JPS61247460A - Stop plug for injection drug - Google Patents
Stop plug for injection drugInfo
- Publication number
- JPS61247460A JPS61247460A JP60089981A JP8998185A JPS61247460A JP S61247460 A JPS61247460 A JP S61247460A JP 60089981 A JP60089981 A JP 60089981A JP 8998185 A JP8998185 A JP 8998185A JP S61247460 A JPS61247460 A JP S61247460A
- Authority
- JP
- Japan
- Prior art keywords
- stopper
- weight
- injection
- rubber
- softener
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Abstract
(57)【要約】本公報は電子出願前の出願データであるた
め要約のデータは記録されません。(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.
Description
【発明の詳細な説明】
〔発明の技術分野〕
本発明は、特殊な熱可塑性エラストマーからなる注射剤
用止栓の改良に関する。DETAILED DESCRIPTION OF THE INVENTION [Technical Field of the Invention] The present invention relates to an improvement in a stopper for injections made of a special thermoplastic elastomer.
注射剤用止栓とは、第１０改正日本薬局方製剤総則１７
に規定される注射剤の止栓を指し、具体的にはリンゲル
液等の輸液が収容された容器の口部又は凍結乾燥製剤用
容器の口部等に注射剤を密封する目的で挿入して使用さ
れるものでおる。この止栓は注射針を差込んで使゛用し
た時には、その止栓の材料の屑等により注射針の穴が詰
まることなく、容器内が大気と連通状態を保持すること
が必要でおる。また、注射針を扱取った際に、注射液が
注射針の差込み箇所から漏れないことが必要でおる。Stoppers for injections are defined in the 10th revised Japanese Pharmacopoeia Preparation General Regulations 17.
It refers to a stopper for injections as specified in 2017, and is specifically used by inserting it into the mouth of a container containing an infusion such as Ringer's solution or the mouth of a container for lyophilized preparations for the purpose of sealing the injection. It is something that will be done. When this stopper is used with a syringe needle inserted, it is necessary that the hole of the syringe needle is not clogged with debris from the material of the stopper and that the inside of the container is kept in communication with the atmosphere. Furthermore, it is necessary that the injection solution does not leak from the insertion point of the injection needle when the injection needle is handled.
ところで、従来の注射剤用止栓としては、イソブチレン
・イソプレン（ブチルゴム）、塩素化ブチルゴム、天然
ゴム、ポリイソプレンゴム、ポリブタジェンゴム、等の
加硫ゴムの材料からなるものが使用されている。By the way, conventional stoppers for injections are made of vulcanized rubber materials such as isobutylene/isoprene (butyl rubber), chlorinated butyl rubber, natural rubber, polyisoprene rubber, polybutadiene rubber, etc. .
しかしながら、加硫ゴムからなる止栓は、以下に示す種
々の問題がある。However, stoppers made of vulcanized rubber have various problems as shown below.
（１）従来の止栓は医療衛生上、完全に満足されるもの
ではない。特に、日本薬局方の注射剤用ゴム栓試験法で
規定する溶出物試験の中の透過率試験（材料から溶出し
てくる微粒子量の測定）や蒸発残留物試験等で規格内で
あっても、加硫ゴム中に残留した重合溶媒、添加物等が
経時的に注射液容器の内部に溶出してくる等の問題があ
る。(1) Conventional stopcocks are not completely satisfactory in terms of medical hygiene. In particular, even if the transmittance test (measuring the amount of particulates eluted from the material) and evaporation residue test, which are part of the eluate tests stipulated by the Japanese Pharmacopoeia's rubber stopper test method for injections, are within the specifications. However, there are problems such as the polymerization solvent, additives, etc. remaining in the vulcanized rubber eluting into the injection solution container over time.
（２）止栓の製造においては、医療衛生性を重視する観
点から工程が繁雑化する問題がおる。即ち、製造におい
て、ゴム中に配合する各種の添加剤、例えば加硫剤、加
硫促進剤、加硫促進助剤、軟化剤、各種無機フィラー類
等の種類や量を厳密に選定することは勿論、加硫工程に
ついても、時間、温度等の条件を細かくコントロールし
、成型した後、数種の薬品で洗浄するという非常に繁雑
な操作を必要とする。(2) In manufacturing stopcocks, there is a problem in that the process becomes complicated from the viewpoint of placing emphasis on medical hygiene. In other words, during manufacturing, it is not necessary to strictly select the types and amounts of various additives to be mixed into rubber, such as vulcanizing agents, vulcanization accelerators, vulcanization accelerators, softeners, and various inorganic fillers. Of course, the vulcanization process also requires very complicated operations such as carefully controlling conditions such as time and temperature, and cleaning with several types of chemicals after molding.
（３）止栓を製品形状に仕上げるのに、前記材料は熱可
塑性が劣るため、生産性が低下し、かつ複雑な形状の製
品を成型するのは困難となる。例えば、凍結乾燥用止栓
の場合、バイアル瓶内の凍結した薬剤の水分を昇華させ
て凍結乾燥機内のコールドトラップまで拡散させるが、
この際に半打栓した栓は瓶の内外を大きく導通させて拡
散効率を高め、しかも乾燥後に全打栓した栓は瓶を完全
に密閉させる構造にしなければならない。しかしながら
、加硫ゴムは材料の流れ性が劣るため、必要な栓構造の
自由な設計を大きく制約している。また、成型後のパリ
除去に際して切断屑や異物の付着等の問題が生じる。(3) In finishing the stopper into a product shape, the material has poor thermoplasticity, which reduces productivity and makes it difficult to mold products with complex shapes. For example, in the case of a stopper for freeze-drying, the water in the frozen drug in the vial is sublimated and diffused to the cold trap in the freeze-dryer.
At this time, the half-sealed stopper must provide a large electrical conduction between the inside and outside of the bottle to increase diffusion efficiency, and the fully-sealed stopper after drying must have a structure that completely seals the bottle. However, vulcanized rubber has poor material flowability, which greatly restricts the freedom to design the necessary plug structure. Further, when removing pars after molding, problems such as adhesion of cutting debris and foreign matter occur.
（４）使用時において、止栓に注射針を差込み、注射液
の出入れを行なう場合、針差しの抵抗が大きく作業性に
難がおる。(4) During use, when a syringe needle is inserted into the stopper and the injection solution is taken in and out, the resistance to inserting the needle is large, making workability difficult.
（５）止栓への注射針の差込み、扱取りに際しゴムの一
部が欠損する、いわゆるコアリング現象が起り、注射液
中に欠損ゴム片が異物として混入する問題がある。また
、注射針の扱取り後に止栓から注射液が漏れるという問
題がある。(5) When inserting and handling the injection needle into the stopper, a so-called coring phenomenon occurs in which a portion of the rubber is broken off, and there is a problem in that the broken pieces of rubber are mixed into the injection solution as foreign matter. Another problem is that the injection solution leaks from the stopper after the injection needle is handled.
（６）加硫ゴムは、成型後にその構造体の一部を再成型
することができないため、製剤設計の支障になっている
。(6) Vulcanized rubber cannot be partially remolded after being molded, which poses a problem in formulation design.
本発明は、残留溶媒、添加物等の経時的な溶出がなく、
成型性が良好で、成型後の洗浄処理等が不要で、更に注
射針の差込みが容易で、注射針の差込み、扱取り時のコ
アリング現象の発生、後取り後の注射液の漏れだし等を
防止し得る製造が簡単で、更に成型後の再成型が可能な
注射剤用止栓を提供しようとするものである。The present invention does not elute residual solvents, additives, etc. over time, and
It has good moldability, does not require cleaning after molding, and is easy to insert the injection needle, causing coring phenomenon when inserting the injection needle and handling, and leakage of injection solution after removal. The object of the present invention is to provide a stopper for injections that is easy to manufacture and can be re-molded after being molded.
本発明は、
（ａ＞一般式
％式％）
〔但し、式中のＡは、モノビニル置換芳香族炭化水素か
らなり、分子量が１５０００〜６００００の重合体ブロ
ック、Ｂは共役ジエンのエラストマーからなる分子［１
６００００〜１８００００の重合体ブロック、ｎは１〜
５の整数を示す。〕にて表わされる共重合体の水素添加
誘導体１００重量部と、
（ｂ）ポリイソブチレン及び／又はポリブテンとパラフ
ィン系ゴム用軟化剤との混合比（重量％）が２０：８０
〜１００：Ｏの軟化剤８０〜２５０重量部と、
（Ｃ）オレフィン系樹脂２０〜８０重量部と、からなり
、かつ硬度（Ｊ Ｉｓ−に６３０１）が３０〜６０の熱
可塑性エラストマー組成物により一部又は全体が構成さ
れていることを特徴とするものである。かかる本発明に
よれば、既述の如く残留溶媒、添加物等の経時的な溶出
がなく、成型性が良好で、成型後の洗浄処理が不要で、
更に注射針の差込みが容易で、注射針の差込み、扱取り
時のコアリング発生、扱取り後の注射液の漏れだし等を
防止し得る製造が簡単で、更に成型後の再成型が可能な
注射剤用止栓を得ることができる。In the present invention, (a>general formula % formula %) [However, A in the formula is a polymer block consisting of a monovinyl-substituted aromatic hydrocarbon and having a molecular weight of 15,000 to 60,000, and B is a molecule consisting of a conjugated diene elastomer. [1
60,000 to 180,000 polymer blocks, n is 1 to
Indicates an integer of 5. ] 100 parts by weight of a hydrogenated derivative of a copolymer represented by (b) a mixture ratio (wt%) of polyisobutylene and/or polybutene and a paraffinic rubber softener of 20:80
~100:O by a thermoplastic elastomer composition consisting of 80 to 250 parts by weight of an O softener and 20 to 80 parts by weight of (C) an olefin resin, and having a hardness (J Is-6301) of 30 to 60. It is characterized by being partially or entirely composed of According to the present invention, as described above, there is no elution of residual solvents, additives, etc. over time, the moldability is good, and cleaning treatment after molding is not required.
Furthermore, it is easy to insert the injection needle, prevents coring during insertion of the injection needle, handling, and leakage of the injection solution after handling.It is easy to manufacture, and can be remolded after molding. A stopper for injections can be obtained.
上記（ａ）成分の一般式にて表わされる重合体ブロック
Ａを構成する単量体のモノビニルＭ換芳香族炭化水素と
しては、種々のものが挙げられるが、特にスチレン、α
−メチルスチレンが好適である。同一般式の重合体ブロ
ックＢの共役ジエン単量体としは、ブタジェンもしくは
イソプレンが好適で、それら両者の混合物でもよい。ブ
タジェンを単一の共役ジエン単量体として使用し、重合
体ブロックＢを形成する場合には、エラストマー性を保
持する目的で、ポリブタジェンにおけるミクロ構造中の
１，２−ミクロ構造が２０〜５０％となる重合条件を採
用することが好ましく、待に１．２−ミクロ構造が３５
〜４５％のものが適している。また、重合体ブロックＢ
の前記共重合体中に占める割合は、少なくとも６５重量
％にすることが好ましい。The monovinyl M-substituted aromatic hydrocarbon monomer constituting the polymer block A represented by the general formula of component (a) above includes various monomers, particularly styrene, α
- Methylstyrene is preferred. The conjugated diene monomer of the polymer block B having the same general formula is preferably butadiene or isoprene, and a mixture of both may be used. When butadiene is used as a single conjugated diene monomer to form polymer block B, the 1,2-microstructure in the microstructure of the polybutadiene is 20 to 50% in order to maintain elastomer properties. It is preferable to adopt polymerization conditions such that the 1.2-microstructure is 35
~45% is suitable. In addition, polymer block B
Preferably, the proportion of the copolymer in the copolymer is at least 65% by weight.
上記重合体ブロックＡ及び重合体ブロックＢの分子量は
成分（ａ）を構成する上、最も重要である。重合体ブロ
ックＡＳＢ共にそれら分子量の下限値（１５０００，６
００００）を外れると、止栓として評価した場合、蒸気
滅菌工程での耐熱性が劣り、容器から外れたり、止栓が
大きく変形したりし、更に機械的強度や圧縮永久歪みが
劣り、しかもコアリング現象、注射液の漏れ現象を発生
する。一方、重合体ブロックＡ、Ｂ共にそれら分子量の
上限値（６００００，１８００００）から外れると、分
子量が大きくなり過ぎ、熱可塑性エラストマーの最大の
特徴の一つである成型性に支障をきたし、ショートショ
ット、デラミネーション、ゲル化等の各種の問題を招く
。こうした重合体ブロックＡの好適な分子量は、２００
００〜４００００、重合体ブロックＢの好適な分子量は
、９００００〜１５００００の範囲である。The molecular weights of the polymer block A and polymer block B are the most important in constituting component (a). The lower limit of the molecular weight of both polymer blocks ASB (15000, 6
0000), when evaluated as a stopper, the heat resistance during the steam sterilization process will be poor, the stopper will come off from the container, the stopper will be greatly deformed, and furthermore, the mechanical strength and compression set will be poor, and the core Ring phenomenon and injection liquid leakage phenomenon occur. On the other hand, if both polymer blocks A and B deviate from the upper limits of their molecular weights (60,000, 180,000), the molecular weight becomes too large, which impedes moldability, which is one of the greatest characteristics of thermoplastic elastomers, and short shot , causing various problems such as delamination and gelation. The preferred molecular weight of such polymer block A is 200
The preferred molecular weight of polymer block B is in the range of 90,000 to 150,000.
上述した一般式のブロック共重合体の製゛造方法として
は。数多くの方法が提案されているが、代表的な方法と
しては、例えば特公昭４２−８７０４号、特公昭４３−
６６３６号に記載された方法がおる。The method for producing the block copolymer of the above general formula is as follows. Many methods have been proposed, but representative methods include, for example, Japanese Patent Publication No. 8704 of 1972 and Japanese Patent Publication No. 43-1989.
There is a method described in No. 6636.
上記（ａ）成分としのブロック共重合体の水素添加誘導
体は、その製造に際しての水素添加において、重合体ブ
ロックＢ中のオレフィン型二重結合の少なくとも５０％
、好ましくは８０％以上が水素添加され、重合体ブロッ
クＡ中の芳香族性不飽和結合の２５％以下が水素添加さ
れたものが好適である。こうした成分（ａ）としては、
市販のポリマーであるＫＲＡＴＯＮ−Ｇ （シェル・ケ
ミカル社製商品名）等を使用できる。In the hydrogenated derivative of the block copolymer as component (a), at least 50% of the olefin type double bonds in the polymer block B is hydrogenated during its production.
, preferably 80% or more is hydrogenated, and preferably 25% or less of the aromatic unsaturated bonds in the polymer block A are hydrogenated. These ingredients (a) include:
A commercially available polymer such as KRATON-G (trade name manufactured by Shell Chemical Company) can be used.
上記成分（ｂ＞としての軟化剤は、合成軟化剤と石油系
軟化剤を特定の割合で混合したものである。合成軟化剤
としては、合成樹脂系、低分子量重合物、合成可塑剤系
とに大別されるが、本発明に使用される合成軟化剤とし
ては、低分子量重合物に分類されているポリイソブチレ
ン、ポリブテンが好ましい。ポリイソブチレンは、イソ
プレンを重合するという常法により容易に入手すること
ができ、粘度平均分子量としては、１５０００〜７００
００程度のものが好ましい。また、ポリブテンはイソブ
チレンを主体とし、一部ｎ、−ブテンが共重合されたも
のであり、４０’Ｃ動粘度が２００〜３５００センチス
トーク、平均分子量として５００〜４０００程度のもの
が使用される。ポリブテンとポリイソブチレンは、各々
単独で使用できるが、両者を任意に混合して使用しても
よい。The softener as the above component (b>) is a mixture of a synthetic softener and a petroleum-based softener in a specific ratio.Synthetic softeners include synthetic resins, low molecular weight polymers, synthetic plasticizers, etc. However, the synthetic softeners used in the present invention are preferably polyisobutylene and polybutene, which are classified as low molecular weight polymers.Polyisobutylene can be easily obtained by the conventional method of polymerizing isoprene. The viscosity average molecular weight is 15,000 to 700.
A value of about 00 is preferable. Further, polybutene is mainly composed of isobutylene and partially copolymerized with n,-butene, and has a 40'C kinematic viscosity of 200 to 3500 centistokes and an average molecular weight of about 500 to 4000. Polybutene and polyisobutylene can each be used alone, but they may also be used in any combination.
一方、石油系軟化剤としのパラフィン系ゴム用軟化剤は
、パラフィン鎖の炭素数が全炭素数中５０％以上占める
ものである。なあ、一般にゴムの軟化、増容、加工性の
向上等に用いられるプロセスオイル又はエクステンダー
オイルと呼ばれる鉱物油系ゴム用軟化剤は、芳香族環、
ナフテン環及びｎパラフィン鎖の三者が組合わさった混
合物である。このうち、ナフテン環炭素数が３０〜４５
％のものがナフテン系、芳香族炭素数が３０％より多い
ものが芳香族系と称される。本発明で使用されるパラフ
ィン系ゴム軟化剤以外の軟化剤は、上記成分（ａ＞との
相溶性や分散性が劣り、機械的物性が低下したり、臭気
が強く、止栓の成分としは不適当である。かかるパラフ
ィン系ゴム軟化剤の性状としては、３７．８°Ｃにおけ
る動粘度が２０〜５００センチストークス、引火点が１
７０〜３００ ’Ｃを示すものが好適である。On the other hand, in a paraffin rubber softener used as a petroleum softener, the number of carbon atoms in the paraffin chain accounts for 50% or more of the total number of carbon atoms. By the way, mineral oil-based rubber softeners called process oils or extender oils, which are generally used to soften rubber, increase volume, improve processability, etc., contain aromatic rings,
It is a mixture of naphthene rings and n-paraffin chains. Among these, the number of carbon atoms in the naphthene ring is 30 to 45
% is called naphthenic type, and those with more than 30% aromatic carbon number are called aromatic type. Softeners other than paraffin-based rubber softeners used in the present invention have poor compatibility and dispersibility with the above component (a), deteriorate mechanical properties, and have a strong odor, making them unsuitable as stopper components. Such a paraffin rubber softener has a kinematic viscosity of 20 to 500 centistokes at 37.8°C and a flash point of 1.
Those exhibiting a temperature of 70 to 300'C are suitable.
本発明は、上述した合成軟化剤と石油系軟化剤を混合、
場合によっては合成軟化剤のみで使用する点に特徴を有
する。即ち、石油系軟化剤であるパラフィン系ゴム用軟
化剤のみを使用する場合、本発明の軟化剤に比較して材
料中から溶出される溶出物、特にコロイド状微粒子（０
，５μｍ〜２００μｍ程度）が経時的に溶出することが
判明した。つまり、パラフィン系ゴム用軟化剤のみを使
用して注射剤用止栓を製造する場合には、止栓の一部を
何等かの他の材料でカバーし、保護する必要が生じるが
、本発明の軟化剤ではそのような必要性は全く生じない
。The present invention mixes the above-mentioned synthetic softener and petroleum softener,
It is characterized by the fact that in some cases, only synthetic softeners are used. That is, when only a paraffin-based rubber softener, which is a petroleum-based softener, is used, compared to the softener of the present invention, the amount of eluates eluted from the material, especially colloidal fine particles (0
, 5 μm to 200 μm) was found to elute over time. In other words, when manufacturing a stopper for injections using only a paraffin-based rubber softener, it is necessary to cover and protect a part of the stopper with some other material. No such need arises with the softeners.
上記ポリイソブチレン及び／又はポリブテンとパラフィ
ン系ゴム用軟化剤の両者の混合割合は、前者が２０〜１
００重量％、後者が８０〜０重置％である。両者の混合
割合において、パラフィン系ゴム用軟化剤の割合が８０
重量％を越えると、前述したコロイド状微粒子の溶出抑
制効果を発揮できず好ましくない。The mixing ratio of both the polyisobutylene and/or polybutene and the paraffin rubber softener is 20 to 1
00% by weight, the latter being 80-0% by weight. In the mixing ratio of both, the ratio of paraffin rubber softener is 80%.
If it exceeds % by weight, the above-mentioned effect of suppressing the elution of colloidal particles cannot be exerted, which is not preferable.
上記軟化剤の配合割合は、成分（ａ）１００重量部に対
して８０〜２５０重量部にすることが必要である。この
理由は、該軟化剤の量を８０重量部未満にすると、柔軟
性が劣り、ゴム弾性が低下して注射液の漏れ現象の原因
になったり、流動性が低下して最終製品の外観や成型性
に支障をきたす。一方、軟化剤の量が２５０重」部を越
えると、軟化剤のブリードアウトが生じ易くなり、止栓
に粘着性を生じる恐れがあり、しかも圧縮永久歪み特性
が低下して注射液の漏れ現象の原因となる。The blending ratio of the softener needs to be 80 to 250 parts by weight per 100 parts by weight of component (a). The reason for this is that if the amount of the softener is less than 80 parts by weight, the flexibility and rubber elasticity will decrease, causing leakage of the injection solution, and the fluidity will decrease, resulting in poor appearance of the final product. This will impede moldability. On the other hand, if the amount of softener exceeds 250 parts by weight, the softener is likely to bleed out, causing the stopper to become sticky, and the compression set properties will deteriorate, causing problems such as leakage of the injection solution. It causes
上記成分（Ｃ）のオレフィン系樹脂としては、エチレン
、プロプレン、ブテン−１、ペンテン−１、ヘキセン−
１，４−メチルペンテン−１等のα−オレフィンを常法
により単独又は共重合の形で重合せしめて得られる結晶
性樹脂である。これらの内でも、成分（Ｃ）として特に
好ましいものは、結晶性プロピレン単独重合体、結晶性
プロピレン−エチレンランダム又はブロック共重合体で
おる。こうしたオレフィン系樹脂の配合量は、成分（ａ
＞１００重量部に対して２０〜８０重量部にすることが
必要である。この理由は、重合体樹脂の量を２０重量部
未満にすると、成型性が劣り、外観不良（ウェルドライ
ン、デラミネーションの発生）が起こる。一方、重合体
樹脂の量が８０重量部を越えると、止栓の硬度が高くな
り過ぎ、注射針の差込み抵抗が大きくなり作業性に問題
を生じる。The olefin resin of the above component (C) includes ethylene, proprene, butene-1, pentene-1, hexene-1,
It is a crystalline resin obtained by polymerizing α-olefins such as 1,4-methylpentene-1, either alone or in copolymerization, by a conventional method. Among these, particularly preferred as component (C) are crystalline propylene homopolymers and crystalline propylene-ethylene random or block copolymers. The blending amount of such olefin resin is as follows:
>100 parts by weight, it is necessary to use 20 to 80 parts by weight. The reason for this is that when the amount of polymer resin is less than 20 parts by weight, moldability is poor and poor appearance (occurrence of weld lines and delamination) occurs. On the other hand, if the amount of the polymer resin exceeds 80 parts by weight, the hardness of the stopper becomes too high, and the insertion resistance of the injection needle increases, causing problems in workability.
上記成分（ａ）、（ｂ）及び（Ｃ）からなる熱可塑性エ
ラストマー組成物を調製するには、例えば単軸押出機、
二軸押出機、バンバリー型インターナルミキサ、各種ニ
ーダ等の一般的な溶融混線機を用いる方法が採用される
。混線に際しての温度は、成分（Ｃ）のオレフィン系樹
脂の溶融温度、例えば１５０〜２５０℃程度の範囲にす
ることが好ましい。時間については、押出機を使用する
場合は、該機械が有する一般的な滞留時間、インターナ
ルミキサの場合は、５〜２０分間程度が好ましい。また
、匍記組成物のｌ製に際しては、必要に応じて滅菌法に
従った熱安定剤、紫外線吸収剤、抗γ線安定剤等の各種
の安定剤、更にはタルク、炭酸カルシウム、ガラス、マ
イカ、カーボンブラック愈どの無機フィラー等の増量剤
又は着色剤等を目的に応じて添加してもよい。例えば、
タルク、マイカ等の板状フィラー類はこれらの添加によ
り材料のガスバリア性を向上させることができる。In order to prepare the thermoplastic elastomer composition consisting of the above components (a), (b) and (C), for example, a single screw extruder,
A method using a general melt mixer such as a twin-screw extruder, a Banbury type internal mixer, or various kneaders is adopted. The temperature at which the wires are crossed is preferably the melting temperature of the olefin resin of component (C), for example, in the range of about 150 to 250°C. Regarding the time, when an extruder is used, the general residence time of the machine is preferred, and when an internal mixer is used, it is preferably about 5 to 20 minutes. In addition, when manufacturing the Hoki composition, various stabilizers such as heat stabilizers, ultraviolet absorbers, anti-gamma ray stabilizers, etc., according to sterilization methods, as well as talc, calcium carbonate, glass, A filler such as an inorganic filler such as mica or carbon black or a coloring agent may be added depending on the purpose. for example,
Addition of plate-like fillers such as talc and mica can improve the gas barrier properties of the material.
上記熱可塑性エラストマー組成物の硬度（ＪＩＳ−に６
３０１）を限定した理由は、その硬度を３０未満にする
と、差込んだ注射針を後取った後に注射剤の漏れ現象を
生じるばかりか、製品の外観性が悪化し、更に機械的強
度も低下する。一方、該組成物の硬度が６０を越えると
、注射針の差込みが困難となるばかりか、注射針を汰取
った後に注射液の漏れ現象を招く。こうした熱可塑性エ
ラストマー組成物を通常の成型法により注射剤用止栓を
製造するが、その止栓は全体が該組成物で構成されても
よいし、積層や部品の組合わせ等の形式で止栓の一部を
該組成物で構成するようにしてもよい。The hardness of the thermoplastic elastomer composition (JIS-6
The reason for limiting the hardness to 301) is that if the hardness is less than 30, not only will the injection agent leak after the inserted injection needle is removed, but the appearance of the product will deteriorate and the mechanical strength will also decrease. do. On the other hand, if the hardness of the composition exceeds 60, it will not only be difficult to insert the injection needle, but also cause leakage of the injection solution after the injection needle is removed. A stopper for injections is manufactured from such a thermoplastic elastomer composition by a conventional molding method, but the stopper may be composed entirely of the composition, or may be formed by laminating or combining parts. A portion of the stopper may be made of the composition.
以下、本発明の実施例を詳細に説明する。 Examples of the present invention will be described in detail below.
実施例１〜４
下記表に示す配合割合の成分（ａ）〜（Ｃ）を、バンバ
リーミキサで１９０°Ｃ，６０ｒｐｍの条件で５分間混
練した。つづいて、これら混線物を止栓試作金型に入れ
て成型し、肉厚５Ｍの８種類（実施例１〜４及び比較例
１〜４）の止栓を製造した。Examples 1 to 4 Components (a) to (C) in the proportions shown in the table below were kneaded in a Banbury mixer at 190°C and 60 rpm for 5 minutes. Subsequently, these interfering materials were put into a stopper prototype mold and molded to produce eight types of stopper plugs (Examples 1 to 4 and Comparative Examples 1 to 4) each having a wall thickness of 5M.
しかして、得られた各止栓について、物性としての硬度
、引張り強度、引張り伸度、圧縮永久歪、並びに止栓特
性としての針疲取り後の液漏れ、コアリング、医療衛生
性、成型品外観、コロイド状微粒子の溶出、及び耐熱性
を調べた。その結果を同表に併記する。なお、前記物性
及び止栓特性は次のような方法により測定した。For each stopper obtained, physical properties such as hardness, tensile strength, tensile elongation, and compression set, as well as stopper characteristics such as liquid leakage after needle fatigue, coring, medical hygiene, and molded product, were determined. The appearance, elution of colloidal fine particles, and heat resistance were examined. The results are also listed in the same table. The physical properties and stopper properties were measured by the following methods.
■硬度；下記表に示す配合割合の成分（ａ）〜（Ｃ）を
、ヘンシルミキサで５分間常温にて混合、均一化した後
、二軸押出機で２００℃、２２Ｏｒｐｍの条件で混練し
、その混線物を２００℃の条件下で射出成型して２ｓ厚
さのシートとし、これを試料としてＪＩＳ−に６３０１
に準じて硬度を測定した。■Hardness: Components (a) to (C) in the proportions shown in the table below are mixed and homogenized using a Henshil mixer at room temperature for 5 minutes, then kneaded using a twin-screw extruder at 200℃ and 22Orpm. The mixed material was injection molded at 200°C to form a 2s thick sheet, and this was used as a sample according to JIS-6301.
Hardness was measured according to.
■引張り強度；前記試料をＪＩＳ−に６３０１に準じて
引張り強度を測定した。(2) Tensile strength: The tensile strength of the sample was measured according to JIS-6301.
■引張り伸度：前記試料をＪ ＩＳ−に６３０１に準じ
て引張り伸度を測定した。(1) Tensile elongation: The tensile elongation of the sample was measured according to JIS-6301.
■圧縮永久歪；前記試料をＪＩＳ−に６３０１に準じて
７０℃、２２時間後の圧縮永久歪を測定した。(2) Compression set: The compression set of the sample was measured at 70°C for 22 hours according to JIS-6301.
■針後取り後の液漏れ；市販されている注射剤セット及
び両頭針（プラスチック針又はステンレス針）を止栓に
差込んだ後、１時間後において針を扱取った時の注射液
の漏れを測定した。■Fluid leakage after needle removal: Leakage of injection liquid when handling the needle 1 hour after inserting a commercially available injection set and double-ended needle (plastic needle or stainless steel needle) into the stopper. was measured.
■コアリング；止栓への針（１２〜２１Ｇ）の差込み時
又は扱取り時のゴム屑の発生を測定した。(2) Coring: The generation of rubber debris was measured when a needle (12 to 21G) was inserted into the stopper or when handled.
■医療衛生性：日本薬局方第１０改正の注射剤用ゴム栓
試験法及び注射剤用プラスチック容器試験法に準じて測
定した。■Medical hygiene: Measured according to the rubber stopper test method for injections and the test method for plastic containers for injections of the Japanese Pharmacopoeia 10th revision.
■成型品外観；インショクジョン成型品のウェルドライ
ン、デラミネーション、フローマークの発生の有無を測
定し、それらにより外観の良否を判定した。■ Appearance of molded product: The presence or absence of weld lines, delamination, and flow marks on the injection molded product was measured, and the quality of the appearance was determined based on these.
■耐熱性；止栓を１２１℃Ｘ５０分間蒸気滅菌した時の
変形の有無を測定した。(2) Heat resistance: The presence or absence of deformation was measured when the stopcock was steam sterilized at 121°C for 50 minutes.
■コロイド状微粒子の測定；森下製薬味製のアミノ酸注
射液（Ａｍｉｙｕ＞が入った溶液に本発明の組成物で製
造した止栓をセットし、１２１°Ｃｘ１ｈｒ殺菌する。(2) Measurement of colloidal fine particles: A stopper made of the composition of the present invention is placed in a solution containing Morishita Pharmaceutical Flavor's amino acid injection (Amiyu) and sterilized at 121°C for 1 hour.
殺菌撲、その溶液中の微粒子をハイ７ツク自動機粒子計
測器で測定し、１０〜２５μｍの大きさが１ｍＲ中で５
０個以下、２５μｍ以上の大きざが５個以下のものを合
格とした。To eliminate sterilization, the fine particles in the solution were measured using a high-seven automatic particle counter, and the particles with a size of 10 to 25 μm were measured in 1 mR.
Those with 0 or less pieces and 5 or less pieces with a size of 25 μm or more were considered to be passed.
但し、上表中の成分（ａ＞〜成分（Ｃ）の詳細は次の通
りである。However, details of components (a> to component (C)) in the above table are as follows.
（ａ） −１：スチレンーブタジエンースチレンブロッ
ク共重合体の水素添加物
重合体Ａの平均分子量（ＧＰＣ法）
重合体Ａの平均分子１ （ＧＰＣ法）
（ａ）−２；スチレン−ブタジェン−スチレンブロック
共重合体の水素添加物
重合体Ａの平均分子量（ＧＰＣ法）
重合体Ａの平均分子ｉｔ （ＧＰＣ法）（ａ） −３：
スチレンーブタジエンースチレン′ブロック共重合体の
水素添加物
重合体Ａの平均分子量（ＧＰＣ法）
重合体Ａの平均分子量（ＧＰＣ法）
（ｂ） −１：パラフィン系ゴム用軟化剤（動粘度：９
６センチストークス
（４０℃）、平均分子！５３９）
（ｂ） −２：ポリブテン（動粘度： ２８０００セン
チストークス（４０℃）、
平均分子量１３５０）
（Ｃ）−１：ポリプロピレン（密度０．８９２ｇ／ｃｒ
ｔｔ” 、ＭＦＲ（２３０℃）１．５ｇ／１０分）
（Ｃ） −２：ポリプロピレン（密度０．９０３９／ｃ
ｔｒｔ３、ＭＦＲ（２３０°Ｃ）！Ｍ／１０分）
（Ｃ）−３：ポリエチレン（密度０．９２０９／ｃｍ”
、ＭＦＲ（１９０℃）
１、０ｇ／１０分）
上記表から明かなように本発明の硬度３０〜６０で、特
定の熱可塑性エラストマーからなる注射剤用止栓は非常
に優れた特性を有することがわかる。(a) -1: Average molecular weight of hydrogenated polymer A of styrene-butadiene-styrene block copolymer (GPC method) Average molecular weight of polymer A 1 (GPC method) (a)-2; Styrene-butadiene- Average molecular weight of hydrogenated styrene block copolymer polymer A (GPC method) Average molecular weight of polymer A it (GPC method) (a) -3:
Average molecular weight of hydrogenated polymer A of styrene-butadiene-styrene' block copolymer (GPC method) Average molecular weight of polymer A (GPC method) (b) -1: Softener for paraffin rubber (kinematic viscosity: 9
6 centistokes (40℃), average molecule! 539) (b) -2: Polybutene (kinematic viscosity: 28000 centistokes (40°C), average molecular weight 1350) (C) -1: Polypropylene (density 0.892 g/cr
tt”, MFR (230°C) 1.5 g/10 min) (C) -2: Polypropylene (density 0.9039/c
trt3, MFR (230°C)! M/10 minutes) (C)-3: Polyethylene (density 0.9209/cm"
, MFR (190°C) 1.0 g/10 min) As is clear from the above table, the stopper for injections of the present invention made of a specific thermoplastic elastomer with a hardness of 30 to 60 has very excellent properties. I understand.
以上詳述した如く、本発明によれば残留溶媒、添加物等
の経時的唇溶出がなく、成型性が良好で、成型後の洗浄
処理が不要で、更に注射針の差込みが容易で、注射針の
差込み、抜取り時のコアリング現象の発生、抜取り後の
注射剤の漏れだし等を防止し得る製造が簡単で４、更に
成型後の再成型が可能な注射剤用止栓を提供できるもの
である。As detailed above, according to the present invention, residual solvents, additives, etc. do not elute from the lips over time, the moldability is good, cleaning treatment after molding is not required, and furthermore, the injection needle can be easily inserted, and the injection It is possible to provide a stopper for injections that is easy to manufacture and can prevent the occurrence of coring phenomenon when inserting and withdrawing the needle, leakage of the injection after withdrawal, etc.4, and can be re-molded after molding. It is.
Claims (1)
らなり、分子量が１５０００〜６００００の重合体ブロ
ック、Ｂは共役ジエンのエラストマーからなる分子量６
００００〜１８００００の重合体ブロック、ｎは１〜５
の整数を示す。〕にて表わされる共重合体の水素添加誘
導体１００重量部と、 （ｂ）ポリイソブチレン及び／又はポリブテンとパラフ
ィン系ゴム用軟化剤との混合比（重量％）が２０：８０
〜１００：０の軟化剤８０〜２５０重量部と、 （ｃ）オレフィン系樹脂２０〜８０重量部と、からなり
、かつ硬度（Ｊ１５−Ｋ６３０１）が３０〜６０の熱可
塑性エラストマー組成物により一部又は全体が構成され
ていることを特徴とする注射剤用止栓。Scope of Claims: (a) General formula A-(B-A)_n [However, A in the formula is a polymer block consisting of a monovinyl-substituted aromatic hydrocarbon and having a molecular weight of 15,000 to 60,000, and B is a conjugated Molecule weight 6 made of diene elastomer
0000 to 180000 polymer blocks, n is 1 to 5
indicates an integer. ] 100 parts by weight of the hydrogenated derivative of the copolymer represented by (b) The mixing ratio (wt%) of polyisobutylene and/or polybutene and paraffin rubber softener is 20:80
80 to 250 parts by weight of a softening agent of ~100:0 and (c) 20 to 80 parts by weight of an olefin resin, and a thermoplastic elastomer composition having a hardness (J15-K6301) of 30 to 60. Or a stopper for an injection, characterized in that the entire structure is made up of:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60089981A JPS61247460A (en) | 1985-04-26 | 1985-04-26 | Stop plug for injection drug |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60089981A JPS61247460A (en) | 1985-04-26 | 1985-04-26 | Stop plug for injection drug |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS61247460A true JPS61247460A (en) | 1986-11-04 |
| JPH024296B2 JPH024296B2 (en) | 1990-01-26 |
Family
ID=13985839
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP60089981A Granted JPS61247460A (en) | 1985-04-26 | 1985-04-26 | Stop plug for injection drug |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS61247460A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0999146A2 (en) | 1998-11-04 | 2000-05-10 | Taisei Plas Co., Ltd. | Pierceable stopper and method of producing the same |
| WO2010103988A1 (en) * | 2009-03-13 | 2010-09-16 | アロン化成株式会社 | Elastomer composition for medical container stopper |
| JP2010227285A (en) * | 2009-03-27 | 2010-10-14 | Aron Kasei Co Ltd | Composite elastomer composition for medical container plug body |
| CN102844373A (en) * | 2010-04-28 | 2012-12-26 | 安隆化成株式会社 | Elastomer composition and stopper for medical container |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007119687A1 (en) | 2006-04-13 | 2007-10-25 | Kaneka Corporation | Composition for rubber stoppers and rubber stoppers for medical use |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5138729A (en) * | 1974-09-27 | 1976-03-31 | Taro Hayashi | Mokuzokaoku no gaihekikochikuhoho |
| JPS5653173A (en) * | 1979-10-09 | 1981-05-12 | Terumo Corp | Gasket for syringe |
| JPS5928965A (en) * | 1982-08-11 | 1984-02-15 | テルモ株式会社 | Gasket for medical container |
| JPS59131613A (en) * | 1983-01-18 | 1984-07-28 | Mitsubishi Petrochem Co Ltd | Preparation of elastomer ic composition |
| JPS61218650A (en) * | 1985-03-25 | 1986-09-29 | Mitsubishi Petrochem Co Ltd | Thermoplastic elastomer |
-
1985
- 1985-04-26 JP JP60089981A patent/JPS61247460A/en active Granted
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5138729A (en) * | 1974-09-27 | 1976-03-31 | Taro Hayashi | Mokuzokaoku no gaihekikochikuhoho |
| JPS5653173A (en) * | 1979-10-09 | 1981-05-12 | Terumo Corp | Gasket for syringe |
| JPS5928965A (en) * | 1982-08-11 | 1984-02-15 | テルモ株式会社 | Gasket for medical container |
| JPS59131613A (en) * | 1983-01-18 | 1984-07-28 | Mitsubishi Petrochem Co Ltd | Preparation of elastomer ic composition |
| JPS61218650A (en) * | 1985-03-25 | 1986-09-29 | Mitsubishi Petrochem Co Ltd | Thermoplastic elastomer |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0999146A2 (en) | 1998-11-04 | 2000-05-10 | Taisei Plas Co., Ltd. | Pierceable stopper and method of producing the same |
| US6607685B2 (en) | 1998-11-04 | 2003-08-19 | Taisei Plas Co., Ltd. | Method of producing pierceable stopper |
| WO2010103988A1 (en) * | 2009-03-13 | 2010-09-16 | アロン化成株式会社 | Elastomer composition for medical container stopper |
| CN102256584A (en) * | 2009-03-13 | 2011-11-23 | 安隆化成株式会社 | Elastomer composition for medical container stopper |
| JP5199456B2 (en) * | 2009-03-13 | 2013-05-15 | アロン化成株式会社 | Elastomer composition for medical container stopper |
| JP2010227285A (en) * | 2009-03-27 | 2010-10-14 | Aron Kasei Co Ltd | Composite elastomer composition for medical container plug body |
| CN102844373A (en) * | 2010-04-28 | 2012-12-26 | 安隆化成株式会社 | Elastomer composition and stopper for medical container |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH024296B2 (en) | 1990-01-26 |
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