JP3797772B2 - Polypropylene resin composition for medical containers - Google Patents

Description

（ただし、Ｒ^１は水素原子又は炭素数１〜４のアルキル基を示し、Ｒ^２及びＲ^３は水素原子又は炭素数１〜１２のアルキル基を示し、Ｍは周期律表第ＩＩＩ族または第ＩＶ族の金属原子を示し、ＸはＭが周期律表第ＩＩＩ族の金属原子を示す場合には、ＨＯ−を示し、Ｍが周期律表第ＩＶ族の金属原子を示す場合には、Ｏ＝又は（ＨＯ）_２−を示す。）により表される環状有機リン酸エステル塩基性多価金属塩の少なくとも一種０．０２５〜０．１５重量％、および
（Ｄ）一般式（ＩＩ）：
Ｍｇ_１−ＸＡｌ_Ｘ（ＯＨ）_２（ＣＯ_３）_Ｘ／２・ｍＨ_２Ｏ （ＩＩ）
（ただし、ｘは０＜ｘ≦０．５であり、ｍは３以下の数である。）で表される複合水酸化物塩化合物０．０１〜０．１０重量％を、下記式（１）の関係を満たすように配合してなる医療容器用ポリプロピレン系樹脂組成物である。
ｂ≦０．０４６−０．０８３ａ （１）
〔ただし、ａは樹脂組成物中の（Ｂ）の有機アルカリ金属塩と（Ｃ）の環状有機リン酸エステル塩基性多価金属塩（Ｉ）の濃度の和（重量％）であり、ｂは樹脂組成物中の（ＩＩ）の濃度（重量％）である。〕
【０００８】
【発明の実施の形態】
１．（Ａ）ポリプロピレン系樹脂
（１）本発明に用いられる結晶性ポリプロピレン系樹脂は、メルトフローレート０．５〜７０ｇ／１０分、好ましくは５〜４０ｇ／１０分を有するものであり、ポリプロピレン単独重合体ないしはエチレンとのランダム共重合体である。共重合体の場合は、エチレン含有量は３．０重量％以下、好ましくは２．０重量％以下であることが必要である。
メルトフローレートが０．５未満では成形加工性の低下をきたし注射剤容器として満足できる成形体が得られない。また、７０以上では機械的強度の低下が著しく実用上の問題が生じる。一方、エチレン含有量が３．０重量％を超えると保存容器の蒸気減菌時に透明性の低下や変形が起こり、また水蒸気や酸素のガスバリヤー性の低下をきたし、保存薬剤や薬液に悪影響を及ぼす。
【０００９】
（２）該樹脂中に含まれる金属チタンは１ｐｐｍ以下であることが必要である。これを達成するためには、重合時にＭｇ担持型の高活性触媒を用いたり、また重合後に脱触工程を設け、ポリマー中の該金属成分を低減させることができる。ポリマー中に該成分が１ｐｐｍを超えると透明性の発現が十分でなかったり、また、局方試験項目の強熱残分項目を満足しなくなる。
【００１０】
（３）プロピレンの単独重合体とエチレンとのランダム共重合体の製造方法
プロピレン（共）重合体の製造方法は、特に限定されないが、立体規則性触媒を使用する重合法が好ましい。立体規則性触媒としては、三塩化チタン、四塩化チタン、トリクロロエトキシチタン等のハロゲン化チタン化合物、前記ハロゲン化チタン化合物とハロゲン化マグネシウムに代表されるマグネシウム化合物との接触物等の遷移金属成分とアルキルアルミニウム化合物又はそれらのハロゲン化物、水素化物、アルコキシド等の有機金属成分との２成分系触媒、更にそれらの成分に窒素、炭素、リン、硫黄、酸素、ケイ素等を含む電子供与性化合物を加えた３成分系触媒が挙げられる。
【００１１】
また、プロピレン（共）重合体の重合反応は、気相、液相のいずれで行ってもよい。例えば液相で重合する場合には、ｎ−ブタン、イソブタン、ｎ−ペンタン、イソペンタン、ヘキサン、ヘプタン、オクタン、シクロヘキサン、ベンゼン、トルエン、キシレン等の不活性炭化水素又は液状モノマー中で行うことができる。重合温度は、通常−８０〜１５０℃であり、好ましくは４０〜１２０℃である。重合圧力は、１〜６０気圧が好ましく、また得られる（共）重合体の分子量の調節は、水素もしくは他の公知の分子量調整剤で行うことができる。重合は連続式又はバッチ式反応で行い、その条件は通常用いられている条件でよい。さらに重合反応は一段で行ってもよく、二段で行ってもよい。
【００１２】
また、あらかじめ前記プロピレン単独重合体とプロピレン−エチレンランダム共重合体を製造しておいて、これを所定割合にて機械的混合を行ってもよい。
【００１３】
２．（Ｂ）及び（Ｃ）造核剤
本発明の組成物に配合する造核剤は、（Ｂ）成分である有機アルカリ金属塩並びに（Ｃ）成分である環状有機リン酸エステル塩基性多価金属塩である。
（Ｂ）成分は、アルカリ金属カルボン酸塩、アルカリ金属β−ジケトナート及びアルカリ金属β−ケト酢酸エステル塩からなる群より選択される少なくとも一種の有機アルカリ金属塩である。
【００１４】
（Ｂ）成分の各アルカリ金属塩化合物を構成するアルカリ金属としては、リチウム、ナトリウム、カリウム等が挙げられる。
【００１５】
上記アルカリ金属カルボン酸塩を構成するカルボン酸としては、例えば酢酸、プロピオン酸、アクリル酸、オクチル酸、イソオクチル酸、ノナン酸、デカン酸、ラウリン酸、ミリスチン酸、パルミチン酸、ステアリン酸、オレイン酸、リシノール酸、１２−ヒドロキシステアリン酸、ベヘン酸、モンタン酸、メリシン酸、β−ドデシルメルカプト酢酸、β−ドデシルメルカプトプロピオン酸、β−Ｎ−ラウリルアミノプロピオン酸、β−Ｎ−メチル−ラウロイルアミノプロピオン酸等の脂肪族モノカルボン酸、マロン酸、コハク酸、アジピン酸、マレイン酸、アゼライン酸、セバシン酸、ドデカンジ酸、クエン酸、ブタントリカルボン酸、ブタンテトラカルボン酸等の脂肪族多価カルボン酸、ナフテン酸、シクロペンタンカルボン酸、１−メチルシクロペンタンカルボン酸、２−メチルシクロペンタンカルボン酸、シクロペンテンカルボン酸、シクロヘキサンカルボン酸、１−メチルシクロヘキサンカルボン酸、４−メチルシクロヘキサンカルボン酸、３，５−ジメチルシクロヘキサンカルボン酸、４−ブチルシクロヘキサンカルボン酸、４−オクチルシクロヘキサンカルボン酸、シクロヘキセンカルボン酸、４−シクロヘキセン−１，２−ジカルボン酸等の脂環式モノ又はポリカルボン酸、安息香酸、トルイル酸、キシリル酸、エチル安息香酸、４−ｔ−ブチル安息香酸、サリチル酸、フタル酸、トリメリット酸、ピロメリット酸等の芳香族モノ又はポリカルボン酸等が挙げられる。
【００１６】
上記アルカリ金属β−ジケトナートを構成するβ−ジケトン化合物としては、例えば、アセチルアセトン、ピバロイルアセトン、パルミトイルアセトン、ベンゾイルアセトン、ピバロイルベンゾイルアセトン、ジベンゾイルメタン等が挙げられる。
【００１７】
また、上記アルカリ金属β−ケト酢酸エステル塩を構成するβ−ケト酢酸エステルとしては、例えば、アセト酢酸エチル、アセト酢酸オクチル、アセト酢酸ラウリル、アセト酢酸ステアリル、ベンゾイル酢酸エチル、ベンゾイル酢酸ラウリル等が挙げられる。
【００１８】
上記（Ｂ）成分であるアルカリ金属カルボン酸塩、アルカリ金属β−ジケトナート又はアルカリ金属β−ケト酢酸エステル塩は各々上記アルカリ金属とカルボン酸、β−ジケトン化合物又はβ−ケト酢酸エステルとの塩であり、従来周知の方法で製造することができる。また、これら（Ｂ）成分の各アルカリ金属塩化合物の中でも、アルカリ金属の脂肪族モノカルボン酸塩、特に、リチウムの脂肪族カルボン酸塩が好ましく、とりわけ炭素数８〜２０の脂肪族モノカルボン酸塩が好ましい。
【００１９】
本発明で用いられる（Ｃ）成分は一般式（Ｉ）：
【化１】

（ただし、Ｒ¹は水素原子又は炭素数１〜４のアルキル基を示し、Ｒ²及びＲ³は水素原子又は炭素数１〜１２のアルキル基を示し、Ｍは周期律表第ＩＩＩ族又は第ＩＶ族の金属原子を示し、ＸはＭが周期律表第ＩＩＩ族の金属原子を示す場合には、ＨＯ−を示し、Ｍが周期律表第ＩＶ族の金属原子を示す場合には、Ｏ＝又は（ＨＯ）₂−を示す。）により表される環状有機リン酸エステル塩基性多価金属塩である。
【００２０】
環状有機リン酸エステル塩基性多価金属塩において、Ｒ¹で示される炭素数１〜４のアルキル基としては、メチル、エチル、プロピル、イソプロピル、ブチル、ｓ−ブチル、イソブチル等が挙げられ、Ｒ²又はＲ³で示される炭素数１〜１２のアルキル基としては、メチル、エチル、プロピル、イソプロピル、ブチル、ｓ−ブチル、ｔ−ブチル、アミル，ｔ−アミル、ヘキシル、ヘプチル、オクチル、イソオクチル、ｔ−オクチル、２−エチルヘキシル、ノニル、イソノニル、デシル、イソデシル、ウンデシル、ドデシル、ｔ−ドデシル等が挙げられる。
【００２１】
また、Ｍで示される周期律表第ＩＩＩ族又は第ＩＶ族の金属原子としては、アルミニウム、ガリウム、ゲルマニウム、錫、チタン、ジルコニウム等が挙げられ、特にアルミニウムが好ましい。
【００２２】
したがって、（Ｃ）成分としては、例えば次に示す化合物が挙げられる。
【００２３】
【化２】

【００２４】
【化３】

【００２５】
【化４】

【００２６】
【化５】

【００２７】
【化６】

【００２８】
【化７】

【００２９】
（Ｃ）成分は、例えば、酸性環状有機リン酸エステルのアルカリ金属塩と多価金属ハロゲン化合物あるいは酸化多価金属ハロゲン化物と反応させ、その後必要に応じて加水分解する方法、酸性環状有機リン酸エステルと多価金属アルコキサイドを反応させ、その後必要に応じて加水分解する方法等により容易に製造することができる。
【００３０】
また、（Ｃ）成分は、その粒径についても特に制限をうけず、例えば、平均粒径０．０１〜５０ミクロンのものを用いることができるが、均一な分散を図るためには、平均粒径が１０ミクロン以下、特に３ミクロン以下の微粒子に粉砕して用いることが好ましい。
【００３１】
３．（Ｄ）中和剤
本発明の組成物に配合する（Ｄ）中和剤としては、一般式（ＩＩ）：
Ｍｇ_１−ＸＡｌ_Ｘ（ＯＨ）_２（ＣＯ_３）_Ｘ／２・ｍＨ_２Ｏ （ＩＩ）
（ただし、ｘは０＜ｘ≦０．５であり、ｍは３以下の数である。）
で表される複合水酸化物塩化合物を用いる。
【００３２】
４．組成物の組成割合
本発明の組成物に配合する成分（Ｂ）並びに成分（Ｃ）の造核剤の添加量は、ポリプロピレン系樹脂中に、成分（Ｂ）が０．０２５〜０．１５重量％、好ましくは０．０３５〜０．０７５重量％である。また、成分（Ｃ）が０．０２５〜０．１５重量％、好ましくは０．０３５〜０．０７５重量％である。
成分（Ｄ）の中和剤の添加量は、ポリプロピレン系樹脂中に、０．０１〜０．１０重量％、好ましくは０．０２〜０．０５重量％である。
さらに、この各添加量は式（１）を満たしていることが必要である。
ｂ≦０．０４６−０．０８３ａ （１）
（ただし、ａは樹脂組成物中の（Ｂ）及び（Ｃ）の濃度の和（重量％）であり、ｂは樹脂組成物中の（Ｄ）の濃度（重量％）である。）
【００３３】
造核剤（Ｂ）成分の添加量が０．０２５重量％未満では、透明性や耐熱性の向上効果が十分でなく、また、０．１５重量％を超えると添加量に見合った透明性向上効果が期待できなくなると共に、逆に局方試験項目中の強熱残分や紫外線吸収スペクトルの安全性能の低下をきたす。（Ｃ）成分の添加量が範囲外であると、（Ｂ）成分の場合と同様に、透明性や耐熱性の改善が不十分であったり安全性の低下をきたしたりする。（Ｂ）成分と（Ｃ）成分の比率は、上記範囲内であると、特に制限を受けないが、（Ｂ）成分の添加量が（Ｃ）成分の添加量の当量である場合に本発明の効果が著しい。
【００３４】
また、中和剤が０．０１重量％未満ではポリプロピレン系樹脂中の触媒残さ成分の中和が不十分となりポリプロピレン系樹脂の経時安定性や透明性が低下し、また０．１０重量％を超えるとそれ自身が透明性低下の原因となったり、また局方試験項目中の強熱残分で満足すべき結果が得られないことになる。
さらに、各添加剤量の関係が、式（１）を外れた場合には、薬剤、薬液容器として必要な透明性、耐熱性、ガスバリヤー性とこれらの保存容器に必須な強熱残分や紫外線吸収スペクトル等の安全性能の最適化が困難となる。
【００３５】
５．ポリプロピレン系樹脂組成物の製造方法
本発明のポリプロピレン系医療用樹脂組成物は、上記（Ａ）、（Ｂ）、（Ｃ）及び（Ｄ）の各成分をヘンシェルミキサー、スーパーミキサー、リボンブレンダー等を用いて、本発明で用いる添加剤の他に一般的に用いられるトリス（２，４−ジ−ｔブチルフェニル）ホスファイトのようなプロセス安定剤やヒンダードアミン系紫外線吸収剤等を配合し、通常の単軸押出機、二軸押出機、バンバリーミキサー、プラベンダー、ロール等で１６０〜２５０℃の温度範囲で溶融混練することにより得ることができる。
【００３６】
【実施例】
以下、実施例により、本発明をさらに詳細に説明するが、本発明はこれらの記載により何ら限定されるものではない。なお、各実施例及び比較例において樹脂原料及び添加剤としては以下のものを使用した。

【００３７】
また、物性測定は以下の方法で行った。
（１）エチレン濃度：¹³Ｃ−ＮＭＲにより組成を検定したエチレン・プロピレンランダムコポリマーを基準物質として７３３ｃｍ^-1の特性吸収体を用いる赤外分光法により、ランダムコポリマー中のエチレン含量を測定した。ペレットをプレス成形により約５００ミクロンの厚さのフィルムとしたものを用いた。
（２）Ｔｉ含量：ポリプロピレン中の灰分を塩酸（塩酸１容＋水１容）に溶解後、１０％アスコルピン酸を加えジアンチピリルメタン溶液で発色させ、３８５ｎｍの吸光度を用いてチタン含有を算出した。
（３）ＭＦＲ：ＪＩＳ Ｋ６７５８、２３０℃ ２．１６Ｋｇ荷重に準拠。
【００３８】
（４）蒸気滅菌：１ミリシート成形品をオートクレーブ滅菌器を用いて１２１℃で１時間の条件で滅菌し、風乾後、透明性（ヘイズ）測定に供した。
（５）ヘイズ値：厚さ１ミリのシート片を用いて、ＪＩＳ Ｋ７１０５に準拠して測定した。
（６）デュポン衝撃強度：厚さ２ミリのシート片を用いて、ＪＩＳ Ｋ７２１１に準拠して２３℃で測定した。
【００３９】
（７）成形性：１ミリシート成形品表面の平滑性（フローマーク等）を目視にて観察し成形性を判定した。
○：ゲート付近からのフローマークが殆ど観察されない。
×：ゲート付近から成形品末端までフローマークが観察される。
【００４０】
（８）第１３改正 日本薬局方一般試験：４５．プラスチック製薬品容器試験法（プラスチック製水性注射剤容器）の１．ポリエチレン製又はポリプロピレン製水性注射剤容器の項の試験法に従って、透明性、外観、水蒸気透過性、重金属、鉛、カドミウム、強熱残分、溶出物、細胞毒性を測定した。但し、試料調製は、０．５ミリ厚で表面積６００ｃｍ²に相当する重量のペレットを秤量し、２１０℃でプレスしてシート片として、長さ約５センチ、幅約０．５センチの大きさに細断し、水で洗った後、室温で乾燥した。これを内容積約３００ｍｌの硬質ガラス製容器に入れ、水２００ｍｌを正確に加え、適当な栓で密封した後、高圧蒸気滅菌器を用いて１２１℃で１時間加熱した後、室温になるまで放置し、この内溶液を試験液とし、別に水につき、同様の方法で空試験液を調製した。
【００４１】
参考例１
Ｔｉ含量が１ｐｐｍ未満のホモポリプロピレン（ＨＰＰ）１００重量部に対して、造核剤としてＮＡ−２１及び中和剤としてミズカラックを表１に示す割合で配合し、さらにホスファイト系酸化防止剤としてＭＡＲＫ２１１２（旭電化工業（株）製）０．１重量部及びヒンダードアミン系紫外線安定剤としてＴＩＮＵＶＩＮ６２２ＬＤ（日本チバガイギー（株）製）０．０５重量部を配合し、スーパーミキサーでドライブレンドした後、５０ミリ径の単軸押出機を用いて溶融混練した。ダイ出口部温度２１０℃でダイから押し出しペレット化した。得られたペレットを射出成形機により、樹脂温度２３０℃、射出圧力９００ｋｇ／ｃｍ^２及び金型温度６０℃で射出成形し、シートを作成した。得られたシートから、試験片を採り、物性を測定した。その結果を表１に示す。
【００４２】
実施例１〜４
表１に示すポリプロピレン系樹脂、造核剤、中和剤を用いて、実施例と同様にして試験片を得、その物性を測定した。その結果を表１に示す。
【００４３】
比較例１〜８
表２に示すポリプロピレン系樹脂、造核剤、中和剤を用いて、実施例と同様にして試験片を得、その物性を測定した。その結果を表２に示す。
【００４４】
【表１】

【００４５】
【表２】

【００４６】
表１及び表２より明らかなように、本発明の組成物である、核剤ＮＡ−２１とリチウムアルミニウム複合水酸化物塩（ミズカラック）を式（１）を満足するように用いた系（参考例１）、同核剤とハイドロタルサイト（ＤＨＴ−４Ａ）を式（１）を満足するように用いた系（実施例１）、実施例１でＭＦＲを変えた系（実施例２）、実施例１で核剤量および中和剤量を変えた系（実施例３）、およびランダムＰＰ（ＲＰＰ）を用いた系（実施例４）は局方試験に合格する組成物である。一方、ソルビトール系核剤を用いた組成物系では溶出物試験のＵＶ吸収や過マンガン酸消費量等で局方試験に不合格（比較例１）、中和剤としてカルシウムステアレートを用いた系では薬液の透明性が不合格（比較例２）、エチレン濃度が請求範囲を超えたＲＰＰを用いた系では滅菌時に変形と透明性が悪化し（比較例３）、ＮＡ−２１の添加量が低濃度側に請求範囲を外れた系では透明性改善が不十分となり（比較例４）、中和剤が低濃度側に請求範囲を外れた系では中和不足のため樹脂劣化による安全性が低下し、ＵＶ吸収や過マンガン酸消費量等で局方試験に不合格となり（比較例５）、ポリプロピレン中の金属チタン濃度が高濃度の系では強熱残分が不合格（比較例６）、ＭＦＲが低流動側に外れた系では成形性が悪化し（比較例７）、ＭＦＲが高流動側に外れた系では衝撃性（デュポンインパクト）が低下し（比較例８）、それぞれ好ましくない。
【００４７】
【発明の効果】
本発明の医療容器用ポリプロピレン系樹脂組成物は、第１３改正 日本薬局方一般試験 ４５．プラスチック製医薬品容器試験法 １．ポリエチレン製又はポリプロピレン製水性注射剤容器 の試験項目をすべて満足し、かつ、薬剤や薬液の保存容器として必要な耐蒸気滅菌性（耐熱性、剛性）、透明性、ガスバリヤー性を保持している。[0001]
BACKGROUND OF THE INVENTION
The present invention particularly relates to the 13th revised Japanese Pharmacopoeia general test among drugs for medical use and chemical storage containers. Test method for plastic drug containers 1. The present invention relates to a polypropylene resin composition suitable for producing a molded article satisfying all the test items of a polyethylene or polypropylene aqueous injection container.
[0002]
[Prior art]
Crystalline propylene polymers are used in various medical devices by taking advantage of their excellent safety and hygiene, molding processability, mechanical properties, and gas barrier properties. In particular, in recent years, the use of ampules and vials as alternative container materials has been increasingly seen as storage containers for drugs and chemical solutions that require a high level of safety and health.
These storage containers maintain heat resistance, devitrification resistance, additive extraction resistance, gas barrier properties of water vapor and oxygen during steam sterilization, and additives used interact with preservatives and chemicals. In particular, the 13th revision Japanese Pharmacopoeia General Examination 45. Test method for plastic drug containers 1. It is essential to satisfy all the test items of polyethylene or polypropylene aqueous injection containers.
[0003]
Conventionally, in order to satisfy these performances, optimization of key performance has been attempted by various combinations of polypropylene homopolymers or random copolymers of ethylene, nucleating agents and neutralizing agents. However, for example, when a sorbitol transparent nucleating agent is used, it does not satisfy the additive extractability and pharmacopoeia test and is unsuitable for these applications, and an aluminum or organophosphate rigid nucleating agent is added. The product exhibited insufficient transparency, and when the addition amount was increased, satisfactory results were not obtained in the ignition residue and ultraviolet absorption spectrum of the pharmacopoeia test.
On the other hand, as a crystalline polypropylene resin used as a base material of a container, a polypropylene homopolymer is used in terms of rigidity, heat resistance, and gas barrier properties, and a random copolymer with ethylene is used in terms of transparency and impact resistance. However, in combination with rigid nucleating agents, heat resistance, transparency and gas barrier properties that are satisfactory as storage containers for drugs and chemicals are not obtained under the conditions that satisfy all the pharmacopoeia tests. It is.
[0004]
[Problems to be solved by the invention]
The present invention is the 13th revision Japanese Pharmacopoeia general examination 45. Test method for plastic drug containers 1. Molded product that satisfies all the test items of polyethylene or polypropylene water-based injection container, and maintains steam sterilization resistance (heat resistance, rigidity), transparency, and gas barrier properties required for storage containers for drugs and chemicals It is providing the polypropylene resin composition for use.
[0005]
[Means for Solving the Problems]
As a result of diligent research to solve the above problems, the inventors of the present invention have added a specific organic alkali metal salt and a cyclic organic phosphate ester polyvalent polyvalent to a crystalline polypropylene having a specific titanium content and a melt flow rate. A polypropylene resin composition suitable for producing a molded product satisfying the test items of the Japanese Pharmacopoeia by adding a specific amount of a nucleating agent comprising a metal salt and a specific composite hydroxide salt compound-based neutralizing agent. The present invention was found and the present invention was completed.
[0006]
That is, the present invention provides (A) a polypropylene homopolymer having a metal titanium content of 1 ppm or less and a melt flow rate of 0.5 to 70 g / 10 minutes, or propylene having an ethylene content of 3 wt% or less.・ To ethylene random copolymer,
(B) 0.025 to 0.15% by weight of at least one organic alkali metal salt selected from the group consisting of alkali metal carboxylates, alkali metal β-diketonates and alkali metal β-ketoacetate salts,
(C) General formula (I):
[0007]
[Chemical 1]

(However, R ¹ represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, R ² and R ³ represent a hydrogen atom or an alkyl group having 1 to 12 carbon atoms, and M represents Group III or Group 1 of the periodic table. X represents a group IV metal atom, X represents HO— when M represents a group III metal atom of the periodic table, and O represents O when a M represents a group IV metal atom of the periodic table. = Or (HO) _2- represents) 0.025 to 0.15 wt% of at least one cyclic organophosphate basic polyvalent metal salt represented by: and (D) the general formula (II) :
Mg _1-X Al _X (OH) ₂ (CO ₃ ) _{X / 2} · mH ₂ O (II)
(Wherein x is 0 <x ≦ 0.5 and m is a number of 3 or less) 0.01 to 0.10% by weight of a composite hydroxide salt compound represented by the following formula (1 ) Is a polypropylene resin composition for medical containers that is blended so as to satisfy the relationship.
b ≦ 0.046−0.083a (1)
[Where a is the sum (wt%) of the concentration of the organic alkali metal salt (B) and the cyclic organophosphate basic polyvalent metal salt (I) of (C) in the resin composition, and b is It is the density | concentration (weight%) of (II) in a resin composition. ]
[0008]
DETAILED DESCRIPTION OF THE INVENTION
1. (A) Polypropylene resin (1) The crystalline polypropylene resin used in the present invention has a melt flow rate of 0.5 to 70 g / 10 minutes, preferably 5 to 40 g / 10 minutes. Random copolymer with ethylene or ethylene. In the case of a copolymer, the ethylene content needs to be 3.0% by weight or less, preferably 2.0% by weight or less.
If the melt flow rate is less than 0.5, the molding processability is lowered, and a molded article satisfactory as an injection container cannot be obtained. On the other hand, when it is 70 or more, the mechanical strength is remarkably lowered, causing a practical problem. On the other hand, if the ethylene content exceeds 3.0% by weight, the transparency of the storage container is reduced or deformed when steam is sterilized, and the gas barrier property of water vapor or oxygen is reduced. Effect.
[0009]
(2) The titanium metal contained in the resin needs to be 1 ppm or less. In order to achieve this, it is possible to use an Mg-supporting highly active catalyst during the polymerization, or to provide a decontacting step after the polymerization, thereby reducing the metal component in the polymer. When the amount of the component exceeds 1 ppm in the polymer, the transparency is not sufficiently exhibited, and the ignition residue item of the pharmacopeia test item is not satisfied.
[0010]
(3) Method for Producing Propylene Homopolymer and Random Copolymer of Ethylene The method for producing propylene (co) polymer is not particularly limited, but a polymerization method using a stereoregular catalyst is preferred. As the stereoregular catalyst, a transition metal component such as a titanium halide compound such as titanium trichloride, titanium tetrachloride, or trichloroethoxytitanium, and a contact product between the titanium halide compound and a magnesium compound typified by magnesium halide; Alkyl aluminum compounds or their two-component catalysts with organometallic components such as halides, hydrides, alkoxides, and addition of electron-donating compounds containing nitrogen, carbon, phosphorus, sulfur, oxygen, silicon, etc. to these components And a three-component catalyst.
[0011]
Further, the polymerization reaction of the propylene (co) polymer may be carried out either in the gas phase or in the liquid phase. For example, when polymerizing in the liquid phase, it can be carried out in an inert hydrocarbon or liquid monomer such as n-butane, isobutane, n-pentane, isopentane, hexane, heptane, octane, cyclohexane, benzene, toluene, xylene and the like. . The polymerization temperature is usually −80 to 150 ° C., preferably 40 to 120 ° C. The polymerization pressure is preferably 1 to 60 atmospheres, and the molecular weight of the obtained (co) polymer can be adjusted with hydrogen or other known molecular weight regulators. The polymerization is carried out by a continuous or batch reaction, and the conditions may be those usually used. Furthermore, the polymerization reaction may be performed in one stage or in two stages.
[0012]
Alternatively, the propylene homopolymer and the propylene-ethylene random copolymer may be produced in advance, and mechanically mixed at a predetermined ratio.
[0013]
2. (B) and (C) Nucleating agent The nucleating agent to be blended in the composition of the present invention comprises (B) component organic alkali metal salt and (C) component cyclic organophosphate basic polyvalent metal. Salt.
The component (B) is at least one organic alkali metal salt selected from the group consisting of alkali metal carboxylates, alkali metal β-diketonates and alkali metal β-ketoacetate salts.
[0014]
(B) As an alkali metal which comprises each alkali metal salt compound of a component, lithium, sodium, potassium, etc. are mentioned.
[0015]
Examples of the carboxylic acid constituting the alkali metal carboxylate include acetic acid, propionic acid, acrylic acid, octylic acid, isooctylic acid, nonanoic acid, decanoic acid, lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, Ricinoleic acid, 12-hydroxystearic acid, behenic acid, montanic acid, melicic acid, β-dodecylmercaptoacetic acid, β-dodecylmercaptopropionic acid, β-N-laurylaminopropionic acid, β-N-methyl-lauroylaminopropionic acid Aliphatic monocarboxylic acids such as malonic acid, succinic acid, adipic acid, maleic acid, azelaic acid, sebacic acid, dodecanedioic acid, citric acid, butanetricarboxylic acid, butanetetracarboxylic acid, and other polyvalent aliphatic carboxylic acids such as naphthene Acid, cyclopentanecarboxylic acid, 1-methyl Cyclopentanecarboxylic acid, 2-methylcyclopentanecarboxylic acid, cyclopentenecarboxylic acid, cyclohexanecarboxylic acid, 1-methylcyclohexanecarboxylic acid, 4-methylcyclohexanecarboxylic acid, 3,5-dimethylcyclohexanecarboxylic acid, 4-butylcyclohexanecarboxylic acid , Cyclooctenecyclohexanecarboxylic acid, cyclohexenecarboxylic acid, cycloaliphatic mono- or polycarboxylic acid such as 4-cyclohexene-1,2-dicarboxylic acid, benzoic acid, toluic acid, xylyl acid, ethylbenzoic acid, 4-t- Aromatic mono- or polycarboxylic acids such as butylbenzoic acid, salicylic acid, phthalic acid, trimellitic acid, pyromellitic acid and the like can be mentioned.
[0016]
Examples of the β-diketone compound constituting the alkali metal β-diketonate include acetylacetone, pivaloylacetone, palmitoylacetone, benzoylacetone, pivaloylbenzoylacetone, dibenzoylmethane, and the like.
[0017]
Examples of the β-ketoacetate constituting the alkali metal β-ketoacetate include ethyl acetoacetate, octyl acetoacetate, lauryl acetoacetate, stearyl acetoacetate, ethyl benzoyl acetate, benzoyl acetate lauryl and the like. It is done.
[0018]
The (B) component alkali metal carboxylate, alkali metal β-diketonate or alkali metal β-ketoacetate salt is a salt of the alkali metal and carboxylic acid, β-diketone compound or β-ketoacetate, respectively. Yes, it can be manufactured by a conventionally known method. Among these alkali metal salt compounds of the component (B), an alkali metal aliphatic monocarboxylate, particularly a lithium aliphatic carboxylate is preferable, and an aliphatic monocarboxylic acid having 8 to 20 carbon atoms is particularly preferable. Salts are preferred.
[0019]
The component (C) used in the present invention is represented by the general formula (I):
[Chemical 1]

(However, R ¹ represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, R ² and R ³ represent a hydrogen atom or an alkyl group having 1 to 12 carbon atoms, and M represents Group III or Group 1 in the periodic table. X represents a group IV metal atom, X represents HO— when M represents a group III metal atom of the periodic table, and O represents O when a M represents a group IV metal atom of the periodic table. = Or (HO) _2- represents a cyclic organophosphate basic polyvalent metal salt.
[0020]
In the cyclic organophosphate basic polyvalent metal salt, examples of the alkyl group having 1 to 4 carbon atoms represented by R ¹ include methyl, ethyl, propyl, isopropyl, butyl, s-butyl, isobutyl, and the like. Examples of the alkyl group having 1 to 12 carbon atoms represented by ² or R ³ include methyl, ethyl, propyl, isopropyl, butyl, s-butyl, t-butyl, amyl, t-amyl, hexyl, heptyl, octyl, isooctyl, Examples include t-octyl, 2-ethylhexyl, nonyl, isononyl, decyl, isodecyl, undecyl, dodecyl, t-dodecyl and the like.
[0021]
In addition, examples of the metal atom of Group III or Group IV of the periodic table represented by M include aluminum, gallium, germanium, tin, titanium, zirconium, and the like, and aluminum is particularly preferable.
[0022]
Accordingly, examples of the component (C) include the following compounds.
[0023]
[Chemical 2]

[0024]
[Chemical 3]

[0025]
[Formula 4]

[0026]
[Chemical formula 5]

[0027]
[Chemical 6]

[0028]
[Chemical 7]

[0029]
Component (C) is, for example, a method of reacting an alkali metal salt of an acidic cyclic organophosphate with a polyvalent metal halogen compound or an oxidized polyvalent metal halide, and then hydrolyzing as necessary, acidic cyclic organophosphate It can be easily produced by a method in which an ester and a polyvalent metal alkoxide are reacted and then hydrolyzed as necessary.
[0030]
Further, the component (C) is not particularly limited with respect to the particle size, and for example, those having an average particle size of 0.01 to 50 microns can be used. It is preferable to pulverize and use fine particles having a diameter of 10 microns or less, particularly 3 microns or less.
[0031]
3. (D) Neutralizing agent As (D) neutralizing agent to be blended in the composition of the present invention, the general formula (II):
Mg _1-X Al _X (OH) ₂ (CO ₃ ) _{X / 2} · mH ₂ O (II)
(However, x is 0 <x ≦ 0.5, and m is a number of 3 or less.)
The compound hydroxide salt compound represented by these is used.
[0032]
4). Composition ratio of composition The amount of component (B) and component (C) nucleating agent added to the composition of the present invention is such that the component (B) is 0.025 to 0.15 weight in the polypropylene resin. %, Preferably 0.035 to 0.075% by weight. Moreover, a component (C) is 0.025 to 0.15 weight%, Preferably it is 0.035 to 0.075 weight%.
The addition amount of the neutralizing agent of component (D) is 0.01 to 0.10% by weight, preferably 0.02 to 0.05% by weight, in the polypropylene resin.
Further, each added amount must satisfy the formula (1).
b ≦ 0.046−0.083a (1)
(Where a is the sum (% by weight) of the concentrations of (B) and (C) in the resin composition, and b is the concentration (% by weight) of (D) in the resin composition.)
[0033]
If the addition amount of the nucleating agent (B) component is less than 0.025% by weight, the effect of improving transparency and heat resistance is not sufficient, and if it exceeds 0.15% by weight, the transparency improvement corresponding to the addition amount is achieved. The effect cannot be expected, and conversely, the ignition residue in the pharmacopoeia test items and the safety performance of the ultraviolet absorption spectrum are lowered. When the addition amount of the component (C) is out of the range, as in the case of the component (B), the improvement of transparency and heat resistance is insufficient or the safety is lowered. The ratio of the component (B) and the component (C) is not particularly limited as long as it is within the above range, but the present invention is applicable when the amount of the component (B) is equivalent to the amount of the component (C). The effect of is remarkable.
[0034]
On the other hand, if the neutralizing agent is less than 0.01% by weight, neutralization of the catalyst residue component in the polypropylene resin becomes insufficient, and the temporal stability and transparency of the polypropylene resin are lowered, and it exceeds 0.10% by weight. In itself, it causes a decrease in transparency, and a satisfactory result cannot be obtained with the ignition residue in the pharmacopoeia test items.
Furthermore, when the relationship between the amounts of the additives is out of the formula (1), transparency, heat resistance, gas barrier properties necessary for the drug and chemical solution containers, and the ignition residue necessary for these storage containers, It becomes difficult to optimize safety performance such as ultraviolet absorption spectrum.
[0035]
5. Method for Producing Polypropylene Resin Composition The polypropylene medical resin composition of the present invention is prepared by using the above components (A), (B), (C) and (D) with a Henschel mixer, a super mixer, a ribbon blender, etc. In addition to the additive used in the present invention, a process stabilizer such as tris (2,4-di-t-butylphenyl) phosphite generally used, a hindered amine UV absorber, etc. It can be obtained by melt-kneading in a temperature range of 160 to 250 ° C. with a single screw extruder, twin screw extruder, Banbury mixer, plastic bender, roll or the like.
[0036]
【Example】
EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited at all by these description. In each of Examples and Comparative Examples, the following materials were used as resin raw materials and additives.

[0037]
The physical properties were measured by the following method.
(1) Ethylene concentration: The ethylene content in the random copolymer was measured by infrared spectroscopy using a characteristic absorber of 733 cm ⁻¹ with an ethylene / propylene random copolymer whose composition was verified by ¹³ C-NMR as a reference substance. The pellets were formed into a film having a thickness of about 500 microns by press molding.
(2) Ti content: After dissolving the ash content in polypropylene in hydrochloric acid (1 volume of hydrochloric acid + 1 volume of water), add 10% ascorbic acid, develop color with diantipyrylmethane solution, and contain titanium content using absorbance at 385 nm. Calculated.
(3) MFR: Compliant with JIS K6758, 230 ° C. 2.16 kg load.
[0038]
(4) Steam sterilization: The 1 mm sheet molded product was sterilized at 121 ° C. for 1 hour using an autoclave sterilizer, air-dried, and subjected to transparency (haze) measurement.
(5) Haze value: Measured according to JIS K7105 using a 1 mm thick sheet piece.
(6) DuPont impact strength: measured at 23 ° C. according to JIS K7211, using a sheet piece having a thickness of 2 mm.
[0039]
(7) Formability: The smoothness (flow mark and the like) of the surface of the 1 mm sheet molded product was visually observed to determine the moldability.
A: Almost no flow mark from the vicinity of the gate is observed.
X: A flow mark is observed from the vicinity of the gate to the end of the molded product.
[0040]
(8) 13th revision Japanese Pharmacopoeia general trial: 45. 1. Plastic chemical container test method (plastic water-based injection container) Transparency, appearance, water vapor permeability, heavy metal, lead, cadmium, residue on ignition, eluate, and cytotoxicity were measured according to the test methods in the section of polyethylene or polypropylene aqueous injection container. However, the sample was prepared by weighing pellets having a thickness of 0.5 mm and corresponding to a surface area of 600 cm ² , and pressing at 210 ° C. to obtain a sheet piece having a length of about 5 cm and a width of about 0.5 cm. After being cut into pieces, washed with water, and dried at room temperature. Put this in a hard glass container with an internal volume of about 300 ml, add exactly 200 ml of water, seal it with an appropriate stopper, heat it at 121 ° C for 1 hour using a high-pressure steam sterilizer, and leave it to room temperature. Then, this solution was used as a test solution, and separately with water, a blank test solution was prepared in the same manner.
[0041]
Reference example 1
NA-21 as a nucleating agent and Mizukarak as a neutralizing agent are blended in proportions shown in Table 1 with respect to 100 parts by weight of homopolypropylene (HPP) having a Ti content of less than 1 ppm, and MARK 2112 as a phosphite antioxidant. After blending 0.1 parts by weight (Asahi Denka Kogyo Co., Ltd.) and 0.05 parts by weight TINUVIN 622LD (Ciba Geigy Japan) as a hindered amine UV stabilizer, 50 mm diameter after dry blending with a super mixer Were melt-kneaded using a single screw extruder. Extruded pellets from the die at a die outlet temperature of 210 ° C. The obtained pellets were injection molded by an injection molding machine at a resin temperature of 230 ° C., an injection pressure of 900 kg / cm ² and a mold temperature of 60 ° C. to prepare a sheet. A test piece was taken from the obtained sheet and measured for physical properties. The results are shown in Table 1.
[0042]
Examples 1-4
Using a polypropylene resin, a nucleating agent, and a neutralizing agent shown in Table 1, test pieces were obtained in the same manner as in the Examples, and their physical properties were measured. The results are shown in Table 1.
[0043]
Comparative Examples 1-8
Using a polypropylene resin, a nucleating agent, and a neutralizing agent shown in Table 2, test pieces were obtained in the same manner as in the Examples, and their physical properties were measured. The results are shown in Table 2.
[0044]
[Table 1]

[0045]
[Table 2]

[0046]
As is clear from Tables 1 and 2, a system using the nucleating agent NA-21 and lithium aluminum composite hydroxide salt (Mizukarak), which is the composition of the present invention, so as to satisfy the formula (1) ( reference) Example 1 ), a system using a nucleating agent and hydrotalcite (DHT-4A) so as to satisfy the formula (1) (Example 1 ), a system in which the MFR was changed in Example 1 (Example 2 ), The system in which the amount of the nucleating agent and the amount of the neutralizing agent are changed in Example 1 (Example 3 ) and the system using random PP (RPP) (Example 4 ) are compositions that pass the pharmacopeia test. On the other hand, the composition system using the sorbitol nucleating agent failed the pharmacopeia test due to UV absorption and permanganate consumption in the eluate test (Comparative Example 1), and the system using calcium stearate as a neutralizing agent. Then, the transparency of the chemical solution failed (Comparative Example 2), and in the system using RPP whose ethylene concentration exceeded the claimed range, deformation and transparency deteriorated during sterilization (Comparative Example 3), and the amount of NA-21 added was Transparency improvement is insufficient in the system out of the claim range on the low concentration side (Comparative Example 4), and in the system in which the neutralizer is out of the claim range on the low concentration side, the neutralization is insufficient and the safety due to resin degradation is Decreased, failed in pharmacopoeia tests due to UV absorption, permanganic acid consumption, etc. (Comparative Example 5), and failed in ignition residue in systems with high metal titanium concentration in polypropylene (Comparative Example 6) In a system in which MFR deviates to the low flow side, the moldability deteriorates (Comparative Example 7 , Shock resistance in a system MFR deviates to the high flow side (DuPont impact) is reduced (Comparative Example 8), respectively undesirable.
[0047]
【The invention's effect】
The polypropylene-based resin composition for medical containers of the present invention is a thirteenth revised Japanese Pharmacopoeia general test. Test method for plastic drug containers 1. Satisfies all test items of polyethylene or polypropylene aqueous injection containers, and maintains steam sterilization resistance (heat resistance, rigidity), transparency, and gas barrier properties necessary for storage containers for drugs and chemicals .

Claims (3)

(A) Polypropylene homopolymer having a metal titanium content of 1 ppm or less and a melt flow rate of 0.5 to 70 g / 10 min, or a propylene / ethylene random copolymer having an ethylene content of 3% by weight or less In addition,
(B) 0.025 to 0.15% by weight of at least one organic alkali metal salt selected from the group consisting of alkali metal carboxylates, alkali metal β-diketonates and alkali metal β-ketoacetate salts,
(C) General formula (I):

(However, R ¹ represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, R ² and R ³ represent a hydrogen atom or an alkyl group having 1 to 12 carbon atoms, and M represents Group III or Group 1 of the periodic table. Represents a group IV metal atom, X represents HO— when M represents a group III metal atom of the periodic table, and O represents O when M represents a group IV metal atom of the periodic table. = Or (HO) _2- represents) 0.025 to 0.15 wt% of at least one cyclic organic phosphate basic polyvalent metal salt represented by: and (D) the general formula (II) :
Mg _1-X AlX (OH) ₂ (CO ₃ ) _{X / 2} · mH ₂ O (II)
(Wherein x is 0 <x ≦ 0.5 and m is a number of 3 or less) 0.01 to 0.10% by weight of a composite hydroxide salt compound represented by
A polypropylene resin composition for medical containers compatible with the 13th revised Japanese Pharmacopoeia, formulated so as to satisfy the relationship of the following formula (1).
b ≦ 0.046−0.083a (1)
[Wherein a is the sum (wt%) of the concentration of the organic alkali metal salt (B) and the cyclic organophosphate basic polyvalent metal salt (I) of (C) in the resin composition, and b is It is the density | concentration (weight%) of (II) in a resin composition. ]   The polypropylene resin composition for medical containers according to claim 1, wherein the organic alkali metal salt is an alkali metal carboxylate.   The polypropylene resin composition for medical containers according to claim 1 or 2, wherein the cyclic organophosphate basic polyvalent metal salt is an aluminum salt.