KR20170008158A - Vacuum drying apparatus and vacuum drying method - Google Patents

Abstract

A vacuum drying apparatus according to the present invention comprises: a drying chamber which accommodates a drying object; a first dehydration unit which is connected to the drying chamber, and has a first collection means capable of being cooled to a first temperature capable of condensing and collecting moisture sublimated from the drying object; a second dehydration unit which is connected to the drying chamber independently from the first dehydration unit, and has a second collection means capable of being cooled to a second temperature lower than the first temperature; a first partition unit which allows the drying chamber and the first dehydration unit to selectively communicate with or be separated from each other; and a second partition unit which allows the drying chamber and the second dehydration unit to selectively communicate with or be separated from each other. The first partition unit and the second partition unit are switching means, which close, after cleaning the drying chamber, the first dehydration unit, and the second dehydration unit, the second dehydration unit while allowing the drying chamber and the first dehydration unit to communicate, to perform first freeze drying, and then close the first dehydration unit while allowing the drying chamber and the second dehydration unit to communicate, to perform second freeze drying.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention [0001] The present invention relates to a vacuum drying apparatus and a vacuum drying method,

TECHNICAL FIELD The present invention relates to a vacuum drying apparatus and a vacuum drying method having a cold trap, and relates to a technique suitable for use in pharmaceutical production.

There has been proposed a vacuum drying apparatus equipped with a cold trap for freeze-vacuum drying of a raw material liquid such as pharmaceuticals, food, cosmetics or chemicals. (For example, Patent Document 1)

According to the conventional vacuum drying apparatus, the vacuum chamber is connected to the drying chamber accommodating the object to be dried through the exhaust path, and the cold trap is installed in the middle of the exhaust path. The steam trapped in the drying chamber can be condensed and trapped in the cold trap to dry the laundry.

In recent years, there has been an increasing demand for " antibody medicine " and " bio medicine " as a trend in freeze-drying apparatuses for medicines.

Because it has higher water activity than conventional chemicals, it should produce a lower water content. For this reason, in the non-patent document 1, a heat exchanger using liquid nitrogen is added to a vacuum freeze-drying device to make a low-temperature state, and the pressure in the freeze-

In addition, in the case of this drug, it is required to prepare the drug without changing the manufacturing method of the test drug.

<Prior Art Literature>

<Patent Literature>

Patent Document 1: Japanese Patent No. 5574318

<Non-patent Document>

&Lt; Non-Patent Document 1 > 33 (2014) p1- p2 Morikosuke, Masahiro Yonekura "Liquefied nitrogen vacuum freeze dryer for biopharmaceuticals" Internet (URL; https://www.tn-sanso-giho.com/pdf/33/tnscgiho33_06.pdf)

However, in the technique disclosed in the non-patent document 1, since the apparatus becomes very large by using liquid nitrogen, there has been a demand for downsizing and space saving. In addition, the use of liquid nitrogen increases the inconvenience of maintenance and operation costs, and therefore, there is a demand for an apparatus and a method which are free from such a cost and have good workability.

In addition, since there is a strict standard in the manufacture of medicines, and since sterilization and cleaning are required in the apparatus, it is not possible to apply the compact apparatus having the excellent freezing ability as it is to the apparatus for medicines.

SUMMARY OF THE INVENTION The present invention has been made in view of the above circumstances, and aims to achieve the following objects.

1. It enables high-performance lyophilization applicable to the manufacture of medicines.

2. It is possible to freeze-dry method with good workability without inconvenience of maintenance and increase of operating cost.

A vacuum drying apparatus according to a first embodiment of the present invention includes a drying chamber for containing an object to be dried, a first chamber connected to the drying chamber and capable of being cooled to a first temperature so as to condense and collect moisture sublimated in the object, A second dewatering unit connected to the drying chamber independently from the first dewatering unit and having a second collecting unit that can be cooled to a second temperature lower than the first temperature, And a second partition part for selectively communicating or desorbing the drying chamber and the second dehydration part, wherein the first partition part and the second partition part, which selectively communicate or desorb the first dehydration part, The partition part cleans the drying chamber, the first dewatering unit and the second dewatering unit, and then communicates the drying chamber and the first dewatering unit, And then performing the second freeze drying by blocking the first dewatering section while communicating the drying chamber and the second dewatering section.

As a result, it is possible to adjust the temperature from -80 ° C to -100 ° C by adding a second collecting means required for the second dewatering unit to a known vacuum drying apparatus. It is possible to provide an apparatus capable of performing vacuum drying up to a water content necessary for a very difficult cooling and drying treatment such as a medicinal preparation while reducing the manufacturing cost of the apparatus without using a large-scale facility using liquid nitrogen. In addition, since the condensation load of steam is divided into the first dehydrating section and the second dehydrating section, the first dehydrating section can withstand a large moisture condensation load at the initial stage of the drying with low degree of vacuum. In addition, the second dewatering section can further perform drying at the end of the drying stage in which the moisture condensation load is low but the degree of vacuum is high. In the vacuum drying apparatus according to the first embodiment, it is possible to switch between the first dehydrating section and the second dehydrating section. It is then possible to increase the final dryness of the laundry (reduce the water content) with simple equipment.

In the vacuum drying apparatus according to the first embodiment of the present invention, the second dehydrating section is connected to a second exhausting section which is in a state in which the second partitioning section can be opened and closed when the second partitioning section is closed.

As the second exhaust means, for example, an exhaust means such as a turbo molecular pump may be provided. And the second evacuation means has a constitution that can be shut off from the drying chamber. Thus, the second dehydrating section can be exhausted while being separated from the drying chamber. It is possible to shut off the exhaust means from the drying chamber in a state in which the second dehydration section is in communication with the drying chamber.

In the vacuum drying apparatus according to the first embodiment of the present invention, the second collecting means is a cryo trap.

This makes it possible to freeze dry the object to be dried at a low moisture content as compared with the conventional method. Alternatively, a method of adsorbing moisture by a cryogenic freezer is also possible.

In the vacuum drying apparatus according to the first embodiment of the present invention, the drying chamber, the first dehydrating section, and the second dehydrating section are respectively washable and hermetically sealable.

Therefore, even when a very severe cleaning and sterilization treatment such as pharmaceutical preparation is performed, the drying time can be shortened and the space can be saved by lyophilizing the drying object with a lower water content than the conventional method.

The vacuum drying apparatus according to the first embodiment of the present invention is provided with a cooling means for setting a predetermined temperature at which the moisture contained in the object to be dried can be sublimated.

This makes it possible to shorten the treatment time and lower the water content when freeze-drying the object to be dried.

In the vacuum drying apparatus according to the first embodiment of the present invention, the dried article may be a material of a pharmaceutical preparation or a pharmaceutical preparation.

As a result, the cryotrap can satisfactorily satisfy the conditions such as cleaning and sterilization required while effectively lowering the water content as the second collecting means.

The vacuum drying method according to the second embodiment of the present invention is a vacuum drying method using the vacuum drying apparatus according to the first embodiment, wherein the first partitioning part and the second partitioning part are opened to separate the drying chamber, A washing step of washing the drying chamber, the first dewatering unit, and the second dewatering unit by opening the first partitioning unit and the second partitioning unit; A first drying step of opening the first partitioning portion to communicate the drying chamber and the first dewatering portion to block the second partitioning portion to block the first dewatering portion and to perform first freeze drying, And the first dehydrating part is closed by closing the first partition part while communicating the drying chamber and the second dehydrating part by opening the first dehydrating part, And a second drying step for drying.

This makes it possible to realize the temperature control from -80 DEG C to -100 DEG C by adding a necessary collection means to the second dehydrating section. Vacuum drying can be carried out until the moisture content is sufficiently lowered in the cooling drying treatment, which requires a very rigorous cleaning and sterilization treatment such as pharmaceutical preparation, while reducing the manufacturing cost of the apparatus because it does not use a large-scale facility using liquid nitrogen. Further, since the condensation load of the water vapor is divided into the first dehydrating section and the second dehydrating section, the first dehydrating section can withstand a large moisture condensation load at the initial stage of the drying with low degree of vacuum. In addition, the second dehydrating section can be additionally dried at the end of the drying stage in which the moisture condensation load is low but the degree of vacuum is high. In the vacuum drying method according to the second embodiment, the first dehydrating part and the second dehydrating part can be switched to continue the treatment. This can increase the final dryness of the substrate (reduce the water content) while maintaining the necessary conditions.

The vacuum drying method according to the second embodiment of the present invention may include a preliminary drying step of preliminarily drying the drying chamber, the first dehydrating section and the second dehydrating section by opening the first partitioning section and the second partitioning section .

This makes it possible to easily remove the washing water remaining in the drying chamber, the first dehydrating section and the second dehydrating section in the washing step. In particular, the moisture of the high-temperature steam used in the sterilization process can be easily removed to a required state.

In the vacuum drying method according to the second embodiment of the present invention, the vacuum drying apparatus is provided with a cooling means for setting a predetermined temperature at which water contained in the object to be dried can be sublimed, And a step of heating by the cooling means in the step of heating.

Thus, the sublimation efficiency during freeze-drying can be improved.

The vacuum drying method according to Embodiment 2 of the present invention may include a step of evacuating by the first evacuation means connected to the first dehydrating portion in a state where the first partition portion is closed in the second drying step .

As a result, in the second drying step, which is the final stage of the freeze-drying step, moisture collected in the first dehydrating part is discharged and preparation for the next cycle is performed simultaneously with the second drying step to improve working efficiency . Or the first dewatering section is not required to be continuously used, it is possible to reduce the size and space of the apparatus without excessively setting the capacity of the first dewatering section.

In the vacuum drying method according to the second embodiment of the present invention, the second dehydrating section is connected to a second exhausting section that is openable and closable when the second partitioning section is closed, and the cleaning step, the sterilizing step, In the receiving step and the first drying step, the second exhaust means is closed.

In this case, while the second partitioning portion is closed, the second dehydrating portion is opened and exhausted to the second exhausting means. When the second partitioning portion is opened, the second dehydrating portion is closed and the second exhausting means Separate. Thus, the second dehydrating section can be cleaned and sterilized, and the drying chamber and the second exhausting means can be prevented from being in a communicating state.

The vacuum drying method according to the second embodiment of the present invention may include a sealing step of sealing the object to be dried in the second drying step while closing the second partition part.

By doing so, the laundry can be sealed with a low water content.

A vacuum drying apparatus according to a third embodiment of the present invention includes a drying chamber for containing an object to be dried, a first collecting means connected to the drying chamber and capable of being cooled to a first temperature capable of collecting and condensing moisture sublimated in the object, A second collecting means connected to the drying chamber independently from the first dewatering portion and capable of being cooled to a second temperature lower than the first temperature, a second collecting means connected to the drying chamber and the first dewatering portion selectively Wherein the first partitioning portion and the sealing means clean the drying chamber and the first dewatering portion, and then the drying chamber and the first dewatering portion are separated from each other by the first partitioning portion and the second partitioning portion, 1 dewatering section to perform a first lyophilization, then the first dewatering section is closed, the second collecting section is cooled to perform a second lyophilization, And a second collecting means for collecting water to be sublimated in the second collecting means by communicating the drying chamber and the first dewatering portion.

Thus, in a known vacuum drying apparatus, the temperature can be adjusted from -80 ° C to -100 ° C by adding a second collecting means. It is possible to provide a device capable of reducing the manufacturing cost of a device without using a large-scale facility using liquid nitrogen, and capable of performing vacuum drying up to a necessary water content even in severe cooling and drying treatments such as pharmaceutical preparations. In addition, since the condensation load of water vapor is divided by the first dehydrating section and the second collecting section, the first dehydrating section can withstand the large moisture condensation load at the initial stage of drying with low degree of vacuum. In addition, the second collecting means can be further dried at the end of the drying stage in which the moisture condensation load is low but the degree of vacuum is high. In the vacuum drying apparatus according to the third embodiment, the first dehydrating section and the second collecting section can be switched. Therefore, it is possible to increase the final drying degree of the laundry to be dried (decrease the water content) with simple equipment.

A vacuum drying method according to a fourth embodiment of the present invention is a vacuum drying method using a vacuum drying apparatus according to the third embodiment, wherein the first partitioning portion is opened to sterilize the drying chamber, the first dehydrating section and the second dehydrating section A washing step of washing the drying chamber, the first dewatering unit and the second dewatering unit by opening the first partitioning unit, a receiving step of storing the drying object in the drying chamber, opening the first partitioning unit, A second drying step of cooling the second collecting means and performing a second freeze drying while closing the first partitioning portion to block the first dehydrating section, The drying object is sealed to raise the temperature of the second collecting means so that the drying chamber and the first dewatering section are brought into communication with each other so that the second collecting means is sublimated Includes a collecting process for collecting water.

As a result, the temperature can be adjusted from -80 ° C to -100 ° C with the addition of the necessary second collecting means. Vacuum drying can be carried out until the moisture content is sufficiently low even in the cooling and drying treatment in which the apparatus manufacturing cost is reduced by not using a large-scale facility using liquid nitrogen, and a very difficult cleaning and sterilization treatment process such as pharmaceutical preparation is required . Further, since the condensation load of the steam is divided by the first dehydrating section and the second collecting section, it is possible to withstand a large moisture condensation load at the initial stage of the drying at a low degree of vacuum in the first dehydrating section. In addition, the second collecting means can further perform drying at the end of the drying stage in which the moisture condensation load is low but the degree of vacuum is high. In the vacuum drying method according to the fourth embodiment, the first dehydrating part and the second collecting part can be switched to continue the treatment. Therefore, it is possible to increase the final degree of drying of the laundry (decrease the water content) while maintaining necessary conditions.

According to the embodiment of the present invention, it is possible to provide a vacuum drying apparatus and a vacuum drying method capable of sufficiently lowering the water content in freeze-drying of a pharmaceutical preparation having strict manufacturing conditions without using a large-scale facility.

1 is a schematic view showing a vacuum drying apparatus according to a first embodiment of the present invention.
2 is a flow chart showing the steps of the vacuum drying method according to the first embodiment of the present invention.
3 is a schematic view showing a vacuum drying apparatus according to a second embodiment of the present invention.
4 is a flowchart showing the steps of the vacuum drying method according to the second embodiment of the present invention.
5 is a graph showing vacuum drying results according to an embodiment of the present invention.
6 is a graph showing vacuum drying results according to an embodiment of the present invention.

Hereinafter, a vacuum drying apparatus and a vacuum drying method according to Embodiment 1 of the present invention will be described with reference to the drawings.

Fig. 1 is a schematic view showing a vacuum drying apparatus of the first embodiment. In Fig. 1, reference numeral 10 denotes a vacuum drying apparatus.

The vacuum drying apparatus 10 according to the present embodiment is used for freeze-vacuum drying the raw material liquid to produce, for example, raw materials for medicines, medicines, medicines and medicines. The material to be dried (F1) is a material of a pharmaceutical preparation or a pharmaceutical preparation. The object to be dried F1 may be in a liquid state in which the raw material liquid is accommodated in the container or may be a solid state (for example, agglomerate or powder) vacuum-freezed in the process before the treatment using the vacuum drying apparatus 10. In the present embodiment, the case where the dried product F1 is a pharmaceutical or pharmaceutical preparation is explained.

1, the vacuum drying apparatus 10 according to the present embodiment includes a drying chamber 11 for accommodating a drying object, a first dewatering unit 12 connected to the drying chamber 11, and a first dewatering unit 12, A second partitioning part 21 connected to the drying chamber 11, a second partitioning part 23 and a control unit 14 (control part).

The first dehydrating section 12 has a first collecting device 17 (first collecting device) that can be cooled to a first temperature at which moisture condensed in the object to be dried F1 can be condensed and collected.

The second dewatering section 13 has a collecting device 18 (collecting means) that can be cooled to a second temperature lower than the first temperature.

The first partitioning part 21 functions as a switching means so that the drying chamber 11 and the first dewatering unit 12 can be selectively communicated or desorbed from each other.

The second partitioning portion 23 functions as a switching means as in the first partitioning portion 21 and is capable of selectively communicating the drying chamber 11 and the second dewatering portion 13 or desorbing them.

The drying chamber (11) is a space for vacuum drying the raw material (F1) as 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 for supporting a tray (not shown) on which the sample F1 is loaded.

Each of the plurality of shelves 11a of the drying chamber 11 is provided with a heater (heating means) 11b. The heater 11b is controlled by a control unit (controller) 14 and can heat and cool the sample F1 loaded on the shelf 11a. The heater 11b may be constituted by, for example, a mechanism for circulating the heat through the inside of the shelf 11a, or a resistance heating heater such as a sheath heater or the like. The set temperature of the heater 11b upon heating is not particularly limited, and may be set at 20 占 폚, for example.

At least one shelf 11a is provided with a temperature sensor 11c. The temperature sensor 11c senses the temperature of the sample F1 mounted on the shelf heated by the heater 11b and outputs the sensed temperature to the control unit 14 as a sensing signal. The temperature sensor 11c can measure the temperature above the shelf 11a and is preferably provided on each of the plurality of shelves 11a.

The drying chamber 11 is connected to the first dewatering unit 12 and the second dewatering unit 13 which are independent from each other and the drying chamber 11 is connected to the drying chamber 11 through a first dewatering unit 12 and a second dewatering unit 13, (First exhausting means) 15 and a pump (second exhausting means) 16, respectively. The vacuum pump 15 is a pump for discharging the gas in the drying chamber 11 and converting the inside of the drying chamber 11 into a predetermined degree of vacuum. As the vacuum pump 15, various vacuum pumps such as a rotary pump or a dry pump can be introduced.

The drying chamber 11 is provided with a cleaning and sterilizing device 19 (cleaning and sterilizing means) for cleaning and sterilizing the interior of the drying chamber 11, the first dewatering portion 12 and the second dewatering portion 13, Respectively. The cleaning and sterilizing device 19 is controlled by the control unit 14. The cleaning and sterilizing device 19 is a device that removes clean water that meets predetermined criteria for steam or a cleaning process at about 122 ° C. used in the sterilization process into the drying chamber 11, the first dehydrating section 12 and the second dehydrating section 13).

In the drying chamber 11, pressure gauges 26 and 27 for measuring the pressure inside the drying chamber 11 are provided. The pressure gauge 26 is a first vacuum gauge capable of measuring all the pressures without being influenced by the measurement indication value according to the type of the measurement gas. For example, a baratron vacuum gauge, a diaphragm pressure gauge And may be a capacitance manometer gauge. The pressure gauge 27 is a vacuum gauge capable of measuring all the pressures using heat conduction. The second gauge is a second vacuum gauge which produces a difference in the measurement indication value according to the kind of the measurement gas. For example, a Pirani vacuum gauge ).

The measurement instruction value of the drying chamber 11 by the first vacuum gauge 26 and the measurement instruction value of the second vacuum gauge 27 during the first drying step S09 or the heating drying step S10 by the first dehydration part 12, (S09) or the heating and drying step (S10) by comparing the measurement instruction value of the drying chamber 11 with the difference between the measurement instruction value and the measurement instruction value. This is the determination step S12 described later.

That is, when the measured values of the pressure gauges 26 and 27 are in the same state in the state where the measured values of the pressure gauges 26 and 27 are distant from each other, the moisture in the drying chamber 11 flows into the first dehydrating section 12, It is possible to switch to the second drying step (S14) by the second dewatering section (13). The measured values of the pressure gauges 26 and 27 are outputted to the control unit 14.

The first dehydrating section 12 communicates the drying chamber 11 with the vacuum pump (first exhausting means) 15, and functions as an exhaust passage (first exhaust passage). The first dehydrating section 12 is provided with a first cold trap 17 (collecting means). The first cold trap 17 constitutes a collecting surface (first collecting surface) capable of collecting and condensing water vapor. The first cold trap 17 is used, for example, as a major cold trap for drying, which is larger than the second cold trap 18 described later and capable of collecting more steam.

The first cold trap (17) of the first dehydrating section (12) is configured to be wound around a tube coil through which a cooling medium flows. In other configurations, the first cold trap may be formed in the form of a flat plate. The first cold trap 17 has a coolant introduction portion 17a and a lead-out portion 17b at both ends of the tube. The inlet portion 17a and the outlet portion 17b of the refrigerant are connected to the first cooling device 17c for supplying and circulating the refrigerant in the first cold trap 17.

The first cooling device 17c is controlled by the control unit 14 to circulate the refrigerant in the first cold trap 17. The first cooling device 17c has a compressor for compressing the refrigerant, a condenser for liquefying the compressed high-temperature and high-pressure refrigerant, an expansion valve for adiabatically expanding the liquid refrigerant, and an evaporator for vaporizing the liquid refrigerant. The first cold trap 17 corresponds to the evaporator. The refrigerant is introduced into the first cold trap 17 from the inlet portion 17a and circulates to the first cold trap 17 as it is drawn out from the outlet portion 17b. As the refrigerant, for example, Freon gas R404A and silicone oil can be used.

The first cooling device 17c cools the surface (first trapping 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 collect and collect most of the water vapor sublimated from the sample F1 in the drying chamber 11. The first temperature value is set according to the type of the sample F1 as the object to be dried, the arrival pressure of the drying chamber, and is in the range of about -40 DEG C to about -20 DEG C in the present embodiment.

A first partitioning portion 21 serving as a switching valve is provided between the drying chamber 11 and the first cold trap 17 in the first dewatering portion 12 and the first cold trap 17, (First exhaust means) 15 is provided with a first switching valve 22 as switching means. Opening and closing of the first partitioning portion 21 and the first switching valve 22 is controlled by the control unit 14. [

The first partitioning part 21 includes a partitioning member 21a capable of closing the open portion of the drying chamber 11, a driving unit 21b for moving the partitioning member 21a, and a driving source 21c for driving the driving unit 21b. Respectively. The driving unit 21b switches between a closed state in which the partition body 21a is in contact with the wall surface and an open state in which the partition body 21a is separated from the wall surface. Opening and closing control of the first partitioning portion 21 is performed through driving of the driving source 21c being controlled by the control unit 14. [ The partition body 21a and the driving portion 21b are configured to be cleanable when the first dewatering portion 12 and the drying chamber 11 are cleaned and sterilized as described later.

The first partitioning portion 21 can be opened to allow the drying chamber 11 and the first dewatering portion 12 to communicate with each other. The drying chamber 11 and the vacuum pump 15 can communicate with each other by opening both the first partitioning portion 21 and the first switching valve 22. [ The gas in the first dehydration section 12 can be discharged by closing the first partitioning section 21 and opening the first switching valve 22. [ The gas discharge in the drying chamber 11 through the first dehydration section 12 can be restricted by blocking both the first partitioning section 21 and the first switching valve 22. [ The vacuum pump 15 and the first switching valve 22 constitute the first exhaust means.

On the other hand, the second dehydrating section 13 functioning as another exhaust passage (second exhaust passage) communicating with the drying chamber 11 is provided with the second cold trap 18. The second cold trap 18 constitutes a collecting surface (second collecting surface) capable of collecting and condensing water vapor. The second cold trap 18 is configured to be cooled to a second temperature lower than the first trapping surface of the first cold trap 17.

In this embodiment, the performance required of the cooling device 17c of the first cold trap 17 is adjustable to a temperature in the vicinity of -50 DEG C to -60 DEG C, and has a large heat capacity. On the other hand, the second cold trap 18 is used for secondary drying and is a trap for adsorbing and treating moisture in the primary drying furnace. Therefore, the performance required for the second cold trap 18 is required to be adjustable to a low temperature (for example, -80 DEG C to -100 DEG C), but the heat capacity may be small. Thus, the second cold trap 18 is smaller than the first cold trap 17. The amount of water vapor that can be collected by the second cold trap 18 is smaller than that of the first cold trap 17. The second cold trap 18 is used as a cold trap for finish drying. For example, when the object to be dried contains about 500 kg of water, the first cold trap 17 is used to dry most of the moisture of the object to be dried and to dry the remaining 1% 2 cold trap 18 is used.

The second cold trap 18 has a cold panel 18a cooled by a mechanical cooling device 18b controlled by the control unit 14. [ The low temperature panel 18a is spaced from the chamber wall and functions as a cryo trap.

The second cold trap 18 is equipped with the cold panel 18a which is frozen by the mechanical cooling device 18b in the second dewatering section 13. [ Such molecules or the like are held in the second dewatering section 13 by condensing moisture or carbon dioxide molecules or the like in the low temperature panel 18a in the second dewatering section 13. [ That is, the second cold trap 18 is configured to reduce water molecules and carbon dioxide molecules in the drying chamber 11.

The low temperature panel 18a can cool down to an ultra-low temperature of, for example, 80 K, by mechanically cooling the helium gas by a mechanical cooling device 18b. The low-temperature panel 18a can increase the degree of vacuum in the drying chamber 11 to a high vacuum that can not reach the exhaust pump 16 or the like by condensing gaseous molecules.

The exhaust pump 16 has a function of evacuating the interior of the second dewatering unit 13 by vacuum, and a turbo molecular pump can be used as the exhaust pump 16.

The second cold trap 18 is formed so that the surface of the low temperature panel 18a (second collecting surface) is lower than the surface temperature of the first cold trap 17, for example, about -70 ° C to -200 ° C, Deg.] C to -120 [deg.] C. If the surface temperature of the low-temperature panel 18a is set too low, high performance of the mechanical refrigerator 18b is required, which is not preferable. If the surface temperature of the low-temperature panel 18a is set too high, the moisture content of the object to be dried F1 can not be lowered to a desired level.

Further, although the second cold trap 18 uses a high performance cryotrap originally as described above, it may also be used under conditions that are significantly different from those generally used.

In the second dewatering section 13, a second partitioning section 23 serving as a switching valve is provided between the drying chamber 11 and the second cold trap 18. A second switching valve (24) is provided as a switching means between the second cold trap (18) and the exhaust pump (second exhaust means) (16). The opening and closing of the second partitioning part 23 and the second switching valve 24 are controlled by the control unit 14.

The second partitioning part 23 is provided with a partition 23a capable of closing a portion opened on the wall surface of the drying chamber 11, a driving part 23b for moving the partitioning body 23a and a driving source for driving the driving part 23b 23c. The driving unit 23b can switch between the closed state in which the partition body 23a is in contact with the wall surface and the open state in which the partition body 23a is separated from the wall surface. The opening and closing control of the second partition part 23 is performed through the drive source 23c being driven and controlled by the control unit 14. [ The partition 23a and the drive portion 23b are configured to be cleanable when the second dehydration section 13 and the drying chamber 11 are cleaned and sterilized as described later.

The second partitioning portion 23 can be opened to allow the drying chamber 11 and the second dewatering portion 13 to communicate with each other. The drying chamber 11 and the exhaust pump (second exhaust means) 16 can communicate with each other by opening both the second partition portion 23 and the second switching valve 24. [ The gas in the second dehydration section 13 can be discharged by closing the second partition 23 and opening the second switch valve 24. [ The second dehydration section 13 and the drying chamber 11 can be independently closed by closing both the second partitioning section 23 and the second switching valve 24. The exhaust pump 16 and the second switching valve 24 constitute a second exhausting means.

The vacuum drying apparatus 10 according to the present embodiment is configured such that the drying chamber 11, the first dewatering unit 12 and the second dewatering unit 13 are cleaned and then the drying chamber 11 and the first dewatering unit 12 The second dewatering section 13 is closed and the first lyophilization process is performed. Thereafter, while the drying chamber 11 and the second dewatering section 13 are communicated with each other, the first dewatering section 12 is closed and the second freeze-drying process is performed.

Accordingly, in the vacuum drying apparatus 10 according to the present embodiment, the drying chamber 11, the first dewatering unit 12, and the second dewatering unit 13 are respectively washable and hermetically sealable.

Specifically, in the first dewatering section 12 and the second dewatering section 13, thermal measures for sterilization, a partition body 21a and a drive section 21b, a partition body 23a, The lower panel 23b and the lower panel 18a (cryotrap) may be covered with a metal such as SUS, SUS316, Au, or Pt. Further, Cu having a good heat transfer may be used for a portion that is not cleaned, that is, a portion not contacting the inner surface of the dewatering portions 12, 13.

The gas does not flow back to the drying chamber 11 from the first dewatering section 12 on the side of the vacuum pump 15 rather than the first switching valve 22 and the first switching valve 22. Likewise, the second switching valve 24 and the second switching valve 22 are configured such that the gas does not flow back to the drying chamber 11 from the second dewatering section 12 on the vacuum pump 16 side.

The cryo trap generally has an In foil embedded in this part to improve the heat conduction at the connection of the refrigeration unit and the trap panel, but it is changed from In foil to gold plating and gold foil.

In the second dehydration section 13, the vacuum drying method of the present embodiment described later is performed in the sterilization step (S03), the cleaning step (S04), the receiving step (S07) and the first drying step (S09) And the exhaust pump 16 side is closed as compared with the second switching valve 24 of FIG.

Hereinafter, the vacuum drying method in this embodiment will be described.

Fig. 2 is a flowchart showing a vacuum drying method of this embodiment.

As shown in Fig. 2, the vacuum drying method of this embodiment includes a preparation step S01, an opening and closing step S02, a sterilization step S03, a cleaning step S04, a preliminary drying step S05, an opening and closing step S06, (S07), an opening and closing step (S08), a first drying step (S09), a heating and drying step (S10), a second evacuation step (S11), a discriminating step (S12), an opening and closing step (S13) (S14), a first evacuation step (S15), a sealing step (S16), an opening and closing step (S17), and a taking-out step (S18).

The vacuum drying method of this embodiment is prepared so that the dried object F1 necessary for the preparation step S01 shown in Fig. 2 can be carried on the shelf 11a. Further, the control unit 14 prepares necessary manufacturing condition information.

Next, as shown in Fig. 2, in the opening and closing process (S02), each partition and the valve are opened and closed by the control of the control unit 14 as follows.

Drying room (11): open

First partition part (21): open

Second partition part 23: Open

First switching valve 22: Closed

Second switching valve 24: Closed

Next, as a sterilization step (S03) shown in Fig. 2, a state set in the opening and closing step (S02), i.e., a state in which the first partitioning part 21 and the second partitioning part 23 are opened, The dehydrating section 12 and the second dehydrating section 13 are communicated with each other and steam is supplied from the cleaning and sterilizing device 19 under the control of the control unit 14. [ Thus, the interior of the drying chamber 11, the first dehydrating section 12, and the second dehydrating section 13 is sterilized.

The exposed portion of the drug product (F1) must be completely sterilized. Therefore, the steam sterilization step (S03) is carried out as the entire process of the drug production process every time the pharmaceutical production process is started. Sterilization required in freeze dryers for pharmaceuticals is to kill bacteria by exposure to steam over 122 ° C for 20 minutes or more.

The pressure of this steam sterilization process is about 210 kPa, 220 kPa ~ 240 kPa. Actually, the steam sterilization process (S03) keeps the inside of the equipment at a high temperature for about 3 hours.

At this time, the tube through which the cooling medium of the first cold trap 17 flows is configured to maintain a temperature of 70 ° C or lower by driving the cooling device 17c to withstand this temperature.

Similarly, when the low-temperature panel 18a of the second cold trap 18 is heated to withstand the temperature, the mechanical refrigerator 18b is driven so that the mechanical refrigerator 18b side is maintained at 70 ° C or lower. The temperature of the mechanical refrigerator 18b is 70 deg. C when heat is transmitted from the low temperature panel 18a, but is kept below the heat resisting temperature of the mechanical refrigerator 18b. Further, heat resistance of the mechanical freezer 18b is improved.

Next, the cleaning process (S04) shown in Fig. 2 is performed in the state set in the opening and closing process (S02), i.e., in the state where the first partitioning portion 21 and the second partitioning portion 23 are opened and the drying chamber 11, The first dehydrating section 12 and the second dehydrating section 13 are communicated with each other and clean water satisfying predetermined criteria is supplied from the cleaning and sterilizing device 19 for cleaning by the control of the control unit 14 . Thus, the interior of the drying chamber 11, the first dehydrating section 12 and the second dehydrating section 13 is cleaned. Unlike vacuum devices in other manufacturing fields such as semiconductors, water is sprayed inside the device to clean. Therefore, it is preferable that the inside of the drying chamber 11, the first dewatering unit 12, and the second dewatering unit 13 do not have as much water as possible.

Next, in the preliminary drying step (S05) shown in Fig. 2, the state set in the opening and closing step (S02), i.e., the state in which the first partitioning portion 21 and the second partitioning portion 23 are opened, The first dehydrating section 12 and the second dehydrating section 13 are communicated with each other and the first cold trap 17 is driven under the control of the control unit 14 to control the drying chamber 11 and the first dehydrating section 12, And the second dewatering section (13) are preliminarily dried to remove the washing water. At this time, the interior of the drying chamber 11 can be heated by the cooling device (cooling means) of the shelf 11a.

In the preliminary drying step (S05), the control unit (14) drives the first cooling device (17c) to circulate the refrigerant in the first cold trap (17), and the first partitioning part (21), the second partitioning part 23 and the first switching valve 22 are opened and the second switching valve 24 is closed and the vacuum pump 15 is driven to supply the gas in the drying chamber 11 to the first dehydrating section 12). As a result, the pressures of the drying chamber 11, the first dewatering unit 12 and the second dewatering unit 13 are lowered, and the water content therein evaporates. The vacuum pump 15 purges gas in the drying chamber 11 including the water vapor, the first dewatering unit 12 and the second dewatering unit 13 through the first exhaust path. The water vapor is collected in the first cold trap 17.

In the preliminary drying step (S05), it is preferable not to drive the second cold trap (18). However, in the second evacuation step (S11) described later, moisture inside the second dehydrating part (13) If it does, it does not.

Then, in the opening and closing process (S06) shown in Fig. 2, each partition and the valve are opened and closed by the control of the control unit 14 as follows.

Drying room (11): open

First partition part (21): open

Second partition part 23: Closed

First switching valve 22: Closed

Second switching valve 24: Closed

Next, as the receiving process S07 shown in Fig. 2, the state set in the opening / closing process (S06), that is, the first partitioning portion 21 is opened to communicate the drying chamber 11 and the first dewatering portion 12 The laundry F1 is carried into the drying chamber 11 while the second partition 23 is closed and the second dewatering unit 13 is kept independent.

Subsequently, as shown in Fig. 2, the partitioning unit and the valves are opened and closed as shown in Fig. 2 under the control of the control unit 14 as the opening and closing step (S08).

Drying room (11): Closed

First partition part (21): open

Second partition part 23: Closed

First switching valve 22: opened

Second switching valve 24: Closed

2, the first partitioning portion 21 is opened to open the drying chamber 11 and the first dewatering portion 12 in the state set in the opening and closing step (S08) The first cold trap 17 is driven under the control of the control unit 14 while the second partition 23 is closed and the second dewatering section 13 is kept independent from the drying chamber 11, The inside of the first dehydrating section 12, in particular, the drying chamber 11 is freeze-dried. As a result, the pressure of the drying chamber 11 and the first dewatering section 12 is lowered, and the water content therein evaporates. The vacuum pump 15 purges gas in the drying chamber 11 including water vapor through the first exhaust path. The water vapor is collected in the first cold trap 17.

Condensed gas such as nitrogen in the gas discharged from the drying chamber 11 is poured into the vacuum pump 15 without condensation in the first cold trap 17. The sample (F1) loaded on the shelf (11a) takes away the latent heat of evaporation from moisture and freezes.

The temperature of the first cold trap 17 in the first drying step (S09) is set to about -40 占 폚.

Next, the drying and drying step (S10) shown in Fig. 2 is performed in the state set in the opening and closing step (S08), namely, in the state set in the drying chamber 11 and the first dewatering section 12 by opening the first partitioning section 21. [ The cooling unit 11b provided in each shelf 11a is driven under the control of the control unit 14 with the second partition 23 closed and the second dehydration unit 13 independent.

The heater (heating means) 11b heats the shelf 11a in the drying chamber 11 to 20 占 폚 to heat the sample F1 loaded on the shelf 11a to promote the drying of the sample F1. Ice contained in the heated sample (F1) sublimates the latent heat in the sample (F1) and sublimes to become vapor.

The vacuum pump 15 discharges the gas in the drying chamber 11 including the water vapor through the first exhaust path. The water vapor in the gas discharged to the vacuum pump 15 emits latent heat at the surface of the first cold trap 17 and is condensed and collected by the first cold trap 17 as ice. Condensed gas such as nitrogen in the gas discharged from the drying chamber 11 is poured into the vacuum pump 15 without condensation in the first cold trap 17.

When the evacuation operation of the drying chamber 11 by the vacuum pump 15 is continued, the drying chamber 11 reaches the reaching pressure of the vacuum pump 15. Further, the condensation point of the water vapor in the drying chamber 11 is lowered, so that the collecting ability of the first cold trap 17 is lowered and the rise of the degree of vacuum in the drying chamber 11 is stopped. When the rise of the degree of vacuum in the drying chamber 11 is stopped, the ice contained in the sample F1 can not sublimate. As a result, since the ice contained in the sample F1 can not cause latent heat in the solid raw material, 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 senses the surface temperature of the sample F1 heated by the heater 11b and outputs the sensed temperature to the control unit 14 as a sensing signal.

At the same time, by continuing the evacuation operation of the drying chamber 11 by the vacuum pump 15, the rise of the degree of vacuum in the drying chamber 11 is stopped. At this time, it is possible to measure all the pressures using the measurement command value and the thermal conductivity of the pressure gauge 26, which is the first vacuum gauge capable of measuring all the pressures without being affected by the measurement command value depending on the kind of the measurement gas, To the control unit 14, a measurement instruction value of the pressure gauge 27, which is the second vacuum gauge in which a difference is caused in the measurement instruction value.

The control unit 14 compares the measurement indication value of the drying chamber 11 by the first vacuum gauge 26 with the measurement indication value of the drying chamber 11 by the second vacuum gauge 27, Is detected at the point of convergence to the minimum. The difference between the measurement indications of the first and second vacuum gauges is compared to determine when the difference between the measurement indication values converges to the minimum at the time of confirmation of the dry end point or the descending curve of the measurement indication curve of the second vacuum gauge The time of the inflection point of the drying end point is detected.

At the same time, the control unit 14 detects that the surface temperature of the sample F1 reaches the upper limit of the heating temperature of the heater 11b in accordance with the detection signal of the temperature sensor 11c.

2, the control unit 14 compares the measurement indication value from the pressure gauges 26, 27 and determines whether or not the temperature detected by the temperature sensor 11c and / If it is determined that the surface temperature of the sample F1 sensed in accordance with the detection signal from the heater 11b reaches the same upper limit as the temperature of the heater 11b, it is determined that this is the end point of the heat drying step S10. In this case, first the first partition 21 is closed, and then the first cold trap 17 is stopped. Further, if the first partitioning portion 21 is closed, the first switching valve 22 may be opened or closed.

Subsequently, as shown in Fig. 2, in the opening and closing step S13, each partition and the valve are opened and closed by the control of the control unit 14 as follows.

Drying room (11): Closed

First partition part (21): Closed

Second partition part 23: Open

First switching valve 22: Closed

Second switching valve 24: Open

Next, in the second drying step (S14) shown in Fig. 2, the drying chamber 11 and the second dewatering section 13 are opened by opening the second partitioning section 23, The second cold trap 18 is driven under the control of the control unit 14 while the first partitioning portion 21 is closed and the first dewatering portion 12 is kept independent from the drying chamber 11, And the inside of the second dehydrating section (13), in particular, the drying chamber (11).

As a result, the pressure in the drying chamber 11 and the second dewatering section 13 is lowered, thereby evaporating moisture inside. The turbo-molecular pump 16 purges the gas in the drying chamber 11 including water vapor through the second exhaust path. The water vapor is trapped by the second cold trap 18, which is the cryotrap.

The heater 11b and the turbo molecular pump 16 are continuously driven in the heating and drying step (S10). Then, the second cold trap 18 starts to be driven before the second partition portion 23 is opened.

The second cold trap 18 is set at a lower temperature than the first cold trap 17, for example, about -100 ° C.

The second cold trap (18) cooled to -100 ° C collects the water vapor that was not captured by the first cold trap (17). At the same time, the pressure in the drying chamber 11 is lowered. As a result, the sublimation of the ice remaining in the sample F1 resumes. The ice remaining in the sample F1 sublimates by latent heat in the sample F1 and the generated water vapor releases latent heat at the surface of the second cold trap 18 and condenses to become ice to be supplied to the second cold trap 18 . The final drying degree of the sample F1 can be increased and the moisture content can be greatly lowered so that the sample F1 subjected to the heat drying step S10 can be further dried by this finish drying. In addition, compared with the moisture removed in the first drying step (S09) and the heating drying step (S10) using the first dewatering section (12), the moisture removed in the second drying step (S14) using the second dewatering section The water content may be about 1%, that is, about 5 kg.

Next, in the closing process (S16) shown in Fig. 2, in the state set in the opening and closing process (S13), that is, when the second partitioning portion 23 is opened and the drying chamber 11 and the second dewatering portion 13 are communicated (Airtight means) (not shown) under the control of the control unit 14 in a state in which the first partitioning portion 21 is closed and the first dewatering portion 12 is made independent, Painting is performed and sealed.

Next, as shown in Fig. 2, the control unit 14 controls the opening and closing of the partition and the valve as follows.

Drying room (11): open

First partition part (21): Closed

Second partition part 23: Closed

First switching valve 22: Closed

Second switching valve 24: Closed

Next, as the take-out step (S18) shown in Fig. 2, the moisture content is lowered to a desired state in the drying chamber 11, and the dried object F1 after the drying process is taken out, and the drying process is finished in the batch.

2, in a part or all of the first drying step (09) and the heating drying step (S10), as the second exhausting step (S11), the state set in the opening and closing step (S08) The first partitioning portion 21 is opened so as to communicate the drying chamber 11 and the first dewatering portion 12 while the second partitioning portion 23 is closed so that the second dewatering portion 13 is independent, The second switching valve 24 is opened and the gas in the second dewatering section 13 which is in this independent state is exhausted to discharge the moisture trapped in the second cold trap 18 to the outside. As a result, it is possible to delay the freeze-drying process of the next batch without delay.

Similarly, in a part or all of the second drying step (S14) shown in Fig. 2, the state set in the opening and closing step (S13) as the first evacuation step (S15), i.e., the state in which the second partitioning part The first switching valve 22 is opened in a state in which the first partitioning part 21 is closed and the first dehydrating part 12 is isolated while the drying chamber 11 and the second dehydrating part 13 are communicated with each other , And the first dehydrating section 12, which is in this independent state, is evacuated to discharge the moisture trapped in the first cold trap 17 to the outside. As a result, it is possible to delay the freeze-drying process of the next batch without delay.

In this embodiment, one of the two switchable cold traps (17) and (18) is used as an independent cryotrap, and it becomes possible to freeze dry the object to be dried up to a low moisture content which could not be attained in the past.

Further, since the conventionally proposed liquid nitrogen has a lower maintenance cost and can change a temperature condition than a method of making a cryogenic condition, it can cope with various drying conditions.

When the second cold trap 18 is operated, the first partition 21 or the second partition 23 is closed and the second cold trap 17 having a lower processing temperature than the first cold trap 17 18 can prevent the possibility of adsorbing the ice attached to the first cold trap 17.

Further, a partitioning valve other than the second partitioning part 23 may be inserted between the second cold trap 18 and the drying chamber 11. [

Alternatively, the low-temperature panel 18a of the second cold trap 18 may be directly provided in the drying chamber 11 according to the type of the object to be dried F1 and the restriction condition depending on the object F1. This configuration is applicable, for example, in the case where the ice attached to the second cold trap 18 is not a problem at the time of delivering the product, for example, when the product F1 is a sealed product.

Further, a cryotrap can be added to the already installed freeze-drying apparatus by drilling a hole like the first cold trap 17 and adding a valve. In this case, it is necessary to adopt the above-mentioned specifications or a configuration equivalent thereto so as to be compatible with the cleaning and sterilization process.

The inside of the drying chamber 11, the first dewatering unit 12 and the second dewatering unit 13 in which the object to be dried F1 is exposed must be completely sterilized in the drying process. Therefore, it is necessary to perform the steam sterilization process and the cleaning process as the entire process of the medicine production process every time the pharmaceutical production process is started. The sterilization treatment required for the freeze-drying equipment used for pharmaceuticals, especially water for injection (WFI) production, is to kill bacteria by exposure to steam over 122 ° C. for 20 minutes or more.

In this steam sterilization process, the pressure inside the drying chamber 11 is about 210 kPa and about 220 kPa to 240 kPa. In fact, the inside of the apparatus is maintained at a high temperature by a steam sterilization process for about three hours. At this time, in the first cold trap 17, the cooling device 17c is operated so as to withstand this temperature, and the temperature is maintained at 70 ° C or lower. Further, in the trap of the second cold trap 18, the compressor of the mechanical freezer 18b is driven while the steam is heated to withstand the temperature, thereby maintaining the temperature at 70 ° C or lower.

In the second cold trap 18, since the mechanical freezer 18b can not be stored at a temperature exceeding 70 캜 for a long time, it is preferable to sterilize the mechanical freezer 18b while cooling the mechanical freezer 18b to the driven state during the sterilization process (S03). In this case, it is necessary to set the output of the mechanical freezer 18b so that the cooling capacity of the mechanical freezer 18b is high and the temperature of the low temperature panel 18a (trap panel) does not reach a temperature sufficient for sterilization.

Further, in the case of the apparatus for manufacturing medicines as in the present embodiment, the body for improving heat transfer at the connection portion between the mechanical refrigerator 18b and the low-temperature panel 18a can be made of gold, gold or the like.

After completion of 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 second drying step (S14) is performed by squeezing the remaining moisture by the second cold trap (18) at -100 deg. Therefore, it is preferable that the first cold trap 17 and the second cold trap 18 are provided in separated rooms (spaces). Further, it is preferable that the heater 11b is not used for the sea ice of the low-temperature panel 18a.

In the second cold trap 18, the cylinder portion of the mechanical freezer 18b is made of SUS316 and SUS316L. The material of the low temperature panel (trap panel) 18a is SUS316, and the heat transfer portion is made of a metal having high corrosion resistance such as gold leaf.

The second drying step (S14) for trapping moisture at a cryogenic temperature and lowering the moisture content of the object to be dried (F1) is a finishing step after the first drying step (S09) in which normal freeze drying is performed, . Therefore, in the vacuum drying apparatus of the present embodiment, there is no need to increase the processing speed to shorten the processing time, and the object is to significantly improve the water content. The second cold trap 18, which has been used as an apparatus for manufacturing an existing semiconductor and a flat panel display (FPD), is selected, and then the second cold trap 18 is used in the vacuum drying apparatus of this embodiment.

The second dehydrating section 13 may be provided and the second collecting device 18 and the exhaust pump 16 may be installed directly in the drying chamber 11. [ In this case, after the sealing step S16 is completed, the first partitioning part 21 is opened while the first collecting device 17 is cooled, the temperature of the second collecting device 18 is raised, The collection step of collecting the water to be sublimated in the device 18 by the first collecting device 17 may be performed.

Hereinafter, a vacuum drying apparatus and a vacuum drying method according to a second embodiment of the present invention will be described with reference to the drawings.

Fig. 3 is a schematic view showing the vacuum drying apparatus of this embodiment. In Fig. 3, reference numeral 10A is a vacuum drying apparatus.

In this embodiment, the second dewatering unit 13 is different from the first embodiment described above. Components other than the second dewatering unit 13 are denoted by the same reference numerals as those in the first embodiment, and a description thereof will be omitted.

In the vacuum drying apparatus 10A according to the present embodiment, the second cold trap 18 (second collecting means, cryotrap) is provided directly inside the drying chamber 11, Is directly connected to the drying chamber 11 through the valve 24, and the second partition part 23 is not provided.

3, the control unit 14, the plurality of shelves 11a, and the like are omitted, and the components corresponding to the vacuum drying apparatus 10A of the first embodiment shown in Fig. 1 are denoted by the same reference numerals, And showed.

Hereinafter, the vacuum drying method of this embodiment will be described.

4 is a flowchart showing a vacuum drying method of this embodiment.

As shown in Fig. 4, the vacuum drying method of the present embodiment includes a preparing step S21, an opening and closing step S22, a sterilization step S23, a cleaning step S24, a preliminary drying step S25, an opening and closing step S26, The first drying step S29, the heating and drying step S30, the determining step S32, the opening and closing step S33, the second drying step S34, the sealing step S36, An opening and closing step (S37), a post-dewatering step (S39), an opening and closing step (S40), and a taking-out step (S38).

The vacuum drying method of this embodiment is the preparation step S21 shown in Fig. 4, and is prepared so as to bring the necessary dried material F1 into the shelf 11a in the same manner as the preparation step S01. Further, the control unit 14 prepares necessary manufacturing condition information.

Next, as shown in Fig. 4, in the opening and closing step (S22), each partition and valve are opened and closed as follows.

Drying room (11): open

First partition part (21): open

First switching valve 22: Closed

Second switching valve 24: Closed

Then, in the sterilization step S23 shown in Fig. 4, the first partitioning portion 21 is opened to establish communication with the drying chamber 11 and the first dewatering portion 12 in the state set in the opening and closing step S22 , And the steam is supplied from the cleaning and sterilizing device (19) under the control of the control unit (14). As a result, the inside of the drying chamber 11 and the first dehydrating section 12 are sterilized.

The portion of the drug product (F1) exposed to the pharmaceutical preparation should be completely sterilized. Therefore, the steam sterilization step (S23) is carried out at every step of the medicine production process every time the pharmaceutical production process is started. Sterilization required in freeze dryers for pharmaceuticals is to kill bacteria by exposure to steam over 122 ° C for 20 minutes or more.

The pressure of this steam sterilization process is about 210 kPa to 220 kPa to 240 kPa. Actually, the inside of the equipment is maintained at a high temperature for about 3 hours in the steam sterilization step (S23).

At this time, the tube through which the cooling medium of the first cold trap 17 flows is configured to maintain a temperature of 70 ° C or lower by driving the cooling device 17c to withstand this temperature.

Similarly, the low temperature panel 18a of the second cold trap 18 is configured such that the mechanical refrigerator 18b is driven to maintain the temperature of the mechanical refrigerator 18b at 70 deg. . The temperature of the mechanical refrigerator 18b is 70 deg. C when heat is transferred from the low temperature panel 18a to the conventional refrigerator, but this is maintained below the heat resisting temperature of the mechanical refrigerator 18b. Further, heat resistance of the mechanical freezer 18b is improved.

4, the first partitioning portion 21 is opened to connect the drying chamber 11 and the first dewatering portion 12 to each other in the state set in the open / close step S22, that is, And is cleaned under the control of the control unit 14 and supplies clean water satisfying a predetermined standard from the sterilizing device 19 for cleaning. Thus, the interior of the drying chamber 11 and the first dewatering section 12 is cleaned. Unlike vacuum devices in other manufacturing fields such as semiconductors, water is sprayed inside the device to clean. For this reason, it is preferable that the inside of the drying chamber 11 and the first dewatering section 12 is structured so that water is not stirred as much as possible.

4, the drying chamber 11 and the first dewatering section 12 are opened in the state set in the open / close step S22, that is, the first partitioning section 21 is opened, And the first cold trap 17 is driven under the control of the control unit 14 to preliminarily dry the drying chamber 11 and the first dewatering section 12 to remove the washing water. At this time, the inside of the drying chamber 11 can be heated by the cooling means 11b of the shelf 11a.

In the preliminary drying step S25, the control unit 14 drives the first cooling device 17c to circulate the refrigerant to the first cold trap 17, and the first partitioning part 21 and the first switching valve 22 The second switching valve 24 is closed and the vacuum pump 15 is driven to discharge the drying chamber 11 through the first dehydrating section 12 which is the first exhaust path. Then, the pressure of the drying chamber (11) and the first dewatering section (12) is lowered to evaporate water inside. The vacuum pump 15 purges the drying chamber 11 including steam and the gas in the first dehydrating section 12 through the first exhaust path. The water vapor is collected in the first cold trap 17.

In addition, it is preferable that the second cold trap 18 is not driven in the preliminary drying step (S25).

Then, in the opening and closing process (S26) shown in Fig. 4, each partition and the valve are opened and closed by the control of the control unit 14 as follows.

Drying room (11): open

First partition part (21): open

First switching valve 22: Closed

Second switching valve 24: Closed

4, the first partitioning portion 21 is opened to allow the drying chamber 11 and the first dewatering portion 12 to communicate with each other in the state set in the opening and closing process (S26) The dried object F1 is carried into the drying chamber 11.

Subsequently, as shown in Fig. 4, in the opening and closing step (S88), each partition and the valve are opened and closed by the control of the control unit 14 as follows.

Drying room (11): Closed

First partition part (21): open

First switching valve 22: opened

Second switching valve 24: Closed

Then, in the first drying step (S29) shown in FIG. 4, the drying chamber 11 and the first dehydrating section 12 are opened by opening the first partitioning section 21, The first cold trap 17 is driven under the control of the control unit 14 in a communicated state to freeze and dry the inside of the drying chamber 11 and the inside of the first dewatering portion 12, Then, the pressure of the drying chamber 11 and the first dewatering section 12 is lowered, and the water content therein evaporates. The vacuum pump 15 purges gas in the drying chamber 11 including water vapor through the first exhaust path. The water vapor is collected in the first cold trap 17.

Condensed gas such as nitrogen in the gas discharged from the drying chamber 11 is poured into the vacuum pump 15 without condensation in the first cold trap 17. The sample F1 loaded on the shelf 11a takes away the latent heat of evaporation from moisture and is frozen.

The first cold trap 17 in the first drying step S29 is set at about -40 ° C.

4, the first partitioning portion 21 is opened to connect the drying chamber 11 and the first dewatering portion 12 to each other in the state set in the opening / closing step (S28) The control unit 14 drives the cooling means 11b provided on each shelf 11a.

The heater (heating means) 11b heats the shelf 11a in the drying chamber 11 to 20 占 폚 and heats the sample F1 loaded on the shelf 11a to promote the drying of the sample F1. The ice contained in the heated sample F1 becomes latent heat in the sample F1 and sublimes to become steam.

The vacuum pump 15 discharges the gas in the drying chamber 11 including the water vapor through the first exhaust path. The vapor in the gasses discharged by the vacuum pump 15 emits latent heat at the surface of the first cold trap 17 and is condensed and collected by the first cold trap 17 as ice. Condensed gas such as nitrogen in the gas discharged from the drying chamber 11 is pumped to the vacuum pump 15 without being condensed in the first cold trap 17.

By continuing the evacuation operation of the drying chamber 11 by the vacuum pump 15, the drying chamber 11 reaches the limit pressure of the vacuum pump 15. Further, by lowering the condensation point of the water vapor in the drying chamber 11, the ability of collecting the first cold trap 17 is lowered, and the rise of the degree of vacuum in the drying chamber 11 is stopped. When the rise of the degree of vacuum in the drying chamber 11 stops, the ice contained in the sample F1 can not sublimate. As a result, since the ice contained in the sample F1 can not cause latent heat in the solid raw material, 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 senses the surface temperature of the sample F1 heated by the heater 11b and outputs the sensed temperature to the control unit 14 as a sensing signal.

At the same time, by continuing the evacuation operation of the drying chamber 11 by the vacuum pump 15, the rise of the degree of vacuum in the drying chamber 11 is stopped. At this time, a vacuum gauge capable of measuring all the pressures using the measurement indication value of the pressure gauge 26, which is the first vacuum gauge, which can measure all the pressures which are not influenced by the measurement indication value according to the kind of the measurement gas, And outputs to the control unit 14 the measurement instruction value of the pressure gauge 27 which is the second vacuum gauge in which the measurement instruction value differs depending on the kind of the measurement gas.

The control unit 14 compares the measurement indication value of the drying chamber 11 by the first vacuum gauge 26 with the measurement indication value of the drying chamber 11 by the second vacuum gauge 27, It detects the point of convergence to the minimum. The difference between the measurement indications of the first and second vacuum gauges is compared and it is judged that the time point at which the difference of the measurement indication value converges to the minimum is determined as the dry end point confirmation point or the descent of the measurement indication curve of the second vacuum gauge The time at the inflection point of the curve is detected as the drying end point.

At the same time, the control unit 14 detects that the surface temperature of the sample F1 reaches the upper limit at which the temperature of the sample F1 becomes equal to the heating temperature of the heater 11b, in accordance with the detection signal from the temperature sensor 11c.

4, the control unit 14 determines whether or not the dry end confirmation point and / or the temperature sensor 11c sensed by the pressure gauges 26, 27, It is determined that the temperature of the sample F1 has reached the upper limit at which the temperature of the sample F1 is equal to the temperature of the heater 11b based on the sensing signal at the heating and drying step S10. In this case, the first partition part 21 is first closed and the driving of the first cold trap 17 is stopped. Further, if the first partitioning portion 21 is closed, the first switching valve 22 may be opened or closed.

Next, as shown in Fig. 4, in the opening and closing process (S33), each partition and the valve are opened and closed by the control of the control unit 14 as follows.

Drying room (11): Closed

First partition part (21): Closed

First switching valve 22: Closed

Second switching valve 24: Open

Next, as the second drying step (S34) shown in Fig. 4, the first dehydrating section (21) is closed while the first partitioning section (21) is closed and the drying chamber (11) The second cold trap 18 and the turbo molecular pump 16 are driven under the control of the control unit 14 to freeze and dry the drying chamber 11 in a state in which the drying chamber 11 and the turbo molecular pump 12 are independent.

Then, the pressure of the drying chamber (11) drops and the moisture inside the drying chamber (11) evaporates. The turbo-molecular pump 16 purges the gas in the drying chamber 11 including water vapor through the second exhaust path. The water vapor is trapped by the second cold trap 18, which is the cryotrap.

In addition, the heater 11b and the turbo molecular pump 16 are continuously driven in the heating and drying step (S30). The second cold trap 18 is set at a lower temperature than the first cold trap 17, for example, about -100 ° C.

The second cold trap 18 cooled to -100 ° C. collects the water vapor that was not caught in the first cold trap 17. As a result, the pressure in the drying chamber 11 is lowered. Then, the sublimation of the ice remaining in the sample F1 resumes. The ice remaining in the sample F1 brings latent heat in the sample F1 and the sublimated water vapor releases latent heat at the surface of the second cold trap 18 to be condensed to ice and is collected by the second cold trap 18 do. According to such finishing drying, the sample F1 subjected to the heat drying step (S30) can be further dried, and the final dryness of the sample (F1) can be increased to greatly reduce the moisture content. The amount of water removed in the first drying step (S29) and the heating and drying step (S30) by using the first dehydrating section (12) 2 The water removed in the drying step (S44) may be about 1%, that is, about 5 kg.

Then, in the closing step S36 shown in Fig. 4, the first partitioning part 21 is closed and the drying chamber 11 and the first dewatering part 12 are made independent The object to be dried F1 is coated with aluminum using sealing means (not shown) under the control of the control unit 14 and sealed.

Subsequently, in the opening and closing step (S37) shown in Fig. 4, each partition and the valve are opened and closed by the control of the control unit 14 as follows.

Drying room (11): Closed

First partition part (21): open

First switching valve 22: opened

Second switching valve 24: Closed

Then, in the post-dewatering step S39 shown in Fig. 4, the first partitioning part 21 is opened to open the drying chamber 11 and the first dewatering unit 12 The operation of the second cold trap 18 is stopped under the control of the control unit 14 and the first cold trap 17 is driven to discharge the melted ice from the cold panel 18a to the first cold trap 17). At this time, it is preferable to drive the heater 11b to thaw the moisture collected in the low-temperature panel 18a. At the same time, the gas in the drying chamber 11 containing water vapor is pumped through the first exhaust path.

Then, in the opening and closing step (S40) shown in Fig. 4, each partition and the valve are opened and closed by the control of the control unit 14 as follows.

Drying room (11): open

First partition part (21): Closed

First switching valve 22: Closed

Second switching valve 24: Closed

Subsequently, in the take-out step (S38) shown in Fig. 4, the moisture content is decreased from the drying chamber 11 to the desired state, the dried object F1 after the drying process is taken out, and the drying process in this batch is finished .

In this embodiment, the same effects as those of the first embodiment can be obtained. In addition, in the conventional vacuum drying apparatus, since the chamber is not newly provided as the second dewatering section 13, the device configuration can be further simplified.

<Examples>

&Lt; Example 1 >

Hereinafter, a first embodiment according to the present invention will be described.

Example 1 was carried out by the vacuum drying apparatus 10A shown in Fig.

The specifications of the vacuum drying apparatus 10A shown in Fig. 3 are as follows.

- the specification of the first cold trap (17)

Actual piping temperature -65 ℃ or less

Refrigerant Direct expansion type Refrigerant R404a

Surface treatment and material SUS304 buff 400 polishing

Pressure change of the drying chamber (11): Within 20 minutes from atmospheric pressure to 13 Pa

The specification of the second cold trap 18

Actual piping temperature -80 ℃ ~ -100 ℃ or less

Mechanical refrigerator (18c) system; Freezer using He

Surface treatment and material SUS316L Buff 400+ Electrolytic polishing

Pressure change of the drying chamber (11): Within 30 minutes from atmospheric pressure to 13 Pa

- moisture contained in the object to be dried (F1) brought into the drying chamber (11); About 500kg.

- the pressure in the drying chamber (11) when switching from the first cold trap (17) to the second cold trap (18); About 1Pa

Vacuum drying treatment was performed in this vacuum drying apparatus, and the pressure P in the drying chamber and the temperature T of the shelf 11a in the treatment were measured. These results are shown in Fig. 5 to Fig.

In Figs. 5 to 6, the abscissa is represented by the processing time in correspondence to the preliminary drying step (S05), the first drying step (S09), the heating drying step (S10) and the second drying step (S14).

5 to 6, (S05), (S09), (S10), and (S14)

- preliminary drying step (S05); Preliminary freezing 2-3 hours

A first drying step (S09); Fast Drying -45 ℃, 24 hours

- a heating and drying step (S10); Rate drying, shelf 20 ℃ 2 hours

- a second drying step (S14); Finishing Drying -100 ℃

to be.

In the second drying step (S14), the final water content was 3 10 ^-2 %.

Further, the water content at the end of the heat drying step (S10) was 3%.

From the results shown in Fig. 5 to Fig. 6, it is possible to improve the water content by about two digits and to change the temperature to a good reproducibility, thereby making it possible to meet various drying conditions .

&Lt; Example 2 >

A second embodiment according to the present invention will be described below.

In the second embodiment, similar to the first embodiment, the vacuum drying apparatus 10A shown in Fig. 3 was used. The specifications of the vacuum drying apparatus 10A of the second embodiment are the same as those of the first embodiment.

In this vacuum drying apparatus, the vacuum drying treatment was performed, and the pressure P of the drying chamber and the temperature T of the shelf 11a in the treatment were measured. The conditions of the preliminary drying step (S05), the first drying step (S09), the heating drying step (S10) and the second drying step (S14) of Example 2 are as follows.

- preliminary drying step (S05); Preliminary freezing 2-4 hours

A first drying step (S09); Rapid drying, at 0 to -45 ° C for 24 to 48 hours

- a heating and drying step (S10); Rate drying shelf 20 ℃ 2 ~ 40 hours

- a second drying step (S14); Finishing Drying -100 ~ -200 ℃

The moisture content at the end of the heat drying step (S10) was 0.99 to 1.82%. On the other hand, when the second cold trap 18 was set to -100 deg. C, the water content after the completion of the second drying step S14 was about 0.46 to 0.64%. When the second cold trap 18 was set to -200 ° C, the water content after the completion of the second drying step (S14) was about 0.42 to 0.43%.

Thus, when the second cold trap 18 is set to -100 DEG C or lower, the water content can be significantly lowered.

From the results of Example 2, it can be seen that the water content can be greatly improved, and at the same time, by changing the temperature to a reproducible temperature, it is possible to satisfy various drying conditions.

&Lt; Industrial applicability >

Examples of application of the present invention include application to freeze-drying, which is required to lower the water content of biopharmaceuticals and antibody drugs.

10: Vacuum dryer
11: Drying room
11a: Shelf
11b: heater (heating means)
11c: Temperature sensor
12: First dehydrating part
13: Second dehydration unit
14: Control unit (control unit)
15: Vacuum pump (first exhaust means)
16: exhaust pump (second exhaust means)
17: first collecting means (first cold trap)
17a:
17b:
17c: cooling device
18: Second collecting means (cryotrap)
18a: low temperature panel
18b: Mechanical freezer
19: Cleaning, sterilization means
21: first partition part
21a:
21b:
21c:
22: first switching valve (first exhausting means)
23: second partition part
23a:
23b:
23c:
24: second switching valve (second exhausting means)
26: Pressure gauge
27: Pressure gauge
F1: Buildings

Claims (14)

A drying chamber for containing the object to be dried;
A first dewatering unit connected to the drying chamber and having a first collecting unit that can be cooled to a first temperature so as to condense and collect moisture sublimated in the drying object;
A second dewatering unit connected to the drying chamber independently of the first dewatering unit and having second collecting means that can be cooled to a second temperature lower than the first temperature;
A first partition part capable of selectively communicating or desorbing the drying chamber and the first dehydrating part;
A second partition part capable of selectively communicating or desorbing the drying chamber and the second dewatering part;
Lt; / RTI &gt;
Wherein the first partitioning portion and the second partitioning portion block the drying chamber, the first dewatering portion and the second dewatering portion, and then communicate the drying chamber and the first dewatering portion while closing the second dewatering portion, And then switching the drying chamber and the second dewatering section to communicate with each other while closing the first dewatering section to perform the second freeze drying. The vacuum drying apparatus according to claim 1, wherein the second dehydrating section is connected to a second exhausting section that is in a state in which the second partitioning section is openable and closable when the second partitioning section is closed. The vacuum drying apparatus according to claim 1, wherein the second collecting means is a cryo trap. The vacuum drying apparatus according to any one of claims 1 to 3, wherein the drying chamber, the first dewatering unit and the second dewatering unit are respectively washable and hermetically sealable. The vacuum drying apparatus according to any one of claims 1 to 3, further comprising a cooling means for setting a predetermined set temperature at which the moisture contained in the object to be dried can be sublimated. The vacuum drying apparatus according to any one of claims 1 to 3, wherein the drying object is a material of a pharmaceutical preparation or a pharmaceutical preparation. A vacuum drying method using the vacuum drying apparatus according to claim 1,
A sterilizing step of opening the first partitioning part and the second partitioning part to sterilize the drying chamber, the first dewatering part and the second dewatering part;
A cleaning step of opening the first partitioning portion and the second partitioning portion to clean the drying chamber, the first dewatering portion and the second dewatering portion;
A receiving step of receiving the object to be dried in the drying chamber;
A first drying step of opening the first partition part to close the second partition part while communicating the drying chamber and the first dewatering part to block the second dewatering part and perform the first freeze drying;
A second drying step of opening the second partitioning portion to communicate the drying chamber and the second dewatering portion to block the first partitioning portion to block the first dewatering portion and perform second freeze drying;
/ RTI &gt; The vacuum drying method according to claim 7, further comprising a preliminary drying step of preliminarily drying the drying chamber, the first dewatering unit and the second dewatering unit by opening the first partitioning portion and the second partitioning portion. The vacuum drying apparatus according to claim 7 or 8, further comprising a cooling means for setting a predetermined set temperature at which the moisture contained in the object to be dried can be sublimated,
And a step of heating by the cooling means in the first drying step. The vacuum drying method according to claim 7 or 8, wherein in the second drying step, exhausting is performed by first exhaust means connected to the first dehydrating portion in a state in which the first partition portion is closed. 9. The air conditioner according to claim 7 or 8, wherein the second dewatering unit is connected to a second exhausting unit that becomes openable and closable when the second partitioning unit is closed,
In the washing step, the sterilizing step, the receiving step and the first drying step,
And the second exhaust means is in a state of being closed. The vacuum drying method according to claim 7 or 8, further comprising a sealing step of sealing the object to be dried in the second drying step while the second partition part is closed. A drying chamber for containing the object to be dried;
A first dewatering unit connected to the drying chamber and having first collecting means that can be cooled to a first temperature capable of collecting and condensing moisture sublimated in the drying object;
Second collecting means connected to the drying chamber independently of the first dewatering portion and being capable of being cooled to a second temperature lower than the first temperature;
A first partition part capable of selectively communicating and desorbing the drying chamber and the first dehydrating part;
A sealing means for sealing the object to be dried;
Lt; / RTI &gt;
Wherein the first partitioning portion and the sealing means clean the drying chamber and the first dewatering portion and then perform the first lyophilization by making the drying chamber and the first dewatering portion communicate with each other so as to close the first dewatering portion, Drying the second drying means to cool the second drying means to cool the drying means to raise the temperature of the second drying means and to bring the drying chamber and the first drying means into communication with each other so that the water sublimated by the second drying means Vacuum drying apparatus, which is a switching means for carrying out the collecting collecting process. A vacuum drying method using the vacuum drying apparatus according to claim 13,
A sterilizing step of sterilizing the drying chamber, the first dewatering unit and the second dewatering unit by opening the first partitioning unit;
A cleaning step of opening the first partitioning portion to clean the drying chamber, the first dewatering portion and the second dewatering portion;
A receiving step of receiving the object to be dried in the drying chamber;
A first drying step of opening the first partitioning part and communicating the drying chamber and the first dewatering part to perform a first lyophilization;
A second drying step of cooling the second collecting means and performing a second freeze-drying while closing the first partitioning portion to block the first dewatering portion;
A collecting step of raising the temperature of the second collecting means by closing the drying object and communicating the drying chamber and the first dewatering portion to collect water sublimated by the second collecting means;
/ RTI &gt;

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