JP5151611B2 - Sealed container and freeze-drying method - Google Patents

Description

  The present invention is carried out by using a sealing plug for storing the content in which the quality is liable to be deteriorated due to moisture absorption in a dry state, a sealing container having such a sealing plug, and suitably using them. It relates to a freeze-drying method.

As a container for storing a pharmaceutical product or the like that is liable to be deteriorated in quality due to moisture absorption and storing it in a dry state, for example, Patent Document 1 is sealed with an elastomer closure having a puncturable region, A moisture sensitive container is disclosed in which at least a portion of the closure is made from a desiccant polymer.
JP 2005-218862 A

  In such a container of Patent Document 1, when the contents are taken out, the injection needle is inserted into the puncturable region of the closure, and the periphery of the injection needle is elastically sealed. . Accordingly, there is an advantage that the sealed state can be maintained even when the contents are taken out in a plurality of times.

  However, this is not necessary when the contents are used up once. Rather, when the needle is stabbed, a part of the closure is scraped off at the heel portion of the needle and becomes a foreign matter (core) and mixed into the contents. Such a problem of contamination is not limited to the container of Patent Document 1 and has been pointed out in the past for a pharmaceutical container of this type generally called a vial sealed with a puncturable elastomeric stopper. Therefore, there has been a demand for an alternative to a conventional product that may be contaminated with foreign matter from the viewpoint of preventing medical errors.

  Further, as a means for drying the contents stored in this type of container, it is conceivable to remove moisture by lyophilization and dry the contents. In this case, if the contents can be freeze-dried in a container and sealed and stored as it is, there is no need for transfer and it is convenient. For this reason, it is a form suitable for performing a series of freeze-drying processes in which an aqueous solution containing the contents to be stored as a solute is frozen and treated under reduced pressure to sublimate moisture. desired.

  In addition, the closure disclosed in Patent Document 1 that is partially made from a desiccant polymer may be left in a normal environment before the container is sealed. Moisture content is absorbed and the original moisture absorption function is impaired. For this reason, after manufacture, it must be prepared for use by storing it in a moisture-impermeable container, and if this is neglected, there is a risk that it cannot be used.

  The present invention has been made in view of the circumstances as described above, and effectively avoids contamination of foreign matters when the contents are taken out and the moisture absorption function being impaired before being used for storage of the contents. In addition, the sealing stopper for storing the content in which the quality is liable to be deteriorated due to moisture absorption in a dry state, the sealing container provided with such a sealing stopper, and these are preferably used. The purpose is to provide a freeze-drying method.

The sealing plug provided in the sealed container according to the present invention is a sealing plug having a moisture absorption function for sealing the opening of the container main body in which the dried contents are stored and maintaining the dried state of the contents. A substrate having a through hole, a side wall portion that hangs in a cylindrical shape from the substrate, a moisture absorbent that is held on an inner surface of the side wall portion, and a top surface side of the substrate, A first sealing member that closes the hole and a second sealing member that is attached to the distal end side of the side wall portion and closes the distal end opening of the side wall portion are provided.

  Further, the sealed container according to the present invention is a sealed container having a container main body in which dried contents are accommodated, and a sealing plug for sealing the opening of the container main body, and the sealing plug is penetrated. A substrate having a hole formed therein, a side wall portion hanging from the substrate in a cylindrical shape, a moisture absorbent held on an inner surface of the side wall portion, and a top surface side of the substrate, A first seal member that closes; and a second seal member that is attached to the distal end side of the side wall portion and closes the front end opening of the side wall portion. A perforation member is attached at a predetermined height position, and a vent hole is formed in the second seal member by the perforation member at the time of sealing.

  Further, the freeze-drying method according to the present invention includes a step of injecting an aqueous solution containing a target substance as a solute into a container body having a perforated member attached therein, a substrate having a through hole, and a cylindrical shape from the substrate. A side wall portion depending on the inner surface of the side wall portion, a hygroscopic agent held on the inner side surface of the side wall portion, a first seal member attached to the top surface of the substrate and closing the through hole, and a tip of the side wall portion And a second sealing member that is attached to the side and closes the tip opening of the side wall, and the second sealing member serves as the perforating member. The step of inserting into the opening of the container body, the step of freezing the aqueous solution, the step of sublimating the frozen water by treatment under reduced pressure, so as to come into contact with and float on the container body, Plug the sealing stopper into the container There as a method having a step of sealing the opening of the.

  According to the present invention as described above, in addition to being able to store a content whose quality is likely to be deteriorated due to moisture absorption in a dry state, it can be used for mixing foreign matter when the content is taken out of the container and storing the content. It can be effectively avoided that the moisture absorption function is impaired before being provided. In addition, since a series of freeze-drying steps can be performed without any trouble in the container, it is possible to freeze-dry the contents in the container, and store them in a sealed state without transferring the contents.

  Hereinafter, preferred embodiments of the present invention will be described with reference to the drawings.

[ Sealed container ]
First, an embodiment of a sealed container according to the present invention will be described.
FIG. 1 is a schematic perspective view showing a sealing stopper provided in an embodiment of a sealed container according to the present invention, and FIGS. 2 and 3 are schematic longitudinal sectional views showing an embodiment of the sealed container according to the present invention.

  In the examples shown in these drawings, the sealed container 1 includes a container body 10 and a sealing plug 20 that seals the inside of the container by sealing the opening of the container body 10. 2 shows a state in which the sealing plug 20 is inserted into the opening of the container body 10 prior to sealing, and FIG. 3 shows a state in which the opening of the container body 10 is sealed with the sealing plug 20. The axes of the container body 10 and the sealing plug 20 that coincide with each other in the state are indicated by a one-dot broken line in the figure. Moreover, the cross section of the sealing plug 20 shown in FIG.2 and FIG.3 is equivalent to the AA cross section of FIG.

  The container main body 10 is formed into a cylindrical shape with a bottom and has a cylindrical body 11 and a bottom 12 that closes one end of the cylindrical part 11. An end opposite to the side closed by the bottom portion 12 is an opening, and a flange portion that protrudes substantially horizontally (in a direction perpendicular to the axial direction of the container body 1) to the outside of the container along the periphery thereof. 13 is formed.

  Further, a piercing member 15 is attached to a predetermined height position in the container body 10 by being supported by a step portion 14 formed on the inner side surface of the container body 10 along the circumferential direction. The piercing member 15 includes an annular substrate 15a and a piercing portion 15b that tapers from the substrate 15a. In the illustrated example, two piercing portions 15b that are axially opposed to each other are connected to the inner periphery of the substrate 15a. It is provided on the side.

  Such a piercing member 15 can be fixed to the inner surface of the container body 10 by being crimped and fixed while being supported by the stepped portion 14 by appropriately adjusting the outer diameter of the substrate 15a. Specific attachment means is not particularly limited. You may make it adhere and fix to the inner surface of the container main body 10 using an adhesive agent. However, even in this case, it is preferable to be attached in a state where it is supported by the stepped portion 14, thereby preventing displacement of the piercing member 15 in the height direction (axial direction). .

  In addition, when attaching the piercing member 15 in the container body 10, the height position is determined based on the relative positional relationship with the sealing plug 20, which will be described later together with the function of the piercing member 15. .

  The sealing plug 20 includes a disk-shaped substrate 21 and a side wall portion 22 that hangs down from the substrate 21 in a cylindrical shape. A through hole 21a is formed in a circular shape substantially at the center of the substrate 21, and the side wall portion 22 hangs coaxially with the through hole 21a. And when the opening part of the container main body 10 is sealed with the sealing plug 20, the lower surface 21 b of the substrate 21 positioned on the outer peripheral side of the side wall part 22 is the flange part 13 formed in the opening part of the container main body 10. The top surface 13a is interviewed.

  In sealing the opening of the container body 10, the side wall 22 of the sealing plug 20 is inserted into the container body 10 coaxially with the body 11. At this time, the outer diameter of the base 22a located in the vicinity of the substrate 21 side of the side wall 22 is set according to the inner diameter of the opening of the container main body 10. For example, the outer diameter of the base 22a of the side wall 22 is set to the container main body 10. By making the diameter slightly larger than the inner diameter of the opening or making the diameters of both substantially coincide with each other, sealing with a stopper is possible.

In particular, when the outer diameter of the base portion 22a of the side wall portion 22 is slightly larger than the inner diameter of the opening portion of the container body 10, the outer surface of the base portion 22a of the side wall portion 22 and the container One or both of the inner side surfaces of the opening of the main body 10 can be tapered. It is also possible to seal the base portion 22a and the flange portion 13 using an O-ring or the like.
Further, in addition to sealing by the stopper, or in place of sealing by the stopper, the lower surface 21b of the substrate 21 of the sealing stopper 20 and the top surface 13a of the flange portion 13 of the container body 10 are melted by heat sealing. It is also possible to bond. Furthermore, a rubber sealing agent or the like can be applied and caulked with an aluminum cap or the like.

  Further, the outer diameter of the main portion 22b excluding the base portion 22a of the side wall portion 22 is set to be relatively small with respect to the outer diameter of the base portion 22a of the side wall portion 22 so as to be smaller than the inner diameter of the container body 10. A step surface 22c perpendicular to the axial direction of the sealing plug 20 is formed at the boundary between 22a and the main portion 22b.

  Each of the container body 10 and the sealing plug 20 as described above is injection-molded using various thermoplastic resins such as a polyester resin such as polyethylene terephthalate, a polyamide resin such as nylon, and a polyolefin resin such as polypropylene. It can be formed into a predetermined shape by appropriate forming means. In order to avoid moisture permeation from the outside into the container, it is preferable to select a resin material with low moisture permeability as appropriate, and as necessary to avoid moisture permeation into the container more effectively. It is also possible to have a multilayer structure. Although depending on the moisture permeability of the selected resin material, the average thickness is preferably about 0.3 to 5 mm in consideration of moldability and handling. Further, considering that the opening of the container body 10 is sealed with the sealing plug 20 by a stopper, the sealing plug 20 is preferably molded using a polyolefin resin having excellent fitting properties.

  The piercing member 15 attached to the container body 10 can be molded using the same resin material as the container body 10 and the sealing plug 20, but the moisture permeability of the piercing member 15 itself is not particularly problematic. Therefore, the container body 10 and the sealing plug 20 may be molded using different types of resin materials. However, considering that it is pressure-bonded and fixed in the container body 10, it is preferable to mold using a polyolefin-based resin having excellent fitting properties, like the sealing plug 20.

As a resin material used for the container body 10 and the sealing stopper 20, a more specific example of a resin material having low moisture permeability is a cyclic olefin copolymer (COC). As the cyclic olefin copolymer resin, an amorphous or low crystalline copolymer of an olefin and a cyclic olefin is preferably used. Ethylene is preferred as the olefin, but other olefins having 3 to 20 carbon atoms such as propylene, 1-butene, 1-pentene, 1-hexene, 1-octene, 3-methyl 1-pentene, 1-decene, etc. The α-olefin can be used alone or in combination with ethylene. The cyclic olefin includes an alicyclic hydrocarbon compound having an ethylenically unsaturated bond and a bicyclo ring, particularly bicyclo [2,2,1] hept-2-ene, tetracyclo [4,4,0,12. , 5,17,10] -3-dodecene and the like, and ethylene-cyclic olefin copolymer is particularly preferable, but the cyclic olefin content in the ethylene-cyclic olefin copolymer is 10 to 50 mol. %, Particularly 12 to 45 mol% is preferred.
Furthermore, you may coat | cover an inorganic thin film, after shape | molding using the resin material mentioned above. As the inorganic thin film, silicon oxide (SiOx) or the like is preferable, and it can be coated by a known PVD method or CVD method.
The resin material used for the container body 10 and the sealing plug 20 may be blended with an antistatic agent such as a polyoxyethylene alkylamine mixed composition, glycerin fatty acid ester, and linear fatty acid saturated monohydric alcohol.

Further, a hygroscopic agent 40 is held on the inner side surface of the side wall portion 22 provided to hang from the sealing plug 20. As a result, a moisture absorbing function for maintaining the dry state of the contents M accommodated in the container body 10 is imparted to the sealing plug 20.
The moisture absorbent 40 is composed of low density polyethylene (LDPE), linear low density polyethylene (LLDPE), ethylene-acrylic acid copolymer (EAA), ethylene-acrylic acid ester copolymer (EAE), ethylene-methacrylic acid copolymer. It can be molded into a predetermined shape by using a resin material obtained by blending at least a hygroscopic material such as zeolite with a polyolefin resin such as a polymer (EMAA). For example, as shown in the drawing, it can be formed into a cylindrical shape coaxial with the side wall portion 22 and can be held in close contact with the inner side surface of the side wall portion 22. Thereby, the hygroscopic agent 40 can be hold | maintained, without providing a special holding means. In addition, the outer surface of the hygroscopic agent 40 can be protected by the side wall portion 22 by being held in close contact with the inner side surface of the side wall portion 22, and the hygroscopic function from the inner side surface of the hygroscopic agent 40 is prioritized. It is possible to demonstrate it.

The zeolite blended as the hygroscopic material preferably has an average particle size of 5 to 70 μm. When it exceeds 70 μm, the total surface area becomes small, and it tends to be difficult to obtain a desired moisture absorption function. On the other hand, if it is less than 5 μm, it tends to condense and secondary particles having a large diameter are produced, and the total surface area tends to be reduced. Moreover, it is preferable that the compounding quantity of a zeolite is 0.1 to 50 weight%. When it exceeds 50% by weight, the moisture absorption is too large and the foam tends to be easily foamed. On the other hand, if it is less than 0.1% by weight, it tends to be difficult to obtain a desired moisture absorption function.
In addition to zeolite, additives such as an antioxidant and a lubricant may be appropriately blended in the resin material forming the hygroscopic agent 40 as necessary.

When providing the hygroscopic function to the sealing plug 20 with such a hygroscopic agent 40, the surface area of the hygroscopic agent 40 is preferably larger than the opening area of the opening of the container body 10. Thereby, the moisture absorption function provided to the sealing plug 20 can be made better. In particular, by increasing the surface area of the hygroscopic agent 40, the initial hygroscopic rate can be improved, whereby the hygroscopic function of the hygroscopic agent 40 is exhibited before the contents M absorb moisture. Is possible.
Moreover, the maximum moisture absorption amount of the hygroscopic agent 40 is determined by the thickness and surface area of the hygroscopic agent 40, and each can be freely changed according to the application.

  Although not particularly illustrated, in order to prevent the contents M from directly touching the moisture absorbent 40, at least the surface opposite to the side facing the inner surface of the side wall portion 22 of the moisture absorbent 40 is disposed on the moisture absorbent 40. It is also possible to cover the surface with a surface protective layer 41 having a moisture permeability that does not inhibit the moisture absorption function. Such a surface protective layer 41 includes, for example, low density polyethylene (LDPE), linear low density polyethylene (LLDPE), ethylene-vinyl acetate copolymer (EVA), ethylene-acrylic acid copolymer (EAA), ethylene. -It is preferable to laminate and form about 5-50 micrometers in thickness using polyolefin resin, such as an acrylic ester copolymer (EAE), an ionomer, and ethylene-methacrylic acid copolymer (EMAA). Furthermore, the resin material used for the surface protective layer 41 may be blended with an antistatic agent such as a polyoxyethylene alkylamine mixed composition, a glycerin fatty acid ester, and a linear fatty acid saturated monohydric alcohol.

  Further, a through hole 21 a is formed in the substrate 21 of the sealing plug 20, and this through hole 21 a is blocked by a first sealing member 30 attached to the top surface side of the substrate 21 of the sealing plug 20. Yes. Further, a similar seal member 31 is also attached to the front end side of the side wall portion 22 depending from the substrate 21 of the sealing plug 20, and the front end opening of the side wall portion 22 is closed by the second seal member 31. Yes. As the sealing members 30 and 31, a metal foil such as an aluminum foil having a low moisture permeability and an excellent gas barrier property is preferably used.

By doing in this way, the hygroscopic agent 40 hold | maintained at the inner surface of the side wall part 22 is isolated from the external environment by the sealing members 30 and 31. FIG. For this reason, even if the sealing plug 20 is left as it is in a normal environment at the time of storage, it is possible to effectively avoid that the original moisture absorbing function of the moisture absorbent 40 is impaired. it can.
In addition, the piercing member 15 as described above is attached in the container main body 10, and when the opening of the container main body 10 is sealed with the sealing plug 20, as shown in FIG. By the perforated portion 15b, a vent hole 31a is formed in the seal member 31 attached to the distal end side of the side wall portion 22, so that the moisture absorbing function of the moisture absorbent 40 is exhibited.

  Here, in the illustrated example, the axial length of the hygroscopic agent 40 is made shorter than the axial length of the side wall portion 22 to avoid interference between the hygroscopic agent 40 and the perforated portion 15b. If there is a dimensional relationship that allows the perforated portion 15b to enter the inner surface side of the moisture absorbent 40, there is no such need. In such a case, the length of the hygroscopic agent 40 in the axial direction may be equal to the length of the side wall 22 in the axial direction. Further, when the vent hole 31a is formed in the sealing member 31 attached to the distal end side of the side wall portion 22 of the sealing plug 20 by the perforated portion 15b, the air permeability with the sealing plug 20 having a moisture absorption function is improved. Therefore, a ventilation groove may be provided on the side surface of the perforated part 15b.

  The position where the piercing member 15 is mounted in the container body 10 is determined based on the relative positional relationship with the sealing plug 20 as described above, but the position where the piercing member 15 is mounted is the position of the container body 10. When sealing the opening with the sealing plug 20, the vent hole 31 a is appropriately set at a position where the vent hole 31 a can be drilled in the seal member 31 attached to the distal end side of the side wall portion 22 by the perforated portion 15 b of the perforated member 51. do it.

  Further, in the piercing member 15, when the side wall portion 22 of the sealing plug 20 is inserted into the opening of the container body 10, the seal member 31 comes into contact with the tip of the piercing portion 15 b of the piercing member 15 as shown in FIG. 2. Accordingly, the sealing plug 20 is attached to a position where the sealing plug 20 is lifted with respect to the container body 10 so that the step surface 22c of the side wall portion 22 is higher than the top surface 13a of the flange portion 13 of the container body 10. Is preferred. Thereby, the inside of the container main body 10 can be communicated with the outside through the gap C formed between the container main body 10 and the sealing plug 20, which will be described later.

  Further, the sealed container 1 in which the opening of the container body 10 is sealed by the sealing plug 20 is, for example, pierced with a hollow cylindrical member 60 having a sharp tip such as an injection needle as shown in FIG. The seal member 30 can be opened by cutting. Then, as shown in the figure, the contents M can be taken out by suction or the like through a cylindrical member 60 that passes through the seal members 30 and 31 and is inserted into the container. Thereby, it is possible to effectively avoid the contamination of foreign matter (the scraped piece of the stopper), which has been regarded as a problem in a vial sealed with a conventional elastomeric stopper.

  Here, FIG. 4 is an explanatory view showing an example of taking out the contents M from the sealed container 1. As specific modes for taking out the contents M from the sealed container 1, various modes such as dissolving the contents M in an appropriate solvent and sucking them can be considered.

[Freeze drying method]
Next, an embodiment of a freeze-drying method according to the present invention, which is preferably performed using the above-described sealed container 1 will be described.
FIG. 5 is a process diagram showing an embodiment of a freeze-drying method according to the present invention. In FIG. 5, the content frozen in a state including moisture in the process of freeze-drying is indicated by a symbol M (f), The contents made dry by sublimating the frozen water are indicated by a symbol M (d).

  In carrying out the freeze-drying method of this embodiment, first, an aqueous solution containing the content M (target substance) to be stored in the sealed container 1 as a solute is prepared, and this is injected into the container body 10. Next, the sealing plug 20 is inserted into the opening of the container body 10, these are transported into the decompression device, and cooled to a predetermined temperature, thereby freezing the aqueous solution injected into the container body 10. Thereby, the content M (f) is frozen in a state containing moisture (see FIG. 5A).

  Next, the frozen moisture is sublimated by treatment under reduced pressure (see FIG. 5B). At this time, the sealing plug 20 inserted into the opening of the container main body 10 is lifted with respect to the container main body 10 as described above, and a gap formed between the container main body 10 and the sealing plug 20. Through C, the inside of the container body 10 is in communication with the outside. For this reason, discharge of the sublimated water out of the container is not hindered.

  Here, the timing when the sealing plug 20 is inserted into the opening of the container body 10 may be after the aqueous solution containing the contents M as a solute is frozen, and when the frozen water is sublimated, the sealing plug 20 is inserted. If 20 is inserted in the opening part of the container main body 10, the time will not be restrict | limited in particular.

Then, after returning to normal pressure with an inert gas such as nitrogen, the sealing plug 20 is plugged. As a result, the dried inside M (d) of the container is sealed in the container, and at the same time, the vent hole 31a is formed in the sealing member 31 by the perforating member 15, and the moisture absorption of the hygroscopic agent 40 is here for the first time. The function is exhibited (see FIG. 5C).
By doing in this way, the contents M can be lyophilized in the container without hindrance, sealed and stored as it is, and there is no need to transfer the container after lyophilization. In addition, the moisture absorbent 40 is isolated from the external environment until the opening of the container body 10 is sealed with the sealing plug 20, so that the moisture absorbing function is impaired before the contents M are stored. It won't get lost.

  While the present invention has been described with reference to the preferred embodiment, the present invention is not limited to the above-described embodiment, and various modifications can be made without departing from the spirit of the present invention. Needless to say.

  For example, in the above-described embodiment, the barrel portion 11 of the container body 10 and the side wall portion 22 provided on the sealing plug 20 so as to hang from the substrate 21 are cylindrical, but as long as these are cylindrical, a rectangular tube shape is used. It may be.

  In the above-described embodiment, the number of the perforated portions 15b provided in the perforated member 15 is two in opposition to the axial symmetry, but the number of the perforated portions 15b is arbitrary. However, if the number of air holes formed in the seal member 31 increases, fragments of the seal member 31 may fall off and be mixed into the contents M. In particular, when the contents are to be taken out as shown in FIG. 4, it is conceivable that when the tubular member 60 penetrates the seal member 31, a fragment of the seal member 31 is dropped. For this reason, the specific shape of the perforated part 15b and the number of the perforated parts 15b provided depend on the diameter of the cylindrical member 60 assumed to be used when the contents M are taken out. It is preferable to set as appropriate to such an extent that fragments do not fall off.

  As described above, the present invention is widely used not only in cases where pharmaceuticals are used as contents, but also in other fields such as foodstuffs, as a technique for storing contents in which deterioration in quality due to moisture absorption is a concern. be able to.

It is a schematic perspective view which shows the sealing stopper with which embodiment of the sealed container which concerns on this invention is provided . It is a schematic longitudinal cross-sectional view which shows embodiment of the sealed container which concerns on this invention. It is a schematic longitudinal cross-sectional view which shows embodiment of the sealed container which concerns on this invention. In embodiment of the sealed container which concerns on this invention, it is explanatory drawing which shows the example which takes out the content. It is process drawing which shows embodiment of the freeze-drying method which concerns on this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Sealed container 10 Container main body 14 Step part 15 Perforated member 15a Substrate 15b Perforated part 20 Seal plug 21 Substrate 21a Through hole 22 Side wall part 22a Base part 30 Seal member (first seal member)
31 Seal member (second seal member)
31a Ventilation hole 40 Desiccant M Contents

Claims (4)

A sealed container having a container main body in which dried contents are stored, and a sealing plug for sealing an opening of the container main body,
The sealing plug is attached to a substrate having a through hole, a side wall portion that hangs in a cylindrical shape from the substrate, a moisture absorbent held on an inner surface of the side wall portion, and a top surface side of the substrate. A first seal member that closes the through hole, and a second seal member that is attached to the distal end side of the side wall portion and closes the front end opening of the side wall portion,
In the container body, a piercing member is attached at a predetermined height position in the container body,
A sealed container characterized in that a vent hole is formed in the second sealing member by the perforating member when sealing. The sealed container according to claim 1 , wherein the piercing member includes an annular substrate and a piercing portion that stands up from the substrate. Wherein the inner surface of the container body along the circumferential direction to form a stepped portion, sealed container according the any one of piercing claims members were allowed to support 1 or 2 in the stepped portion. Injecting an aqueous solution containing the target substance as a solute into a container body having a perforated member attached therein;
A substrate having a through-hole formed therein, a side wall portion hanging from the substrate in a cylindrical shape, a moisture absorbent held on an inner surface of the side wall portion, and the through-hole attached to the top surface side of the substrate And a second seal member attached to the front end side of the side wall portion and closing the front end opening of the side wall portion, and can be sealed with a stopper. Inserting the sealing plug into the opening of the container body so that the second sealing member is in contact with the perforating member and is in a state of being lifted with respect to the container body;
Freezing the aqueous solution;
A process of sublimating the frozen water by treatment under reduced pressure,
A freeze-drying method characterized by comprising a step of sealing the opening of the container body by plugging the sealing plug.

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