JP4483037B2

JP4483037B2 - Resin container for enclosing medical liquid and port member

Info

Publication number: JP4483037B2
Application number: JP2000184921A
Authority: JP
Inventors: 藤男野上
Original assignee: Ajinomoto Co Inc
Current assignee: Ajinomoto Co Inc
Priority date: 2000-06-20
Filing date: 2000-06-20
Publication date: 2010-06-16
Anticipated expiration: 2020-06-20
Also published as: JP2002000702A

Description

【０００１】
【発明の属する技術分野】
本発明は、医療用液体、例えば、静脈投与用輸液剤、液状栄養剤、腹膜透析液などを収容する可撓性容器に関し、特に２以上の成分を投与直前に混合可能に収容する多室の容器、及び可撓性容器に組込まれ溶着により生じる不要粒子を散逸させないポート部材に関する。
【０００２】
【従来の技術】
医療用液体、例えば人体に点滴により栄養を供給する輸液は、典型的には、ポート部材を備える樹脂製の可撓性容器に収容される。ポート部材は、中空針等の連通具で貫通可能な閉鎖体等の閉鎖体を備え、閉鎖体を貫通した連通具を介し、容器内へミネラル液等を注入することや容器内の液体を注出し点滴用チューブ内へ送ることが可能にされる。また、容器の相対する内壁面の一部を剥離可能に接着して形成される接着部により容器内を第１室及び第２室に仕切り、各室に異なる薬液を収容するもの（ダブルバッグ）が知られる。医療用液体を可撓性容器内へ充填する一般的方法は、液体を無菌的な不活性ガス雰囲気下で閉鎖体を外した注出口から容器内へ充填する段階、その後、注出口の外方端を閉鎖体により閉塞する段階から成る。
【０００３】
特開平７−１７８１５１号公報又は特公平６−２６５６３号公報は、剥離可能な隔離手段により２つの個室が形成された可撓性樹脂からなる容器の第１室に脂肪乳剤及びアミノ酸を収容し、第２室に糖と電解質を収容し、投与時に第１室又は第２室を外から押圧して隔離手段を離間させ両室の液を混合する容器を開示する。また、特公平５−１０９４５号公報は、第１室又は第２室が輸液排出口（注出口）に連通され、注出口の外方端がゴム栓で閉鎖され、容器内の輸液が、投与時に点滴用チューブに取付られた中空針をゴム栓に突き刺し、中空針を介し容器内と点滴用チューブ内を連通させ、容器内から点滴用チューブ内へ重力の作用で送られる容器を開示する。
【０００４】
特開平１１−２６２５１３号公報は、ポリプロピレン又はそのポリマー組成物の混注口／排出口（ポート部材）を備え、混注口／排出口のくもり価が７５％以下で、且つロックウェル硬さが７５以上である医療用容器を開示する。この公報は、容器シートの材料をアイソタクチックタイプのポリプロピレンコポリマーとすること、混注口／排出口の材料をアイソタクチックタイプ又はシンジオタクチックタイプのポリプロピレンとし、混注口／排出口の保持具の材料をポリプロピレンとすること等を開示する。容器シートのくもり価や剥離可能な接着部の形成については、開示されていない。
【０００５】
特開平９−２４５８１号公報は、医薬多室バッグを非ＰＶＣ（非塩化ビニル）多層フィルムで製造すること、非ＰＶＣ多層フィルムの内層をＶＩＣＡＴ軟化点が１３０℃のポリプロピレンランダムコポリマーとすること等を開示する。ポリプロピレンランダムコポリマーは、プロピレン・α−オレフィン共重合体の一種である。この公報は、ポート部材の形成、剥離可能な接着部の形成等は開示していない。
【０００６】
特許第２７０６０２５号公報は、多層フィルムを用いて形成した容器を開示する。この多層フイルムは、ポリオレフィンを主成分とする３層から成り、外気に触れる外層は、ポリプロピレンとエチレン・α−オレフィン共重合体との混合物、内層が密度０．９２５ｇ／ｃｍ³以上の連鎖状エチレン・α−オレフィン共重合体樹脂、中間層が密度０．９２５ｇ／ｃｍ³以下の連鎖状エチレン・α−オレフィン共重合体を含む単層又は多層で形成される。この公報は、ポート部材の形成、剥離可能な接着部の形成等は開示していない。
【０００７】
【発明が解決しようとする課題】
本発明の第１の目的は、医療用液体中に可塑剤の溶出の可能性がなく廃棄処理の問題のない多室形式の樹脂製容器を提供することである。本発明の他の目的は、ポート部材と容器本体の樹脂フィルムとの間の接着不良のない樹脂製容器を提供することである。本発明の別の目的は、ポート部材の筒体とキャップ状の保持具との間に滅菌加熱による容器内部の高圧に耐える十分な強度の溶着部を備えるポート部材を提供することである。本発明の更に別の目的は、筒体と保持具との間の溶着部の形成により生じるハミダシ（バリ）を散逸しないポート部材を提供することである。
【０００８】
本発明の更に別の目的は、容器本体を複数の分室に区画する剥離可能な接着部を容易に製造できる樹脂製容器を提供することであり、人体に点滴により投与される液状栄養剤を収容する樹脂製容器であって、ビタミンやミネラルの微量成分を変質を避けて投与直前に混合するため分室に収容保持し、必要なときに容易に混合することが可能な容器を提供することである。
【０００９】
本発明の更に別の目的は、第十三改正日本薬局方解説書一般試験法に記載されている１１５℃以上とりわけ１２１℃の滅菌を行っても容器の透明度が維持でき、容器内部の液体の様子が容易に観察できる透明度の高い樹脂製容器を提供することである。これにより、従来の透明度の低い容器では検知率が上がらなかったカメラ撮像による医療用液体を充填した樹脂製容器内の異物検査（特開平１１−１２５６０４号公報）において、検知率を向上させることが可能となる。また、本発明の容器を採用することにより異物検査装置を製造・検査ラインに組み込むことができ、従来人による目視検査を行っていた場合に比べ省力化できる。さらに、医療用液体を充填した樹脂製容器のみならず、容器の製袋時において、また医療用液体充填工程に搬送される空容器共に異物検査がしやすくなり不良品を確実に排除できる。他方、医療用液体が輸液である場合、これを患者に投与する際、投与量を適切に制御するため、あるいは点滴終了の時期を確認するために液位を監視する必要がある。この際、容器内の液面の視認性が低いと輸液管理に支障をきたす。透明度の高い本発明の容器は、液位が見やすく前記輸液管理上優れた効果を奏する。本発明の其の他の目的及び利点は、図面及び以下の説明から明瞭にされる。
【００１０】
【課題を解決するための手段】
本発明の医療用液体を封入する樹脂製容器は、袋状の樹脂製容器本体及び少なくとも１つのポート部材を備え、容器本体内部が相対する内壁面の一部を液密に且つ剥離可能に接着して形成される接着部により複数の分室に区画され、接着部は、容器本体外部からの１０〜４０ｋｇｆの押圧力により剥離可能であり、接着部が剥離することにより接着部の両側の分室が互いに連通し分室内の液体が混合される。ポート部材は、ゴム栓等の閉鎖体、筒体及び保持具を備え、閉鎖体を貫通する中空針等の連通具を介し容器本体内の液体を注出又は容器本体内へ液体を注入可能であり、ポート部材を構成する筒体及び容器本体の内壁面は、いずれもＶＩＣＡＴ軟化点が１２１℃以上のプロピレン・α−オレフィンランダム共重合体により形成される。
【００１１】
本発明の医療用液体を封入する樹脂製容器は、次の構成を備えることができる。（１）容器本体は、実質的にスチレンエラストマーを含有しない樹脂により形成される。本発明容器を例えば輸液容器とした場合、各種栄養剤を含む収容液が直接静脈内に投与される。従って、樹脂製容器は人体に対して毒性を発現しない樹脂で構成されなければならない。また、主原料となる樹脂のみならずそれに添加される各種のエラストマーも同様に毒性の有無についての配慮が必要である。そこで、本発明の容器及びポート部材は、好ましい実施態様において、環境ホルモンとしての作用が懸念されるスチレンエラストマーを実質的に含有しない樹脂により形成される。
【００１２】
（２）容器本体は、プロピレン・α−オレフィンランダム共重合体からなる単層の樹脂フィルムで形成される。（３）容器本体は、プロピレン・α−オレフィンランダム共重合体からなる内層を備える多層の樹脂フィルムで形成される。（４）筒体及び容器本体の内壁面を構成するプロピレン・α−オレフィンランダム共重合体は、プロピレン−エチレンランダム共重合体である。（５）容器の滅菌後の透明度が８０％以上である。
【００１３】
本発明の医療用液体を封入する樹脂製容器に取付けられるポート部材は、閉鎖体、筒体及び保持具からなり、閉鎖体を貫通する連通具を介し容器本体内の液体を注出又は容器本体内へ液体を注入可能可能であり、閉鎖体の周囲が筒体と保持具の間に挟持される。筒体は、容器本体内部に配置される内方端、容器本体を形成するフィルムに液密に接着される外周面、並びに閉鎖体及び保持具を支持する外方端を有し、筒体の外方端は、外方環状凸部、上部外周面、並びに上部外周面の下方に配置される大径部を有する。保持具は、キャップ状であり、環状の天板部分、及び天板部分外周から下方へ伸長する円筒部分を有し、筒体の外方環状凸部と保持具の天板部分又はその近傍の内面との間に溶着部が形成される。筒体の大径部と保持具の円筒部分の間に粒子封止部が形成される。
【００１４】
本発明の医療用液体を封入する樹脂製容器に取付けられるポート部材は、次の構成を有することができる。（６）筒体の外方端は、外方環状凸部の端面と上部外周面が交叉し形成される環状角部を有し、保持具は、天板部分の内面外周部と円筒部分の内周面上端とを連結する円錐面部分を有し、溶着部は、筒体の環状角部が保持具の円錐面部分に超音波エネルギーにより加熱溶着されて形成される。（７）外方環状凸部は、その端面から突出する断面三角形状の突起を有し、溶着部は、保持具の天板部分の内面と断面三角形状の突起の先端部分が超音波エネルギーにより加熱溶着されて形成される。（８）筒体の上部外周面の大径部は、フランジ部により形成され、粒子封止部は、筒体のフランジ部が保持具の円筒部分の端面に係合されて形成される。
【００１５】
（９）筒体の上部外周面の大径部は、下方へ向って直径が増加するテーパ部により形成され、粒子封止部は、筒体のテーパ部が保持具の円筒部分の端面付近に係合されて形成される。（１０）筒体の外方端は、同心状に配置される内方環状凸部及び環状溝部を更に有する。（１１）閉鎖体は、外方端付近の中空部を閉鎖する円板部分、円板部分の外周部から下方へ伸長する内方環状垂下部、外方端付近の筒体内周面に嵌合する外周面、外周面から半径方向外方へ伸長する環状板部、環状板部の外周から垂下する外方環状垂下部、環状板部の外周から上方へ伸長する外方環状凸部、外周面と外方環状垂下部の間に形成される下方環状溝、円板部分の外方と外方環状凸部との間に形成される上方環状溝を有する。（１２）筒体はその下方に縮径部を有し、縮径部の外周面が容器本体の樹脂フィルムに接着される。
【００１６】
本発明のポート部材を容器本体に接着する方法は、筒体の縮径部の外周面が溶着可能に予熱される工程、その後に容器本体を形成する樹脂フィルムの開口部へ当接し成形溶接する工程を含み、成形溶接する工程は、ダイを樹脂フィルムの外方から樹脂フィルムに当て、加熱しながら押圧し接着し成形する工程を含む。
【００１７】
本発明のポート部材は、その内部にビタミン類を有効成分とする凍結乾燥物を収容することができる。より具体的には、例えば特公平７−１１６０２２記載のビタミン類の凍結乾燥容器に用いられているバイアルに替え、本発明のポート部材を凍結乾燥用容器として用いることができる。そして、前記凍結乾燥物を収容するポート部材は常法によりピンホールなく容器本体へ溶着されることはもちろんである（特開平１０−４３２７２公報や特開平１０−１６５４８０公報）。
【００１８】
【発明の実施の態様】
図面を参照し、本発明の実施例を説明する。図１は、本発明の医療用液体を封入する多室容器の実施例の概略平面図、図２は、図１の多室容器の概略側面図、図３は、図１の線Ｔ−Ｔに沿うポート部材付近の断面図である。これらの図において、対応する部分には、同一の符号を付し、重複した説明を省略する。図１〜図３において、医療用液体を封入する樹脂製容器１は、袋状の樹脂製容器本体２及び３つのポート部材３、３を備える。容器本体２は、接着部１８，１９により複数の分室Ｃ１〜Ｃ４に区画され、それぞれ医療用液体Ｍ１、２又は粉末等固形薬剤を収容可能にされる。
【００１９】
容器本体内を複数の分室に区画する接着部１８，１９は、容器本体の相対する内壁面１４、１６の一部が液密に且つ剥離可能に接着して形成される。接着部は、各分室Ｃ１〜Ｃ４に薬剤Ｍ１、Ｍ２、又は固形薬剤を収容した状態で容器外部から人手で１０〜４０ｋｇｆの押圧力Ｆ、−Ｆを加えることにより剥離され、それにより複数の分室Ｃ１〜Ｃ２に収容された医療用液体Ｍ１〜Ｍ２が混合される。分室Ｃ１、Ｃ３、Ｃ４にポート部材３、３，３が設けられ、例えば、ポート部材の閉鎖体を貫通する中空針等の連通具４を介して容器内の液体を注出すること又は容器内へ液体を注入することが可能にされる。
【００２０】
図４〜図７は、ポート部材３を構成する保持具７０、筒体４０、ゴム栓からなる閉鎖体６０、及び組立状態の断面図である。これらの図において、対応する部分には、同一の符号を付し、重複した説明を省略する。
図４に示すように、保持具７０は、環状の天板部分７１、天板部分外周から下方へ伸長し端面７８を備える円筒部分７２、天板部分内周端７４付近から下方へ伸長する環状凸部７３、及び円筒部分７２の内周面７６の上端と天板部分内面７５の外周部を連結する円錐面部分７７を有する。
【００２１】
ここで本発明容器及び本発明容器を他の容器と組み合わせたキット製剤とした場合、収容可能な医療用液体又は固形薬剤に配合される成分としては、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が挙げられる。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。さらに、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。
【００２２】
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、アマニ油等の植物油、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。また、水溶性及び脂溶性の各ビタミン、例えばパルミチン酸レチノール、塩酸チアミン、リン酸リボフラビンナトリウム、塩酸ピリドキシン、シアノコバラミン、アスコルビン酸、コレカルシフェロール、酢酸トコフェロール、ニコチン酸アミド、パントテン酸カルシウム、葉酸、ビオチン、メナテトレノン、フィトナジオン等を、また電解質及び微量元素（ミネラル）として塩化ナトリウム、酢酸ナトリウム、硫酸マグネシウム、塩化マグネシウム、塩化カルシウム、リン酸二カリウム、リン酸一ナトリウム、グリセロリン酸カルシウム、塩化第二鉄、塩化マンガン、硫酸銅、硫酸亜鉛、ヨウ化カリウム等を挙げることができる。前記各成分の配合量は、投与される患者の要求量によって適宜決定される。
【００２３】
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。
【００２４】
本発明の容器は、前記各成分の安定性を実質的に損なうことなく収容できる特徴を具備している。好ましい態様としては、糖、電解質及びアミノ酸の各薬液をＣ１もしくはＣ２にそれぞれ収容し、小室Ｃ３に微量元素（ミネラル）の水溶液又は固形薬剤、ポート部材もしくはＣ４にビタミン類を凍結乾燥物（固形薬剤）あるいは水溶液として収容する経中心静脈栄養用キット製剤の形態を挙げることができる。これにより、配合変化する各成分を各区画室に隔離でき、各成分とくに配合変化しやすい成分を品質劣化させることなく経中心静脈栄養用の各成分を容器内に長期間収容できる。同様に、経腸成分栄養剤についての前述の効果を奏する。
【００２５】
また、別の態様としては、ポート部材に連通具等の連通具（ＷＯ９５／００１０１公報）を取り付け、ビタミン入りのバイアル又はプレフィルドシリンジ（特表平５−５０１９８３、特表平７−５０１００２）を接合した複数薬剤収容のキット製剤の形態としてもよい。この際、容器および連通具と連通具に連結されるバイアル又はプレフィルドシリンジは、連通操作が容易に行えるように剛性もしくは準剛性のトレーに収容される形態がより好ましい。更にビタミン類を前記キット製剤に収容する場合は、このトレーの全面、あるいは部分的に遮光フィルムが積層されていることが好ましい。また、トレーを形成する樹脂層の一つに水分非透過性、ガス非透過性のバリアーフィルムからなる層を設けてもよい。
【００２６】
更に、別の形態としては、前記バイアル、プレフィルドシリンジに替え固形薬剤の入った樹脂製の小袋を本発明の容器端部に、内層面が剥離することで対向する両室が連通可能となるよう連結したキット製剤としてもよい。なお、樹脂製小袋は、収容する薬剤の劣化を防止するための多重包装であってもよく、脱酸素剤、乾燥剤を包装内に収容しておくこともできる（ＷＯ９２／０８４３４公報）。
【００２７】
図５に示すように、筒体４０は、容器内部に配置される内方端４１、内方端において容器内部に連通される中空部４３を囲む内周面４４、容器を形成する樹脂フィルムに液密に接着される外周面４５、並びに閉鎖体及び保持具を支持する外方端４２を有する。外方端４２は、内方環状凸部５３、環状溝部５４、外方環状凸部５５、上部外周面５６、外方環状凸部５５の端面と上部外周面５６とが交叉して形成される環状角部５８並びに上部外周面の下方に配置されるフランジ部（大径部）５７を有する。
【００２８】
図６に示すように、閉鎖体（ゴム栓）６０は、円板部分６１、円板部分の外周部から下方へ伸長する内方環状垂下部６２、内方環状垂下部６２の外周面６３の上部から半径方向外方へ伸長する環状板部６４、環状板部６４の外周から垂下する外方環状垂下部６６、環状板部６４の外周から上方へ伸長する外方環状凸部６７、外周面６３と外方環状垂下部６６の間に形成される下方環状溝６５、円板部分の外方と外方環状凸部６７との間に形成される上方環状溝６８を有する。
【００２９】
図７に示すように、筒体４０の外方端４２に閉鎖体６０が嵌合され、保持具（キャップ）７０が閉鎖体６０を押さえるように組立られる。図４の保持具７０の断面図に示すように、保持具７０は、環状の天板部分７１、天板部分７１の外方端から下方へ伸長する円筒部分７２、円筒部分の下方の端面７８、天板部分７１の内周端７４付近から下方へ伸長する環状凸部７３、円筒部分７２の内周面７６の上端と天板部分７１の内面７５の外周部を連結する円錐面部分７７等を有する。
筒体４０、保持具（キャップ）７０、及び閉鎖体６０が組立られた図７の状態において、筒体の環状角部５８と保持具の円錐面部分７７が超音波振動エネルギーにより加熱溶着され、溶着部５９が形成される。溶着部５９は、筒体４０と保持具７０とを高強度で連結し、容器の加熱滅菌のため容器内部が高圧になる場合にも閉鎖体６０の移動を保持具７０が押さえ、外方端から外れないようにすることが可能にする。加熱溶着において、環状角部５８がエネルギー・ダイレクターを形成し、この部分に超音波振動が集中伝達され、局部的な摩擦熱が発生し、樹脂が溶融され溶着される。
【００３０】
図７において、筒体４０の筒体のフランジ部５７と保持具の円筒部分７２の端面７８が密封係合され、封止部７９が形成される。封止部７９は、溶着部の形成工程により生じるハミダシ（ばり）の通過を防止する。ハミダシは、超音波振動エネルギーによる樹脂の加熱溶着工程おいて必然的に発生し、容器に薬液を混注する際に使用されるクリーンベンチのフィルターを詰まらせ、クリーンベンチの清浄度を低下させる原因となっていた。図７のポート部材においても、溶着を確実に行うために、環状角部５８の外方にハミダシが発生するが、粒子封止部７９が形成されているため、ポート部材の外へ散逸されることはない。
【００３１】
図８は、容器本体に使用可能な非ＰＶＣ（非塩化ビニル）多層フィルム６の図解的な断面図である。多層フィルム６は、容器の内壁面１４又は１６を備える内層１４１、容器の外面を形成する外層１４４、及び中央層１４２、１４３を備える。内層１４１と外層１４４は、ＶＩＣＡＴ軟化点が１２１℃以上のプロピレン・α−オレフィンランダム共重合体、好ましくは、プロピレン−エチレンランダム共重合体により形成される。中央層１４２、１４３は、プロピレン−エチレンランダム共重合体とエチレン・α−オレフィン共重合体の混合樹脂で形成される。なお、中央層１４２、１４３は、３層若しくは４層であってもよく、その内の１層に水分非透過性、ガス非透過性のバリアーフイルムからなる層を設けてもよい。
【００３２】
容器本体は、図８の非ＰＶＣ（非塩化ビニル）多層フィルム６に代えて、単層のＶＩＣＡＴ軟化点が１２１℃以上のプロピレン・α−オレフィンランダム共重合体、好ましくは、プロピレン−エチレンランダム共重合体、例えば、三菱化学から販売されている商品名ＳＰＸ８０００番シリーズ、ＳＰＸ９０００番シリーズにより形成され得る。容器を形成する樹脂は、環境ホルモンとしての問題が懸念されるスチレン系エラストマーを含有しないものが適している。
【００３３】
また、容器を形成する樹脂は、ＶＩＣＡＴ軟化点が１２１℃以上のプロピレン・α−オレフィンランダム共重合体、好ましくは、プロピレン−エチレンランダム共重合体を使用し、容器内部の液体を容器外部から充分観察できるように、滅菌工程後の透明度が８０％以上であるようにされる。透明度は、試験片に対する標準光源からの光線の照射量と試験片を透過した光線の量の比であり、ヘイズ価とも呼ばれ、日本薬局方規格に規定される。
【００３４】
図７の実施例においては、筒体の環状角部５８と保持具の円錐面部分７７が超音波振動エネルギーにより加熱溶着され、溶着部５９が形成されるが、保持具に円錐面部分７７を形成する代わりに、筒体の外方環状凸部５５の端面から突出する断面三角形状の突起を設け、この突起の先端部分と保持具の天板部分の内面７５との間に溶着部を形成することができる。また、図７の実施例においては、筒体の上部外周面５６の下方にフランジ５７を設け、フランジ５７に保持具の端面７８を押圧し粒子封止部７９が形成されるが、フランジ５７に代え上部外周面５６に下方へ進むに従って直径が大きくなるテーパ部を設け、保持具の端面７８付近の内周面とテーパ部を係合させ、粒子封止部とすることができる。
【００３５】
図３及び図７に示すように、ポート部材３の筒体４０は、好ましくは下方部分の直径が縮小され縮径部４６とされ、この縮径部４６の外周面において容器本体の樹脂フィルムの内壁面１４，１６に接着される。縮径部４６の外周面と容器本体の樹脂フィルムの内壁面１４，１６との接着方法は、縮径部４６の外周面を予熱し、縮径部４６の厚さの約５０％を溶着温度、例えば、１８０℃にする段階、予熱された縮径部４６を、容器本体の樹脂フィルムの内壁面１４，１６の開口部へ挿入する段階、及びダイにより樹脂フィルムを加熱しながらその外方から予熱された縮径部４６の外周面へ押圧し、樹脂フィルムと外周面を溶着成形する段階を含む。
【００３６】
ポート部材３の筒体４及び保持具７０は、容器本体を形成するフィルムの材料と同じＶＩＣＡＴ軟化点が１２１℃以上のプロピレン・α−オレフィンランダム共重合体、好ましくは、プロピレン−エチレンランダム共重合体により形成されることにより、ポート部材３の容器本体への溶着不良が低減される。また、同一のそれ樹脂ペレットを容器の接着のための樹脂に使用することにより、樹脂の品質管理が容易であり、樹脂の品質変動による各部の接着不良率を低くすることができる。
【００３７】
図９は、固形薬剤Ｎを収容するポート部材３の概略断面図である。容器本体に収容される点滴用栄養剤又は経腸成分栄養剤に、安定性が悪く分解し易いビタミン類を含めるため、ビタミン類は、凍結乾燥され、層状の固形薬剤Ｎの形態において、ポート部材３の筒体４０の内方中空部４３に収容される。またビタミン類以外に、抗生物質等の薬剤が固形薬剤Ｎの形態で中空部４３に収容され得る。固形薬剤Ｎは、好ましくは、ポート部材３が容器本体の固着部２１に熱溶着される前に筒体４０内に収容される。またポート部材３が固形薬剤を収容する場合は、ポート部材の内方中空部に連通する容器本体の分室Ｃ４は、空室にされる。容器本体内の液体が人体へ投与するため容器外から押圧され接着部が剥離され混合されるとき、ポート部材に連通する分室の接着部も剥離され、分室及び固形薬剤の周囲へ液体が流入され固形薬剤が液体中へ溶解混合される。
【００３８】
図１０Ａは、薬剤バイアルが隣接されるポート部材の概略平面断面図であり、図１０Ｂは、図１０Ａの線Ｓ−Ｓに沿う断面図である。薬剤バイアル３２は、ビタミン、ミネラル、抗生物質、その他の薬剤成分を固形薬剤又は液状薬剤の形態で収容する。図１０Ａ及びＢにおいて、薬剤バイアル３２は、ポート部材３に一体に形成された円筒形ケース３５の内部にケースの軸方向に摺動可能に支持される。連通具３４が針先端をそれぞれポート部材３の閉鎖体６０及び薬剤バイエルの閉鎖体３３に隣接して配置される。薬剤バイエル３２はプレフィルドシリンジにより置換することができる。
【００３９】
図１０Ａ、図１０Ｂの例において、容器本体２は、Ｃ１〜Ｃ３の３区画（Ｃ３が小室）を有する経中心静脈栄養用キット製剤に係る容器であることができる。この場合において、容器Ｃ３に、薬剤バイアル３２に収容された薬剤以外の成分が収容されることがのぞましい。例えば、薬剤バイアル３２にビタミン類が収容される場合、容器Ｃ３には、微量元素製剤（例として商品名：エレメンミック、味の素ファルマ社製）が収容されることが好ましい。更に、Ｃ３室に前述の植物油等を有効成分とする脂肪乳剤を収容してもよい。薬剤バイアル３２をプレフィルドシリンジに置換した場合は、プレフィルドシリンジの薬剤収容部を連通可能にゴム栓等の閉鎖体で２室に分離し２室にビタミン類と微量元素製剤をそれぞれ分離して収容する形態が好ましい。
【００４０】
図１０Ｂに明瞭に示すように、薬剤バイエル３２、ポート部材３及び容器本体２は、剛性又は準剛性のあるトレー８０の凹部８１に収容され、凹部８１の開口部は、カバーフィルム８３により覆われ密封される。薬剤バイアル３２の底部に隣接するトレー８０は、薬剤投与の際に指で薬剤バイアル３２を貫通具３４の方へ押圧するための隙間８２を備える。薬剤バイアル３２をポート部材３の方へ押圧し移動させると、連通具（この場合両頭針）３４の各針先端が薬剤バイエル３２の閉鎖体３３及びポート部材の閉鎖体６０をそれぞれ貫通し、薬剤バイエル３２内部が連通具３４を介し流体連通される。それ故、容器本体内の液体を人体へ投与するため、薬剤バイエル３２を移動させて容器分室内と連通させ、容器外から容器内の液体を押圧し接着部を剥離させ分室の液体を混合させると、薬剤バイエル３２内の薬剤が容器内の液体に混合される。この場合、ポート部材及び容器本体が剛性のあるトレーにより支持されるから、薬剤バイエルを容易に正確に摺動させることができる。
【００４１】
【発明の効果】
本発明の医療用液体を封入する樹脂製容器は、ポート部材を構成する筒体及び保持具並びに容器本体の内壁面がいずれもＶＩＣＡＴ軟化点が１２１℃以上のプロピレン・α−オレフィンランダム共重合体、好ましくは、プロピレン−エチレンランダム共重合体により形成され、スチレン系のエラストマーを含有しない故に、必要な透明度を備え、溶着不良が低く、且つ封入される医療用液体へのスチレン系のエラストマーによる環境ホルモンの溶出のない容器を提供することができる。本発明の樹脂製容器は、滅菌工程後の透明度が高く、容器本体、容器内部を良好に観察することができる。
【００４２】
本発明において、筒体の外方環状凸部と保持具の天板部分又はその近傍の内面との間が超音波振動エネルギーにより加熱溶着され、溶着部が形成され、筒体上部と保持具の間が強固に連結される。それ故、容器が医療用液体を収容し滅菌のため高圧室内で例えば２０分間１２１℃に維持されポート部材の閉鎖体に容器内から比較的大きな圧力が作用する場合にも、閉鎖体は、保持具によりしっかり押圧され、抜出すことがない。また、筒体の大径部と保持具の円筒部分の端面が密封係合され、封止部が形成されるから、溶着部の形成工程により生じるハミダシ（ばり）がポート部材の外部へ散逸することが防止される。
【００４３】
本発明においては、筒体の外周面を予熱し、筒体の厚さの約５０％を溶着温度にし、予熱された筒体を、容器本体の樹脂フィルムの内壁面の開口部へ挿入し、ダイにより樹脂フィルムを加熱しながらその外方から予熱された筒体の外周面へ押圧し、樹脂フィルムと外周面を溶着成形するので、筒体外周面と容器本体の樹脂フィルムの間が良好に溶着され密封される。
【００４４】
本発明の樹脂製容器は、滅菌工程後の透明度が高いため、カメラ撮像による医療用液体を充填した樹脂製容器内の異物検査において検知率を向上させることができ、高コストの目視検査を少なくることができる。また、容器の製造時及び医療用液体の充填工程前の容器の搬送時においても異物検査を容易に確実に行うことができ、不良製品を排除できる。また、医療用液体が輸液である場合、液位の監視が容易に正確に行うことができ投与量の制御、点滴終了時期の決定を容易に正確に行うことができる。
【図面の簡単な説明】
【図１】本発明の医療用液体を封入する多室容器の実施例の概略平面図。
【図２】図１の多室容器の概略側面図。
【図３】図１の線Ｔ−Ｔに沿う断面図。
【図４】ポート部材の実施例の保持具（キャップ）の概略断面図。
【図５】ポート部材の実施例の筒体の概略断面図。
【図６】ポート部材の実施例の閉鎖体（ゴム栓）の概略断面図。
【図７】ポート部材の実施例の保持具、筒体及び閉鎖体を組合わせた概略断面図。
【図８】容器本体に使用可能な多層フィルムの概略断面図。
【図９】固形薬剤を収容するポート部材の概略断面図。
【図１０】図１０Ａは、薬剤バイアルが隣接されるポート部材の概略平面断面図であり、図１０Ｂは、図１０Ａの線Ｓ−Ｓに沿う断面図である。
【符号の説明】
Ｍ１、Ｍ２：医療用液体、Ｎ：固形薬剤、Ｃ１、Ｃ２、Ｃ３、Ｃ４：分室、Ｆ、−Ｆ：押圧力。１：多室容器、２：容器本体、３：ポート部材、４：連通具、１４，１６：内壁面、１８，１９：接着部、２１、２２：固着部、２３：吊り下げ孔、３２：薬剤バイエル、３３：閉鎖体、３４：連通具、３５：ケース、４０：筒体、４２：外方端、４３：中空部、４４：内周面、４５：外周面、５５：外方環状凸部、５６：上部外周面、５７：大径部、５８：環状角部、６０：閉鎖体、６１：円板部分、６２：内方環状垂下部、６３：外周面、６４：環状板部、６５：下方環状溝、６６：外方環状垂下部、６７：外方環状凸部、６８：上方環状溝、７０：保持具、７１：天板部分、７２：円筒部分、７７：円錐面部分、７９：粒子封止部、８０：トレー、８１：凹部、８２：隙間、８４：カバーフィルム。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a flexible container for storing medical fluids, for example, intravenous fluids, liquid nutrients, peritoneal dialysis fluid, and the like, and in particular, a multi-chamber containing two or more components so that they can be mixed immediately before administration. The present invention relates to a container and a port member which is incorporated in a flexible container and does not dissipate unnecessary particles generated by welding.
[0002]
[Prior art]
A medical fluid, for example, an infusion for supplying nutrients to a human body by infusion, is typically contained in a resin-made flexible container having a port member. The port member is provided with a closing body such as a closing body that can be penetrated by a communication tool such as a hollow needle, and injects a mineral liquid or the like into the container through the communication tool that penetrates the closing body. It can be sent into the dispensing tube. Also, the container is partitioned into a first chamber and a second chamber by an adhesive portion formed by releasably bonding a part of the opposing inner wall surface of the container, and different chemicals are stored in each chamber (double bag) Is known. A common method for filling medical fluid into a flexible container is to fill the container from a spout with the closure removed under a sterile inert gas atmosphere and then to the outside of the spout. It consists in closing the end with a closure.
[0003]
Japanese Patent Application Laid-Open No. 7-178151 or Japanese Patent Publication No. 6-26563 contains a fat emulsion and an amino acid in the first chamber of a container made of a flexible resin in which two individual chambers are formed by a separating means that can be peeled off. Disclosed is a container in which sugar and electrolyte are accommodated in a second chamber, and the first chamber or the second chamber is pressed from the outside at the time of administration to separate the separating means and mix the liquid in both chambers. Japanese Patent Publication No. 5-10945 discloses that the first chamber or the second chamber communicates with an infusion outlet (outlet), the outer end of the outlet is closed with a rubber stopper, and the infusion in the container is administered. A container that is sometimes fed from the inside of the container into the drip tube by the action of gravity is disclosed by piercing a rubber stopper with a hollow needle attached to the drip tube and communicating the inside of the container with the inside of the drip tube via the hollow needle.
[0004]
Japanese Patent Application Laid-Open No. 11-262513 includes a mixed injection port / discharge port (port member) of polypropylene or a polymer composition thereof, a cloudiness value of the mixed injection port / discharge port is 75% or less, and a Rockwell hardness is 75 or more. A medical container is disclosed. In this publication, the material of the container sheet is an isotactic polypropylene copolymer, the material of the mixed injection port / discharge port is an isotactic type or syndiotactic type polypropylene, and the mixed injection port / discharge port holder It discloses that the material is polypropylene. The cloudiness value of the container sheet and the formation of the peelable adhesive part are not disclosed.
[0005]
Japanese Patent Application Laid-Open No. 9-24581 describes that a multi-chamber bag is manufactured with a non-PVC (non-vinyl chloride) multilayer film, and that the inner layer of the non-PVC multilayer film is a polypropylene random copolymer having a VICAT softening point of 130 ° C. Disclose. Polypropylene random copolymer is a kind of propylene / α-olefin copolymer. This publication does not disclose formation of a port member, formation of a peelable adhesive portion, or the like.
[0006]
Japanese Patent No. 2706625 discloses a container formed using a multilayer film. This multilayer film is composed of three layers mainly composed of polyolefin. The outer layer that comes into contact with the outside air is a mixture of polypropylene and an ethylene / α-olefin copolymer, and the inner layer has a density of 0.925 g / cm. ^Three The above chain ethylene / α-olefin copolymer resin, the intermediate layer has a density of 0.925 g / cm ^Three It is formed of a single layer or a multilayer containing the following chain ethylene / α-olefin copolymer. This publication does not disclose formation of a port member, formation of a peelable adhesive portion, or the like.
[0007]
[Problems to be solved by the invention]
A first object of the present invention is to provide a multi-chamber type resin container that does not have the possibility of elution of a plasticizer in a medical liquid and has no problem of disposal. Another object of the present invention is to provide a resin container having no poor adhesion between the port member and the resin film of the container body. Another object of the present invention is to provide a port member having a weld portion having a sufficient strength to withstand the high pressure inside the container caused by sterilization heating between the cylinder of the port member and the cap-shaped holder. Still another object of the present invention is to provide a port member that does not dissipate burrs caused by formation of a welded portion between a cylinder and a holder.
[0008]
Still another object of the present invention is to provide a resin container that can easily manufacture a peelable adhesive portion that divides a container body into a plurality of compartments, and contains a liquid nutrient that is administered to a human body by infusion. It is a resin container that contains minute components of vitamins and minerals, avoiding alteration, and is mixed and held immediately before administration, and can be easily mixed when necessary. .
[0009]
Still another object of the present invention is to maintain the transparency of the container even when sterilized at 115 ° C. or higher, particularly 121 ° C., as described in the 13th revised Japanese Pharmacopoeia Manual, General Test Method. The object is to provide a highly transparent resin container that can be easily observed. As a result, the detection rate can be improved in the foreign substance inspection (Japanese Patent Laid-Open No. 11-125604) in a resin container filled with medical liquid by camera imaging, which does not increase the detection rate in a conventional container with low transparency. It becomes possible. In addition, by employing the container of the present invention, the foreign substance inspection apparatus can be incorporated into the production / inspection line, and labor can be saved compared to the case where a conventional visual inspection is performed by a person. Further, not only the resin container filled with medical liquid but also the empty container transported to the medical liquid filling process at the time of bag making of the container can be easily inspected for foreign matters, and defective products can be surely excluded. On the other hand, when the medical liquid is an infusion, it is necessary to monitor the liquid level in order to properly control the dose or to confirm the timing of the end of the infusion when the liquid is administered to the patient. At this time, if the visibility of the liquid level in the container is low, infusion management is hindered. The container of the present invention having high transparency is easy to see the liquid level and has an excellent effect on the infusion management. Other objects and advantages of the present invention will become apparent from the drawings and the following description.
[0010]
[Means for Solving the Problems]
The resin container for enclosing the medical liquid of the present invention includes a bag-shaped resin container main body and at least one port member, and a part of the inner wall faced to the inside of the container main body is adhered in a liquid-tight and peelable manner. The bonded portion is divided into a plurality of compartments by the formed adhesive portion, and the adhesive portion can be peeled off by a pressing force of 10 to 40 kgf from the outside of the container body. The liquid in the branch chamber communicates with each other and is mixed. The port member includes a closure body such as a rubber plug, a cylinder body, and a holder, and can discharge liquid in the container body or inject liquid into the container body through a communication tool such as a hollow needle that penetrates the closure body. In addition, both the cylindrical body constituting the port member and the inner wall surface of the container main body are formed of a propylene / α-olefin random copolymer having a VICAT softening point of 121 ° C. or higher.
[0011]
The resin container for enclosing the medical liquid of the present invention can have the following configuration. (1) The container body is formed of a resin that does not substantially contain a styrene elastomer. When the container of the present invention is used as an infusion container, for example, a containing liquid containing various nutrients is directly administered intravenously. Accordingly, the resin container must be made of a resin that does not exhibit toxicity to the human body. In addition, not only the resin as the main raw material but also various elastomers added thereto need to be considered for the presence or absence of toxicity. Therefore, in a preferred embodiment, the container and the port member of the present invention are formed of a resin that does not substantially contain a styrene elastomer that is feared to act as an environmental hormone.
[0012]
(2) The container body is formed of a single layer resin film made of a propylene / α-olefin random copolymer. (3) The container body is formed of a multilayer resin film including an inner layer made of a propylene / α-olefin random copolymer. (4) The propylene / α-olefin random copolymer constituting the inner wall surface of the cylinder and the container body is a propylene-ethylene random copolymer. (5) The transparency of the container after sterilization is 80% or more.
[0013]
The port member attached to the resin container enclosing the medical liquid of the present invention comprises a closing body, a cylindrical body, and a holder, and the liquid in the container body is poured out or the container body through the communication tool penetrating the closing body. The liquid can be injected into the inside, and the periphery of the closing body is sandwiched between the cylinder and the holder. The cylindrical body has an inner end disposed inside the container main body, an outer peripheral surface that is liquid-tightly bonded to a film forming the container main body, and an outer end that supports the closing body and the holder. The outer end has an outer annular convex portion, an upper outer peripheral surface, and a large-diameter portion disposed below the upper outer peripheral surface. The holder has a cap shape and has an annular top plate portion and a cylindrical portion extending downward from the outer periphery of the top plate portion, and the outer annular convex portion of the cylinder and the top plate portion of the holder or the vicinity thereof. A welded portion is formed between the inner surface. A particle sealing portion is formed between the large diameter portion of the cylindrical body and the cylindrical portion of the holder.
[0014]
The port member attached to the resin container enclosing the medical liquid of the present invention can have the following configuration. (6) The outer end of the cylindrical body has an annular corner formed by intersecting the end surface of the outer annular convex portion and the upper outer peripheral surface, and the holder is formed by the inner peripheral portion of the top plate portion and the cylindrical portion. The welding portion has a conical surface portion that connects the upper end of the inner peripheral surface, and the welded portion is formed by heating and welding the annular corner portion of the cylindrical body to the conical surface portion of the holder by ultrasonic energy. (7) The outer annular projection has a triangular projection protruding from its end surface, and the welded portion is formed by ultrasonic energy at the inner surface of the top plate portion of the holder and the tip of the triangular projection. It is formed by heat welding. (8) The large diameter portion of the upper outer peripheral surface of the cylindrical body is formed by a flange portion, and the particle sealing portion is formed by engaging the flange portion of the cylindrical body with the end surface of the cylindrical portion of the holder.
[0015]
(9) The large diameter portion of the upper outer peripheral surface of the cylindrical body is formed by a tapered portion whose diameter increases downward, and the particle sealing portion has a tapered portion of the cylindrical body near the end surface of the cylindrical portion of the holder. Formed by engagement. (10) The outer end of the cylindrical body further includes an inner annular convex portion and an annular groove portion arranged concentrically. (11) The closing body is fitted to a disc portion that closes the hollow portion near the outer end, an inner annular hanging portion that extends downward from the outer peripheral portion of the disc portion, and a cylindrical peripheral surface near the outer end. An outer peripheral surface, an annular plate portion extending radially outward from the outer peripheral surface, an outer annular hanging portion depending from the outer periphery of the annular plate portion, an outer annular convex portion extending upward from the outer periphery of the annular plate portion, an outer peripheral surface And a lower annular groove formed between the outer annular hanging portion and an upper annular groove formed between the outer side of the disk portion and the outer annular convex portion. (12) The cylindrical body has a reduced diameter portion below, and the outer peripheral surface of the reduced diameter portion is bonded to the resin film of the container body.
[0016]
The method of adhering the port member of the present invention to the container main body is a step in which the outer peripheral surface of the reduced diameter portion of the cylindrical body is preheated so as to be weldable, and then abuts on the opening of the resin film forming the container main body and is welded The step of forming and welding including the steps includes a step of applying the die to the resin film from the outside of the resin film, pressing and adhering the die while heating, and forming.
[0017]
The port member of the present invention can accommodate a lyophilized product containing vitamins as active ingredients. More specifically, for example, the port member of the present invention can be used as a freeze-drying container instead of a vial used in a freeze-drying container for vitamins described in JP-B-7-116022. And the port member which accommodates the said freeze-dried material is naturally welded to a container main body without a pinhole by a conventional method (Unexamined-Japanese-Patent Nos. 10-43272 and 10-165480).
[0018]
BEST MODE FOR CARRYING OUT THE INVENTION
Embodiments of the present invention will be described with reference to the drawings. 1 is a schematic plan view of an embodiment of a multi-chamber container enclosing a medical fluid of the present invention, FIG. 2 is a schematic side view of the multi-chamber container of FIG. 1, and FIG. 3 is a line TT of FIG. FIG. In these drawings, corresponding parts are denoted by the same reference numerals, and redundant description is omitted. 1 to 3, a resin container 1 that encloses a medical liquid includes a bag-shaped resin container body 2 and three port members 3 and 3. The container body 2 is partitioned into a plurality of compartments C1 to C4 by the adhesive portions 18 and 19, and can accommodate a solid medicine such as medical liquids M1 and M2 or powder, respectively.
[0019]
The adhesion portions 18 and 19 that divide the inside of the container body into a plurality of compartments are formed by adhering a part of the opposing inner wall surfaces 14 and 16 of the container body so as to be liquid-tight and peelable. The adhesive part is peeled off by manually applying 10-40 kgf of pressing force F, -F from the outside of the container in a state where the medicines M1, M2 or the solid medicine are accommodated in each of the compartments C1-C4. Medical liquids M1 to M2 contained in C1 to C2 are mixed. Port members 3, 3, and 3 are provided in the compartments C1, C3, and C4. For example, the liquid in the container is poured out through the communication tool 4 such as a hollow needle that passes through the closed body of the port member. It is possible to inject liquid into
[0020]
4 to 7 are a cross-sectional view of the holder 70 constituting the port member 3, the cylindrical body 40, the closing body 60 made of a rubber plug, and the assembled state. In these drawings, corresponding parts are denoted by the same reference numerals, and redundant description is omitted.
As shown in FIG. 4, the holder 70 has an annular top plate portion 71, a cylindrical portion 72 that extends downward from the outer periphery of the top plate portion and includes an end surface 78, and an annular shape that extends downward from the vicinity of the inner peripheral end 74 of the top plate portion. The convex part 73 and the conical surface part 77 which connects the upper end of the inner peripheral surface 76 of the cylindrical part 72 and the outer peripheral part of the top plate part inner surface 75 are provided.
[0021]
Here, when the container of the present invention and the kit preparation in which the container of the present invention is combined with other containers, the components to be blended with the medical liquid or solid medicine that can be stored include reducing sugars such as glucose, fructose, maltose, and the like. Various amino acids blended in amino acid preparations that have been used for the purpose of nutritional supplementation as infusions can be mentioned. 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. Furthermore, each of the amino acids may be partially or wholly in the form of an N-acyl derivative, for example, N-acetyl-L-cysteine.
[0022]
Ingredients other than reducing sugar and amino acids include soybean oil, cottonseed oil, safflower oil, corn oil, palm oil, perilla oil, sesame oil, linseed oil, and other vegetable oils, fish oils, chemically synthesized triglycerides, Examples thereof include medium chain fatty acid triglycerides and long chain fatty acid triglycerides. Water-soluble and fat-soluble vitamins such as retinol palmitate, thiamine hydrochloride, riboflavin sodium phosphate, pyridoxine hydrochloride, cyanocobalamin, ascorbic acid, cholecalciferol, tocopherol acetate, nicotinamide, calcium pantothenate, folic acid, biotin , Menatetrenone, phytonadione, etc., and electrolytes and trace elements (minerals) such as sodium chloride, sodium acetate, magnesium sulfate, magnesium chloride, calcium chloride, dipotassium phosphate, monosodium phosphate, calcium glycerophosphate, ferric chloride, chloride Manganese, copper sulfate, zinc sulfate, potassium iodide and the like can be mentioned. The amount of each component is appropriately determined according to the required amount of the patient to be administered.
[0023]
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.
[0024]
The container of the present invention is characterized by being able to be accommodated without substantially impairing the stability of each component. As a preferred embodiment, each chemical solution of sugar, electrolyte, and amino acid is stored in C1 or C2, respectively, an aqueous solution of a trace element (mineral) or a solid drug in the chamber C3, and a vitamin or lyophilized product (solid drug) in the port member or C4. Or a formulation of transcentral parenteral nutrition kits contained as an aqueous solution. Thereby, each component which changes the composition can be isolated in each compartment, and each component for transcentral parenteral nutrition can be accommodated in the container for a long time without deteriorating the quality of each component, particularly the component which is easily changed. Similarly, the effects described above for enteral component nutrients are achieved.
[0025]
Further, as another aspect, a communication device such as a communication device (WO 95/00101) is attached to the port member, and a vitamin-filled vial or a prefilled syringe (Special Table Hei 5-501983, Special Table Hei 7-501002) is attached. It is good also as the form of the kit formulation of the jointed multiple medicine accommodation. At this time, it is more preferable that the vial or the prefilled syringe connected to the container and the communication tool is stored in a rigid or semi-rigid tray so that the communication operation can be easily performed. Further, when vitamins are contained in the kit preparation, it is preferable that a light-shielding film is laminated on the entire surface or a part of the tray. In addition, a layer made of a moisture impermeable and gas impermeable barrier film may be provided on one of the resin layers forming the tray.
[0026]
Furthermore, as another form, it replaces with the said vial and a prefilled syringe, and the both chambers which oppose can be connected by peeling the resin-made small bag containing a solid medicine to the container edge part of this invention, and an inner layer surface peeling. A linked kit preparation may be used. The resin sachet may be a multiple package for preventing deterioration of the medicine to be contained, and an oxygen scavenger and a desiccant can be contained in the package (WO92 / 08434).
[0027]
As shown in FIG. 5, the cylindrical body 40 has an inner end 41 arranged inside the container, an inner peripheral surface 44 surrounding the hollow portion 43 communicating with the inside of the container at the inner end, and a resin film forming the container. It has an outer peripheral surface 45 that is liquid-tightly bonded and an outer end 42 that supports the closure and retainer. The outer end 42 is formed by crossing the inner annular convex portion 53, the annular groove portion 54, the outer annular convex portion 55, the upper outer peripheral surface 56, and the end surface of the outer annular convex portion 55 and the upper outer peripheral surface 56. It has an annular corner portion 58 and a flange portion (large diameter portion) 57 disposed below the upper outer peripheral surface.
[0028]
As shown in FIG. 6, the closing body (rubber plug) 60 includes a disc portion 61, an inner annular hanging portion 62 that extends downward from the outer circumferential portion of the disc portion, and an outer circumferential surface 63 of the inner annular hanging portion 62. An annular plate part 64 extending radially outward from the upper part, an outer annular hanging part 66 depending from the outer periphery of the annular plate part 64, an outer annular convex part 67 extending upward from the outer periphery of the annular plate part 64, and an outer peripheral surface 63 and a lower annular groove 65 formed between the outer annular hanging portion 66 and an upper annular groove 68 formed between the outer side of the disk portion and the outer annular convex portion 67.
[0029]
As shown in FIG. 7, the closing body 60 is fitted to the outer end 42 of the cylindrical body 40, and the holder (cap) 70 is assembled so as to hold the closing body 60. As shown in the sectional view of the holder 70 in FIG. 4, the holder 70 includes an annular top plate portion 71, a cylindrical portion 72 extending downward from the outer end of the top plate portion 71, and an end surface 78 below the cylindrical portion. An annular convex portion 73 extending downward from the vicinity of the inner peripheral end 74 of the top plate portion 71, a conical surface portion 77 connecting the upper end of the inner peripheral surface 76 of the cylindrical portion 72 and the outer peripheral portion of the inner surface 75 of the top plate portion 71, etc. Have
In the state of FIG. 7 in which the cylindrical body 40, the holder (cap) 70, and the closing body 60 are assembled, the annular corner 58 of the cylindrical body and the conical surface portion 77 of the holder are heated and welded by ultrasonic vibration energy, A weld 59 is formed. The welding part 59 connects the cylinder 40 and the holder 70 with high strength, and the holder 70 suppresses the movement of the closing body 60 even when the inside of the container becomes high pressure due to heat sterilization of the container. It is possible to prevent it from coming off. In the heat welding, the annular corner portion 58 forms an energy director, ultrasonic vibration is concentrated and transmitted to this portion, local frictional heat is generated, and the resin is melted and welded.
[0030]
In FIG. 7, the cylindrical flange portion 57 of the cylindrical body 40 and the end surface 78 of the cylindrical portion 72 of the holder are hermetically engaged to form a sealing portion 79. The sealing part 79 prevents the passage of burrs generated by the process of forming the welded part. Hamidashi is inevitably generated in the process of heat-welding the resin with ultrasonic vibration energy, causing clogging of the clean bench filter used when mixing chemicals into the container, and reducing cleanliness of the clean bench. It was. Also in the port member of FIG. 7, in order to surely perform the welding, scooping is generated outside the annular corner portion 58, but since the particle sealing portion 79 is formed, it is dissipated out of the port member. There is nothing.
[0031]
FIG. 8 is a schematic cross-sectional view of a non-PVC (non-vinyl chloride) multilayer film 6 that can be used for the container body. The multilayer film 6 includes an inner layer 141 that includes the inner wall surface 14 or 16 of the container, an outer layer 144 that forms the outer surface of the container, and central layers 142 and 143. The inner layer 141 and the outer layer 144 are formed of a propylene / α-olefin random copolymer having a VICAT softening point of 121 ° C. or more, preferably a propylene-ethylene random copolymer. The central layers 142 and 143 are formed of a mixed resin of a propylene-ethylene random copolymer and an ethylene / α-olefin copolymer. The central layers 142 and 143 may be three layers or four layers, and one of them may be provided with a layer made of a moisture impermeable and gas impermeable barrier film.
[0032]
Instead of the non-PVC (non-vinyl chloride) multilayer film 6 in FIG. 8, the container body is a propylene / α-olefin random copolymer having a VICAT softening point of 121 ° C. or higher, preferably a propylene-ethylene random copolymer. The polymer may be formed by, for example, trade name SPX8000 series, SPX9000 series sold by Mitsubishi Chemical. As the resin forming the container, a resin that does not contain a styrenic elastomer, which is a concern for environmental hormones, is suitable.
[0033]
The resin forming the container is a propylene / α-olefin random copolymer having a VICAT softening point of 121 ° C. or higher, preferably a propylene-ethylene random copolymer, and the liquid inside the container is sufficiently discharged from the outside of the container. As can be observed, the transparency after the sterilization step is set to 80% or more. Transparency is the ratio of the amount of light irradiated from a standard light source to the test piece and the amount of light transmitted through the test piece, also called the haze value, and is defined in the Japanese Pharmacopoeia standard.
[0034]
In the embodiment of FIG. 7, the annular angular portion 58 of the cylindrical body and the conical surface portion 77 of the holder are heat-welded by ultrasonic vibration energy to form a welded portion 59, but the conical surface portion 77 is formed on the holder. Instead of forming, a projection having a triangular cross-section projecting from the end face of the outer annular convex portion 55 of the cylindrical body is provided, and a weld portion is formed between the tip portion of this projection and the inner surface 75 of the top plate portion of the holder. can do. In the embodiment of FIG. 7, a flange 57 is provided below the upper outer peripheral surface 56 of the cylinder, and the end surface 78 of the holder is pressed against the flange 57 to form the particle sealing portion 79. Instead, the upper outer peripheral surface 56 is provided with a tapered portion whose diameter increases as it goes downward, and the inner peripheral surface near the end surface 78 of the holder and the tapered portion are engaged with each other to form a particle sealing portion.
[0035]
As shown in FIGS. 3 and 7, the cylindrical body 40 of the port member 3 is preferably reduced in diameter at the lower portion to form a reduced diameter portion 46, and the outer peripheral surface of the reduced diameter portion 46 is formed of the resin film of the container body. Bonded to the inner wall surfaces 14 and 16. The bonding method between the outer peripheral surface of the reduced diameter portion 46 and the inner wall surfaces 14 and 16 of the resin film of the container main body is to preheat the outer peripheral surface of the reduced diameter portion 46, and about 50% of the thickness of the reduced diameter portion 46 is welded. For example, the step of 180 ° C., the step of inserting the preheated reduced diameter portion 46 into the openings of the inner wall surfaces 14 and 16 of the resin film of the container body, and the outside while heating the resin film with a die The method includes a step of pressing the outer peripheral surface of the preheated reduced diameter portion 46 to weld-mold the resin film and the outer peripheral surface.
[0036]
The cylindrical body 4 and the holder 70 of the port member 3 are made of a propylene / α-olefin random copolymer having a VICAT softening point of 121 ° C. or higher, preferably the propylene / ethylene random copolymer. By being formed by coalescence, poor welding of the port member 3 to the container body is reduced. In addition, by using the same resin pellet as the resin for bonding the container, the quality control of the resin is easy, and the adhesion failure rate of each part due to the quality fluctuation of the resin can be lowered.
[0037]
FIG. 9 is a schematic cross-sectional view of the port member 3 that houses the solid medicine N. The infusion nutrient or enteral component nutrient contained in the container body contains vitamins that are unstable and easily decomposed, so that the vitamins are freeze-dried and in the form of a layered solid drug N, the port member 3 is accommodated in the inner hollow portion 43 of the cylindrical body 40. In addition to vitamins, drugs such as antibiotics can be accommodated in the hollow portion 43 in the form of a solid drug N. The solid medicine N is preferably accommodated in the cylindrical body 40 before the port member 3 is thermally welded to the fixing portion 21 of the container body. Moreover, when the port member 3 accommodates a solid medicine, the compartment C4 of the container body communicating with the inner hollow portion of the port member is made empty. When the liquid in the container body is pressed from outside the container for administration to the human body and the adhesive part is peeled and mixed, the adhesive part of the compartment communicating with the port member is also peeled off, and the liquid flows into the surroundings of the compartment and the solid medicine. The solid drug is dissolved and mixed into the liquid.
[0038]
10A is a schematic plan cross-sectional view of a port member to which a drug vial is adjacent, and FIG. 10B is a cross-sectional view taken along line SS of FIG. 10A. The drug vial 32 contains vitamins, minerals, antibiotics, and other drug components in the form of a solid drug or a liquid drug. 10A and 10B, the drug vial 32 is supported in a cylindrical case 35 integrally formed with the port member 3 so as to be slidable in the axial direction of the case. The communicating tool 34 is arranged with the needle tip adjacent to the closing body 60 of the port member 3 and the closing body 33 of the medicine bayer, respectively. The drug Bayer 32 can be replaced by a prefilled syringe.
[0039]
10A and 10B, the container body 2 can be a container related to a trans-central parenteral nutrition kit preparation having three sections C1 to C3 (C3 is a small chamber). In this case, it is preferable that components other than the drug stored in the drug vial 32 are stored in the container C3. For example, when vitamins are stored in the drug vial 32, the container C3 preferably stores a trace element preparation (for example, trade name: ELEMENTIC, manufactured by Ajinomoto Pharma Co., Ltd.). Furthermore, you may accommodate the fat emulsion which uses the above-mentioned vegetable oil etc. as an active ingredient in C3 room. When the drug vial 32 is replaced with a prefilled syringe, the drug container of the prefilled syringe is separated into two chambers with a closed body such as a rubber plug so that the drug container can be communicated, and vitamins and trace element preparations are separately stored in the two chambers. Form is preferred.
[0040]
As clearly shown in FIG. 10B, the drug bayer 32, the port member 3, and the container body 2 are accommodated in the concave portion 81 of the rigid or semi-rigid tray 80, and the opening portion of the concave portion 81 is covered with the cover film 83. Sealed. The tray 80 adjacent to the bottom of the drug vial 32 includes a gap 82 for pressing the drug vial 32 toward the penetrating device 34 with a finger during drug administration. When the drug vial 32 is pressed and moved toward the port member 3, the tips of the communicating tools (in this case, double-ended needles) 34 penetrate the closing body 33 of the drug bayer 32 and the closing body 60 of the port member, respectively. The inside of the Bayer 32 is in fluid communication via the communication tool 34. Therefore, in order to administer the liquid in the container body to the human body, the drug bayer 32 is moved to communicate with the container compartment, the liquid in the container is pressed from outside the container, the adhesive portion is peeled off, and the liquid in the compartment is mixed. Then, the medicine in the medicine Bayer 32 is mixed with the liquid in the container. In this case, since the port member and the container main body are supported by the rigid tray, the medicine bayer can be easily and accurately slid.
[0041]
【The invention's effect】
The resin container enclosing the medical liquid of the present invention is a propylene / α-olefin random copolymer in which the cylinder and the holder constituting the port member and the inner wall surface of the container main body each have a VICAT softening point of 121 ° C. or higher. Preferably, it is formed of a propylene-ethylene random copolymer and does not contain a styrenic elastomer, so that it has the necessary transparency, has a low welding failure, and is an environment with a styrenic elastomer in a sealed medical fluid. A container free from hormone elution can be provided. The resin container according to the present invention has high transparency after the sterilization process, and the container body and the inside of the container can be observed well.
[0042]
In the present invention, the outer annular convex portion of the cylinder and the top plate portion of the holder or the inner surface in the vicinity thereof are heat-welded by ultrasonic vibration energy to form a welded portion, and the upper portion of the cylinder and the holder The space is firmly connected. Therefore, even when a container contains medical liquid and is maintained at 121 ° C. for 20 minutes in a high-pressure chamber for sterilization and a relatively large pressure acts on the closure of the port member from within the container, the closure is retained. It is firmly pressed by the tool and does not come out. In addition, since the large-diameter portion of the cylindrical body and the end surface of the cylindrical portion of the holder are hermetically engaged to form the sealing portion, the burrs generated by the welding portion forming process are dissipated to the outside of the port member. It is prevented.
[0043]
In the present invention, the outer peripheral surface of the cylinder is preheated, the welding temperature is about 50% of the thickness of the cylinder, and the preheated cylinder is inserted into the opening of the inner wall surface of the resin film of the container body, While the resin film is heated by the die, it is pressed against the outer peripheral surface of the cylinder that has been preheated from the outside, and the resin film and the outer peripheral surface are fusion-molded, so the gap between the outer peripheral surface of the cylindrical body and the resin film of the container body is good. Welded and sealed.
[0044]
Since the resin container of the present invention has high transparency after the sterilization process, the detection rate can be improved in the foreign object inspection in the resin container filled with medical liquid by camera imaging, and the costly visual inspection is reduced. Can. In addition, foreign matter inspection can be performed easily and reliably at the time of manufacturing the container and at the time of transporting the container before the filling step of the medical liquid, and defective products can be eliminated. When the medical liquid is an infusion, the liquid level can be easily and accurately monitored, and the dosage can be controlled and the drip end time can be determined easily and accurately.
[Brief description of the drawings]
FIG. 1 is a schematic plan view of an embodiment of a multi-chamber container enclosing a medical liquid of the present invention.
2 is a schematic side view of the multi-chamber container of FIG. 1. FIG.
FIG. 3 is a cross-sectional view taken along line TT in FIG.
FIG. 4 is a schematic cross-sectional view of a holder (cap) of an embodiment of a port member.
FIG. 5 is a schematic cross-sectional view of a cylindrical body of an embodiment of a port member.
FIG. 6 is a schematic sectional view of a closing body (rubber plug) of an embodiment of a port member.
FIG. 7 is a schematic cross-sectional view of a combination of a holder, a cylinder, and a closing body of an embodiment of a port member.
FIG. 8 is a schematic cross-sectional view of a multilayer film that can be used for a container body.
FIG. 9 is a schematic cross-sectional view of a port member that contains a solid medicine.
10A is a schematic plan cross-sectional view of a port member to which a drug vial is adjacent, and FIG. 10B is a cross-sectional view taken along line SS of FIG. 10A.
[Explanation of symbols]
M1, M2: medical liquid, N: solid drug, C1, C2, C3, C4: compartment, F, -F: pressing force. 1: Multi-chamber container, 2: Container body, 3: Port member, 4: Communication tool, 14, 16: Inner wall surface, 18, 19: Adhering part, 21, 22: Adhering part, 23: Hanging hole, 32: Drug Bayer, 33: Closure, 34: Communication tool, 35: Case, 40: Tube, 42: Outer end, 43: Hollow part, 44: Inner peripheral surface, 45: Outer peripheral surface, 55: Outer annular convex Part, 56: upper outer peripheral surface, 57: large diameter part, 58: annular corner, 60: closed body, 61: disc part, 62: inner annular hanging part, 63: outer peripheral surface, 64: annular plate part, 65: Lower annular groove, 66: Outer annular hanging portion, 67: Outer annular projection, 68: Upper annular groove, 70: Holder, 71: Top plate portion, 72: Cylindrical portion, 77: Conical surface portion, 79: Particle sealing part, 80: Tray, 81: Recess, 82: Gap, 84: Cover film.

Claims

A port member (3) attached to a resin container for enclosing medical liquid, comprising a closing body (60), a cylindrical body (40) and a holder (70), via a communication tool penetrating the closing body. The liquid in the container body can be poured out or injected into the container body, the periphery of the closing body is sandwiched between the cylinder and the holder, and the cylinder is an inner end disposed inside the container body. (41) An outer peripheral surface that is liquid-tightly bonded to the film forming the container body, and an outer end (42) that supports the closing body and the holder, and the outer end of the cylinder is an outer ring. The holder has a convex portion, an upper outer peripheral surface, and a large-diameter portion (57) disposed below the upper outer peripheral surface, and the holder extends downward from the annular top plate portion (71) and the outer periphery of the top plate portion. It has a cylindrical part (72) and is welded between the outer annular convex part of the cylinder and the top plate part of the holder or the inner surface in the vicinity thereof. (59) is formed, the port member, characterized in that the particle sealing portion (79) is formed between the cylindrical portion of the large-diameter portion (57) and the holder of the cylindrical body.

The port member according to claim 1 , wherein the outer end of the cylindrical body has an annular corner (58) formed by intersecting the end surface of the outer annular convex portion and the upper outer peripheral surface. It has a conical surface portion (77) that connects the outer peripheral surface of the inner surface of the plate portion and the upper end of the inner peripheral surface of the cylindrical portion, and the welded portion (59) has an annular corner (58) of the cylindrical body that is a conical surface of the holder. Port member formed by heating and welding to the portion (77) with ultrasonic energy.

2. The port member according to claim 1 , wherein the outer annular convex portion has a triangular cross-sectional protrusion protruding from an end surface thereof, and the welded portion (59) has a triangular cross-section with the inner surface of the top plate portion of the holder. A port member formed by heat-welding the tip portion of the protrusion of the protrusion with ultrasonic energy.

The port member according to any one of claims 1 to 3 , wherein the large-diameter portion is formed by a flange portion, and the particle sealing portion (79) is a cylindrical flange portion (57) of the cylindrical body. A port member formed by being engaged with an end face of the portion (72).

The port member according to any one of claims 1 to 3 , wherein the large-diameter portion is formed by a tapered portion whose diameter increases downward, and the particle sealing portion (79) is a tapered portion of the cylindrical body. Is a port member formed by engaging near the end face of the cylindrical portion (72) of the holder.

The port member according to any one of claims 1 to 5 , wherein the outer end (42) of the cylindrical body further includes an inner annular convex portion (53) and an annular groove portion (54) arranged concentrically. And a closing body (60) comprising: a disc portion (61) for closing a hollow portion near the outer end; an inner annular hanging portion (62) extending downward from the outer peripheral portion of the disc portion; and an outer end An outer peripheral surface (63) fitted to the peripheral surface of the cylindrical body in the vicinity, an annular plate portion (64) extending radially outward from the outer peripheral surface, an outer annular drooping portion (66) hanging from the outer periphery of the annular plate portion, An outer annular convex portion (67) extending upward from the outer periphery of the annular plate portion, a lower annular groove (65) formed between the outer peripheral surface and the outer annular hanging portion, and an outer portion and an outer annular shape of the disc portion. A port member comprising an upper annular groove (68) formed between the convex portion (67).

The port member according to any one of claims 1 to 6 , wherein the cylindrical body has a reduced diameter portion (46) below, and the outer peripheral surface of the reduced diameter portion is bonded to the resin film of the container body. Element.

The port member according to any one of claims 1 to 7 , wherein the port member communicates with a compartment in which a solid medicine is contained and a liquid in the container body is not contained.

The port member according to claim 8 , wherein the solid drug contains a lyophilized vitamin.

A method for adhering the port member according to any one of claims 1 to 9 to a container body, wherein the container body is formed after the outer peripheral surface of the reduced diameter portion (46) of the cylindrical body is preheated so as to be welded. A method in which the resin film is brought into contact with the opening and welded.

A resin container for enclosing a medical liquid,
A bag-shaped resin container main body and at least one port member according to any one of claims 1 to 9 are provided, and a part of an inner wall faced to the inside of the container main body is adhered in a liquid-tight and peelable manner. The bonded portion is divided into a plurality of compartments, and the bonded portion can be peeled by a pressing force of 10 to 40 kgf from the outside of the container body, and the compartments on both sides of the bonded portion communicate with each other by peeling the bonded portion. The liquid in the compartment is mixed ,
Both the cylindrical body which comprises a port member, and the inner wall surface of a container main body are formed with the propylene * alpha-olefin random copolymer whose VICAT softening point is 121 degreeC or more.

The container according to claim 11 , wherein the container body is formed of a resin that does not substantially contain a styrene elastomer.

The container according to claim 11 , wherein the container body is formed of a single layer resin film made of a propylene / α-olefin random copolymer.

The container according to claim 11 , wherein the container body is formed of a multilayer resin film having an inner layer made of a propylene / α-olefin random copolymer.

The container according to any one of claims 11 to 14 , wherein the propylene / α-olefin random copolymer is a propylene-ethylene random copolymer.

The container according to any one of claims 11 to 15 , wherein the transparency of the container body after sterilization is 80% or more.

The container according to any one of claims 11 to 16 , wherein a solid medicine is accommodated in one port member, and the port member communicates with a compartment that does not contain a liquid.

The container according to any one of claims 11 to 16 , wherein one compartment contains an aqueous solution of a trace element or a vitamin.

18. The container of claim 17 , wherein the solid drug comprises lyophilized vitamins.

The container according to any one of claims 11 to 16, wherein a communication tool and a drug vial or a prefilled syringe are disposed adjacent to one port member, and are accommodated in a resin tray having rigidity or semi-rigidity together with the container body.

When the drug vial or prefilled syringe is pressed toward the port member, one end of the communication tool passes through the closure of the port member and communicates with one chamber in the container body, and the other enters the drug vial or prefilled syringe. 21. The container of claim 20 , wherein the container is capable of communication.