JP2009196666A - Sealing stopper, sealed container, and freeze drying method - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a sealing stopper configured so that ingress of foreign matter is effectively avoided when the contents are taken out, the contents that may be degraded in its quality by moisture absorption are stored while kept dry, to provide a sealing container that has such a sealing stopper, and to further provide a freeze drying method that is achieved using such a sealing stopper and sealed container suitably. <P>SOLUTION: The container is sealed by closing the opening of a container body 10 by means of the sealing stopper 20 that is equipped with a base plate 21 in which a through-hole 21a is made, a cylindrical sidewall 22 extending downward from the base plate 21, a sealing member 30 mounted on the top face of the base plate 21, thereby closing the through-hole 21a, and a moisture absorber 40 held inside the sidewall 22. Thus, the contents M can be stored while kept dry. <P>COPYRIGHT: (C)2009,JPO&INPIT

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.

  The present invention has been made in view of the circumstances as described above, and effectively avoids mixing of foreign matters when taking out the contents, and is in a state where the contents in which the deterioration in quality due to moisture absorption is a concern are dried. It aims at providing the sealing stopper for storing as it is, the sealing container provided with such a sealing stopper, and the freeze-drying method implemented suitably using these.

  The sealing plug according to the present invention is a sealing plug having a moisture absorption function for sealing the opening of the container body in which the dried contents are stored and maintaining the dried state of the contents, and the through hole has a through hole. A perforated substrate, a side wall portion that hangs in a cylindrical shape from the substrate, a seal member that is attached to the top surface side of the substrate and closes the through hole, and is held on the inner side surface of the side wall portion It is the structure provided with a hygroscopic agent.

  Further, in the sealed container according to the present invention, the opening of the container main body is attached to the substrate on which the through-hole is formed, the side wall portion that hangs down in a cylindrical shape from the substrate, and the top surface side of the substrate. The sealing member includes a sealing member that includes a sealing member that closes the through hole and a hygroscopic agent that is held on the inner surface of the side wall.

  In addition, 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, a substrate having a through hole, a side wall portion that hangs in a cylindrical shape from the substrate, and the substrate The container body includes a seal member that is attached to the top surface of the wall and closes the through-hole, and a hygroscopic agent that is held on the inner surface of the side wall portion, and can be sealed with a stopper. The outer diameter of the base portion on the substrate side of the side wall portion is set according to the inner diameter of the opening portion, and the outer diameter of the main portion of the side wall portion excluding the base portion is set with respect to the outer diameter of the base portion. The container main body has a relatively small diameter, and a plurality of protrusions hanging from a step surface formed at the boundary between the base portion and the main portion, and a plurality of protrusions provided on the outer surface of the main portion. The step of placing in contact with the inner periphery of the opening, freezing the aqueous solution Step, the step of sublimating the frozen water is treated under reduced pressure, and stoppered the sealing stopper, is as a method having a step of sealing the opening portion of the container body.

  According to the present invention as described above, in addition to being able to store in a dry state the content that may be deteriorated in quality due to moisture absorption, it is also possible to effectively avoid contamination when removing the content from the container. it can. 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.

[Sealing stoppers and sealed containers]
First, an embodiment of a sealing stopper and a sealing container according to the present invention will be described.
FIG. 1 is a schematic perspective view showing an embodiment of a sealing stopper according to the present invention, and FIG. 2 is a schematic longitudinal sectional view showing an embodiment of a 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. FIG. 2 shows a state in which the sealing plug 20 is placed in the opening of the container main body 10 prior to sealing, and the axes of the container main body 10 and the sealing plug 20 that coincide with each other in this state are indicated by a dashed line in the figure. Yes. Moreover, the cross section of the sealing plug 20 shown in FIG. 2 is equivalent to the AA cross section of FIG.

  The container body 10 has a barrel portion 11 that is molded into a bottomed cylindrical shape and has a substantially constant inner diameter, and a bottom portion 12 that closes one end of the barrel portion 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.

  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 opening slightly larger than the inner diameter of the opening, or by making both diameters 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. At the same time, on the outer surface of the main portion 22b of the side wall portion 22, a plurality of (in the example shown in the figure) hangs substantially flush with the base portion 22a from a step surface 22c formed at the boundary between the base portion 22a and the main portion 22b. Four projections 22d are provided at equal angular intervals along the circumferential direction.

  Thus, when the sealing plug 20 is plugged, when the sealing plug 20 is placed in the opening of the container body 10, as shown in FIG. 2, the protrusion 22d provided on the sealing plug 20 side. Comes into contact with the inner peripheral edge of the opening of the container body 10, and the sealing plug 20 is lifted with respect to the container body 10. Thereby, the inside of the container body 10 can be communicated to the outside through the gap C formed between the inner surface of the container body 10 and the main portion 22b of the side wall portion 22 of the sealing plug 20. This will be described later.

  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.

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 closed by a sealing member 30 attached to the top surface side of the substrate 11 of the sealing plug 2. As the sealing member 30, a metal foil such as an aluminum foil having a low moisture permeability and an excellent gas barrier property is preferably used.

  The sealed container 1 in which the opening of the container body 10 is sealed by the sealing plug 20 is, for example, as shown in FIG. 3 by piercing a hollow cylindrical member 60 having a sharp tip such as an injection needle. The seal member 30 can be opened by cutting. As shown in the figure, the contents M can be taken out by suction or the like through the cylindrical member 60 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. 3 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 that is carried out by suitably using the sealed container 1 having the above-described sealing plug 20 will be described.
FIG. 4 is a process diagram showing an embodiment of a freeze-drying method according to the present invention. In FIG. 4, 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 placed in the opening of the container body 10, and these are transported into the decompression device and cooled to a predetermined temperature, thereby freezing the aqueous solution injected into the container body 10. As a result, the content M (f) is frozen in a state containing moisture (see FIG. 4A).

  Next, the water that has been frozen by processing under reduced pressure is sublimated (see FIG. 4B). At this time, the sealing plug 20 placed in the opening of the container main body 10 is lifted with respect to the container main body 10 as described above, and the inner side surface of the container main body 10 and the side wall portion of the sealing plug 20. The inside of the container body 10 is in communication with the outside through a gap C formed between the main portion 22b of 22 and the main portion 22b. For this reason, discharge of the sublimated water out of the container is not hindered.

  Here, the time when the sealing plug 20 is placed in the opening of the container body 10 may be after the aqueous solution containing the contents M as a solute is frozen, and is sealed when the frozen water is sublimated. If the stopper 20 is mounted in the opening part of the container main body 10, the time in particular will not be restrict | limited. Further, moisture sublimated by freeze-drying is not easily captured by the hygroscopic agent 40, and there is no possibility that the hygroscopic function of the hygroscopic agent 40 is impaired.

Then, after returning to normal pressure with an inert gas such as nitrogen, the sealing plug 20 is plugged. As a result, the dried M (d) in the container is sealed in the container (see FIG. 4C).
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.

  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, four protrusions 22d suspended from the cross section so as to be flush with the base portion 22a are provided at equiangular intervals along the circumferential direction of the main portion 22b. However, the protrusions 22d are provided. The number is not limited to this. Considering the stability when the sealing plug 20 is placed on the opening of the container body 10, it is preferable to provide three or more protrusions 22d symmetrically.

  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 embodiment of the sealing stopper 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 Sealing container 10 Container main body 20 Seal plug 21 Substrate 21a Through-hole 22 Side wall part 22a Base part 22b Main part 22c Step surface 22d Protrusion 30 Seal member 40 Desiccant M Contents

Claims (8)

A sealing plug having a hygroscopic function for sealing the opening of the container body in which the dried contents are stored and maintaining the dried state of the contents,
A substrate having a through-hole formed therein;
A side wall portion that hangs in a cylindrical shape from the substrate;
A seal member attached to the top surface of the substrate and closing the through hole;
And a hygroscopic agent retained on the inner surface of the side wall. In accordance with the inner diameter of the opening of the container main body, the outer diameter of the base portion on the substrate side of the side wall is set so as to enable sealing with a stopper, and
A plurality of portions that hang from a step surface formed at the boundary between the base and the main portion, with the outer diameter of the main portion of the side wall portion excluding the base portion being relatively small with respect to the outer diameter of the base portion. The sealing plug according to claim 1, wherein the protrusion is provided on an outer surface of the main portion. The hygroscopic agent is formed in a cylindrical shape coaxial with the side wall portion, and is held in close contact with the inner side surface of the side wall portion,
The sealing plug according to claim 1, wherein a surface area of the hygroscopic agent is larger than an opening area of the opening of the container body.   The sealing plug according to any one of claims 1 to 3, wherein at least a surface opposite to a side facing the inner surface of the side wall portion of the hygroscopic agent is covered with a moisture-permeable surface protective layer.   The sealing stopper according to any one of claims 1 to 4, comprising an olefin resin.   The sealing stopper according to any one of claims 1 to 5, wherein the hygroscopic agent comprises an olefin resin composition containing at least zeolite. The opening of the container body
A substrate having a through hole, a side wall portion that hangs in a cylindrical shape from the substrate, a seal member that is attached to the top surface of the substrate and closes the through hole, and an inner surface of the side wall portion; A sealed container characterized by being sealed by a sealing stopper provided with a moisture absorbent to be held. Injecting an aqueous solution containing the target substance as a solute into the container body,
A substrate having a through hole, a side wall portion that hangs in a cylindrical shape from the substrate, a seal member that is attached to the top surface of the substrate and closes the through hole, and an inner surface of the side wall portion; An outer diameter of the base portion on the substrate side of the side wall portion according to the inner diameter of the opening portion of the container body, so that sealing with a stopper is possible. The outer diameter of the main portion of the side wall portion excluding the base portion is made relatively small with respect to the outer diameter of the base portion, and is suspended from a step surface formed at the boundary between the base portion and the main portion. Placing a plurality of protrusions on a sealing plug provided on the outer surface of the main part in a state where the protrusions are in contact with the inner peripheral edge of the opening of 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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