JP3604269B2 - Polypropylene resin composition for medical containers - Google Patents

Description

（ただし、Ｒ^１は直接結合、硫黄又は炭素数１〜９のアルキレン基又はアルキリデン基であり、Ｒ^２及びＲ^３は水素原子又は炭素数１〜８のアルキル基であり、ＭはＮａであり、ｎはＭの価数である。）、
または（ｂ_２）一般式（ＩＩ）：
【０００８】
【化４】

（ただし、Ｒ^４は水素原子又は炭素数１〜８のアルキル基であり、ＭはＮａであり、ｎはＭの価数である。）により表されるフォスフェート系化合物、０．０５〜０．３０重量％と、
（Ｃ）一般式（ＩＩＩ）：
Ｍｇ_１−ｘＡｌ_ｘ（ＯＨ）_２（ＣＯ_３）_ｘ／２・ｍＨ_２Ｏ （ＩＩＩ）
（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、０．０２〜０．０５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：樹脂組成物中の（Ｉ）または（ＩＩ）の濃度（重量％）、ｂ：樹脂組成物中の（ＩＩＩ）の濃度（重量％）である。）
【０００９】
【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５ｇ／１０分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、４０ｇ／１０分を超えると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。
【００１０】
（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。
【００１１】
（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。
【００１２】
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。また、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、これをプロピレン単独重合体と所定割合にて機械的混合を行ってもよい。
【００１３】
２．（Ｂ）造核剤
本発明の組成物に配合する（Ｂ）造核剤は、（ｂ_１）一般式（Ｉ）または（ｂ_２）一般式（ＩＩ）で表される有機リン酸金属塩化合物である。
【００１４】
【化５】

（ただし、Ｒ^１は直接結合、硫黄又は炭素数１〜９のアルキレン基又はアルキリデン基であり、Ｒ^２及びＲ^３は水素原子又は炭素数１〜８のアルキル基であり、ＭはＮａであり、ｎはＭの価数である。）
【００１５】
【化６】

（ただし、Ｒ^４は水素原子又は炭素数１〜８のアルキル基であり、ＭはＮａであり、ｎはＭの価数である。）
【００１６】
本発明で使用可能な一般式（Ｉ）で表される有機リン酸金属塩化合物としては、ナトリウム−２，２’−メチレン−ビス−（４，６−ジ−ｔ−ブチルフェニル）フォスフェート、ナトリウム−２，２’−エチリデン−ビス−（４，６−ジ−ｔ−ブチルフェニル）フォスフェート、ナトリウム−２，２’−エチリデン−ビス−（４−ｉ−プロピル−６−ｔ−ブチルフェニル）フォスフェート、ナトリウム−２，２’−ブチリデン−ビス−（４，６−ジメチルフェニル）フォスフェート、ナトリウム−２，２’−ブチリデン−ビス−（４，６−ジ−ｔ−ブチルフェニル）フォスフェート、ナトリウム−２，２’−ｔ−オクチルメチレン−ビス−（４，６−メチルフェニル）フォスフェート、ナトリウム−２，２’−ｔ−オクチルメチレン−ビス−（４，６−ジ−ｔ−ブチルフェニル）フォスフェート、ナトリウム−２，２’−メチレン−ビス−（４−メチル−６−ｔ−ブチルフェニル）フォスフェート、ナトリウム−２，２’−メチレン−ビス−（４−エチル−６−ｔ−ブチルフェニル）フォスフェート、ナトリウム（４，４’−ジメチル−６，６’−ジ−ｔ−ブチル−２，２’−ビフェニル）フォスフェート、ナトリウム−２，２’−エチリデン−ビス−（４−ｓ−ブチル−６−ｔ−ブチルフェニル）フォスフェート、ナトリウム−２，２’−メチレン−ビス−（４，６−ジ−メチルフェニル）フォスフェート、ナトリウム−２，２’−メチレン−ビス−（４，６−ジ−エチルフェニル）フォスフェート等が挙げられる。これらのうち、特にナトリウム−２，２’−メチレン−ビス−（４，６−ジ−ｔ−ブチルフェニル）フォスフェートが好ましい。
【００１７】
また、一般式（ＩＩ）で表される有機リン酸金属塩化合物としては、ナトリウム−ビス−（４−ｔ−ブチルフェニル）フォスフェート、ナトリウム−ビス−（４−メチルフェニル）フォスフェート、ナトリウム−ビス−（４−エチルフェニル）フォスフェート、ナトリウム−ビス−（４−ｉ−プロピルフェニル）フォスフェート、ナトリウム−ビス−（４−ｔ−オクチルフェニル）フォスフェート、およびこれらの２種以上の混合物を例示することができる。
【００１８】
３．（Ｃ）中和剤
本発明の組成物に配合する（Ｃ）中和剤としては、一般式（ＩＩＩ）で表される複合水酸化物塩化合物である。
Ｍｇ_１−ｘＡｌ_ｘ（ＯＨ）_２（ＣＯ_３）_ｘ／２・ｍＨ_２Ｏ （ＩＩＩ）
（ただし、ｘは０≦ｘ≦０．５であり、ｍは３以下の数である。）
【００１９】
４．組成物の組成割合
本発明の組成物に配合する一般式（Ｉ）または一般式（ＩＩ）の造核剤の添加量は、ポリプロピレン系樹脂中に、０．０５〜０．３０重量％、好ましくは０．０７〜０．１５重量％である。また、一般式（ＩＩＩ）の中和剤の添加量は、ポリプロピレン系樹脂中に、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：樹脂組成物中の（Ｉ）または（ＩＩ）の濃度（重量％）ｂ：樹脂組成物中の（ＩＩＩ）の濃度（重量％）である。）
【００２０】
造核剤の量が０．０５重量％未満では透明性や耐熱性が不十分となり、また０．３０重量％を超えると添加量に見合った性能が期待できないばかりか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。また、中和剤が０．０２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０．０５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。また、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。
【００２１】
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）及び（Ｃ）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。
【００２２】
【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。
（Ａ）結晶性ポリプロピレン
ホモポリプロピレン（ＨＰＰ）：ＭＦＲ １５ｇ／１０分
ランダムポリプロピレン（ＲＰＰ）：エチレン濃度 ０．４重量％、ＭＦＲ１５ｇ／１０分
（Ｂ）造核剤
ＮＡ−１１：フォスフェート系核剤（旭電化工業（株）製）
ゲルオールＭＤ：ソルビトール系核剤（新日本理化（株）製）
（Ｃ）中和剤
ミズカラック：リチウムアルミニウム複合水酸化物塩（水澤化学工業（ 株）製）
ＤＨＴ−４Ａ：マグネシウム・アルミニウム・ハイドロオキサイド・カ ーボネート・ハイドレート（協和化学工業（株）製）
Ｃａ−Ｓｔ：カルシウムステアレート（日東化学（株）製）
【００２３】
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。
【００２４】
（４）蒸気滅菌：１ｍｍ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１ｍｍ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２ｍｍのシート片を用いて、ＪＩＳ Ｋ７２１１に準拠して２３℃で測定した。
【００２５】
（７）成形性：１ｍｍ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。
【００２６】
（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６００ｃｍ^２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。
【００２７】
実施例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−１１及び中和剤としてＤＨＴ−４Ａ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。
【００２８】
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１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。
【００２９】
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。
【００３０】
【表１】

【００３１】
【表２】

【００３２】
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−１１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で核剤量及び中和剤量を変えた系（実施例３）及びランダムポリプロピレン（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澄明性が不合格（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−１１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。
【００３３】
【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]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a medicine for medical use and a medicine storage container, in particular, the thirteenth revised Japanese Pharmacopoeia General Test. Plastic drug container test method 1. The present invention relates to a polypropylene-based resin composition suitable for producing a molded article satisfying all test items of a polyethylene or polypropylene aqueous injection container.
[0002]
[Prior art]
Crystalline propylene-based polymers are used in various medical devices, taking advantage of their excellent safety and health properties, moldability, mechanical properties, and gas barrier properties. In particular, in recent years, use as an alternative container material for ampoules and vials as a storage container for medicines and drug solutions that require a high level of safety and health has come to be seen.
These storage containers maintain heat resistance during steam sterilization, resistance to devitrification, resistance to extraction of additives, gas barrier properties for water vapor and oxygen, and the additives used interact with storage drugs and chemicals. 45, specifically, the 13th revision of the Japanese Pharmacopoeia, General Study. Plastic drug container test method 1. It is an essential requirement that all the test items of the aqueous injection container made of polyethylene or polypropylene be satisfied.
[0003]
Conventionally, in order to satisfy these performances, various combinations of a polypropylene homopolymer or a random copolymer with ethylene, a nucleating agent and a neutralizing agent have been attempted to optimize key performances. However, for example, when a sorbitol-based transparent nucleating agent is used, it is not suitable for these applications because it does not satisfy the additive extraction resistance and the local test, and an aluminum-based or organophosphate-based rigid nucleating agent is added. In the case of those which did not exhibit sufficient transparency, or when the amount of addition was increased, satisfactory results were not obtained in the ignition residue and ultraviolet absorption spectrum of the local test.
On the other hand, as the crystalline polypropylene resin as the base material of the container, a polypropylene homopolymer in terms of rigidity, heat resistance, and gas barrier properties, and a random copolymer with ethylene in terms of transparency and impact resistance. It is preferable that, in combination with a rigid nucleating agent, under the conditions satisfying all the localization tests, heat resistance, transparency, and gas barrier properties that are satisfactory as storage containers for drugs and chemicals are not obtained. It is.
[0004]
[Problems to be solved by the invention]
The present invention is based on the 13th revised Japanese Pharmacopoeia General Test 45. Plastic drug container test method 1. A molded product that satisfies all of the test items for the polyethylene or polypropylene aqueous injection container and retains the steam sterilization resistance (heat resistance, rigidity), transparency, and gas barrier properties required as a storage container for drugs and chemical solutions. To provide a polypropylene resin composition for use.
[0005]
[Means for Solving the Problems]
The present inventors have conducted intensive studies in order to solve the above-mentioned problems, and found that a crystalline phosphate having a specific titanium content and a melt flow rate has a specific phosphate nucleating agent and a specific composite hydroxide salt compound. By adding a specific amount of a system neutralizer, a polypropylene resin composition suitable for producing a molded article satisfying the test items of the Japanese Pharmacopoeia 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 based on JIS K6758, 230 ° C, and 2.16 kg load of 5 to 40 g / 10 minutes, Or to a propylene / ethylene random copolymer having an ethylene content of 3% by weight or less,
(B) (b ₁ ) General formula (I):
[0007]
Embedded image

(However, R ¹ is a direct bond, sulfur or an alkylene group or an alkylidene group having 1 to 9 carbon atoms, R ² and R ³ are a hydrogen atom or an alkyl group having 1 to 8 carbon atoms, and M is Na , N is the valence of M.),
Or (b ₂ ) general formula (II):
[0008]
Embedded image

(Where R ⁴ is a hydrogen atom or an alkyl group having 1 to 8 carbon atoms, M is Na and n is a valence of M), and a phosphate compound represented by the formula: .30% by weight,
(C) General formula (III) :
Mg _1-x Al _x (OH) ₂ (CO ₃ ) _{x / 2} · mH ₂ O (III)
(However, x is 0 ≦ x ≦ 0.5, and m is a number of 3 or less.)
Is a polypropylene resin composition for a medical container, which comprises 0.02 to 0.05% by weight of a composite hydroxide salt compound represented by the following formula (1).
b ≦ 0.046−0.083a (1)
(However, a: concentration (% by weight) of (I) or (II) in the resin composition, b: concentration (% by weight ) of (III) in the resin composition.)
[0009]
BEST MODE FOR CARRYING OUT THE INVENTION
1. (A) Polypropylene resin (1) The crystalline polypropylene resin used in the present invention has a melt flow rate of 5 to 40 g / 10 minutes, and is a polypropylene homopolymer or a random copolymer with ethylene. is there. In the case of a copolymer, the ethylene content must be 3.0% by weight or less, preferably 2.0% by weight or less. If the melt flow rate is less than 5 g / 10 minutes , the molding processability will decrease, and a molded article satisfactory as an injection container will not be obtained. On the other hand, when the amount exceeds 40 g / 10 minutes, the mechanical strength is remarkably reduced, which causes a practical problem. On the other hand, if the ethylene content exceeds 3.0% by weight, transparency and deformation occur during the sterilization of the steam in the storage container, and the gas barrier properties of water vapor and oxygen are reduced, which adversely affects the preservative agent and the chemical solution. Exert.
[0010]
(2) The metal titanium contained in the resin must be 1 ppm or less. In order to achieve this, a highly active catalyst carrying Mg is used at the time of polymerization, or a desorption step is provided after the polymerization, so that the metal component in the polymer can be reduced. When the content of the component exceeds 1 ppm in the polymer, transparency is not sufficiently exhibited, and the ignition residue item in the test items of the Pharmacopoeia is not satisfied.
[0011]
(3) Method for producing random copolymer of propylene homopolymer and ethylene The method for producing the propylene (co) polymer is not particularly limited, but a polymerization method using a stereoregular catalyst is preferred. Examples of the stereoregular catalyst include titanium trichloride, titanium tetrachloride, titanium halide compounds such as trichloroethoxy titanium, and transition metal components such as a contact product of the titanium halide compound and a magnesium compound represented by magnesium halide. Alkali aluminum compounds or their two-component catalysts with organometallic components such as halides, hydrides, alkoxides, and the like, and electron-donating compounds containing nitrogen, carbon, phosphorus, sulfur, oxygen, silicon, etc. Ternary catalysts.
[0012]
The polymerization reaction of the propylene (co) polymer may be performed in any of a gas phase and a liquid phase. For example, when polymerizing in a liquid phase, it can be carried out in an inert hydrocarbon such as n-butane, isobutane, n-pentane, isopentane, hexane, heptane, octane, cyclohexane, benzene, toluene, xylene or a liquid monomer. . The polymerization temperature is usually from -80 to 150C, preferably from 40 to 120C. The polymerization pressure is preferably from 1 to 60 atm. The molecular weight of the (co) polymer obtained 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 commonly used. Further, the polymerization reaction may be performed in one step or two steps. Alternatively, a propylene / ethylene random copolymer may be produced and then mechanically mixed with a propylene homopolymer at a predetermined ratio.
[0013]
2. (B) Nucleating Agent The (B) nucleating agent to be added to the composition of the present invention is (b ₁ ) a metal salt of an organic phosphate represented by the general formula (I) or (b ₂ ). Compound.
[0014]
Embedded image

(However, R ¹ is a direct bond, sulfur or an alkylene group or an alkylidene group having 1 to 9 carbon atoms, R ² and R ³ are a hydrogen atom or an alkyl group having 1 to 8 carbon atoms, and M is Na , N is the valence of M.)
[0015]
Embedded image

(However, R ⁴ is a hydrogen atom or an alkyl group having 1 to 8 carbon atoms, M is Na , and n is a valence of M.)
[0016]
Examples of the organophosphate metal salt compound represented by the general formula (I) that can be used in the present invention include sodium-2,2′-methylene-bis- (4,6-di-t-butylphenyl) phosphate, Sodium-2,2'-ethylidene-bis- (4,6-di-t-butylphenyl) phosphate, sodium-2,2'-ethylidene-bis- (4-i-propyl-6-t-butylphenyl) ) Phosphate, sodium-2,2'-butylidene-bis- (4,6-dimethylphenyl) phosphate, sodium-2,2'-butylidene-bis- (4,6-di-t-butylphenyl) phosphate Fate, sodium-2,2'-t-octylmethylene-bis- (4,6-methylphenyl) phosphate, sodium-2,2'-t-octylmethylene-bis- (4,6- Di-t-butylphenyl) phosphate, sodium-2,2'-methylene-bis- (4-methyl-6-t-butylphenyl) phosphate, sodium-2,2'-methylene-bis- (4- Ethyl-6-t-butylphenyl) phosphate, sodium (4,4'-dimethyl-6,6'-di-t-butyl-2,2'-biphenyl) phosphate, sodium-2,2'-ethylidene -Bis- (4-s-butyl-6-t-butylphenyl) phosphate, sodium-2,2'-methylene-bis- (4,6-di-methylphenyl) phosphate, sodium-2,2 ' -Methylene-bis- (4,6-di-ethylphenyl) phosphate and the like. Of these, sodium-2,2'-methylene-bis- (4,6-di-t-butylphenyl) phosphate is particularly preferred.
[0017]
Examples of the organic phosphoric acid metal salt compound represented by the general formula (II) include sodium-bis- (4-t-butylphenyl) phosphate, sodium-bis- (4-methylphenyl) phosphate, and sodium-bis- (4-methylphenyl) phosphate. Bis- (4-ethylphenyl) phosphate, sodium-bis- (4-i-propylphenyl) phosphate, sodium-bis- (4-t-octylphenyl) phosphate, and mixtures of two or more thereof Examples can be given.
[0018]
3. (C) Neutralizing agent The (C) neutralizing agent blended in the composition of the present invention is a complex hydroxide salt compound represented by the general formula (III) .
Mg _1-x Al _x (OH) ₂ (CO ₃ ) _{x / 2} · mH ₂ O (III)
(However, x is 0 ≦ x ≦ 0.5, and m is a number of 3 or less.)
[0019]
4. Composition ratio of composition The amount of the nucleating agent of the general formula (I) or the general formula (II) to be added to the composition of the present invention is 0.05 to 0.30% by weight, preferably, in the polypropylene resin. Is 0.07 to 0.15% by weight. The amount of the neutralizing agent represented by the general formula (III) is 0.02 to 0.05% by weight in the polypropylene resin. Further, it is necessary that each of the addition amounts satisfies the expression (1).
b ≦ 0.046−0.083a (1)
(However, a: concentration (% by weight) of (I) or (II) in the resin composition, b: concentration (% by weight ) of (III) in the resin composition.)
[0020]
When the amount of the nucleating agent is less than 0.05% by weight, transparency and heat resistance become insufficient, and when the amount exceeds 0.30% by weight, not only performance corresponding to the added amount cannot be expected, but also a strong The heat residue and the safety performance of the ultraviolet absorption spectrum are reduced. On the other hand, if the neutralizing agent is less than 0.02 % by weight, the neutralization of the catalyst residue component in the polypropylene-based resin is insufficient, and the temporal stability and transparency of the polypropylene-based resin are reduced, and the content exceeds 0.05 % by weight. And itself may cause a decrease in transparency, and satisfactory results cannot be obtained with ignition residue in the local test items. When the relationship between the amounts of the additives deviates from the formula (1), the transparency, heat resistance and gas barrier properties required for a medicine and a chemical solution container and the residue of an ignition residue required for these preservation containers are reduced. It becomes difficult to optimize safety performance such as an ultraviolet absorption spectrum.
[0021]
5. Method for Producing Polypropylene-Based Resin Composition The polypropylene-based medical resin composition of the present invention is obtained by mixing the components (A), (B) and (C) with a Henschel mixer, a super mixer, a ribbon blender or the like. In addition to the additives used in the present invention, a process stabilizer such as tris (2,4-di-tbutylphenyl) phosphite, a hindered amine-based ultraviolet absorber, and the like, which are generally used, are blended, and an ordinary single screw extruder is used. And melt kneading with a twin-screw extruder, a Banbury mixer, a pravender, a roll or the like in a temperature range of 160 to 250 ° C.
[0022]
【Example】
Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited by these descriptions. In each of the examples and comparative examples, the following were used as resin raw materials and additives.
(A) Crystalline polypropylene homopolypropylene (HPP): MFR 15 g / 10 minutes Random polypropylene (RPP): ethylene concentration 0.4% by weight, MFR 15 g / 10 minutes (B) Nucleating agent NA-11: phosphate-based nucleating agent (Asahi Denka Kogyo Co., Ltd.)
Gerol MD: Sorbitol nucleating agent (Nippon Rika Co., Ltd.)
(C) Neutralizing agent Mizukarak: lithium aluminum composite hydroxide salt (manufactured by Mizusawa Chemical Industry Co., Ltd.)
DHT-4A: Magnesium aluminum hydroxide carbonate hydrate (manufactured by Kyowa Chemical Industry Co., Ltd.)
Ca-St: calcium stearate (manufactured by Nitto Chemical Co., Ltd.)
[0023]
The physical properties were measured by the following methods.
(1) Ethylene concentration: The ethylene content in the random copolymer was measured by infrared spectroscopy using a characteristic absorber of 733 cm ^-1 using an ethylene / propylene random copolymer whose composition was examined by ¹³ C-NMR as a reference substance. A pellet was formed into a film having a thickness of about 500 microns by press molding.
(2) Ti content: The ash content in polypropylene was dissolved in hydrochloric acid (1 volume of hydrochloric acid + 1 volume of water), 10% ascorbic acid was added, and the color was developed with a diantipyrylmethane solution, and the titanium content was determined using the absorbance at 385 nm. Calculated.
(3) MFR: Based on JIS K6758, 230 ° C, 2.16 kg load.
[0024]
(4) Steam sterilization: A 1 mm sheet molded product was sterilized at 121 ° C. for 1 hour using an autoclave sterilizer, air-dried, and then 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. using a 2 mm thick sheet piece in accordance with JIS K7211.
[0025]
(7) Formability: The smoothness (flow mark, etc.) of the surface of a 1 mm sheet molded product was visually observed to determine the formability.
：: Almost no flow mark is observed near the gate.
X: Flow marks are observed from the vicinity of the gate to the end of the molded product.
[0026]
(8) 13th revision Japanese Pharmacopoeia general test: 45. Plastic pharmaceutical container test method (plastic aqueous injection container) The transparency, appearance, water vapor permeability, heavy metals, lead, cadmium, ignition residue, eluate, and cytotoxicity were measured in accordance with the test methods described in the section of the polyethylene or polypropylene aqueous injection container. However, for sample preparation, pellets having a thickness of 0.5 mm and a weight equivalent to a surface area of 600 cm ² were weighed and pressed at 210 ° C. to form sheet pieces having a length of about 5 cm and a width of about 0.5 cm. And 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 with an appropriate stopper, heat at 121 ° C. for 1 hour using a high-pressure steam sterilizer, and leave until reaching room temperature. Then, a blank test solution was prepared in the same manner as described above, using the inner solution as a test solution and separately using water.
[0027]
Example 1
With respect to 100 parts by weight of homopolypropylene (HPP) having a Ti content of less than 1 ppm, NA-11 as a nucleating agent and DHT-4A as a neutralizing agent were blended in the proportions shown in Table 1, and a phosphite-based antioxidant was further added. 0.1 parts by weight of MARK 2112 (manufactured by Asahi Denka Kogyo Co., Ltd.) and 0.05 parts by weight of TINUVIN 622LD (manufactured by Nippon Ciba Geigy Co., Ltd.) as a hindered amine-based ultraviolet stabilizer were mixed by dry blending with a super mixer, and then 50 parts by weight. The mixture was melt-kneaded using a single-screw extruder having a millimeter diameter. It was extruded from the die at a die exit temperature of 210 ° C. and pelletized. The obtained pellet was 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 form a sheet. A test piece was taken from the obtained sheet, and the physical properties were measured. Table 1 shows the results.
[0028]
Examples 1 to 4
Using a polypropylene resin, a nucleating agent, and a neutralizing agent shown in Table 1, a test piece was obtained in the same manner as in Example 1, and the physical properties were measured. Table 1 shows the results.
[0029]
Comparative Examples 1 to 8
Using a polypropylene resin, a nucleating agent, and a neutralizing agent shown in Table 2, a test piece was obtained in the same manner as in the example, and the physical properties were measured. Table 2 shows the results.
[0030]
[Table 1]

[0031]
[Table 2]

[0032]
As is clear from Tables 1 and 2, a system using the nucleating agent NA-11 and hydrotalcite (DHT-4A), which are the compositions of the present invention, so as to satisfy the formula (1) (Example 1) ), The 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 were changed in Example 1 (Example 3 ), and the system in which random polypropylene (RPP) was used (Example 2 ). Example 4 ) is a composition that passes the local test.
On the other hand, a composition using a sorbitol-based nucleating agent failed the Pharmacopoeia test due to UV absorption and permanganic acid consumption in an eluate test (Comparative Example 1), and a system using calcium stearate as a neutralizing agent , The clarity of the drug solution was rejected (Comparative Example 2), and the system using RPP having an ethylene concentration exceeding the claimed range deteriorated in deformation and transparency during sterilization (Comparative Example 3), and the amount of NA-11 added was reduced. In a system out of the claimed range on the low concentration side, the transparency improvement is insufficient (Comparative Example 4), and in a system out of the claimed range on the low concentration side, the neutralization is insufficient and the safety due to resin deterioration is low. It decreased in UV absorption, permanganic acid consumption, etc., and failed the local test (Comparative Example 5). In the system where the concentration of titanium metal in polypropylene was high, the residue on ignition failed (Comparative Example 6). In a system in which the MFR was out of the low flow side, the moldability deteriorated (Comparative Example 7). , Shock resistance in a system MFR deviates to the high flow side (DuPont impact) is reduced (Comparative Example 8), respectively undesirable.
[0033]
【The invention's effect】
The thirteenth revised Japanese Pharmacopoeia General Test of the polypropylene resin composition for medical containers of the present invention 45. Plastic drug container test method 1. It satisfies all the test items for polyethylene or polypropylene aqueous injection containers, and retains the steam sterilization resistance (heat resistance and rigidity), transparency, and gas barrier properties required for storage of drugs and chemical solutions. .

Claims (1)

(A) a polypropylene homopolymer having a metal titanium content of 1 ppm or less and a melt flow rate based on JIS K6758 at 230 ° C. and a load of 2.16 kg of 5 to 40 g / 10 minutes, or an ethylene content of 3 Weight percent or less of propylene / ethylene random copolymer,
(B) (b ₁ ) General formula (I):

(However, R ¹ is a direct bond, sulfur or an alkylene group or an alkylidene group having 1 to 9 carbon atoms, R ² and R ³ are a hydrogen atom or an alkyl group having 1 to 8 carbon atoms, and M is Na , N is the valence of M.),
Or (b ₂ ) general formula (II):

(Where R ⁴ is a hydrogen atom or an alkyl group having 1 to 8 carbon atoms, M is Na and n is a valence of M), and a phosphate compound represented by the formula: .30% by weight,
(C) General formula (III):
Mg _1-x Al _x (OH) ₂ (CO ₃ ) _{x / 2} · mH ₂ O (III)
(However, x is 0 ≦ x ≦ 0.5, and m is a number of 3 or less.)
A polypropylene resin composition for a medical container, which comprises 0.02 to 0.05% by weight of a composite hydroxide salt compound represented by the following formula (1).
b ≦ 0.046−0.083a (1)
(However, a: concentration (% by weight) of (I) or (II) in the resin composition, b: concentration (% by weight ) of (III) in the resin composition.)