiment, the thickness of the displacer 60 is reduced to reduce the mass, and the reduced thickness part. The covering portions 75 and 76 are wound around the 72c and 72d, so that the amount of refrigerant gas passing through the low temperature portion and the room temperature portion can be reduced, and heat loss can be reduced.

  In the above embodiment, the step cuts 67 and 77 are configured to have two grooves. However, as shown in FIG. 13, as the step cut 87, the grooves 87a, 87b, and 87c are alternately arranged at three positions. It can also be set as the structure which has the cut | interruptions 87d and 87e used as two sliding parts.

  As an application example of the present invention, a bakable super trap used in an ultra-high vacuum apparatus can be cited.

10 ... Vacuum drying device 11 ... Drying chamber (chamber)
11a ... shelf 11b ... heater (temperature control means)
11c ... temperature sensor 12 ... first dehydrating unit 14 ... control unit (control unit)
15 ... Vacuum pump (first exhaust means)
16 ... Exhaust pump (second exhaust means)
17 ... 1st collection means (1st cold trap)
17a ... introducing part 17b ... leading part 17c ... cooling unit 19 ... cleaning / sterilizing means 21 ... first partition part 21a ... partitioning body 22 ... first switching valve (first exhaust means)
23 ... 2nd partition part 23a ... Partition body 24 ... 2nd switching valve (2nd exhaust means)
26 ... Pressure gauge 27 ... Pressure gauge F1 ... To-be-dried object (deaeration source)
30 ... Second dewatering section (cryo trap)
31 ... Case 31a ... Pin 38 ... Cryo trap 38a ... Low temperature panel 40 ... Mechanical refrigerator (refrigerator)
40a ... Drive source 41 ... Cylinder 42 ... Low temperature expansion chamber 42a ... Expansion chamber side surface 42b ... Inner bottom surface 43a ... Side outer layer 43b ... Bottom outer layer 43c ... Inner side surface 44 ... Suction valve 45 ... Discharge valve 50 ... Compressors 50a-50c ... Circulation path 51 ... Adsorber 60 ... Displacer 61 ... Regenerator 62 ... Outer peripheral side 62a, 62b ... Groove 63 ... Lid 64 ... Room temperature end 64a ... Helium gas inlet 65, 66 ... Wear ring 67 ... Step cuts 67a, 67b ... Groove 67c ... cut 68 ... spring pin 69 ... helium gas outlet 72 ... outer peripheral side portion 72c, 72d ... thinning portion 73 ... lid portion 75, 76 ... covering portion 77 ... step cut 77a, 77b ... groove 77c ... cut 87 ... Step cuts 87a, 87b, 87c ... grooves 87d, 87e ... cuts

Claims (19)

A cryotrap that cools the inside of a case connected to a chamber that is a degassed space for steam sterilization, having a refrigerator having a cylinder in which a reciprocating displacer is stored and a compressor for circulating helium. And
The cryotrap, wherein the displacer has a heat resistant temperature equal to or higher than a temperature condition in the steam sterilization process.   The cryotrap according to claim 1, wherein an outer surface of the cylinder exposed to the deaerated space is made of SUS316L.   The cryotrap according to claim 1, wherein the inner surface of the cylinder on the low temperature side is made of copper.   2. The cryo of claim 1, wherein the displacer is provided with a wear ring that slides on the inner surface of the cylinder on an outer surface on a low temperature end side that is the low temperature side of the cylinder and an opposite end side thereof. trap.   2. The cryotrap according to claim 1, wherein a wear ring provided around an outer surface on the displacer low temperature end side is provided at a position sliding with an inner surface on the cylinder low temperature side made of copper.   The wear ring provided on the outer surface on the displacer cold end side is narrower than the wear ring provided on the outer surface on the opposite side to the displacer low temperature end side. The cryotrap according to 1.   A wear ring provided around an outer surface opposite to the displacer low temperature end side is provided at a position where the wear ring slides with an inner surface opposite to the cylinder low temperature side made of SUS316L. The cryotrap according to claim 1.   The thermal expansion absorption groove | channel (step cut) spaced apart in the circumferential direction of the said displacer is provided in the wear ring circumferentially provided in the outer surface of the said displacer, and sliding with the said cylinder inner surface. Cryo trap.   The cryotrap according to claim 8, wherein the circumferential position of the thermal expansion absorption groove is shifted depending on a position of the displacer in a reciprocating direction.   The thermal expansion absorption groove is provided with a sliding portion that slides in a circumferential direction and maintains a sealed state in a reciprocating direction of the displacer when the wear ring is thermally expanded. Item 15. The cryotrap according to Item 9.   A lid for closing the end on the displacer low-temperature end side is provided, and the lid is fitted to the outer peripheral side of the displacer, and by a spring pin penetrating from the outer peripheral side of the displacer to the lid. The cryotrap according to claim 1, wherein the cryotrap is locked.   The inside of the displacer is a regenerator, and a lid that closes the end of the displacer at the low temperature end is provided, and the outer side of the displacer opens at a position closer to the regenerator than the lid. The cryotrap according to claim 1, wherein a plurality of helium gas ejection ports are provided.   2. The cryotrap according to claim 1, wherein the displacer is made of a material selected from bakelite, polyether ether ketone, and polyphenylene sulfide.   The displacer is made of SUS316L, and a thinned portion having a thickness dimension thinner than a portion sliding with the cylinder inner surface is provided on an outer surface that does not slide with the cylinder inner surface. The cryotrap according to 1.   15. The cryotrap according to claim 14, wherein the displacer made of SUS316L is provided with a coating portion made of resin at the thinned portion.   The cryotrap according to claim 1, wherein the cylinder has a bottomed cylindrical shape made of SUS316L, and the low temperature side inner surface and the low temperature side inner bottom portion of the cylinder are made of copper.   The cryotrap according to claim 1, wherein a thickness of SUS316L made of copper at an outer surface position on the low temperature side of the cylinder is 0.1 to 2 mm.   The cryotrap according to claim 1, wherein an adsorber for removing contamination of helium is provided in a circulation path from the refrigerator to the compressor. The cryotrap according to any one of claims 1 to 18,
A vacuum drying apparatus comprising: a chamber which is a space to be deaerated.

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