JP4691773B2

JP4691773B2 - Drug enclosing container set and manufacturing method thereof

Info

Publication number: JP4691773B2
Application number: JP2000321487A
Authority: JP
Inventors: 耕司梅北
Original assignee: Ajinomoto Co Inc
Current assignee: Ajinomoto Co Inc
Priority date: 2000-10-20
Filing date: 2000-10-20
Publication date: 2011-06-01
Anticipated expiration: 2020-10-20
Also published as: JP2002126039A

Description

【０００１】
【発明の属する技術分野】
本発明は、複数の薬剤（溶液の場合と、粉末、粒状等の固体の場合とを含む）封入容器が閉鎖された連通機構を介し連結される薬剤封入容器セットに関する。本発明は、特に薬剤封入バイアルと可撓性バッグが閉鎖された連通機構を介して連結され使用直前に手動によりバイアル内の薬剤が無菌的に薬液に混合可能な薬剤封入容器セットに関する。本発明は、更に滅菌又は殺菌工程数を最少にし且つ滅菌又は殺菌工程を改良した薬剤封入容器セットの製造方法に関する。
【０００２】
【従来の技術】
病院等の医療機関において、点滴により患者の静脈に投与されるビタミン剤、微量元素製剤等の複数の薬剤は、配合変化による品質劣化を生じないよう投与直前に輸液等の薬液に混合して投与される。この混合作業を簡便且つ無菌的に行なえるよう、従来種々の薬剤封入容器セット及びその製造方法の工夫がなされてきた。
【０００３】
特開平１０−２４０８８号は、無菌保証が成された状態で、薬剤封入バイアル等を少ない部品で簡易に接続した輸液容器を提供することを目的とした薬剤封入容器セットを開示する。この薬剤封入容器セットは、樹脂製容器であり複数の室を有し、室と室との隔離条部の少なくとも一部が外側から開放可能なピールシール部又は弱シール部で形成され、第１室に薬液が収容され、第２室に充填容器が接続され、充填容器は薬液に混合される薬剤を収容し、充填容器の開口を閉じる蓋体又は膜体が第２室の外側から押圧することにより充填容器内へ押し込むことが可能であり、蓋体又は膜体が充填容器内へ押し込まれることにより第２室内と充填容器内が連通される。高圧蒸気滅菌処理した樹脂製容器と薬剤を収容したバイアルは、無菌、無塵室内で接続され、その後第２室のみが電子照射滅菌され、第２室内の一旦外界に晒された充填容器の外面と共に滅菌処理される。
【０００４】
実公平６−４２６７６号公報は、バイアル中の薬剤を、容易且つ安全にバッグ内の点滴用薬液に添加する目的の輸液バッグを開示する。この輸液バッグは、ゴム栓によって封止されたバイアルの口部を接続可能な口部材を有する。口部材は、外周面下部が合成樹脂製シートの一方の開口端に融着され、下端が封止膜により密閉され、上部外周に雄ネジを備える有底円筒状部品３、有底円筒状部品に挿入され、上端が閉塞され、この閉塞された部分を貫通して、先端が穿刺刃の中空針６が固定され、下端が穿刺刃である棒状部品４、有底円筒状部品の雄ネジに螺合する雌ネジを備える下部小径部及び小径部と区画部を介して一体成形されバイアルの口部が嵌合される大径部を有し区画部を中空針が刺通する第２部品５、並びに第２部品の大径部の開口端を閉塞するシール１０を有する。先端が穿刺刃である代わりに棒状部品の端部に固定したゴム栓６３を設けることができる。
【０００５】
【発明が解決しようとする課題】
本発明の目的は、第１薬剤封入容器、１又は複数の第２薬剤封入容器、及び第１薬剤封入容器と第２薬剤封入容器を連結する閉鎖された連通機構を備え、閉鎖された連通機構は、第１薬剤封入容器又は第２薬剤封入容器の外部から手動により液体連通状態にすることができる薬剤封入容器セットを提供することである。特に薬剤封入バイアルと可撓性輸液バッグが閉鎖された連通機構により連結された薬剤封入容器セットを提供し、閉鎖された連通機構が薬剤の使用直前に手動により異物を発生することなく無菌的に開放され両容器内の薬剤を迅速且つ容易に混合、調製することが可能な薬剤封入容器セットを提供することである。本発明の他の目的は、あらかじめ第２薬剤封入容器に無菌的に収容された品質劣化し易い薬剤について、第１薬剤封入容器と同時に滅菌又は殺菌し、その際受ける加熱又は電子線、γ線、紫外線等の照射の影響から保護可能な薬剤封入容器セットを提供することである。
【０００６】
本発明の別の目的は、第１薬剤封入容器、１又は複数の第２薬剤封入容器、及び第１薬剤封入容器と第２薬剤封入容器を連結する閉鎖された連通機構を備え、閉鎖された連通機構は、第１薬剤封入容器又は第２薬剤封入容器の外部から手動により異物を生じることなく液体連通状態にすることができる薬剤封入容器セットを、滅菌又は殺菌工程を簡略化し容易且つ能率的に製造可能な製造方法を提供することである。特に滅菌又は殺菌工程で使用される高熱、電子線、γ線、紫外線等に対する耐性の異なる薬剤を収容する第１薬剤封入容器及び第２薬剤封入容器を同時に滅菌又は殺菌処理することにより製造工程を簡略化することにある。
【０００７】
本発明の更に別の目的は、第１薬剤封入容器と第２薬剤封入容器を連結する閉鎖された連通機構を備える薬剤封入容器セットにおいて、閉鎖された連通機構の構成を改良し、薬剤封入容器セットの保管又は運搬時に第１薬剤封入容器と第２薬剤封入容器の液体連通を確実に遮断することができ、且つ薬剤投与直前に外部から手動で異物を発生することなく容易且つ確実に連通機構を液体連通可能状態に操作することができるようにすることである。本発明のその他の目的及び利点は、以下の説明において明かにされる。
【０００８】
【課題を解決するための手段】
本発明は、各請求項に記載の特徴を有する。第１に、本発明の薬剤封入容器セットを製造する方法は、第１薬剤封入容器と第２薬剤封入容器が閉鎖された連通機構により連結され、閉鎖された連通機構は、手動により連通状態にすることができる薬剤封入容器セットを製造する。この製造方法は、１又は複数の第２薬剤封入容器と第１薬剤封入容器を閉鎖された連通機構を介し連結する工程、１又は複数の第２薬剤封入容器の外面の少なくとも一部を保護体により覆う工程、並びに連結された第１薬剤封入容器及び保護体により覆われた第２薬剤封入容器を同時に加熱、電子線、γ線又は紫外線により滅菌又は殺菌処理し薬剤封入容器セットを滅菌又は殺菌する工程を含む。保護体は、滅菌又は殺菌工程の加熱、電子線、γ線、紫外線等による薬剤の品質劣化を防止する。本発明の薬剤封入容器セットを製造する方法において、閉鎖された連通機構は、第１薬剤封入容器と前記バイアルを連通する通路、該通路を閉鎖する閉鎖体、及び閉鎖体を移動させる手段を含む。
【０００９】
本発明の薬剤封入容器セットを製造する方法は、次の特徴を備えることができる。（１）第２薬剤封入容器に収容される薬剤の耐熱温度が、第２薬剤封入容器に収容される薬剤の耐熱温度より低い。（２）滅菌又は殺菌工程が高圧蒸気滅菌又は熱水シャワー滅菌により行われる。（３）保護体は、断熱体からなり、この断熱体は、樹脂製断熱材、セラミック、密閉空間、又は第２薬剤封入容器の外面に隣接する冷却材からなる。（４）断熱体は、滅菌又は殺菌工程において第２薬剤封入容器の薬剤に対する加熱処理の影響を軽減する性能を備える。（５）滅菌又は殺菌工程は、電子線、γ線又は紫外線を容器セット全体へ照射することにより行われ、保護体は、電子線、γ線又は紫外線の遮蔽体、即ち電子線、γ線又は紫外線を透過させないか又は僅かの量だけ透過させる金属体、ガラス、樹脂等によりなる。（６）第２薬剤封入容器は、薬剤を封入したガラス又は樹脂製のバイアルである。（７）閉鎖された連通機構は、第１薬剤封入容器と前記バイアルを連通する通路、該通路を閉鎖する閉鎖体、閉鎖体を移動させるか又は閉鎖体に貫通路を形成し通路を開通させる手段を含む。（８）第１薬剤封入容器は、閉鎖された連結機構を連結する連結口部に封止膜を備えず、前記連結機構の閉鎖体により輸液を封入した可撓性バッグである。（９）必要に応じて滅菌又は殺菌工程の後に保護体を第２薬剤封入容器の外面から除去する工程を更に含む。
【００１０】
本発明の薬剤封入容器セットは、第１薬剤封入容器、１又は複数の第２薬剤封入容器、及び第１薬剤封入容器と第２薬剤封入容器を連結する閉鎖された連通機構を備える。閉鎖された連通機構は、第１薬剤封入容器又は第２薬剤封入容器の外部から手動により連通状態にすることができるものである。本発明の薬剤封入容器セットは、１又は複数の第２薬剤封入容器、第１薬剤封入容器、及び閉鎖された連通機構を、同時に且つ１又は複数の第２薬剤封入容器の外面の少なくとも一部を保護体で覆うことにより第２薬剤封入容器内の薬剤を加熱、電子線、γ線又は紫外線による滅菌又は殺菌工程で変質しない保護状態で滅菌又は殺菌処理される。本発明の薬剤封入容器セットにおいて、第１薬剤封入容器は、可撓性の輸液バッグであり、第２薬剤封入容器は、剛固な筒状口部を有する容器であり、閉鎖された連通機構は、容器の筒状口部と輸液バッグ内を薬剤が通過するように連通状態にする通路、筒状口部に液密に挿着され通路を閉じる閉鎖体、及び挿着された閉鎖体を筒状口部から移動させ通路を開くための操作具を備える。
【００１１】
本発明の薬剤封入容器セットは、次の特徴を備えることができる。（１０）滅菌又は殺菌工程は、高温によりなされ、保護体は、断熱体であり、樹脂製断熱材、セラミック、密閉空間、又は第２薬剤封入容器の外面に隣接する冷却材からなる。（１１）密閉空間を利用する代替法としては、第２薬剤封入容器を例えば熱水シャワー滅菌器中に組み込まれた部分冷却装置内に収容して、この部分冷却装置内の密閉空間を循環水等で冷却し、滅菌時の第２薬剤封入容器内の温度上昇を防止する方法を挙げることができる。（１２）第１薬剤封入容器は、可撓性の輸液バッグからなり、隣接する薬液又は薬剤封入室の間の仕切りが剥離容易な接着部により形成される。（１３）第２薬剤封入容器は、剛固な筒状口部を有する容器である。（１４）閉鎖された連通機構は、筒状口部と輸液バッグ内を連通可能な通路、筒状口部に液密に挿着され通路を閉じる閉鎖体、及び閉鎖体を筒状口部から移動させ通路を開くための操作具を備える。（１５）第２薬剤封入容器は、ガラス又は樹脂製のバイアルである。（１６）操作具は、一端が閉鎖体に係合され輸液バッグ内に他端を有する操作ロッドを備える。（１７）操作ロッドは輸液バッグの外部から手動で操作し閉鎖体を移動させ通路を開くことができる。（１８）閉鎖された連通機構は、筒状口部と輸液バッグ内を連通可能な通路、筒状口部に液密に挿着され通路を閉じる閉鎖体、及び閉鎖体を貫通するように移動可能な中空針を備える。（１９）滅菌又は殺菌工程は、電子線、γ線又は紫外線を容器セット全体へ照射することにより行われ、保護体は、電子線、γ線又は紫外線の半透過体又は微透過体である。
【００１３】
本発明の薬剤封入容器セットは、第１薬剤封入容器、１又は複数の第２薬剤封入容器、第２薬剤封入容器の外面の少なくとも一部を覆う保護体、及び第１薬剤封入容器と第２薬剤封入容器を連結する閉鎖された連通機構を備え、閉鎖された連通機構は第１薬剤封入容器又は第２薬剤封入容器の外部から手動により連通状態にすることができるものであり、保護体は第２薬剤封入容器内の薬剤を加熱、電子線、γ線又は紫外線による滅菌又は殺菌工程の高温、電子線、γ線又は紫外線から保護するものである。
【００１４】
本発明の薬剤封入容器セットにおいて、第１薬剤封入容器は少なくとも１つの薬剤封入室を備える可撓性バッグからなり、第２薬剤封入容器はガラス又は樹脂製のバイアルであり、前記可撓性バッグは剛固な筒状首部を備え、閉鎖された連通機構は、筒状首部に液密に接続され中央に貫通孔を有するフランジ、フランジから伸長しバイアルの筒状口部外周に嵌合可能な嵌合部、フランジから筒状首部内へ伸長する支持体、筒状口部の内部及び貫通孔を含みバイアル内部と前記可撓性バッグ内部を液体連通可能な通路、バイアルの筒状口部内周面に液密に挿着され通路を閉じる閉鎖体、及び閉鎖体に一端を結合され筒状首部内へ伸長する操作体を備える。保護体は、一端においてフランジ外周部に係合される外筒部材及び外筒部材の他端を閉じる端板からなる外殻、及びバイアルと外殻との間に配置される断熱材からなる。
本発明の薬剤封入容器セットにおいて、支持体は、フランジの貫通孔のまわりから筒状首部内へ伸長する筒状体を含み、筒状体は、通路を形成する透孔及び操作体を摺動可能に支持する支持部を備えることができる。また、本発明の薬剤封入容器セットにおいて、滅菌又は殺菌工程は、第１薬剤封入容器、１又は複数の第２薬剤封入容器、及び閉鎖された連通機構を、同時に滅菌又は殺菌することを含み、第１薬剤封入容器と第２薬剤封入容器は、それぞれ滅菌又は殺菌工程における加熱又は電子線、γ線、紫外線の照射に耐える安定な薬剤を収容することができる。
【００１６】
【発明の実施の態様】
図１は、本発明の第１実施例の薬剤封入容器セットの要部概略断面図、図２は、図１の薬剤封入容器セットにおいて閉鎖体の一例として栓体４０がガラス製バイアル（第２薬剤封入容器）２０内へ押し込まれ連通機構が連通状態にされた状態の要部概略断面図である。図１に示す薬剤封入容器セット５は、可撓性輸液バッグ（第１薬剤封入容器）１０、薬剤封入バイアル２０、バイアル２０の外面の少なくとも一部を覆う断熱体３０、及び輸液バッグ１０とバイアル２０を連結する閉鎖された連通機構５０を備える。閉鎖された連通機構５０は、輸液バッグ１０の外部から手動により液体連通状態にすることができるように構成される。
【００１７】
第１薬剤封入容器は、図１０のような例えば剥離可能な隔壁で仕切られた多室バッグに、前記各薬剤成分を粉末又は液体で充填し収容することができる。第１薬剤封入容器に収容される薬剤は、例えば、静脈投与用輸液剤、液状栄養剤等の医療用食餌療法用飲料・食品、腹膜透析液、臓器保存液、臓器等の洗浄に用いられる洗浄剤である。各薬剤に配合される成分の例ととしては、ブドウ糖、フルクトース、マルトース等の還元糖、従来より輸液として栄養補給等を目的として利用されてきているアミノ酸製剤に配合されている各種のアミノ酸等が挙げられる。
【００１８】
なお、各アミノ酸は遊離形態である必要はなく、金属塩、有機酸塩等の薬理学的に許容される塩の形態でもよい。また、各アミノ酸は、生体内で加水分解され遊離アミノ酸に変換されるエステルの形態でもよい。更に、上記各アミノ酸はそれ等の一部又は全部をＮ‐アシル誘導体の形態、例えばＮ‐アセチル‐Ｌ‐システインの形態としてもよい。還元糖とアミノ酸以外の成分としては、栄養補給等を目的とした大豆油、綿実油、サフラワー油、トウモロコシ油、ヤシ油、シソ油、エゴマ油、アマニ油糖の植物油、魚油，化学合成トリグリセリド、中鎖脂肪酸トリグリセリド、長鎖脂肪酸トリグリセリド等を挙げることができる。
【００１９】
また、経腸成分栄養剤の場合は、デキストリン、カゼインナトリウム、卵白加水分解物、植物性蛋白質、乳清蛋白質、脱脂粉乳を前述の成分に加えることができる。各成分の輸液剤としての配合・調製には特別の制限はなく、適宜常法によることができる。
【００２０】
バイアル、即ち第２薬剤封入容器２０に収容される薬剤の１例としては、ビタミン剤、微量元素配合剤、抗生物質、抗腫瘍剤、抗潰瘍剤、血栓溶解剤、ホルモン剤、ステロイド剤、止血剤等を挙げることができる。特に、第１薬剤封入容器に高カロリー輸液用基本液を充填収容した場合の第２薬剤封入容器には、ビタミン剤もしくは微量元素配合剤を収容することが好ましい。また、二つの第２薬剤封入容器にビタミン剤と微量元素配合剤をそれぞれ収容したものを前記第１薬剤封入容器に双方連結した組み合わせも好ましい。
第２薬剤封入容器２０に収容される薬剤において、耐熱性の低い成分を含む場合は、ろ過法による無菌化処理が行なわれる。また、水溶液状態での保存安定性に問題がある成分においては、ろ過法により微生物を取り除いた水溶液を、バイアル内で無菌的に凍結乾燥される。
【００２１】
微量元素配合剤は、ガラスアンプルに充填された製剤として塩化第ニ鉄、塩化マンガン、硫酸亜鉛、硫酸銅、ヨウ化カリウムを有効成分とする高カロリー輸液用微量元素製剤（商品名：エレメンミック、味の素ファルマ製）が知られている。出願人は、各有効成分の適正配合量を検討したうえで、塩化マンガンの配合量を減じた製剤（塩化第ニ鉄９．４６ｍｇ／２ｍＬ、塩化マンガン０．１９７９ｍｇ／２ｍＬ、硫酸亜鉛１７．２５ｍｇ／２ｍＬ、硫酸銅１．２４８ｍｇ／２ｍＬ、ヨウ化カリウム０．１６６ｍｇ／２ｍＬ）の適切な容器を検討した。従来の微量元素製剤は、有効成分を常法に従って注射用蒸留水に溶解し、この溶解液をガラスアンプルに充填・密封した後加熱滅菌されたいた。しかし、このアンプル充填製剤は、カット時にガラス片の混入等の問題点があったので、出願人は前記塩化マンガン減量製剤において、ガラス製あるいは樹脂製のバイアルにマンガン減量微量元素製剤を充填したバイアル充填型製剤を創作した。
【００２２】
前記バイアル充填型のマンガン減量微量元素製剤は、本発明の第２薬剤封入容器に充填される好ましい薬剤例として挙げることができる。なお、従来の微量元素製剤をバイアル充填型の製剤に変更することにより本発明の第２薬剤容器として好適に利用できることはもちろん、バイアル充填型の製剤そのものにおいても、ガラス片の混入を危惧することなく内容液をシリンジで吸引し、各種の輸液バッグに微量元素製剤を注入することができる。更に前記バイアル充填型の製剤単体は、輸液容器のポート部に両頭針とそのホルダ等が連結されたハーフキットタイプの高カロリー輸液用基本液を充填した輸液容器に適用可能となりアンプル製剤とは異なる優れた適用性を発揮する。
【００２３】
可撓性輸液バッグ１０は、可撓性樹脂フィルムに囲まれた第１室１１及び第２室１８を含み、第１室と第２室の間が剥離可能な接着部１９により仕切られ、第１室１１に剛固なポート部１２が設けられ、第１室１１と第２室１８内にそれぞれ輸液が収容される。連通機構５０は、中央に貫通孔５２を有するフランジ５１を備え、フランジ５１の上面または嵌合部５４の内周面がバイアル２０の首部２２がパッキン２９を介して気密に装着され、フランジ５１の下面が可撓性バッグのポート部１２の端部フランジ部１３に気密に熔着される。連通機構５０は、更にフランジ５１から伸長しバイアルの首部２２の外周面に嵌合可能な嵌合部５４、フランジ５１から輸液バッグのポート部１２内へ伸長する円筒形支持体５６、ポート部１２の内部及び貫通孔５２を含みバイアル内部と輸液バッグ内部を液体連通可能な通路５５、バイアル２０の首部２２内周面に液密に挿着され通路５５を閉じる栓体４０、及び栓体４０に一端を接続されポート部１２内へ伸長する操作ロッド４６を備える。
【００２４】
バイアルの首部２２の端部とフランジ５１の上面の間に密封のためのパッキン２９が配置される。係合部５４は、バイアルの首部２２の外周面のくぼみに嵌合合する３個以上の嵌合爪５３を備える。操作ロッド４６は、フランジ５１の中央の貫通孔５２を通り、円筒形の支持体５６及び支持体５６の端板に設けた支持孔５８を通り伸長し、輸液バッグの第１室１１内に端部４５を有する。また操作ロッド４６は、栓体４０をバイアル側へ押し込んだ状態を維持するため貫通孔５２又は支持孔５８の通過の抵抗を大きくする弾性変形可能な複数の係止部端部４４、４７を備える。操作ロッド４６は、薬剤の投与直前に単に輸液バッグ１０の外側からバイアル２０の内方へ押すことにより、操作ロッド４６の先端の栓体４０をバイアル内へ押し込み、通路５５を開通させることができる。通路５５を開通し、輸液バッグ内の輸液を通路を介してバイアル内へ流入させることにより、バイアル内の乾燥固形薬剤２１が第１室の輸液により溶解され、さらに溶解液を第１室に戻すことによりバイアル内の薬剤が輸液と共に患者に点滴投与可能にされる。
【００２５】
断熱体３０は、一端においてフランジ５１の外周部に係合される外筒部材３１及び外筒部材３１の他端を閉じる端板３２からなる外殻、及びバイアル２０の外面と外殻内面との間に配置される断熱材２５を含む。断熱体３０はバイアル２０内の薬剤を加熱滅菌処理による高熱から保護する機能を備えるため、発泡樹脂、空気層等により形成される。薬剤封入容器セット５の薬剤の点滴投与時に容器セット５を吊り下げることができるように、端板３２に吊り具３３が取付けられる。
【００２６】
図１に示す薬剤封入容器セット５は、ろ過滅菌された薬剤溶液を無菌的に凍結乾燥するなど封入薬剤が無菌化処理済みのバイアル２０と輸液バッグ１０を閉鎖された連通機構５０により連結し且つバイアル２０の外面を断熱体３０で覆った状態で滅菌又は殺菌される。図１のセット５において、栓体４０は、バイアル２０の密封機能及びバイアル内と輸液バッグ１０内部とを分離する機能を備える。輸液バッグの第１室１１内に伸長する操作ロッド４６等の滅菌処理を必要とする連通機構の各構成部品は、第１室１１に収容された輸液に浸漬されているので、薬液封入容器セット５全体の加熱滅菌処理時に一緒に滅菌される。
【００２７】
なお、従来２つの薬剤封入容器を連結する方法としては、実公平６−４２６７６号公報記載のように、液体封入容器中の液体が薬剤入り容器に流入しないよう、両容器を分離するゴム栓、封止膜等の封止体が設置されていた。本発明の１つの形態においては、第１薬剤封入容器側に封止体を設けず、第１、第２薬剤封入容器の分離は、第２薬剤封入容器の栓体によりなされる。第２薬剤封入容器の栓体表面は、直接第１薬剤封入容器中の薬液と接し、且つ連通機構をはじめとする滅菌が必要な各部品も第１薬剤封入容器中に封入された液体に接する状態に設置される。そのため封入された医療用薬液の滅菌工程と同時に滅菌が必要な連通機構の各部品を滅菌することができる。
【００２８】
本発明の１つの形態においては、封止体を使用せず、薬剤入り容器の遮蔽体を、薬剤入り容器自身の密封と、液体封入容器中の液体と薬剤入り容器を分離する目的とに利用している。従って、薬剤入り容器の遮蔽体表面は、直接液体封入容器中の液体と接し、且つ連通具をはじめとする滅菌が必要な各部品も液体封入容器内に封入された液体に接する状態に設置されていることから、液体封入容器に封入された液体の滅菌操作と同時に滅菌が必要な各部品を滅菌することができる。
【００２９】
図２は、図１の薬剤封入容器セットにおいて栓体４０がバイアル２０内へ押し込まれて連通機構が連通状態にされた状態の要部概略断面図である。栓体４０は、操作ロッド４６を可撓性輸液バッグの外側から手動でバイアル２０の方へ押圧することにより、バイアル２０の筒状口部内面から摺動、離脱され、バイアル内へ押し込まれる。操作ロッド４６の外径は、バイアル２０の筒状口部内径より小さくされ、輸液バッグ１０内の輸液が開通した流路Ｆを通じてバイアル内へ流入し、その後バイアル内の薬剤を溶解した輸液が輸液バッグ内へ戻り、輸液バッグの下部の薬液排出口１６の栓体１７を穿刺する中空針に連通される図示されない点滴管をへて患者に投与される。
【００３０】
連通機構の支持体５６は、フランジ５１の貫通孔５２のまわりから輸液バッグのポート部１２内へ伸長する筒状部を含み、筒状部は、側面に通路を形成する透孔５７を備え、端面に操作ロッド４６を摺動可能に支持する支持孔５８を備える。操作ロッド４６は、環状の係止部４４、４７を備え、これらが貫通孔５２又は支持孔５８に係合され、操作ロッド４６を所定位置に維持可能であり、栓体４０は、バイアル内で固定されるため栓体４０で通路を塞ぐことがなく、薬液は、バイアル内へスムースに流入し、排出される。支持孔５８の両側の係止部４４は支持孔５８に係合し操作ロッド４６を栓体４０がバイアルの首部にある状態に維持するが、操作ロッド４６が手動で所定の押圧力で押圧されると操作ロッドの移動を許し、通路を開放する。係止部４７は通路が開放されたとき、支持孔５８に係合し、栓体及び操作ロッドを通路の開放位置に維持する。
【００３１】
図３は、第２薬剤封入容器の変形例の２室瓶１２０の断面図である。２室瓶１２０は、首部１２２に隣接し薬液１２１を収容する第１室１２５及び第１室とくびれ部１２４を介して隣接し薬剤２１を収容する第２室１２６を備える。首部１２２は栓体４０により閉鎖され、くびれ部１２４は、内部に第２栓体１２７が液密に挿着され閉鎖される。くびれ部１２４の内径は、首部１２２の内径より大きくされ、栓体４０がくびれ部１２４を通過可能にされる。栓体４０は、操作ロッド４６の端部に結合され、操作ロッド４６を２室瓶１２０の方へ押圧することにより２室瓶内へ押し込まれ、第１室１２５と輸液バッグ１０内が連通される。操作ロッド４６を更に押圧することにより、くびれ部１２４の第２栓体１２７が移動され、第２室１２６と第１室、及び輸液バッグ１０内が連通される。この２室瓶１２０は、２種の薬剤を２室内に分けて収容し、１回の操作で輸液バッグ内の輸液と混合することができる。
【００３２】
図４Ａは、バイアル２０の首部２２又は２室瓶の首部１２２を塞ぐことが可能な栓体４０の側面図、図４Ｂは、栓体４０の中心軸線を含む断面図である。図４Ａに示すように栓体４０は、頭部４３、頭部４３から伸びるスカート部４１、頭部４３のまわりを取巻く２条の環状凸部４２、及び頭部４３に操作ロッドの端部を受入れるための凹所３９を備える。凹所３９は、連通操作、バイアル内部の減圧あるいは輸送中の振動等で操作ロッドが栓体４０から抜けないように栓体内部側に入り口部より拡張された操作ロッド挿入部３８を有する。２条の環状凸部４２は、栓体をバイアル２０の筒状口部に液密に挿着することにより生ずる密封機能を増強する。
【００３３】
図５は、本発明の第２実施例の薬剤封入容器セット６の概略断面図であり、図６は、図５の薬剤封入容器セット６の連通機構が連通状態にされた状態の概略断面図である。この実施例においては、バイアル２０の栓体４０を中空の連通具１４４により刺通することにより連通具１４４内の管路１４２を経てバイアル内部と輸液バッグ１０の第１室１１とを連通する連通路が形成される。連通具１４４は、支持体１５６内を伸長し輸液バッグ１０内に端部１４１を有し、連通具１４４内の通路１４２が端部１４１において輸液バッグ内部と連通する。連通具１４４は可撓性輸液バッグの外側から手動でバイアル２０の方へ押圧することにより、鋭利な先端１４５がバイアル２０の筒状口部を閉鎖する栓体４０を刺通し、連通具１４４の先端開口１４３がバイアル内に位置され、バイアル２０内と輸液バッグ１０内が、開口１４３及び通路１４２を介し液体連通状態にされる。連通具１４４は、その外周部に支持孔１１４に係合し、栓体を刺通する前の連通具１４４の位置（図５）、又は栓体を刺通した後の連通具の位置（図６）を維持するための複数のリブ１４６を備える。
【００３４】
図５に示す薬剤封入容器セット６の組立及び滅菌工程は、次のように行われる。輸液バッグ１０は、図示しない輸液を収容し、封止膜１４０により端部が閉じられた連結口部１１２内に連通具１４４を収容し、連結口部１１２に雄ネジを備えた状態で準備される。バイアル２０は、図示しない薬剤を収容し刺通可能な栓体４０により閉じられ断熱体３０により被覆し断熱体の外殻３１と一体に円筒形連結端１３２を設け、連結端１３２の内周面に雌ネジを備え、栓体４０の外周付近と連結端との間に通路１５５の周りを液密に密封するパッキン２９を備えた状態で準備される。輸液バッグ１０の連結口部１１２とバイアル側の連結端とを螺合させ、図５に示すように薬剤封入容器セット６を組立てる。断熱体３０の構造機能は、第１薬剤封入容器の滅菌に必要な滅菌温度雰囲気において、バイアルに収容された薬剤が品質劣化することのないように選定される。組立られた薬剤封入容器セット６全体を滅菌器内で加熱し滅菌処理する。
【００３５】
図５の構成の薬剤封入容器セット６を用いて薬剤を点滴投与する場合の手順を説明する。まず柔軟な輸液バッグ１０の外部から連通具１４４の幾分膨大化された端部１４１を栓体４０の方へ押圧し、連通具１４４の鋭利な先端１４５を隔壁１４０及び栓体４０を貫通して進め（図６）、先端１４５に隣接する先端開口１４３をバイアル２０内部と連通させ、それにより、輸液バッグ１０内とバイアル２０内を、先端開口１４３（図６）、通路１４２を介し連通させる。この連通路を介し輸液バッグ１０内の輸液をバイアル２０内へ流入させ、バイアル内の薬剤を流入した輸液に溶解し流動化する。バイアル２０内の混合流動化した薬剤を、重力等により、薬液バッグ１０内へ戻して、薬液と薬剤の混合液を薬液バッグ内に形成する。次に吊り具（図示されない）を点滴用架台に係合し薬液排出口１６の栓体１７を中空針で穿刺し中空針及び中空針に連通されるチューブ等を介し混合薬液を患者に点滴投与する。
【００３６】
図７は、本発明の第３実施例の薬剤封入容器セット７の概略断面図である。第１又は第２実施例の部材と同様な部材には、同様の符号が付され説明が省略される。この実施例の薬剤封入容器セット７は、第１実施例（図１）及び第２実施例（図５、図６）と同様に、輸液バッグ１０、断熱体３０により覆われた樹脂製のバイアル２０、及び連通機構５０から成る。この実施例の連通機構５０は、構造が極めて簡単化されている。即ち、バイアルの蓋３４と一体に形成され、先端が閉じられた管状部材２３２からなり、管状部材２３２の先端に破断可能部分９０が設けられ、輸液バッグ１０の外部から曲げ力を加える等により破断可能部分９０を破断し、バイアル２０の内部と輸液バッグ１０の内部を通路２４２を介し液体連通状態とすることができる。
【００３７】
図８は、本発明の第４実施例の薬剤封入容器セット８の概略断面図である。第１〜第３実施例の部材と同様な部材には、同様の符号が付され説明が省略される。この実施例の薬剤封入容器セット８は、輸液バッグ１０、断熱体３０により覆われた薬剤バッグ２２０、及び連通機構１５０から成る。この実施例の連通機構５０は、構造が極めて簡単化されている。即ち、輸液バッグ１０の第１室１１の縁部１４に開口を設けその開口内面と薬剤バッグ２２０の第１室２１１の開口外面を接着し、輸液バッグ１０の第１室１１内部と薬剤バッグ２２０の第１室２１１内部の間を連通する通路３４２が形成されている。通路３４２は、剥離可能接着部１１９を設けて閉鎖されるが、輸液バッグ１０の第１室１１と薬剤バッグ２２０の第１室２１１が空室とされる場合は、輸液バッグ１０の剥離可能接着部１９又は薬液バッグ２２０の剥離可能接着部２１９が通路３４２を閉鎖するので、通路３４２の剥離可能接着部１１９は省略可能である。
【００３８】
薬剤バッグ２２０及び連通機構１５０は、必要に応じて複数個設けられる。各部薬剤バッグの外面を覆う断熱体３０の断熱性能は、各薬剤バッグに封入される薬剤が加熱滅菌処理工程において耐熱温度を超えない温度に維持されるように選定される。断熱体３０は、樹脂製断熱材、セラミック又は断熱空間とすることができる。また断熱体は、加熱滅菌処理における高温から第２薬剤封入容器（薬剤バッグ）内の薬剤を保護する目的で冷却材により形成され得る。
【００３９】
図８の構成の薬剤封入容器セット８を用いて薬剤を点滴投与する場合の手順を説明する。まず薬液バッグ内の薬液と薬剤バッグ内の薬剤を混合し流動化する作業を行う。即ち、比較的多量の薬液を封入した薬液バッグ１０の第２室１８内の薬液に外部から押圧力を加えて、剥離可能接着部１９を剥離させ薬液を第１室１１へ流入させる。通路３４２に剥離可能接着部が設けられる場合は、更に第１室１１及び押圧力を加え通路の剥離可能接着部を剥離させ薬液を薬剤バッグ２２０の第１室２１１へ流入させる。薬剤バッグ２２０の第２室２１内に固形薬剤が封入される場合は、更に薬液バッグ１０及び第１室２１１及び薬剤バッグ２２０の第１室２１１に外部から押圧力を加えて、剥離可能接着部を剥離させ、両バッグ内を通路により連通状態とし、薬液と薬剤を混合し流動化させる。薬剤バッグ２２０内に薬液が封入される場合は、薬剤バッグ２２０にも押圧力を加え剥離可能接着部を剥離させ両バッグ内を通路により連通状態とし、薬液と薬剤を混合し流動化する。次に吊り具３３を点滴用架台に係合し薬液排出口１６の栓体１７を中空針で穿刺し中空針及び中空針に連通されるチューブ等を介し混合薬液を患者に点滴投与する。
【００４０】
図９は、本発明の第５実施例の薬剤封入容器セットの概略断面図である。第１〜第４実施例の部材と同様な部材には、同様の符号が付され説明が省略される。図９の薬剤封入容器セットは、図１の薬剤封入容器セットから断熱体３０を除いた構成を有する。即ち、図９は、本発明の第５実施例の薬剤封入容器セットの要部概略断面図である。図９に示す薬剤封入容器セット５は、樹脂製輸液バッグ（第１薬剤封入容器）１０、薬剤封入バイアル２０、及び輸液バッグ１０とバイアル２０を連結する閉鎖された連通機構５０を備える。バイアルの首部２２の端部とフランジ５１の上面の間に密封のためのパッキン２９が配置される。係合部５４は、バイアルの首部２２の外周面のくぼみに係合する３個以上の係合爪５３を備える。フランジ５１の周囲から下方へ円筒部５１’が垂下し、ポート部１２を覆う。
【００４１】
図９の容器セットは、組立てた状態において保護体無しで蒸気滅菌、電子線照射、γ線照射又は紫外線照射により滅菌又は殺菌工程を行う。それ故、第１薬剤封入容器と第２薬剤封入容器は、いずれも滅菌又は殺菌工程の熱、電子線、γ線又は紫外線に対し同様の耐性を備え、変質しないことがもとめられる。図９の容器セットにおいて、操作ロッド４６は、フランジ５１の中央の貫通孔５２を通り、円筒形の支持体５６及び支持体５６の端板に設けた支持孔５８を通り伸長し、輸液バッグの第１室１１内に端部４５を有する。閉鎖された連通機構５０は、輸液バッグ１０の外部から手動により液体連通状態にすることができるように構成される。
【００４２】
第１薬剤封入容器は、図１０に示す多室バッグ１０により形成され得る。図１０の多室バッグ１０は、周縁部１５、２つのポート部１２、１２、吊り下げ部３３を備え、剥離可能な隔壁１９、１９’で仕切られた各薬剤成分が複数の室Ｃ１〜Ｃ４へ各薬剤成分が充填し収容される。多室バッグの各室Ｃ１〜Ｃ４に収容される薬剤は、例えば、静脈投与用輸液剤、液状栄養剤等の医療用食餌療法用飲料・食品、腹膜透析液、臓器保存液、臓器等の洗浄に用いられる洗浄剤である。各薬剤に配合される成分は、ブドウ糖、フルクトース、マルトース等の還元糖、従来より輸液として栄養補給を目的として利用されてきているアミノ酸製剤に配合されている各種のアミノ酸である。また、ビタミン剤、微量元素製剤を各室に収容し得る。
【００４３】
【発明の効果】
本発明の薬剤封入容器セットは、第１薬剤封入容器又は第２薬剤封入容器の外部から手動により薬剤を連通可能な連通状態にすることができるものであり、投与直前に細菌汚染を生じることなく、第１薬剤封入容器と複数の第２薬剤封入容器内の薬剤を連通状態の連通機構を介してを混合することができる。
【００４４】
本発明の薬剤封入容器セットは、第１薬剤封入容器（薬液バッグ）と耐熱温度、電子線、γ線、紫外線等に対する耐性が異なる第１薬剤封入容器に添加すべき薬剤を同時にして、且つ薬剤成分を損傷することなく高温蒸気、電子線照射、γ線照射、紫外線照射を用いる滅菌又は殺菌工程を行うことが可能である。本発明は慣用の無菌保証が容易な高圧蒸気滅菌、シャワー滅菌等の加熱滅菌法で薬剤封入容器セット全体を滅菌又は殺菌することができる。また薬剤封入容器セット全体を確実に且つ簡単に無菌保証することができる。
【００４５】
本発明の薬剤封入容器セットは、組立後に全体的に滅菌工程がなされるから、組立作業を費用と手数のかかる無菌室で行う必要がなくなり、費用及び時間を大きく節減することができる。本発明の栓体を押外す図１の例においては、穿刺の必要がないため、コアリング等の異物混入がなく、薬液溶解時の流路が広く確保される。そのため薬剤溶解時のポンピング操作が不要になり、また薬剤溶解時間が短縮される。更に穿刺針を使用しないから、作業中に看護婦が負傷する心配がない。
【００４６】
本発明の図１乃至図６の実施例においては、連通操作は、連通具を押すだけであり、作業者（看護婦）のトレーニングが不要である。
【図面の簡単な説明】
【図１】本発明の第１実施例の薬剤封入容器セットの要部概略断面図。
【図２】図１の薬剤封入容器セットの連通機構が連通状態にされた状態の要部概略断面図。
【図３】第１実施例の第２薬剤封入容器の変形例の２室瓶を示す概略断面図。
【図４】図４Ａは栓体の概略側面図、図４Ｂは栓体の画略断面図。
【図５】本発明の第２実施例の薬剤封入容器セットの概略断面図。
【図６】図５の薬剤封入容器セットの連通機構が連通状態にされた状態の概略断面図。
【図７】本発明の第３実施例の薬剤封入容器セットの概略断面図。
【図８】本発明の第４実施例の薬剤封入容器セットの概略断面図。
【図９】本発明の第５実施例の薬剤封入容器セットの概略断面図。
【図１０】本発明の薬剤封入容器セットの第１薬剤封入容器に使用可能な多室容器の概略断面図である。
【符号の説明】
５、６、７、８：薬剤封入容器セット、１０：輸液バッグ（第１薬剤封入容器、多室容器）、１１：第１室、１２：ポート部、１３：フランジ部、１４：シール部、１５：周縁部、１６：排出口、１７：栓体、１８：第２室（薬液部）、１９：剥離可能接着部、２０：バイアル（第２薬剤封入容器）、２１：薬剤、２２：首部、２５：断熱材、３０：保護体（断熱体）、３１：外殻、３３：吊り下げ具、３４：蓋、４０：栓体、４１：スカート部、４２：環状凸部、４３：頭部、４４：凹所、４６：操作ロッド（操作具）、５０：連通機構、５１：フランジ、５２：貫通孔、５５：通路、５６：支持体、５８：支持孔、９０：折取部、１１２：連結口部、１１４：支持孔、１１９：剥離可能接着部、１２０：２室瓶（第２薬剤封入容器）、１２１：薬液、１２４：くびれ部、１２６：第２室、１２７：中栓体、１４４：中空針、１４０：封止膜、１４１：端部、１４２：通路、１４３：先端開口、１４４：連通具、１４５：先端、１４６：リブ、１５０：連通機構、２１９：剥離可能接着部、２２０：２室バッグ（第２薬剤封入容器）、２３２：管状部材、２４２、３４２：通路。
Ｆ：流路。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a drug enclosure set in which a plurality of medicament enclosures (including solutions and solids such as powders and granules) are connected via a closed communication mechanism. In particular, the present invention relates to a drug-filled container set in which a drug-filled vial and a flexible bag are connected via a closed communication mechanism, and the drug in the vial can be mixed aseptically with a drug solution manually just before use. The present invention further relates to a method for producing a drug-enclosed container set in which the number of sterilization or sterilization steps is minimized and the sterilization or sterilization steps are improved.
[0002]
[Prior art]
In medical institutions such as hospitals, multiple drugs such as vitamins and trace element preparations administered to a patient's vein by infusion are mixed and administered in a drug solution such as an infusion solution immediately before administration so as not to cause quality deterioration due to changes in the composition. Is done. In order to perform this mixing operation simply and aseptically, various kinds of drug-enclosed container sets and methods for producing the same have been devised.
[0003]
Japanese Patent Laid-Open No. 10-24088 discloses a drug-filled container set for the purpose of providing an infusion container in which a drug-filled vial or the like is simply connected with few parts in a state where sterility is guaranteed. This drug enclosure container set is a resin container and has a plurality of chambers, and at least a part of a separating strip portion between the chambers is formed by a peel seal portion or a weak seal portion that can be opened from the outside. A chemical solution is stored in the chamber, a filling container is connected to the second chamber, the filling container stores the drug mixed with the chemical solution, and a lid or a film body that closes the opening of the filling container presses from the outside of the second chamber. Thus, it can be pushed into the filling container, and the second chamber and the filling container are communicated with each other by pushing the lid or film into the filling container. The plastic container sterilized by high-pressure steam and the vial containing the drug are connected in a sterile, dust-free chamber, and then only the second chamber is sterilized by electron irradiation, and the outer surface of the filled container once exposed to the outside in the second chamber And sterilized together.
[0004]
Japanese Utility Model Publication No. 6-42676 discloses an infusion bag for the purpose of easily and safely adding a drug in a vial to an infusion drug solution in the bag. This infusion bag has a mouth member capable of connecting a mouth portion of a vial sealed with a rubber stopper. The mouth member has a bottomed cylindrical part 3 with a lower outer peripheral surface fused to one open end of the synthetic resin sheet, a lower end sealed with a sealing film, and a male screw on the upper outer periphery. The hollow needle 6 having a puncture blade at the tip is fixed and the lower end is a stick-shaped part 4 having a puncture blade and a male screw of a bottomed cylindrical part. Second part 5 having a small diameter part having a female screw to be screwed together and a small diameter part and a large diameter part which is integrally formed through the partition part and into which the mouth of the vial is fitted, and through which the hollow needle pierces the partition part. And a seal 10 for closing the open end of the large diameter portion of the second part. Instead of the tip being a puncture blade, a rubber stopper 63 fixed to the end of the rod-shaped part can be provided.
[0005]
[Problems to be solved by the invention]
An object of the present invention is to provide a closed communication mechanism including a first drug enclosure container, one or more second drug enclosure containers, and a closed communication mechanism that connects the first drug enclosure container and the second drug enclosure container. Is to provide a drug enclosure set that can be manually brought into a liquid communication state from the outside of the first drug enclosure or the second drug enclosure. In particular, the present invention provides a drug-filled container set in which a drug-filled vial and a flexible infusion bag are connected by a closed communication mechanism, and the closed communication mechanism is aseptically free from manual generation of foreign substances immediately before the use of the drug. It is an object of the present invention to provide a drug-filled container set that is opened and can quickly and easily mix and prepare drugs in both containers. Another object of the present invention is to preliminarily sterilize or sterilize simultaneously with the first drug enclosing container about the easily deteriorated drug previously aseptically stored in the second drug enclosing container, and receive the heating or electron beam, γ ray Another object of the present invention is to provide a drug container set that can be protected from the effects of irradiation with ultraviolet rays or the like.
[0006]
Another object of the present invention includes a first drug enclosure container, one or more second drug enclosure containers, and a closed communication mechanism that connects the first drug enclosure container and the second drug enclosure container, and is closed. The communication mechanism can easily and efficiently simplify the sterilization or sterilization process of a drug-filled container set that can be in a liquid communication state without causing foreign matter manually from the outside of the first drug-filled container or the second drug-filled container. It is to provide a manufacturing method that can be manufactured. In particular, the manufacturing process is performed by simultaneously sterilizing or sterilizing the first and second drug-containing containers containing the drugs having different resistance to high heat, electron beam, γ-ray, ultraviolet rays, etc. used in the sterilization or sterilization process. It is to simplify.
[0007]
Still another object of the present invention is to improve the configuration of a closed communication mechanism in a drug enclosure container set including a closed communication mechanism that connects a first drug enclosure and a second drug enclosure, The liquid communication between the first drug enclosure and the second drug enclosure can be reliably interrupted when storing or transporting the set, and the communication mechanism is easy and reliable without any foreign matter being manually generated from the outside immediately before drug administration. Is to be able to be operated in a liquid communicable state. Other objects and advantages of the present invention will become apparent in the following description.
[0008]
[Means for Solving the Problems]
  The present invention has the features described in the claims. 1stly, the manufacturing method of the chemical | medical agent enclosure container set of this invention is connected with the communication mechanism with which the 1st chemical | medical agent enclosure container and the 2nd chemical | medical agent enclosure were closed, and the closed communication mechanism was made into a communication state manually. A set of drug enclosures that can be made. This manufacturing method includes a step of connecting one or a plurality of second drug enclosure containers and a first drug enclosure container via a closed communication mechanism, and at least a part of an outer surface of the one or more second drug enclosure containers is a protector. And simultaneously connecting the connected first drug enclosure container and the second drug enclosure container covered by the protector.By heating, electron beam, gamma ray or ultraviolet raySterilizing or sterilizing and sterilizing or sterilizing the drug-enclosed container set. The protector prevents the deterioration of the quality of the drug due to heating in the sterilization or sterilization process, electron beam, γ-ray, ultraviolet rays or the like.In the method for producing the drug enclosure container set of the present invention, the closed communication mechanism includes a passage communicating the first drug enclosure and the vial, a closing body for closing the passage, and means for moving the closing body. .
[0009]
The method for producing the drug-enclosed container set of the present invention can have the following features. (1) The heat resistance temperature of the medicine accommodated in the second medicine enclosure is lower than the heat resistance temperature of the medicine contained in the second medicine enclosure. (2) The sterilization or sterilization step is performed by high-pressure steam sterilization or hot water shower sterilization. (3) The protective body is made of a heat insulator, and the heat insulator is made of a resin heat insulating material, ceramic, a sealed space, or a coolant adjacent to the outer surface of the second drug enclosure. (4) The heat insulator has the performance of reducing the influence of the heat treatment on the medicine in the second medicine-sealing container in the sterilization or sterilization process. (5) The sterilization or sterilization step is performed by irradiating the entire container set with an electron beam, γ-rays or ultraviolet rays, and the protector is an electron beam, γ-rays or ultraviolet ray shielding body, that is, an electron beam, γ-rays or It is made of a metal body, glass, resin, or the like that does not transmit ultraviolet light or transmits a small amount. (6) The second drug enclosure is a glass or resin vial containing a drug. (7) The closed communication mechanism includes a passage communicating the first drug enclosure and the vial, a closing body closing the passage, moving the closing body, or forming a through passage in the closing body to open the passage. Including means. (8) The first drug enclosing container is a flexible bag that does not include a sealing film at the connection port portion that connects the closed connection mechanism, and in which the infusion is sealed by the closing body of the connection mechanism. (9) The method further includes a step of removing the protective body from the outer surface of the second drug enclosure after the sterilization or sterilization step, if necessary.
[0010]
  The drug enclosure container set of the present invention includes a first drug enclosure, one or more second drug enclosures, and a closed communication mechanism that connects the first drug enclosure and the second drug enclosure. The closed communication mechanism can be manually connected from the outside of the first drug enclosure or the second drug enclosure. The drug enclosure container set according to the present invention includes one or more second drug enclosure containers,First drug enclosure,as well asClosed communication mechanismAt the same timeAnd covering at least part of the outer surface of the one or more second drug enclosures with a protective body.ByThe drug in the second drug enclosureBy heating, electron beam, gamma ray or ultraviolet raySterilized or sterilized in a protected state that does not deteriorate during the sterilization or sterilization process.In the drug enclosure set of the present invention, the first drug enclosure is a flexible infusion bag, and the second drug enclosure is a container having a rigid cylindrical mouth, and is a closed communication mechanism. Are a passage that communicates with the cylindrical mouth portion of the container and the inside of the infusion bag so that the medicine passes, a closed body that is liquid-tightly inserted into the cylindrical mouth portion and closes the passage, and an inserted closed body. An operating tool is provided for moving from the cylindrical mouth to open the passage.
[0011]
  The drug enclosure container set of the present invention can have the following features. (10) The sterilization or sterilization process is performed at a high temperature, and the protector is a heat insulator, and is made of a resin heat insulating material, ceramic, a sealed space, or a coolant adjacent to the outer surface of the second drug enclosure. (11) As an alternative method of using the sealed space, the second medicine-sealed container is accommodated in, for example, a partial cooling device incorporated in a hot water shower sterilizer, and circulating water is circulated through the sealed space in the partial cooling device. The method of cooling by etc. and preventing the temperature rise in the 2nd chemical | medical agent enclosure container at the time of sterilization can be mentioned. (12) The first drug enclosure is a flexible infusion bagThe partition between adjacent chemical solutions or drug enclosures is formed by an easily peelable adhesive part. (13) The second drug enclosure is a container having a rigid cylindrical mouth. (14) The closed communication mechanism includes a passage capable of communicating with the cylindrical mouth portion and the inside of the infusion bag, a closed body that is liquid-tightly inserted into the cylindrical mouth portion and closes the passage, and the closed body from the tubular mouth portion. An operating tool for moving and opening the passage is provided. (15) The second drug enclosure is a glass or resin vial. (16) The operation tool includes an operation rod having one end engaged with the closing body and the other end in the infusion bag. (17) The operating rod can be manually operated from the outside of the infusion bag to move the closing body and open the passage. (18) The closed communication mechanism is a passage that can communicate with the cylindrical mouth and the infusion bag, a closed body that is liquid-tightly inserted into the tubular mouth and closes the passage, and moves so as to penetrate the closed body. With possible hollow needles. (19) The sterilization or sterilization step is performed by irradiating the entire container set with an electron beam, γ-rays, or ultraviolet rays, and the protective body is a semi-transmissive body or a finely transmissive body of electron beams, γ-rays, or ultraviolet rays.
[0013]
  The drug enclosure container set of the present invention includes a first drug enclosure, one or more second drug enclosures, a protective body covering at least a part of the outer surface of the second drug enclosure, and the first drug enclosure and the second A closed communication mechanism for connecting the drug enclosure, the closed communication mechanism can be manually connected from the outside of the first drug enclosure or the second drug enclosure; The drug in the second drug enclosureBy heating, electron beam, gamma ray or ultraviolet rayIt protects against high temperatures, electron beams, gamma rays or ultraviolet rays in the sterilization or sterilization process.
[0014]
  In the drug enclosure container set of the present invention, the first drug enclosure is a flexible bag having at least one drug enclosure, and the second drug enclosure is a glass or resin vial,The flexible bagHas a rigid cylindrical neck, and the closed communication mechanism is connected to the cylindrical neck in a fluid-tight manner and has a through-hole in the center. The flange extends from the flange to the outer periphery of the cylindrical mouth of the vial.Mating part that can be fittedA support extending from the flange into the cylindrical neck, the inside of the cylindrical mouth and the inside of the vial including the through-holeThe flexible bagInsideliquidA communication path, a closing body that is liquid-tightly inserted into the inner peripheral surface of the cylindrical mouth portion of the vial and closes the passage, and an operating body that is connected to the closing body and extends into the cylindrical neck portion. The protector includes an outer cylinder member engaged with the outer peripheral portion of the flange at one end, an outer shell including an end plate closing the other end of the outer cylinder member, and a heat insulating material disposed between the vial and the outer shell.
    In the drug enclosure set of the present invention, the support includes a cylindrical body that extends from around the through hole of the flange into the cylindrical neck, and the cylindrical body slides through the through hole and the operation body that form a passage. A support portion that can be supported can be provided. Further, in the drug enclosure container set of the present invention, the sterilization or sterilization step includes simultaneously sterilizing or sterilizing the first drug enclosure, the one or more second drug enclosures, and the closed communication mechanism, The first drug enclosure and the second drug enclosure can each contain a stable drug that can withstand heating or irradiation with electron beams, γ rays, and ultraviolet rays in a sterilization or sterilization process.
[0016]
BEST MODE FOR CARRYING OUT THE INVENTION
FIG. 1 is a schematic cross-sectional view of an essential part of a drug enclosure container set according to a first embodiment of the present invention. FIG. 2 is a glass vial (second vial) as an example of a closure body in the drug enclosure container set of FIG. It is a principal part schematic sectional drawing of the state pushed into the chemical | medical agent enclosure container 20 and the communication mechanism in the communication state. A drug enclosure container set 5 shown in FIG. 1 includes a flexible infusion bag (first drug enclosure) 10, a drug enclosure vial 20, a heat insulator 30 that covers at least a part of the outer surface of the vial 20, and the infusion bag 10 and the vial. A closed communication mechanism 50 for connecting the two members 20 is provided. The closed communication mechanism 50 is configured so that it can be manually in a liquid communication state from the outside of the infusion bag 10.
[0017]
The first drug enclosing container can be filled with each drug component with powder or liquid in a multi-chamber bag partitioned by, for example, a removable partition wall as shown in FIG. The medicine accommodated in the first medicine-sealed container is, for example, a liquid used for washing medical dietary beverages / foods such as intravenous fluids, liquid nutrients, peritoneal dialysis fluid, organ preservation solution, organs, etc. It is an agent. Examples of ingredients blended in each drug include reducing sugars such as glucose, fructose and maltose, and various amino acids blended in amino acid preparations conventionally used for nutritional supplementation as an infusion. Can be mentioned.
[0018]
Each amino acid need not be in a free form, and may be in the form of a pharmacologically acceptable salt such as a metal salt or an organic acid salt. Each amino acid may be in the form of an ester that is hydrolyzed and converted to a free amino acid in vivo. Further, each of the amino acids may be partially or wholly in the form of an N-acyl derivative, for example, N-acetyl-L-cysteine. Components other than reducing sugar and amino acids include soybean oil, cottonseed oil, safflower oil, corn oil, palm oil, perilla oil, sesame oil, flaxseed oil vegetable oil, fish oil, chemically synthesized triglyceride, Examples thereof include medium chain fatty acid triglycerides and long chain fatty acid triglycerides.
[0019]
In the case of enteral component nutrients, dextrin, casein sodium, egg white hydrolyzate, vegetable protein, whey protein, and nonfat dry milk can be added to the aforementioned components. There is no special restriction | limiting in the mixing | blending and preparation as an infusion agent of each component, According to a conventional method suitably.
[0020]
As an example of the medicine accommodated in the vial, that is, the second medicine enclosing container 20, vitamin agent, trace element combination agent, antibiotic, antitumor agent, antiulcer agent, thrombolytic agent, hormone agent, steroid agent, hemostasis An agent etc. can be mentioned. In particular, it is preferable that the second drug-filled container when the first drug-filled container is filled with the basic solution for high-calorie infusion contains a vitamin agent or a trace element compounding agent. Also preferred is a combination in which two second drug enclosing containers each containing a vitamin agent and a trace element combination are connected to the first drug enclosing container.
When the medicine accommodated in the second medicine enclosing container 20 contains a component having low heat resistance, sterilization processing by a filtration method is performed. Moreover, in the component which has a problem in the storage stability in aqueous solution state, the aqueous solution which removed the microorganisms by the filtration method is aseptically freeze-dried in the vial.
[0021]
The trace element formulation is a high-calorie infusion-based trace element formulation (trade name: Elementalmic, which contains ferric chloride, manganese chloride, zinc sulfate, copper sulfate, potassium iodide as active ingredients as a formulation filled in a glass ampoule. Ajinomoto Pharma) is known. The applicant studied the appropriate blending amount of each active ingredient and then reduced the blending amount of manganese chloride (ferric chloride 9.46 mg / 2 mL, manganese chloride 0.1979 mg / 2 mL, zinc sulfate 17.25 mg / 2 mL, copper sulfate 1.248 mg / 2 mL, potassium iodide 0.166 mg / 2 mL). Conventional trace element preparations were sterilized by heating after dissolving an active ingredient in distilled water for injection according to a conventional method, filling the sealed solution in a glass ampule and sealing. However, since this ampoule-filled preparation had problems such as mixing of glass pieces at the time of cutting, the applicant applied to the above-mentioned manganese chloride weight loss preparation in a vial in which a glass or resin vial was filled with a manganese weight loss trace element preparation. A filling formulation was created.
[0022]
The vial-filled manganese-decreasing trace element preparation can be given as a preferred example of a medicine filled in the second medicine-sealed container of the present invention. It should be noted that the conventional trace element formulation can be suitably used as the second drug container of the present invention by changing to a vial-filled formulation, and of course, the vial-filled formulation itself may be mixed with glass fragments. Instead, the content liquid can be sucked with a syringe and the trace element preparation can be injected into various infusion bags. Furthermore, the vial-filled formulation alone can be applied to an infusion container filled with a half-kit type high-calorie infusion basic solution in which a double-ended needle and its holder are connected to the port portion of the infusion container, which is different from an ampoule formulation. Excellent applicability.
[0023]
The flexible infusion bag 10 includes a first chamber 11 and a second chamber 18 surrounded by a flexible resin film, and the first chamber and the second chamber are separated by an adhesive 19 that can be peeled off. A rigid port portion 12 is provided in the first chamber 11, and infusion solutions are accommodated in the first chamber 11 and the second chamber 18, respectively. The communication mechanism 50 includes a flange 51 having a through hole 52 in the center. The upper surface of the flange 51 or the inner peripheral surface of the fitting portion 54 is attached to the neck portion 22 of the vial 20 through the packing 29 in an airtight manner. The lower surface is hermetically welded to the end flange portion 13 of the port portion 12 of the flexible bag. The communication mechanism 50 further extends from the flange 51 and can be fitted to the outer peripheral surface of the neck portion 22 of the vial. The cylindrical support 56 extends from the flange 51 into the port portion 12 of the infusion bag. A passage 55 including a through hole 52 and a fluid communication between the inside of the vial and the inside of the infusion bag, a plug body 40 that is liquid-tightly attached to the inner peripheral surface of the neck portion 22 of the vial 20, and the plug body 40. An operating rod 46 that is connected at one end and extends into the port portion 12 is provided.
[0024]
Sealing packing 29 is disposed between the end of the vial neck 22 and the upper surface of the flange 51. The engaging portion 54 includes three or more fitting claws 53 that fit into the recesses on the outer peripheral surface of the neck portion 22 of the vial. The operation rod 46 extends through the through hole 52 in the center of the flange 51, extends through the cylindrical support 56 and the support hole 58 provided in the end plate of the support 56, and ends in the first chamber 11 of the infusion bag. Part 45. The operation rod 46 also includes a plurality of elastically deformable locking end portions 44 and 47 that increase the resistance of passage through the through hole 52 or the support hole 58 in order to maintain the state where the stopper 40 is pushed into the vial. . The operating rod 46 can be pushed just into the vial 20 from the outside of the infusion bag 10 just before administration of the drug, thereby pushing the plug 40 at the tip of the operating rod 46 into the vial and opening the passage 55. . By opening the passage 55 and allowing the infusion solution in the infusion bag to flow into the vial through the passage, the dry solid medicine 21 in the vial is dissolved by the infusion solution in the first chamber, and the solution is returned to the first chamber. This allows the drug in the vial to be instilled into the patient along with the infusion.
[0025]
The heat insulator 30 includes an outer cylinder member 31 that is engaged with an outer peripheral portion of the flange 51 at one end, an outer shell that includes an end plate 32 that closes the other end of the outer cylinder member 31, and an outer surface of the vial 20 and an inner surface of the outer shell. Insulating material 25 is disposed between them. Since the heat insulator 30 has a function of protecting the medicine in the vial 20 from high heat due to heat sterilization, it is formed of a foamed resin, an air layer, or the like. A lifting tool 33 is attached to the end plate 32 so that the container set 5 can be suspended at the time of instillation of the drug in the drug enclosure container set 5.
[0026]
The drug-filled container set 5 shown in FIG. 1 connects a vial 20 that has been sterilized with a sealed drug solution, such as aseptically freeze-drying a drug solution sterilized by filtration, and an infusion bag 10 by a closed communication mechanism 50. Sterilization or sterilization is performed with the outer surface of the vial 20 covered with the heat insulator 30. In the set 5 of FIG. 1, the stopper 40 has a sealing function of the vial 20 and a function of separating the inside of the vial and the inside of the infusion bag 10. Each component of the communication mechanism that requires sterilization, such as the operation rod 46 that extends into the first chamber 11 of the infusion bag, is immersed in the infusion contained in the first chamber 11, so that the chemical solution enclosure set 5. Sterilized together during the entire heat sterilization process.
[0027]
In addition, as a method of connecting two conventional drug enclosures, as described in Japanese Utility Model Publication No. 6-42676, a rubber stopper that separates both containers so that the liquid in the liquid enclosure does not flow into the medicine container, A sealing body such as a sealing film was installed. In one embodiment of the present invention, no sealing body is provided on the first drug enclosure container side, and the first and second drug enclosure containers are separated by a plug of the second drug enclosure container. The plug body surface of the second drug enclosure is in direct contact with the drug solution in the first drug enclosure, and each component that requires sterilization including the communication mechanism is also in contact with the liquid enclosed in the first drug enclosure. Installed in a state. Therefore, it is possible to sterilize each component of the communication mechanism that needs to be sterilized at the same time as the sterilization process of the enclosed medical drug solution.
[0028]
In one embodiment of the present invention, the sealing body is not used, and the shielding body of the medicine container is used for sealing the medicine container itself and for the purpose of separating the liquid in the liquid enclosure and the medicine container. is doing. Therefore, the surface of the shielding body of the container containing the medicine is directly in contact with the liquid in the liquid enclosure, and each component that requires sterilization such as a communication device is also in contact with the liquid enclosed in the liquid enclosure. Therefore, it is possible to sterilize each part that needs to be sterilized simultaneously with the sterilization operation of the liquid sealed in the liquid sealed container.
[0029]
FIG. 2 is a schematic cross-sectional view of a main part in a state in which the stopper 40 is pushed into the vial 20 and the communication mechanism is in a communication state in the drug enclosure container set of FIG. The stopper 40 is slid and detached from the inner surface of the cylindrical mouth of the vial 20 by manually pressing the operating rod 46 from the outside of the flexible infusion bag toward the vial 20 and is pushed into the vial. The outer diameter of the operating rod 46 is made smaller than the inner diameter of the cylindrical mouth of the vial 20, and the infusion solution in the infusion bag 10 flows into the vial through the open channel F, and then the infusion solution in which the medicine in the vial is dissolved is infused. It returns to the inside of the bag and is administered to the patient through a drip tube (not shown) connected to a hollow needle that pierces the plug 17 of the drug solution outlet 16 at the lower part of the infusion bag.
[0030]
The support 56 of the communication mechanism includes a cylindrical portion that extends from around the through hole 52 of the flange 51 into the port portion 12 of the infusion bag, and the cylindrical portion includes a through hole 57 that forms a passage on the side surface. A support hole 58 for slidably supporting the operation rod 46 is provided on the end surface. The operation rod 46 includes annular locking portions 44 and 47, which are engaged with the through hole 52 or the support hole 58, so that the operation rod 46 can be maintained at a predetermined position. Since it is fixed, the plug 40 does not block the passage, and the chemical solution flows smoothly into the vial and is discharged. The locking portions 44 on both sides of the support hole 58 engage with the support hole 58 to maintain the operation rod 46 in a state where the stopper 40 is at the neck of the vial. However, the operation rod 46 is manually pressed with a predetermined pressing force. Then, the movement of the operating rod is allowed and the passage is opened. When the passage is opened, the locking portion 47 engages with the support hole 58 and maintains the stopper and the operating rod in the opening position of the passage.
[0031]
FIG. 3 is a cross-sectional view of a two-chamber bottle 120 which is a modification of the second drug enclosure. The two-chamber bottle 120 includes a first chamber 125 that is adjacent to the neck portion 122 and that stores the drug solution 121 and a second chamber 126 that is adjacent to the first chamber via the constricted portion 124 and stores the drug 21. The neck portion 122 is closed by the plug body 40, and the constricted portion 124 is closed by inserting the second plug body 127 in a liquid-tight manner inside. The inner diameter of the constricted portion 124 is made larger than the inner diameter of the neck portion 122 so that the plug 40 can pass through the constricted portion 124. The stopper 40 is coupled to the end of the operation rod 46, and is pushed into the two-chamber bottle by pressing the operation rod 46 toward the two-chamber bottle 120, so that the first chamber 125 and the infusion bag 10 communicate with each other. The By further pressing the operation rod 46, the second stopper 127 of the constricted portion 124 is moved, and the second chamber 126, the first chamber, and the infusion bag 10 are communicated. The two-chamber bottle 120 can store two kinds of medicines in two chambers and mix them with the infusion in the infusion bag in one operation.
[0032]
4A is a side view of the stopper 40 that can close the neck 22 of the vial 20 or the neck 122 of the two-chamber bottle, and FIG. 4B is a cross-sectional view including the central axis of the stopper 40. As shown in FIG. 4A, the plug body 40 has a head 43, a skirt 41 extending from the head 43, two annular protrusions 42 surrounding the head 43, and an end of the operation rod on the head 43. A recess 39 for receiving is provided. The recess 39 has an operation rod insertion portion 38 that is extended from the entrance to the inside of the stopper so that the operation rod does not come out of the stopper 40 due to communication operation, decompression inside the vial or vibration during transportation. The two annular protrusions 42 reinforce the sealing function generated by inserting the stopper into the cylindrical mouth portion of the vial 20 in a liquid-tight manner.
[0033]
FIG. 5 is a schematic cross-sectional view of the drug enclosure container set 6 of the second embodiment of the present invention, and FIG. 6 is a schematic cross-sectional view of a state in which the communication mechanism of the drug enclosure container set 6 of FIG. It is. In this embodiment, the stopper 40 of the vial 20 is pierced by the hollow communication device 144 so that the inside of the vial and the first chamber 11 of the infusion bag 10 communicate with each other through the pipe line 142 in the communication device 144. A passage is formed. The communication tool 144 extends in the support 156 and has an end portion 141 in the infusion bag 10, and the passage 142 in the communication tool 144 communicates with the inside of the infusion bag at the end portion 141. The communication tool 144 is manually pressed from the outside of the flexible infusion bag toward the vial 20, whereby the sharp tip 145 pierces the plug body 40 that closes the cylindrical mouth of the vial 20, and the tip of the communication tool 144. The opening 143 is located in the vial, and the vial 20 and the infusion bag 10 are brought into fluid communication via the opening 143 and the passage 142. The communication tool 144 engages with the support hole 114 on the outer periphery thereof, and the position of the communication tool 144 before the plug body is pierced (FIG. 5) or the position of the communication tool after the plug body is pierced (FIG. 5). A plurality of ribs 146 are provided to maintain 6).
[0034]
The assembly and sterilization process of the drug enclosure container set 6 shown in FIG. 5 is performed as follows. The infusion bag 10 accommodates an infusion solution (not shown), accommodates the communication tool 144 in the connection port portion 112 whose end is closed by the sealing film 140, and is prepared in a state where the connection port portion 112 is provided with a male screw. The The vial 20 contains a medicine (not shown), is closed by a pierceable stopper 40, is covered with a heat insulator 30, and is provided with a cylindrical connecting end 132 integrally with an outer shell 31 of the heat insulating body. Are provided with a female screw, and a packing 29 for liquid-tightly sealing the periphery of the passage 155 between the vicinity of the outer periphery of the plug body 40 and the connecting end. The connection port portion 112 of the infusion bag 10 and the connection end on the vial side are screwed together to assemble the drug enclosure container set 6 as shown in FIG. The structural function of the heat insulator 30 is selected so that the quality of the drug contained in the vial does not deteriorate in the sterilization temperature atmosphere necessary for sterilization of the first drug enclosure. The assembled medicine container set 6 as a whole is heated and sterilized in a sterilizer.
[0035]
A procedure in the case of injecting a drug using the drug enclosure container set 6 having the configuration shown in FIG. 5 will be described. First, the somewhat enlarged end portion 141 of the communication tool 144 is pressed from the outside of the flexible infusion bag 10 toward the plug body 40, and the sharp tip 145 of the communication tool 144 passes through the partition wall 140 and the plug body 40. (FIG. 6), the tip opening 143 adjacent to the tip 145 is communicated with the inside of the vial 20, whereby the inside of the infusion bag 10 and the inside of the vial 20 are communicated via the tip opening 143 (FIG. 6) and the passage 142. . The infusion solution in the infusion bag 10 is caused to flow into the vial 20 through this communication path, and the medicine in the vial is dissolved and fluidized in the infused infusion solution. The mixed and fluidized drug in the vial 20 is returned to the drug solution bag 10 by gravity or the like to form a drug solution and drug mixture in the drug solution bag. Next, a hanging tool (not shown) is engaged with an infusion stand, the plug 17 of the medicinal solution discharge port 16 is punctured with a hollow needle, and the mixed medicinal solution is instilled to the patient via a tube connected to the hollow needle and the hollow needle. To do.
[0036]
FIG. 7 is a schematic cross-sectional view of the drug enclosure container set 7 of the third embodiment of the present invention. The same members as those of the first or second embodiment are denoted by the same reference numerals, and description thereof is omitted. The drug-filled container set 7 of this embodiment is a resin vial covered with an infusion bag 10 and a heat insulator 30 as in the first embodiment (FIG. 1) and the second embodiment (FIGS. 5 and 6). 20 and a communication mechanism 50. The communication mechanism 50 of this embodiment is extremely simplified in structure. That is, it is formed of a tubular member 232 that is formed integrally with the lid 34 of the vial and is closed at the tip. A breakable portion 90 is provided at the tip of the tubular member 232, and is broken by applying a bending force from the outside of the infusion bag 10. The possible portion 90 can be broken, and the inside of the vial 20 and the inside of the infusion bag 10 can be brought into a liquid communication state via the passage 242.
[0037]
FIG. 8 is a schematic cross-sectional view of the medicine enclosure container 8 of the fourth embodiment of the present invention. The same members as those of the first to third embodiments are denoted by the same reference numerals and description thereof is omitted. The drug enclosure container set 8 of this embodiment includes an infusion bag 10, a drug bag 220 covered with a heat insulator 30, and a communication mechanism 150. The communication mechanism 50 of this embodiment is extremely simplified in structure. That is, an opening is provided in the edge 14 of the first chamber 11 of the infusion bag 10 and the inner surface of the opening is bonded to the outer surface of the opening of the first chamber 211 of the drug bag 220, and the inside of the first chamber 11 of the infusion bag 10 and the drug bag 220. A passage 342 communicating with the interior of the first chamber 211 is formed. The passage 342 is closed by providing a peelable adhesive portion 119, but if the first chamber 11 of the infusion bag 10 and the first chamber 211 of the drug bag 220 are empty, the peelable adhesive of the infusion bag 10 Since the peelable adhesive portion 219 of the portion 19 or the chemical solution bag 220 closes the passage 342, the peelable adhesive portion 119 of the passage 342 can be omitted.
[0038]
A plurality of drug bags 220 and communication mechanisms 150 are provided as necessary. The heat insulation performance of the heat insulator 30 that covers the outer surface of each drug bag is selected so that the drug sealed in each drug bag is maintained at a temperature that does not exceed the heat resistant temperature in the heat sterilization process. The heat insulator 30 can be a resin heat insulating material, ceramic, or heat insulating space. The heat insulator can be formed of a coolant for the purpose of protecting the drug in the second drug enclosure (drug bag) from the high temperature in the heat sterilization process.
[0039]
A procedure in the case of injecting a drug using the drug enclosure container set 8 having the configuration shown in FIG. 8 will be described. First, the work of mixing and fluidizing the drug solution in the drug solution bag and the drug in the drug bag is performed. That is, a pressing force is applied from the outside to the chemical solution in the second chamber 18 of the chemical solution bag 10 in which a relatively large amount of chemical solution is sealed, and the peelable adhesive portion 19 is peeled off to flow the chemical solution into the first chamber 11. When the peelable adhesive portion is provided in the passage 342, the first chamber 11 and the pressing force are further applied to peel the peelable adhesive portion of the passage, and the chemical solution flows into the first chamber 211 of the drug bag 220. When a solid medicine is sealed in the second chamber 21 of the medicine bag 220, a pressing force is further applied to the medicine solution bag 10, the first chamber 211, and the first chamber 211 of the medicine bag 220 from the outside, and the peelable adhesive portion The two bags are made to communicate with each other by a passage, and the chemical solution and the drug are mixed and fluidized. When the drug solution is sealed in the drug bag 220, a pressing force is also applied to the drug bag 220 to peel off the peelable adhesive portion so that both bags communicate with each other through a passage, and the drug solution and the drug are mixed and fluidized. Next, the hanger 33 is engaged with an infusion stand, the plug 17 of the medicinal solution discharge port 16 is punctured with a hollow needle, and the mixed medicinal solution is instilled into the patient via a hollow needle and a tube connected to the hollow needle.
[0040]
FIG. 9 is a schematic cross-sectional view of a drug enclosure container set according to a fifth embodiment of the present invention. The same members as those of the first to fourth embodiments are denoted by the same reference numerals, and description thereof is omitted. The medicine enclosure container set of FIG. 9 has a configuration in which the heat insulator 30 is removed from the medicine enclosure container set of FIG. That is, FIG. 9 is a schematic cross-sectional view of an essential part of a drug enclosure container set according to a fifth embodiment of the present invention. The drug enclosure container set 5 shown in FIG. 9 includes a resin infusion bag (first drug enclosure) 10, a drug enclosure vial 20, and a closed communication mechanism 50 that connects the infusion bag 10 and the vial 20. Sealing packing 29 is disposed between the end of the vial neck 22 and the upper surface of the flange 51. The engaging portion 54 includes three or more engaging claws 53 that engage with a recess in the outer peripheral surface of the neck portion 22 of the vial. A cylindrical portion 51 ′ hangs downward from the periphery of the flange 51 and covers the port portion 12.
[0041]
The container set in FIG. 9 is sterilized or sterilized by steam sterilization, electron beam irradiation, γ-ray irradiation, or ultraviolet irradiation without a protector in the assembled state. Therefore, both the first drug enclosure and the second drug enclosure are required to have the same resistance to heat, electron beam, γ-rays or ultraviolet rays in the sterilization or sterilization process and not to be altered. In the container set of FIG. 9, the operating rod 46 extends through the central through hole 52 of the flange 51, extends through the cylindrical support 56 and the support hole 58 provided in the end plate of the support 56, and The first chamber 11 has an end 45. The closed communication mechanism 50 is configured so that it can be manually in a liquid communication state from the outside of the infusion bag 10.
[0042]
The first drug enclosure can be formed by the multi-chamber bag 10 shown in FIG. The multi-chamber bag 10 of FIG. 10 includes a peripheral portion 15, two port portions 12, 12, and a hanging portion 33, and each drug component partitioned by a detachable partition wall 19, 19 ′ includes a plurality of chambers C1 to C4. Each drug component is filled and stored. The medicine accommodated in each of the rooms C1 to C4 of the multi-chamber bag is, for example, medical dietary beverages / foods such as intravenous fluids and liquid nutrients, peritoneal dialysis solution, organ preservation solution, organ washing, etc. It is a cleaning agent used for. The components blended in each drug are reducing sugars such as glucose, fructose and maltose, and various amino acids blended in amino acid preparations conventionally used for nutritional supplementation as an infusion solution. In addition, vitamins and trace element preparations can be accommodated in each room.
[0043]
【The invention's effect】
The drug container set according to the present invention can be brought into a communication state in which the drug can be communicated manually from the outside of the first drug container or the second drug container without causing bacterial contamination immediately before administration. The medicines in the first medicine enclosure and the plurality of second medicine enclosures can be mixed through the communication mechanism in the communication state.
[0044]
The drug enclosing container set of the present invention is the same as the first drug enclosing container (chemical solution bag) and the first drug enclosing container having different resistance to heat resistant temperature, electron beam, γ-ray, ultraviolet ray and the like. It is possible to perform a sterilization or sterilization process using high-temperature steam, electron beam irradiation, γ-ray irradiation, or ultraviolet irradiation without damaging the drug component. The present invention can sterilize or sterilize the entire drug-enclosed container set by a conventional heat sterilization method such as high-pressure steam sterilization or shower sterilization, which can easily guarantee sterility. In addition, it is possible to ensure the sterility of the entire medicine-enclosed container set reliably and easily.
[0045]
Since the sterilization process is generally performed after the assembly of the drug enclosure container set of the present invention, it is not necessary to perform the assembling work in an aseptic room which is expensive and troublesome, and the cost and time can be greatly reduced. In the example of FIG. 1 in which the plug of the present invention is pushed out, there is no need for puncturing, so there is no foreign matter such as coring, and a wide flow path is ensured when dissolving the chemical solution. Therefore, a pumping operation at the time of drug dissolution becomes unnecessary, and the drug dissolution time is shortened. Furthermore, since no puncture needle is used, there is no risk of injury to the nurse during work.
[0046]
In the embodiment of FIG. 1 to FIG. 6 of the present invention, the communication operation only pushes the communication tool, and no operator (nurse) training is required.
[Brief description of the drawings]
FIG. 1 is a schematic cross-sectional view of an essential part of a drug enclosure set according to a first embodiment of the present invention.
FIG. 2 is a schematic cross-sectional view of a main part in a state where a communication mechanism of the drug enclosure container set of FIG. 1 is in a communication state.
FIG. 3 is a schematic cross-sectional view showing a two-chamber bottle of a modification of the second drug enclosure in the first embodiment.
4A is a schematic side view of the plug body, and FIG. 4B is a schematic cross-sectional view of the plug body.
FIG. 5 is a schematic cross-sectional view of a drug enclosure container set according to a second embodiment of the present invention.
6 is a schematic cross-sectional view of a state in which a communication mechanism of the drug enclosure container set of FIG. 5 is in a communication state.
FIG. 7 is a schematic cross-sectional view of a drug enclosure container set according to a third embodiment of the present invention.
FIG. 8 is a schematic sectional view of a drug enclosure container set according to a fourth embodiment of the present invention.
FIG. 9 is a schematic sectional view of a drug enclosure container set according to a fifth embodiment of the present invention.
FIG. 10 is a schematic cross-sectional view of a multi-chamber container that can be used for the first drug enclosure container of the drug enclosure set of the present invention.
[Explanation of symbols]
5, 6, 7, 8: Drug enclosure container set, 10: Infusion bag (first drug enclosure container, multi-chamber container), 11: First chamber, 12: Port part, 13: Flange part, 14: Seal part, 15: peripheral part, 16: discharge port, 17: plug, 18: second chamber (medical solution part), 19: peelable adhesive part, 20: vial (second drug enclosing container), 21: drug, 22: neck part , 25: heat insulating material, 30: protective body (heat insulating body), 31: outer shell, 33: hanging tool, 34: lid, 40: plug, 41: skirt, 42: annular convex, 43: head , 44: recess, 46: operation rod (operation tool), 50: communication mechanism, 51: flange, 52: through hole, 55: passage, 56: support, 58: support hole, 90: break-off portion, 112 : Connection port part, 114: support hole, 119: peelable adhesive part, 120: two-chamber bottle (second drug enclosure), 1 1: Chemical solution, 124: Constricted part, 126: Second chamber, 127: Inner plug, 144: Hollow needle, 140: Sealing membrane, 141: End part, 142: Passage, 143: Opening at the tip, 144: Communication tool 145: tip, 146: rib, 150: communication mechanism, 219: peelable adhesive part, 220: two-chamber bag (second drug enclosure), 232: tubular member, 242 and 342: passage.
F: Channel.

Claims

第１薬剤封入容器と第２薬剤封入容器が閉鎖された連通機構により連結され、閉鎖された連通機構は、手動により薬剤を通過可能な連通状態にすることができる薬剤封入容器セットを製造する方法であって、
１又は複数の第２薬剤封入容器と第１薬剤封入容器を閉鎖された連通機構を介し連結する工程、１又は複数の第２薬剤封入容器の外面の少なくとも一部を保護体により覆う工程、並びに連結された第１薬剤封入容器及び保護体により覆われた第２薬剤封入容器を同時に加熱、電子線、γ線又は紫外線により滅菌又は殺菌する工程を含み、
保護体は、滅菌又は殺菌工程において第２薬剤封入容器内の薬剤が変質しないように保護可能であり、
閉鎖された連通機構は、第１薬剤封入容器と前記バイアルを連通する通路、該通路を閉鎖する閉鎖体、及び閉鎖体を移動させる手段を含むことを特徴とする方法。A method of manufacturing a drug enclosure container set in which a first medicine enclosure and a second medicine enclosure are connected by a closed communication mechanism, and the closed communication mechanism can be in a communication state in which a medicine can be manually passed. Because
Connecting the one or more second drug enclosure containers and the first drug enclosure container via a closed communication mechanism, covering at least a part of the outer surface of the one or more second drug enclosure containers with a protector, and A step of simultaneously sterilizing or sterilizing the connected first drug enclosure container and the second drug enclosure container covered with the protective body with electron beam, γ-ray or ultraviolet ray ,
Protection body, Ri protectable der as agents of the second agent within the enclosure is not deteriorated in sterilization or disinfection process,
The closed communication mechanism includes a passage for communicating the first drug enclosure and the vial, a closing body for closing the passage, and means for moving the closing body .

滅菌又は殺菌工程は、加熱処理によって行なわれ、第２薬剤封入容器に収容される薬剤の耐熱温度が、第１薬剤封入容器に収容される薬剤の耐熱温度より低く、保護体は、断熱体であり、断熱体は、樹脂製断熱材、セラミック、密閉空間、又は第２薬剤封入容器の外面に隣接する冷却材からなり、第２薬剤封入容器の薬剤に対する加熱処理の影響を軽減する性能を備える請求項１の方法。 The sterilization or sterilization step is performed by heat treatment, and the heat resistance temperature of the medicine accommodated in the second medicine sealing container is lower than the heat resistance temperature of the medicine accommodated in the first medicine sealing container, and the protective body is a heat insulator. Yes, the heat insulator is made of a resin heat insulating material, ceramic, a sealed space, or a coolant adjacent to the outer surface of the second drug enclosure container, and has a performance of reducing the influence of the heat treatment on the drug in the second drug enclosure container. The method of claim 1.

滅菌又は殺菌工程は、電子線、γ線又は紫外線の照射により行われ、保護体は、電子線、γ線又は紫外線の遮蔽体である請求項１の方法。 The method according to claim 1, wherein the sterilization or sterilization step is performed by irradiation with electron beam, γ-ray or ultraviolet ray, and the protective body is an electron beam, γ-ray or ultraviolet ray shielding body.

第２薬剤封入容器は、薬剤を封入したガラス又は樹脂製のバイアルである請求項１乃至３のいずれか１項の方法。 The method according to any one of claims 1 to 3, wherein the second medicine enclosure is a glass or resin vial containing the medicine.

第１薬剤封入容器は、輸液を前記連通機構の閉鎖体により封入した可撓性輸液バッグである請求項１乃至４のいずれか１項の方法。The method according to any one of claims 1 to 4, wherein the first drug enclosure is a flexible infusion bag in which an infusion is enclosed by a closing body of the communication mechanism.

滅菌又は殺菌工程の後に保護体を第２薬剤封入容器の外面から除去する工程を更に含む請求項１乃至５のいずれか１項の方法。The method according to any one of claims 1 to 5 , further comprising a step of removing the protective body from the outer surface of the second drug enclosure after the sterilization or sterilization step.

薬剤封入容器セットであって、第１薬剤封入容器、１又は複数の第２薬剤封入容器、及び第１薬剤封入容器と第２薬剤封入容器を連結する閉鎖された連通機構を備え、閉鎖された連通機構は、第１薬剤封入容器又は第２薬剤封入容器の外部から手動により薬剤を連通可能な連通状態にすることができるものであり、第１薬剤封入容器、１又は複数の第２薬剤封入容器、及び閉鎖された連通機構を、同時に且つ１又は複数の第２薬剤封入容器の外面の少なくとも一部を保護体で覆うことにより第２薬剤封入容器内の薬剤を加熱、電子線、γ線又は紫外線による滅菌又は殺菌工程で変質しない保護状態として滅菌又は殺菌してなり、
第１薬剤封入容器は、可撓性の輸液バッグであり、第２薬剤封入容器は、剛固な筒状口部を有する容器であり、閉鎖された連通機構は、容器の筒状口部と輸液バッグ内を薬剤が通過するように連通状態にする通路、筒状口部に液密に挿着され通路を閉じる閉鎖体、及び挿着された閉鎖体を筒状口部から移動させ通路を開くための操作具を備える薬剤封入容器セット。A drug enclosure set comprising a first drug enclosure, one or more second drug enclosures, and a closed communication mechanism connecting the first drug enclosure and the second drug enclosure. The communication mechanism can be in a communication state in which the drug can be manually communicated from the outside of the first drug sealed container or the second drug sealed container, and the first drug sealed container, one or a plurality of second drug sealed The container and the closed communication mechanism are heated at the same time and at least a part of the outer surface of the one or more second drug enclosure containers is covered with a protective body to heat the drug in the second drug enclosure container , electron beam, γ-ray or Ri Na sterilization or disinfection to a protection state which is not deteriorated by sterilization or sterilization step by ultraviolet light,
The first drug enclosing container is a flexible infusion bag, the second drug enclosing container is a container having a rigid cylindrical mouth, and the closed communication mechanism is connected to the cylindrical mouth of the container. A passage that allows the medicine to pass through the infusion bag, a closed body that is liquid-tightly inserted into the cylindrical mouth and closes the passage, and the inserted closed body is moved from the cylindrical mouth to move the passage. A drug enclosure set with an operation tool for opening .

滅菌又は殺菌工程は高圧蒸気又は熱水シャワーによる加熱処理によりなされ、保護体は、樹脂製断熱材、セラミック、密閉空間、又は冷却材からなる断熱体である請求項７の薬剤封入容器セット。The drug-filled container set according to claim 7 , wherein the sterilization or sterilization step is performed by heat treatment using high-pressure steam or hot water shower, and the protective body is a heat insulator made of resin heat insulating material, ceramic, sealed space, or cooling material.

滅菌又は殺菌工程は、電子線、γ線又は紫外線の照射により行われ、保護体は、電子線、γ線又は紫外線の遮蔽体からなる請求項７の薬剤封入容器セット。Sterilization or disinfection process, an electron beam is carried out by irradiation with γ-rays or ultraviolet rays, the protective body, an electron beam, the drug enclosed container set according to claim 7 comprising a shield of γ-rays or ultraviolet light.

第２薬剤封入容器は、ガラス又は樹脂製のバイアルであり、操作具は、一端が閉鎖体に係合され輸液バッグ内に他端を有する操作ロッドを備え、操作ロッドは輸液バッグの外部から手動で操作し閉鎖体を移動させ通路を開くことができる請求項７乃至９のいずれか１項の薬剤封入容器セット。The second drug enclosure is a glass or resin vial, and the operation tool includes an operation rod having one end engaged with the closing body and having the other end in the infusion bag. The operation rod is manually operated from the outside of the infusion bag. The medicine enclosure container set according to any one of claims 7 to 9, which can be operated to move the closing body to open the passage.

第１薬剤封入容器は、薬液封入室及び薬剤封入室を備える可撓性バッグからなり、隣接する薬液又は薬剤封入室の間の仕切りが剥離容易な接着部により形成される請求項７乃至１０の薬剤封入容器セット。First agent enclosure is made of a flexible bag with a drug solution-filled chamber and drug-filled chamber, the claims 7 to 10 partition between adjacent drug solution or drug-filled chamber is formed by easily adhesive portion peeling Drug container set.

滅菌又は殺菌工程の後に保護体が第２薬剤封入容器の外面から除去されたものである請求項７乃至１１のいずれか１項の薬剤封入容器セット。The drug enclosure set according to any one of claims 7 to 11 , wherein the protective body is removed from the outer surface of the second drug enclosure after the sterilization or sterilization step.

薬剤封入容器セットであって、第１薬剤封入容器、１又は複数の第２薬剤封入容器、第２薬剤封入容器の外面の少なくとも一部を覆う保護体、及び第１薬剤封入容器と第２薬剤封入容器を連結する閉鎖された連通機構を備え、閉鎖された連通機構は第１薬剤封入容器又は第２薬剤封入容器の外部から手動により薬剤が通過可能な連通状態にすることができるものであり、保護体は第２薬剤封入容器内の薬剤が加熱、電子線、γ線又は紫外線による滅菌又は殺菌工程により変質しないように保護するものであり、
第１薬剤封入容器は少なくとも１つの薬剤封入室を備える可撓性バッグからなり、前記可撓性バッグは剛固な筒状首部を備え、第２薬剤封入容器はガラス又は樹脂製のバイアルであり、閉鎖された連通機構は、筒状首部に液密に接続され中央に貫通孔を有するフランジ、フランジから伸長しバイアルの筒状口部外周に嵌合可能な嵌合部、フランジから筒状首部内へ伸長する支持体、筒状口部の内部及び貫通孔を含みバイアル内部と前記可撓性バッグ内部を液体連通可能な通路、バイアルの筒状口部内周面に液密に挿着され通路を閉じる閉鎖体、及び閉鎖体に一端を接続され筒状首部内へ伸長する操作体を備え、保護体は、一端においてフランジ外周部に係合される外筒部材及び外筒部材の他端を閉じる端板からなる外殻、及びバイアルと外殻との間に配置される断熱材からなる薬剤封入容器セット。A medicine enclosure container set, a first medicine enclosure, one or more second medicine enclosures, a protective body covering at least a part of the outer surface of the second medicine enclosure, and the first medicine enclosure and the second medicine A closed communication mechanism for connecting the enclosure is provided, and the closed communication mechanism can be brought into a communication state in which the medicine can be manually passed from the outside of the first medicine enclosure or the second medicine enclosure. , protective body all SANYO to protect the drug in the second drug enclosed vessel heating, not degenerated electron beam, the sterilization or disinfection process by γ-rays or ultraviolet rays,
The first drug enclosure is a flexible bag having at least one drug enclosure, the flexible bag has a rigid cylindrical neck, and the second drug enclosure is a glass or resin vial. The closed communication mechanism includes a flange that is liquid-tightly connected to the cylindrical neck and has a through hole in the center, a fitting portion that extends from the flange and can be fitted to the outer periphery of the cylindrical mouth of the vial, and the cylindrical neck from the flange A support body extending inward, a passage including the inside of the cylindrical mouth portion and the through hole, and a fluid communication between the inside of the vial and the inside of the flexible bag, and a passage which is liquid-tightly inserted into the inner peripheral surface of the cylindrical mouth portion of the vial A closed body, and an operating body connected at one end to the closed body and extending into the cylindrical neck, and the protective body includes an outer cylinder member engaged at one end with the outer peripheral portion of the flange and the other end of the outer cylinder member. Outer shell with closed end plate, and vial and outer shell Drug enclosure set of heat insulating material disposed between.

支持体は、フランジの貫通孔のまわりから筒状首部内へ伸長する筒状体を含み、筒状体は、通路を形成する透孔及び操作体を摺動可能に支持する支持部を備える請求項１３の薬剤封入容器セット。The support body includes a cylindrical body that extends from around the through hole of the flange into the cylindrical neck, and the cylindrical body includes a through hole that forms a passage and a support portion that slidably supports the operation body. Item 13. A medicine-enclosed container set according to item 13 .

滅菌又は殺菌工程は、第１薬剤封入容器、１又は複数の第２薬剤封入容器、及び閉鎖された連通機構を、同時に滅菌又は殺菌することを含み、第１薬剤封入容器と第２薬剤封入容器は、それぞれ滅菌又は殺菌工程における加熱又は電子線、γ線、紫外線の照射に耐える安定な薬剤を収容する請求項１３又は１４の薬剤封入容器セット。The sterilization or sterilization step includes simultaneously sterilizing or sterilizing the first drug enclosure, the one or more second drug enclosures, and the closed communication mechanism, and the first drug enclosure and the second drug enclosure 15. The medicine-filled container set according to claim 13 or 14 , which contains a stable medicine that can withstand heating or electron beam, γ-ray, and ultraviolet irradiation in a sterilization or sterilization process, respectively.