JP2001106242A5

JP2001106242A5 -

Info

Publication number: JP2001106242A5
Application number: JP1999285796A
Authority: JP
Filing date: 1999-10-06
Publication date: 2005-10-27

Description

【０００４】
【発明が解決しようとする課題】
上記のような従来の凍結乾燥容器では、凍結乾燥庫からの取出し、及び密閉容器への詰替えの間において、処理済の被乾燥材料が周辺環境（外気）に暴露され、ちりや雑菌（塵埃や微生物）などの異物が入り込む危険性があった。さらに、従来の凍結乾燥容器を用いたバルク凍結乾燥方法では、被乾燥材料がバイアルを用いたバイアル凍結乾燥方法に比べて大気と接触する面積が大きいので、異物の混入だけでなく水分の増加や、被乾燥材料の酸化による含有量の低下を引き起こすという問題点があった。 0004
[Problems to be Solved by the Invention]
In the conventional freeze-drying container as described above, the treated material to be dried is exposed to the surrounding environment (outside air) during removal from the freeze-drying container and refilling into a closed container, and dust and germs (dust) are exposed. There was a risk of foreign matter such as ( or microorganisms) entering. Furthermore, in the conventional bulk freeze-drying method using a freeze-drying container, the area in which the material to be dried comes into contact with the atmosphere is larger than that in the vial freeze-drying method using a vial. , There is a problem that the content is lowered due to oxidation of the material to be dried.

上記のような問題点を解決しようとした従来の凍結乾燥容器としては、例えば簡単な操作で封止し、異物の混入を防止し得る封止機構付き凍結乾燥トレイが提案されている（実開平７−４１３９５号公報参照）。また、少なくともその一部が、疎水性で多孔性の、菌密でありながら水蒸気透過性の膜で作られ管または袋として構成された容器も提案されている（特公平４−５０８３０号公報参照）。しかしながら、前者の封止機構付き凍結乾燥トレイは、繰り返しての使用を前提としているため、その清浄化や滅菌のために多くの人手を要した。また、後者の菌密で水蒸気透過性の膜で作られ管または袋は、使い捨て可能であるので人手を要しないが、処理後の水分の増加を防ぐことは困難なものであった。 The freeze drying vessel prior to attempting to solve the above problem, for example, sealed with a simple operation, freeze drying trays with sealing mechanism capable of preventing foreign substances have been proposed (real Hei 7-41395 (see). In addition, a container in which at least a part thereof is made of a hydrophobic, porous, bacterially dense but water vapor permeable membrane and formed as a tube or a bag has also been proposed (see Japanese Patent Publication No. 4-50830). ). However, since the former freeze-drying tray with a sealing mechanism is premised on repeated use, a lot of manpower is required for its cleaning and sterilization. Further, the latter tube or bag made of a dense and water vapor permeable membrane is disposable and does not require manpower, but it is difficult to prevent an increase in water content after the treatment.

この発明は、上記のような問題点を解決するためになされたものであり、処理済の被乾燥材料が周辺環境の外気に接触する機会を最小にして、ちりや雑菌などの異物の混入だけでなく、吸湿による水分の増加や被乾燥材料の酸化による含有量の低下を極力抑制できる凍結乾燥容器、及びそれを用いた凍結乾燥方法を提供することを目的とする。 The present invention has been made to solve the above-mentioned problems, minimizing the chance that the treated material to be dried comes into contact with the outside air of the surrounding environment, and only mixing foreign substances such as dust and germs. Instead, it is an object of the present invention to provide a freeze-drying container capable of suppressing an increase in water content due to moisture absorption and a decrease in content due to oxidation of a material to be dried as much as possible, and a freeze-drying method using the same.

《実施例》
図１は本発明の実施例である凍結乾燥容器の構成を示す斜視図であり、図２は図１に示したポ−トの半打栓状態での構成を示す拡大断面図である。図１及び図２において、本実施例の凍結乾燥容器１０は、被乾燥材料を密封して収容するための気密及び液密な可撓性材料からなる袋体２０と、前記袋体２０に気密及び液密に取り付けられ、少なくとも半打栓状態及び完全打栓状態の二状態を採り得るポート３０とを備えている。尚、被乾燥材料は、液体の状態でポート３０から袋体２０に分注され、後に詳述するように凍結乾燥庫内で凍結乾燥処理されて、凍結乾燥容器に密封された状態で凍結乾燥庫から取り出される。被乾燥材料の具体例には、例えば２７％の「フルマリン」（登録商標）溶液である注射用フロモキセフナトリウム水溶液がある。 "Example"
FIG. 1 is a perspective view showing the configuration of a freeze-drying container according to an embodiment of the present invention, and FIG. 2 is an enlarged cross-sectional view showing the configuration of the port shown in FIG. 1 in a semi-plugged state. In FIGS. 1 and 2, the freeze-drying container 10 of the present embodiment is airtight in a bag body 20 made of an airtight and liquid-tight flexible material for sealing and accommodating the material to be dried, and the bag body 20. And a port 30 that is airtightly mounted and can take at least two states, a semi-plugged state and a fully plugged state. The material to be dried is dispensed from the port 30 into the bag body 20 in a liquid state, freeze-dried in a freeze-drying chamber as described in detail later, and freeze-dried in a state of being sealed in a freeze-drying container. Taken out of the warehouse. Specific examples of the material to be dried include, for example , an aqueous solution of flomoxef sodium for injection , which is a 27% "flumarin" (registered trademark) solution.

以下、本実施例の凍結乾燥容器１０を用いた凍結乾燥方法について、図５の（ａ）及び図５の（ｂ）を参照して説明する。図５の（ａ）は図１に示した凍結乾燥容器を凍結乾燥庫内に配置して、所定の凍結乾燥処理を実施しているときの状態を示す説明図であり、図５の（ｂ）は同凍結乾燥処理を終了してポートを完全打栓状態としたときの状態を示す説明図である。図５の（ａ）において、凍結乾燥容器１０は、被乾燥材料１１を袋体２０の内部に入れた状態、かつポート３０が半打栓状態で凍結乾燥庫の棚板５０上に配置されている。凍結乾燥庫は、公知の汎用的な凍結乾燥庫が利用され、その内部には、外部からの遠隔操作によって上下方向に移動可能な棚板５１が設けられている。さらに、この凍結乾燥庫の内部には、好ましくは二つの高さ調節用治具である高さ調整ゲージ５２が凍結乾燥容器１０を挟むように配置されている。 Hereinafter, the freeze-drying method using the freeze-drying container 10 of this example will be described with reference to (a) of FIG. 5 and (b) of FIG. FIG. 5A is an explanatory view showing a state when the freeze-drying container shown in FIG. 1 is arranged in the freeze-drying chamber and a predetermined freeze-drying treatment is performed, and FIG. 5B is shown in FIG. ) Is an explanatory diagram showing a state when the freeze-drying process is completed and the port is in a completely plugged state. In FIG. 5A, the freeze-drying container 10 is arranged on the shelf board 50 of the freeze-drying cabinet with the material to be dried 11 inside the bag body 20 and the port 30 in a semi-plugged state. There is. As the freeze-drying cabinet, a known general-purpose freeze-drying cabinet is used, and a shelf board 51 that can be moved in the vertical direction by remote control from the outside is provided inside the freeze-drying cabinet. Further, inside the freeze-drying cabinet, preferably, two height adjusting gauges 52, which are height adjusting jigs, are arranged so as to sandwich the freeze-drying container 10.

図５の（ｂ）に示した完全打栓状態では、ちりや雑菌などの異物が凍結乾燥容器１０内の処理済の被乾燥材料１１に混入するおそれはほとんどない。このため、完全打栓状態とした後は、凍結乾燥庫の周囲環境に影響されることなく、凍結乾燥容器１０を凍結乾燥庫から取出すことができる。尚、発明者等は、上述の凍結乾燥容器１０（容量２Ｌまたは２.５Ｌ、ポ−トの開口直径９.５ｃｍ、通気孔合計面積７０.８ｃｍ^２）を液体の被凍結乾燥試料で充填し、凍結乾燥庫内で予備凍結：−４０℃、４時間、一次乾燥：−２℃、１０Ｐａ、８０時間以上、二次乾燥：６０℃、２Ｐａ、１０時間の条件で凍結乾燥処理を行った。そして、それらの処理の後、凍結乾燥庫内でポート３０を完全打栓状態とした。その後、袋体２０を開封して検査したところ、完全に無菌で異物の混入がないことを確認した。

In the completely plugged state shown in FIG. 5 (b), there is almost no possibility that foreign substances such as dust and germs are mixed in the processed material 11 to be dried in the freeze-drying container 10. Therefore, the freeze-drying container 10 can be taken out from the freeze-drying container without being affected by the surrounding environment of the freeze-drying container after the completely plugged state. The inventors have filled the above-mentioned freeze-drying container 10 (capacity 2L or 2.5L, port opening diameter 9.5 cm, total vent hole area 70.8 cm ² ) with a liquid freeze-dried sample. Preliminary freezing: −40 ° C. for 4 hours, primary drying: -2 ° C., 10 Pa, 80 hours or more, secondary drying: 60 ° C., 2 Pa, 10 hours. Then, after those treatments, the port 30 was completely plugged in the freeze-drying chamber. After that, when the bag body 20 was opened and inspected, it was confirmed that the bag body 20 was completely sterile and free from foreign matter.

Claims

It is provided with a bag body for sealing and accommodating the material to be dried, and a port that is airtightly and liquid-tightly attached to the bag body and can take at least two states, a semi-plugged state and a fully plugged state. Freeze-drying container.

Bag is constituted by a flexible material, further a metal film layer, the metal film layer in contact disposed inside the pouch, inert resin layer which is inert to the dried material, and the metal The freeze-drying container according to claim 1, further comprising a reinforcing resin layer provided on the outside of the bag in contact with the film layer.

Lyophilization container according to claim 2, characterized in that metallic film layer is made of aluminum.

Lyophilization container according to claim 2, characterized in that inactive resin layer is constituted by a low density polyethylene (LDPE).

Lyophilization container according to claim 2, characterized in that it is constituted by a preparative (PET) - reinforcement resin layer is polyethylene Terefutare.

The port comprises a lid and a pedestal that is secured to a portion of the bag with a hole suitable for insertion of the lid.
Lyophilization container according to claim 1 in accordance with the relative position of the seat body and the lid, characterized in that a half strokes plug state and a fully stoppered state.

Port - DOO is, high or low density polyethylene (LDPE or HDPE), polyethylene Terefutare - claim DOO (PET), polypropylene (PP), or characterized in that it is formed of a resin material that combines these 6 The freeze-drying container described in.

The lid is provided around the disk-shaped top, a substantially cylindrical side wall having a stepped diameter-expanded portion at the connection with the top, and the vicinity of the lower end of the side wall. It is provided with a first annular protrusion protruding outward, and a plurality of ventilation holes provided between the connection portion of the side wall portion with the top and the first annular protrusion. The lyophilization container according to claim 6 or 7.

Enlarged diameter portion a stepped, lyophilization container according to claim 8, wherein the provided so as to surround the vicinity of the lower end of the stepped increased diameter portion, and having a second annular projection which projects outwardly ..

Accept the seat body, surrounds the hole of the seat body, said ring cylindrical portion on the inner peripheral surface with a matching annular groove in the first annular projection of the cover of the hole, and the hole in the opposite direction of the The freeze-drying container according to claim 6 or 7, further comprising a plurality of legs extending from the ring-cylindrical portion.

A freeze-drying method according to any one of claims 1 to 10, wherein a predetermined freeze-drying treatment is performed on the material to be dried contained in the freeze-drying container.

This is a freeze-drying method in which the material to be dried is placed in a freeze-drying container equipped with a port capable of taking at least two states, a semi-stopped state and a completely plugged state, and a predetermined freeze-drying treatment is performed in the freeze-drying chamber. hand,
After the freeze-drying step of performing the freeze-drying treatment and the freeze-drying step are completed with the port in a semi-plugged state, the port is changed from a half-plugged state to a completely plugged state in the freeze-drying chamber. A freeze-drying method comprising a step of sealing the inside of the.