Freeze-drying tray

Abstract

This invention provides a freeze-drying tray suitable for suppressing the occurrence of collapses during the primary drying stage of the freeze-drying process. [Solution] The freeze-drying tray 100 comprises a tray body 20 having an opening 23a, an inlet 30 for injecting liquid material into the internal space S of the tray body 20, and a ventilation member 10 that is positioned to close the opening 23a and includes a ventilation membrane 11. The Gurley air permeability of the ventilation member 10 is in the range of 0.10 seconds / 100 mL or more and 3.20 seconds / 100 mL or less.

Description

Technical Field

[0001] The present invention relates to trays for freeze-drying, and particularly to sealed trays for freeze-drying.

Background Art

[0002] Conventionally, as methods for freeze-drying liquid materials such as chemical solutions, there are a method of dispensing the liquid material into a vial, freeze-drying it, and then sealing it as it is, and a method of injecting the liquid material into a tray made of stainless steel or the like, freeze-drying it, pulverizing the freeze-dried product, and then dividing it into small portions and sealing it in a container such as a vial. The latter is widely used because it is excellent in production efficiency in that a large amount of liquid material can be freeze-dried together. For example, Patent Document 1 discloses a freeze-drying technique using a tray with an open top.

[0003] In recent years, from the viewpoints of hygiene and safety, etc., it has been demanded to reduce the scattering and / or contamination of liquid materials in the freeze-drying process. In response to this demand, recently, a freeze-drying technique using a sealed tray in which the upper surface of a tray with an open top is sealed and the inside is sealed has been proposed. According to the sealed tray, since the freeze-drying process can be carried out while confining the liquid material, the scattering and / or contamination of the liquid material is reduced.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] However, when freeze-drying is carried out using conventional sealed trays, the temperature of the sublimation surface in the drying area may rise too high during the primary drying stage, causing the frozen area to re-thaw (collapse). When collapse occurs, the quality of the freeze-dried product deteriorates.

[0006] Therefore, the present invention aims to provide a freeze-drying tray suitable for suppressing the occurrence of collapses in the primary drying stage of the freeze-drying process. [Means for solving the problem]

[0007] As a result of diligent research, the inventors have found that the above objective can be achieved by employing a ventilation membrane in a sealed tray and adjusting the degree of ventilation of the ventilation membrane to a certain range.

[0008] The present invention A tray body having an opening, The tray body has an inlet for injecting liquid material into its internal space, A ventilation member including a ventilation membrane is arranged to close the aforementioned opening, Equipped with, The Gurley air permeability of the aforementioned permeable membrane is in the range of 0.10 seconds / 100 mL or more and 3.20 seconds / 100 mL or less. Freeze-drying trays, To provide. [Effects of the Invention]

[0009] According to the present invention, it is possible to provide a freeze-drying tray suitable for suppressing the occurrence of collapses in the primary drying stage of the freeze-drying process. [Brief explanation of the drawing]

[0010] [Figure 1] Figure 1 is a schematic plan view showing an example of a freeze-drying tray according to the present invention. [Figure 2] Figure 2 is a cross-sectional view along the line II-II in Figure 1. [Figure 3]FIG. 3 is a perspective view schematically showing the tray for freeze-drying of FIG. 1. [Figure 4] FIG. 4 is a cross-sectional view schematically showing the ventilation member provided in the tray for freeze-drying of the present invention. [Figure 5] FIG. 5 is a plan view schematically showing a modified example of the tray for freeze-drying of the present invention. [Figure 6] FIG. 6 is a cross-sectional view taken along line VI-VI of FIG. 5. [Figure 7] FIG. 7 is a perspective view schematically showing the tray for freeze-drying of FIG. 5. [Figure 8] FIG. 8 is a graph showing the temperature change of the sublimation surface of the drying part in the primary drying stage of the freeze-drying process using the trays for freeze-drying of Example 2 and Comparative Example 1. [Figure 9] FIG. 9 is a freeze-drying program showing the set shelf temperature and set pressure of the vacuum freeze-dryer used in the examples. <0000​​​​​​​​​​​​​​​​​​​​​​​​​​​​In a fourth embodiment of the present invention, for example, in a freeze-drying tray according to any one of the first to third embodiments, the ventilation member further includes a support layer that supports the ventilation membrane.

[0015] In a fifth embodiment of the present invention, for example, in a freeze-drying tray according to any one of the first to fourth embodiments, the tray body has a bottom and a side portion extending upward from the periphery of the bottom, the side portion being made of a resin material and the bottom portion being made of a sheet-like member.

[0016] In a sixth aspect of the present invention, for example, in a freeze-drying tray according to the fifth aspect, the lower end of the side portion has a flange extending outward, and the periphery of the bottom portion is joined to the flange.

[0017] In a seventh aspect of the present invention, for example, in a freeze-drying tray according to any one of the first to sixth aspects, when viewed from above, 50% or more of the upper surface of the freeze-drying tray is a ventilation area.

[0018] Embodiments of the present invention will be described below with reference to the drawings. The present invention is not limited to the following embodiments.

[0019] [Freeze-drying tray] An example of a freeze-drying tray according to this embodiment is shown in Figures 1 to 3. Figure 1 is a schematic plan view of the freeze-drying tray 100. Figure 2 is a cross-sectional view along line II-II in Figure 1. Figure 3 is a schematic perspective view of the freeze-drying tray 100. The freeze-drying tray 100 comprises a tray body 20 having an opening 23a, an inlet 30 for injecting liquid material into the internal space S of the tray body 20, and a ventilation member 10 arranged to close the opening 23a. The ventilation member 10 includes a ventilation membrane 11. The Gurley air permeability of the ventilation member 10 is in the range of 0.10 seconds / 100 mL or more and 3.20 seconds / 100 mL or less.

[0020] In this specification, "liquid material" means a material that is fluid at room temperature. Examples of liquid materials include liquid pharmaceuticals (drug solutions) and liquid food products. Liquid materials are typically drug solutions.

[0021] The freeze-drying tray 100 of this embodiment is a sealed tray in which a ventilation member 10 is positioned to close the opening 23a of the tray body 20. Therefore, compared to using a conventional tray with an open top, the scattering and / or contamination of liquid material can be reduced during the freeze-drying process.

[0022] The freeze-drying process is typically carried out using a vacuum freeze-dryer. A vacuum freeze-dryer includes, for example, a chamber for freeze-drying liquid materials, a cold trap for recondensing vaporized water vapor, and a vacuum pump for maintaining a high vacuum inside the apparatus. Figure 9 shows a freeze-drying program that displays the set shelf temperature and set pressure of a vacuum freeze-dryer used in the embodiment described later. As shown in Figure 9, the freeze-drying process mainly consists of freezing stage A, primary drying stage B, and secondary drying stage C. In freezing stage A, a tray containing the liquid material is placed in the chamber and the liquid material is frozen. A frozen section is formed in freezing stage A. In primary drying stage B, the pressure inside the chamber is reduced by a vacuum pump, causing the free water contained in the frozen section to sublimate. A dried section is formed in primary drying stage B. In secondary drying stage C, the water incorporated as bound water in freezing stage A is removed. A freeze-dried product is obtained in secondary drying stage C. Although the time scale is omitted in Figure 9, the time required for freezing stage A is, for example, 2 to 5 hours. The time required for the primary drying stage B is, for example, 60 to 70 hours. The time required for the secondary drying stage C is, for example, 8 to 10 hours. The time for each stage is set appropriately according to the type of liquid material and the size of the tray.

[0023] In the primary drying stage B, the sublimation of free water progresses from the surface of the frozen area toward the deeper parts. The vapor generated at the sublimation surface is released to the outside of the sealed tray. As sublimation progresses, the sublimation surface gradually recedes toward the deeper parts, increasing the thickness of the dried portion while decreasing the thickness of the frozen portion, until finally the frozen portion transitions into the dried portion. The inventors have newly discovered a problem in the primary drying stage B: if the release of vapor from the internal space of the tray to the outside is stagnant, the pressure inside the tray increases due to the excess vapor, and consequently the temperature of the sublimation surface of the dried portion rises too high, causing a collapse in the frozen portion. Hereafter, the temperature at which a collapse occurs may be referred to as the "collapse temperature." The collapse temperature varies depending on the composition of the liquid material, etc. The occurrence of a collapse in the primary drying stage B leads to a decrease in the quality of the freeze-dried product that is ultimately obtained. Specifically, the freeze-dried product shrinks, separates, and solidifies, reducing its redispersibility (condensation) with water, as well as its appearance. The inventors of this invention further investigated this problem and came to the conclusion that by adjusting the degree of air permeability of the permeable membrane used in sealed trays to a certain range in order to improve air permeability while ensuring water resistance, the occurrence of collapse during the primary drying stage can be suppressed.

[0024] In the freeze-drying tray 100 of this embodiment, the Gurley air permeability of the ventilation member 10 is in the range of 0.10 seconds / 100 mL or more and 3.20 seconds / 100 mL or less. If the Gurley air permeability of the ventilation member 10 is 0.10 seconds / 100 mL or more, sufficient water resistance is ensured, so leakage of liquid material is avoided. If the Gurley air permeability of the ventilation member 10 is 3.20 seconds / 100 mL or less, the stagnation of vapor release from the internal space S to the outside is suppressed in the primary drying stage B, so that the temperature of the sublimation surface in the drying section does not rise too rapidly. As a result, the occurrence of collapse can be suppressed.

[0025] Gurley air permeability can be measured in accordance with the air permeability measurement method B (Gurley method) specified in JIS L1096:2010.

[0026] Furthermore, even if the size of the ventilation member 10 is less than the size of the test specimen in the Gurley method (approximately 50 mm x 50 mm), the Gurley air permeability can still be evaluated by using a measuring jig. An example of a measuring jig is a polycarbonate disc with a thickness of 2 mm and a diameter of 47 mm, with a through hole (having a circular cross-section with a diameter of 1.5 mm) in the center. The measurement of Gurley air permeability using this measuring jig can be carried out as follows.

[0027] A sample piece of the ventilation member 10 to be evaluated is fixed to one side of the measuring jig so as to cover the opening of the through-hole of the measuring jig. The fixing is done so that during the measurement of the Gurley air permeability, air passes only through the opening and the effective test portion of the sample piece (the portion that overlaps with the opening when viewed from a direction perpendicular to the main surfaces 11a and 11b of the ventilation membrane 11), and the fixing portion does not obstruct the passage of air in the effective test portion of the sample piece. For fixing the sample piece, double-sided adhesive tape with a vent hole punched out in the center that matches the shape of the opening can be used. The double-sided adhesive tape should be placed between the measuring jig and the sample piece so that the circumference of the vent hole and the circumference of the opening coincide. Next, the measuring jig with the sample piece fixed is set in a Gurley air permeability tester so that the fixing surface of the sample piece is on the downstream side of the airflow during measurement, and the time t1 for 100 mL of air to pass through the sample piece is measured. Next, the measured time t1 was set to the effective test area of ​​642 [mm²] as defined in JIS L1096:2010 Permeability Measurement Method B (Gurley Method). 2 The value t per ] is given by the formula t = {(t1) × (area of ​​the effective test portion of the sample piece [mm²] 2 ]) / 642[mm 2 The conversion value t obtained by ]} can be used as the Gurley permeability of the ventilation member 10. When the above disc is used as a measuring jig, the area of ​​the effective test portion of the sample piece is the area of ​​the cross-section of the through hole. It has been confirmed that the Gurley permeability measured without using a measuring jig for a ventilation member 10 that meets the size of a test piece in the Gurley method agrees well with the Gurley permeability measured using a measuring jig for a sample piece made by cutting the ventilation member 10 into small pieces, that is, the use of a measuring jig does not substantially affect the measured value of the Gurley permeability.

[0028] The upper limit of the Gurley air permeability of the ventilation member 10 may be 3.00 seconds / 100 mL, 2.50 seconds / 100 mL, 2.00 seconds / 100 mL, 1.50 seconds / 100 mL, or even 1.00 seconds / 100 mL.

[0029] The thickness of the breathable membrane 11 is, for example, 5 μm or more and 50 μm or less. By having the thickness of the breathable membrane 11 within the above range, sufficient water resistance and strength can be ensured in the breathable member 10. The upper limit of the thickness of the breathable membrane 11 may be 35 μm or 30 μm. The lower limit of the thickness of the breathable membrane 11 may be 10 μm or 15 μm.

[0030] The thickness of the breathable membrane 11 can be determined by measuring the thickness at any five points on the breathable membrane 11 and taking the average of these measurements.

[0031] Figure 4 is a schematic cross-sectional view showing the ventilation member 10 of the freeze-drying tray 100. As shown in Figure 4, the ventilation member 10 comprises a ventilation membrane 11 having one main surface 11a and the other main surface 11b. As shown in Figure 2, the main surface 11a faces the outside of the freeze-drying tray 100. The main surface 11b faces the internal space S.

[0032] For example, resin materials such as polyethylene (PE), polypropylene (PP), and polyethylene terephthalate (PET) can be used as the material for forming the permeable membrane 11. The permeable membrane 11 may also be a resin-based porous membrane formed from PE, PP, or PET.

[0033] The permeable membrane 11 may include a porous fluororesin membrane. A porous fluororesin membrane is a membrane formed by making a fluororesin membrane porous by stretching or the like, typically by biaxial stretching. The porous fluororesin membrane may have countless pores formed during stretching, more specifically, pores that are the gaps between countless fluororesin fibrils formed during stretching.

[0034] Examples of fluororesins included in porous fluororesin membranes include polytetrafluoroethylene (PTFE), polychlorotrifluoroethylene, tetrafluoroethylene-hexafluoropropylene copolymer, and tetrafluoroethylene-ethylene copolymer.

[0035] The fluororesin may be PTFE. That is, the porous fluororesin membrane may be a porous PTFE membrane. Since the porous PTFE membrane has excellent water resistance, it is suitable for use in freeze-drying trays 100.

[0036] The ventilation film 11 may be treated with an oil-repellent coating. Preferably, the oil-repellent coating is applied to at least the main surface 11b of the ventilation film 11. With this configuration, it is possible to prevent some of the liquid material injected into the internal space S from sticking to the main surface 11b of the ventilation film 11. The oil-repellent coating may be applied to both the main surface 11a and the main surface 11b.

[0037] The oil-repellent treatment can be performed by applying an oil-repellent solution to the breathable film 11. The oil-repellent agent is not particularly limited, but a fluorine-based oil-repellent agent is preferred. The fluorine-based oil-repellent agent is preferably one or more selected from the group consisting of acrylic polymers having fluorine-containing side chains, urethane polymers having fluorine-containing side chains, and silicone polymers having fluorine-containing side chains. For example, as the oil-repellent agent, a mixture of an oil-repellent agent containing a polymer with the compound shown in the following chemical formula (a) as a monomer and a solvent can be used. CH2=C(CH3)COOCH2CH2C5F 10 CH2C4F9···(a) As a solvent, a mixed solution of 1,1,2,2-tetrafluoroethoxy-1-(2,2,2-trifluoro)ethane (AGC Corporation, AE-3000) and metaxylene hexafluoride can be used.

[0038] Furthermore, commercially available fluorine-based oil repellents can be used as described above. For example, Daikin's "Unidyne®" series; Shin-Etsu Chemical's X-70-029C; and AGC Seimi Chemical's "SF Coat®" series (e.g., SIF-200) can be used. Additionally, silicone-based polymer fluorine-based oil repellents include, for example, Shin-Etsu Chemical's KP-801M.

[0039] For the solvent used in the oil-repellent solution, a fluorine-based solvent with high affinity for fluorine-based side chains is preferred. Commercially available fluorine-based solvents with high affinity for fluorine-based side chains can be used. Examples of commercially available products include FS Thinner manufactured by Shin-Etsu Chemical Co., Ltd. and Fluorinert manufactured by Sumitomo 3M Co., Ltd. These may be used individually or in mixtures of two or more.

[0040] The drying process after application of the oil-repellent solution is not particularly limited and may be natural drying (air drying) or heat drying.

[0041] As shown in Figure 4, in this embodiment, the ventilation member 10 further includes a support layer 12 that supports the ventilation membrane 11.

[0042] The support layer 12 has a net-like, mesh-like, or non-woven fabric-like form and is breathable in the thickness direction. The breathability of the support layer 12 is usually higher than that of the breathable membrane 11. The support layer 12 ensures the strength and rigidity of the breathable membrane 11 and improves handling. In addition, the support layer 12 has the function of suppressing damage when it is attached to the tray body 20 and when the freeze-drying tray 100 is used.

[0043] As shown in Figure 4, the support layer 12 is positioned on the side of the main surface 11a of the breathable membrane 11. This structure prevents some of the liquid material injected into the internal space S from adhering to the support layer 12.

[0044] The materials constituting the support layer 12 are not limited and include, for example, metals such as aluminum and stainless steel, resins such as polyolefins (polyethylene, polypropylene, etc.), polyesters (polyethylene terephthalate, etc.), polyamides (aliphatic polyamides, aromatic polyamides, etc.), and composite materials thereof.

[0045] The material constituting the support layer 12 is typically a polyolefin-based nonwoven fabric. The support layer 12 may also be a polypropylene net.

[0046] As shown in Figures 1 to 3, in this embodiment, the tray body 20 has a bottom portion 21, a side portion 22 extending upward from the peripheral edge 21p of the bottom portion 21, and an upper portion 23. An opening 23a is formed in the upper portion 23.

[0047] In this embodiment, the upper part 23 of the tray body 20 further has a peripheral edge 23p surrounding the opening 23a. As shown in Figure 2, the peripheral edge 23p has a back surface 23s facing the internal space S. The ventilation member 10 is joined to the back surface 23s so as to close the opening 23a. That is, the ventilation member 10 closes the opening 23a from the internal space S side. The method of joining the ventilation member 10 and the back surface 23s of the tray body 20 is not particularly limited. For example, the ventilation member 10 and the back surface 23s of the tray body 20 may be welded together by heat welding from the ventilation membrane 11 side of the ventilation member 10. Alternatively, for example, the ventilation member 10 and the back surface 23s may be joined by a joining layer (not shown). The joining layer is, for example, an adhesive layer or a bonding layer. The configuration of the joining layer is not limited as long as it is possible to join the ventilation member 10 and the back surface 23s.

[0048] As shown in Figure 2, the internal space S is defined by the bottom 21, the side 22, and the ventilation member 10. The liquid material injected into the internal space S becomes a freeze-dried product through a freeze-drying process.

[0049] As shown in Figure 2, the side portion 22 and the upper portion 23 of the tray body 20 may be integrally molded. The side portion 22 and the upper portion 23 may be integrally molded from the same material.

[0050] In this embodiment, the sides 22 and upper part 23 of the tray body 20 are made of a resin material. The bottom 21 of the tray body 20 is made of a sheet-like material. The tray body 20 has a periphery 21p of the bottom 21 joined to the lower end 22e of the side 22. With this structure, for example, after the freeze-drying process is completed, the freeze-dried material can be easily removed by inverting the freeze-drying tray 100 and cutting open the sheet-like material. The method of joining the periphery 21p of the bottom 21 and the lower end 22e of the side 22 is not particularly limited. For example, the periphery 21p of the bottom 21 and the lower end 22e of the side 22 may be welded together by heat welding from the sheet-like material side of the bottom 21. Alternatively, for example, the periphery 21p of the bottom 21 and the lower end 22e of the side 22 may be joined by a joining layer (not shown). The joining layer is, for example, an adhesive layer or a bonding layer. The configuration of the joining layer is not limited as long as it is possible to join the peripheral edge 21p of the bottom portion 21 and the lower end 22e of the side portion 22.

[0051] As shown in Figures 2 and 3, the lower end 22e of the side portion 22 may have a flange 22f extending outward. The peripheral edge 21p of the bottom portion 21 may be in close contact with the flange 22f. With such a structure, the bottom portion 21 and the side portion 22 can be more firmly attached.

[0052] For example, polypropylene (PP), polyethylene terephthalate (PET), olefin-based materials, nylon, etc., can be used as the material constituting the sheet-like member that forms the bottom portion 21. Typically, the material constituting the sheet-like member is polypropylene.

[0053] For example, polypropylene (PP), polycarbonate (PC), olefin-based materials, etc., can be used as the resin material forming the side portion 22 and the upper portion 23. The resin material is typically polypropylene. The resin material forming the side portion 22 and the resin material forming the upper portion 23 may be the same or different.

[0054] In this embodiment, the inlet 30 is located on a part of the peripheral edge 23p of the upper part 23. However, the location of the inlet 30 is not particularly limited. The inlet 30 may be located, for example, on a part of the side part 22.

[0055] As shown in Figure 3, in this embodiment, the inlet 30 has a cylindrical lid receiving portion 31 and a lid body 32 that can be attached to or removed from the lid receiving portion 31. The outer circumferential surface of the lid receiving portion 31 has a male screw shape. The inner circumferential surface of the lid body 32 has a female screw shape (not shown) that screws into the male screw shape of the lid receiving portion 31. With this structure, liquid can be easily injected from the inlet 30 into the internal space S.

[0056] In the examples shown in Figures 1 to 3, the freeze-drying tray 100 has a rectangular parallelepiped shape. However, the shape of the freeze-drying tray 100 is not limited to the examples shown in Figures 1 to 3. The freeze-drying tray 100 may, for example, have a cylindrical shape.

[0057] As shown in Figure 1, in this embodiment, when viewed from above, the upper surface of the freeze-drying tray 100 is a ventilation area 10a of 50% or more. When viewed from above, the upper surface of the freeze-drying tray 100 may be a ventilation area 10a of 60% or more, 70% or more, 80% or more, or even 90% or more. As shown in Figure 2, the area of ​​the ventilation area 10a may be smaller than the area of ​​the ventilation member 10.

[0058] The internal space S of the freeze-drying tray 100 is, for example, 40mm to 400mm in width, 40mm to 300mm in depth, and 10mm to 50mm in height. With such a structure, the freeze-drying process is easily facilitated.

[0059] In this embodiment, the capacity of the tray body 20 is 2.0 L or less. The capacity of the tray body 20 may also be 1.8 L or less. With this configuration, a sufficient ventilation area can be secured. Furthermore, in the internal space S, the surface area of ​​the injected liquid material can be increased while the depth (thickness) of the liquid material can be reduced. Moreover, the freeze-drying tray 100 of this embodiment can be suitably used not only when manufacturing freeze-dried products, but also, for example, when carrying out a freeze-drying process in a laboratory.

[0060] Note that the freeze-drying tray 100 is not limited to the structure shown in Figures 1 to 3. Figures 5 to 7 show modified examples of the freeze-drying tray 100. As shown in Figures 5 to 7, the lower end 22e of the side portion 22 does not have to have an outwardly extending flange 22f. The freeze-drying tray 101 shown in Figures 5 to 7 has the same structure as the freeze-drying tray 100 shown in Figures 1 to 3, except that the lower end 22e of the side portion 22 does not have a flange 22f. Therefore, for the freeze-drying tray 101, the same reference numerals are used for elements that are the same as those in the freeze-drying tray 100, and their explanations are omitted.

[0061] As shown in Figures 5 to 7, the peripheral edge 21p of the bottom portion 21 may be in close contact with the end face of the lower end 22e of the side portion 22. The side portion 22 and the bottom portion 21 may be configured to be flush with each other on the outer circumference of the freeze-drying tray 100.

[0062] [How to use the freeze-drying tray] The freeze-drying tray 100 can be used, for example, as follows: First, liquid material is injected into the internal space S of the freeze-drying tray 100 from the inlet 30. The freeze-drying tray 100 containing the liquid material is placed in the chamber of a vacuum freeze-dryer, and the freeze-drying process is carried out. After the freeze-drying process is completed, the freeze-drying tray 100 is removed from the chamber, inverted, and the freeze-dried material is recovered by cutting open the sheet-like member at the bottom 21. The recovered freeze-dried material is divided into lumps or further crushed, then placed in containers such as vials and sealed.

[0063] [Method for manufacturing freeze-drying trays] The following describes an example of a manufacturing method for freeze-drying tray 100.

[0064] The ventilation member 10 can be manufactured, for example, by the following method. First, a raw fluororesin porous membrane is prepared. The raw fluororesin porous membrane can be manufactured by known methods. For example, if the raw fluororesin porous membrane is a PTFE porous membrane, a mixture of PTFE fine powder and a molding aid is extruded to form a sheet. Next, the sheet mixture is rolled, and the molding aid is dried and removed by heating to form a sheet molded body. Next, the sheet molded body is stretched in the longitudinal direction (rolling direction), then stretched in the width direction, and then fired. In this way, the raw fluororesin porous membrane can be manufactured. The properties of the PTFE porous membrane can be adjusted by the rolling and stretching conditions. The ventilation member 10 is obtained by laminating a support layer 12 to the main surface 11a of the ventilation membrane 11. For example, a polypropylene net can be used as the support layer 12.

[0065] Next, the ventilation member 10 is joined to the back surface 23s of the upper part 23 so as to close the opening 23a, on the side part 22 and upper part 23 which are integrally molded from resin material. At this time, the ventilation member 10 is positioned so that the main surface 11b of the ventilation membrane 11 faces the internal space S. After joining the ventilation member 10, the lower end 22e of the side part 22 is joined to the peripheral edge 21p of the bottom part 21 which is formed from a sheet-like material. Finally, the lid 32 is attached to the lid receiving part 31 of the upper part 23. This completes the freeze-drying tray 100. [Examples]

[0066] The present invention will be described in more detail below with reference to examples. The present invention is not limited to the examples shown below.

[0067] In this embodiment, the Gurley permeability of the permeable film was evaluated by the method described above. The freeze-drying process was carried out using a vacuum freeze-dryer (Triomaster A04, manufactured by Nitto Denko Corporation). The temperature of the sublimation surface of the dried section was observed using the TMbySR method.

[0068] (Example 1) As the ventilation member in Example 1, a stretched PTFE porous membrane (manufactured by Nitto Denko Corporation, NTF9304-L01) with a Gurley air permeability of 0.10 seconds / 100 mL was used.

[0069] (Example 2) In Example 2, a stretched PTFE porous membrane (manufactured by Nitto Denko Corporation, NTF1033-N01) with a Gurley air permeability of 0.73 seconds / 100 mL was used as the ventilation member.

[0070] (Example 3) In Example 3, a stretched PTFE porous membrane (manufactured by Nitto Denko Corporation, NTF1232-S01) with a Gurley air permeability of 2.50 seconds / 100 mL was used as the ventilation member.

[0071] (Comparative Example 1) For Comparative Example 1, a stretched PTFE porous membrane (manufactured by Nitto Denko Corporation, NTF2133A-S06) with a Gurley air permeability of 3.23 seconds / 100 mL was used as the ventilation member.

[0072] (Comparative Example 2) For Comparative Example 2, a stretched PTFE porous membrane (Nitto Denko Corporation, NTF9201-L01) with a Guarley air permeability of 0.05 seconds / 100 mL was used as the permeable membrane.

[0073] A freeze-drying tray having the structure shown in Figure 1 was fabricated using the method described above. A co-extruded sheet of PP and PE was used as the sheet-like member constituting the bottom 21 of the tray body 20. The sides 22 and top 23 of the tray body 20 were integrally molded using PP. The internal space S of the freeze-drying tray had dimensions of 360 mm in length, 233 mm in depth, and 32 mm in height. When viewed from above, 78% of the top surface of the freeze-drying tray was a ventilation area. The ventilation members 10 used were those of Examples 1-3 and Comparative Examples 1-2. A polypropylene net (lattice structure, mesh size: 600-800 μm, fiber diameter: 230 μm) was used as the support layer 12 of the ventilation member 10.

[0074] A lactose aqueous solution (concentration: 5 wt%) was used as the liquid material. The collapse temperature of lactose is -31°C. The lactose aqueous solution was poured into the freeze-drying trays prepared as described above in Examples 1-3 and Comparative Examples 1-2, and the freeze-drying process was carried out. The maximum temperature T from the start of the primary drying stage to 25 hours was measured. 25 The time t until the primary drying stage was completed and the presence or absence of liquid leakage were evaluated. Time t was defined as the time it took for the temperature of the sublimation surface in the drying section to reach the chamber shelf temperature of -20°C. The presence or absence of liquid leakage was confirmed by visual inspection. The results are shown in Table 1.

[0075] [Table 1]

[0076] Figure 8 shows the temperature change of the sublimation surface in the drying section during the primary drying stage of the freeze-drying process using freeze-drying trays in Example 2 and Comparative Example 1. The graph in Figure 8 is a graph of the temperature change of the sublimation surface in the drying section during the primary drying stage, calculated based on the temperature of the sublimation surface in the drying section calculated using the TMbySR method.

[0077] As shown in Figure 8, the freeze-drying tray of Example 2 showed a suppressed temperature rise in the initial stages of the primary drying compared to the freeze-drying tray of Comparative Example 1. As can be seen from Figure 8, the maximum temperature T from the start of the primary drying stage up to 25 hours later... 25 This can be considered the maximum temperature at the beginning of the primary drying stage. As shown in Table 1 and Figure 8, in Comparative Example 1, the maximum temperature T 25The temperature was -30°C, which was higher than the collapse temperature of lactose (-31°C). On the other hand, in Examples 1-3, the maximum temperature was between -36°C and -31°C, which was below the collapse temperature of lactose. This is thought to be because, in Examples 1-3, the Guarley permeability of the permeable membrane was in the range of 0.10 seconds / 100 mL or more and 3.20 seconds / 100 mL or less, which suppressed the temperature of the sublimation surface in the drying area from rising too high during the primary drying stage. From these results, it is inferred that the freeze-drying trays of Examples 1-3 can suppress the occurrence of collapse during the primary drying stage of the freeze-drying process.

[0078] In addition, as shown in Table 1 and Figure 8, the freeze-drying trays of Examples 1 to 3 showed a shorter time t until the primary drying stage was completed compared to the freeze-drying tray of Comparative Example 1. Thus, the freeze-drying process could be shortened using the freeze-drying trays of Examples 1 to 3.

[0079] The freeze-drying tray in Comparative Example 2 has a maximum temperature T 25 The temperature was -37°C, which was below the collapse temperature of lactose. However, the permeability of the permeable membrane was too high, which reduced its water resistance and caused leakage. [Industrial applicability]

[0080] The freeze-drying tray of the present invention is suitable for freeze-drying liquid materials such as chemical solutions. [Explanation of Symbols]

[0081] 10 Ventilation components 10a Ventilation section 11. Ventilated membrane 11a One main surface 11b The other main surface 12 Support layer 20 Tray Body 21 Bottom 21p Periphery 22 Side 22e bottom edge 22f flange 23 Top 23a opening 23p Periphery 23s back side 30 Inlet 31 Lid receiving part 32 Lid S interior space 100,101 Freeze-drying trays

Claims

1. A tray body having an opening, The tray body has an inlet for injecting liquid material into its internal space, A ventilation member including a ventilation membrane is arranged to close the aforementioned opening, Equipped with, The Gurley air permeability of the aforementioned ventilation member is in the range of 0.10 seconds / 100 mL or more and 3.20 seconds / 100 mL or less. Freeze-drying tray.

2. The aforementioned ventilation membrane includes a porous fluororesin membrane. A freeze-drying tray according to claim 1.

3. The aforementioned fluororesin porous membrane is a polytetrafluoroethylene porous membrane. A freeze-drying tray according to claim 2.

4. The ventilation member further includes a support layer that supports the ventilation membrane. A freeze-drying tray according to claim 1.

5. The tray body has a bottom and sides that extend upward from the periphery of the bottom, The side portion is formed of a resin material, and the bottom portion is formed of a sheet-like member. A freeze-drying tray according to claim 1.

6. The lower end of the side portion has a flange extending outward, and the periphery of the bottom portion is joined to the flange. A freeze-drying tray according to claim 5.

7. When viewed from above, more than 50% of the upper surface of the freeze-drying tray is a ventilation area. A freeze-drying tray according to claim 1.

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