JP2005073930A - Prefilled syringe filled with glycyrrhizinic acid solution - Google Patents
Prefilled syringe filled with glycyrrhizinic acid solution Download PDFInfo
- Publication number
- JP2005073930A JP2005073930A JP2003307717A JP2003307717A JP2005073930A JP 2005073930 A JP2005073930 A JP 2005073930A JP 2003307717 A JP2003307717 A JP 2003307717A JP 2003307717 A JP2003307717 A JP 2003307717A JP 2005073930 A JP2005073930 A JP 2005073930A
- Authority
- JP
- Japan
- Prior art keywords
- gasket
- outer cylinder
- prefilled syringe
- aqueous solution
- syringe
- 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
- 229940071643 prefilled syringe Drugs 0.000 title claims abstract description 24
- 229960004949 glycyrrhizic acid Drugs 0.000 title claims abstract description 18
- 235000019410 glycyrrhizin Nutrition 0.000 title claims abstract description 18
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 title claims abstract description 18
- 229920002545 silicone oil Polymers 0.000 claims abstract description 17
- VTAJIXDZFCRWBR-UHFFFAOYSA-N Licoricesaponin B2 Natural products C1C(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2)C(O)=O)C)(C)CC2)(C)C2C(C)(C)CC1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O VTAJIXDZFCRWBR-UHFFFAOYSA-N 0.000 claims abstract description 15
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000001685 glycyrrhizic acid Substances 0.000 claims abstract description 15
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 claims abstract description 15
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 229920003002 synthetic resin Polymers 0.000 claims abstract description 6
- 239000000057 synthetic resin Substances 0.000 claims abstract description 6
- 239000007864 aqueous solution Substances 0.000 claims description 24
- 229920005989 resin Polymers 0.000 claims description 7
- 239000011347 resin Substances 0.000 claims description 7
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 6
- 239000011247 coating layer Substances 0.000 claims description 6
- 239000011737 fluorine Substances 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 229920001971 elastomer Polymers 0.000 abstract description 21
- 239000000806 elastomer Substances 0.000 abstract description 14
- 239000000314 lubricant Substances 0.000 abstract description 7
- 239000005060 rubber Substances 0.000 abstract description 7
- 230000003993 interaction Effects 0.000 abstract description 4
- -1 polytetrafluoroethylene Polymers 0.000 description 18
- 239000004743 Polypropylene Substances 0.000 description 7
- 229920001155 polypropylene Polymers 0.000 description 7
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 6
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 229920000098 polyolefin Polymers 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- ILRKKHJEINIICQ-OOFFSTKBSA-N Monoammonium glycyrrhizinate Chemical compound N.O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@H]1CC[C@]2(C)[C@H]3C(=O)C=C4[C@@H]5C[C@](C)(CC[C@@]5(CC[C@@]4(C)[C@]3(C)CC[C@H]2C1(C)C)C)C(O)=O)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O ILRKKHJEINIICQ-OOFFSTKBSA-N 0.000 description 4
- 229920005549 butyl rubber Polymers 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 229920003048 styrene butadiene rubber Polymers 0.000 description 4
- 239000004471 Glycine Substances 0.000 description 3
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 3
- VLSOAXRVHARBEQ-UHFFFAOYSA-N [4-fluoro-2-(hydroxymethyl)phenyl]methanol Chemical compound OCC1=CC=C(F)C=C1CO VLSOAXRVHARBEQ-UHFFFAOYSA-N 0.000 description 3
- 239000003708 ampul Substances 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 229920000728 polyester Polymers 0.000 description 3
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 3
- 239000004810 polytetrafluoroethylene Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 3
- 230000001954 sterilising effect Effects 0.000 description 3
- 238000004659 sterilization and disinfection Methods 0.000 description 3
- BFKJFAAPBSQJPD-UHFFFAOYSA-N tetrafluoroethene Chemical group FC(F)=C(F)F BFKJFAAPBSQJPD-UHFFFAOYSA-N 0.000 description 3
- 229920000089 Cyclic olefin copolymer Polymers 0.000 description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
- 239000005977 Ethylene Substances 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000004049 embossing Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 229920013653 perfluoroalkoxyethylene Polymers 0.000 description 2
- 229920002493 poly(chlorotrifluoroethylene) Polymers 0.000 description 2
- 239000005023 polychlorotrifluoroethylene (PCTFE) polymer Substances 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- 229920002379 silicone rubber Polymers 0.000 description 2
- 239000004945 silicone rubber Substances 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 239000004812 Fluorinated ethylene propylene Substances 0.000 description 1
- 244000043261 Hevea brasiliensis Species 0.000 description 1
- 208000036647 Medication errors Diseases 0.000 description 1
- 229920000459 Nitrile rubber Polymers 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000010696 ester oil Substances 0.000 description 1
- HQQADJVZYDDRJT-UHFFFAOYSA-N ethene;prop-1-ene Chemical group C=C.CC=C HQQADJVZYDDRJT-UHFFFAOYSA-N 0.000 description 1
- 229920000840 ethylene tetrafluoroethylene copolymer Polymers 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000004519 grease Substances 0.000 description 1
- 238000001746 injection moulding Methods 0.000 description 1
- 229920003049 isoprene rubber Polymers 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 230000001050 lubricating effect Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000010445 mica Substances 0.000 description 1
- 229910052618 mica group Inorganic materials 0.000 description 1
- 229920003052 natural elastomer Polymers 0.000 description 1
- 229920001194 natural rubber Polymers 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 229920009441 perflouroethylene propylene Polymers 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920001084 poly(chloroprene) Polymers 0.000 description 1
- 229920003207 poly(ethylene-2,6-naphthalate) Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920001230 polyarylate Polymers 0.000 description 1
- 229920001083 polybutene Polymers 0.000 description 1
- 239000011112 polyethylene naphthalate Substances 0.000 description 1
- 229920000139 polyethylene terephthalate Polymers 0.000 description 1
- 239000005020 polyethylene terephthalate Substances 0.000 description 1
- 229920000306 polymethylpentene Polymers 0.000 description 1
- 229920003225 polyurethane elastomer Polymers 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 239000010734 process oil Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
- 229940079827 sodium hydrogen sulfite Drugs 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229920006132 styrene block copolymer Polymers 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229920002803 thermoplastic polyurethane Polymers 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000004073 vulcanization Methods 0.000 description 1
- 239000004711 α-olefin Substances 0.000 description 1
Abstract
Description
本発明は、グリチルリチン酸又はその塩類を含有する水溶液が充填されているプレフィルドシリンジに関するものである。 The present invention relates to a prefilled syringe filled with an aqueous solution containing glycyrrhizic acid or a salt thereof.
従来から、アンプル製剤は、注射筒への薬液への移し変えの際に、アンプルカット時に発生する微細な破片の混入や細菌汚染の可能性が指摘されてきた。さらに移し変えの際の繁雑さや投薬過誤の可能性も医療現場では問題となっている。
例えば、グリチルリチン酸モノアンモニウム水溶液を含有するアンプル製剤は、１回の投与量や投与頻度が多いことから、プレフィルドシリンジ化がより求められている製剤といえる。
そこで、プレフィルドシリンジ化を検討したところ、プレフィルドシリンジに収納し、滅菌後、激しく振とうして長時間置くと、目視可能な異物が微量ではあるが発生することがわかった。プレフィルドシリンジは輸送時の振動が避けられないことや保管期間が長いことから、異物発生の可能性は大きいと考えられ、この問題は医療上でも重大であり、これを解決したプレフィルドシリンジは提供されていないのが現状である。
Conventionally, it has been pointed out that ampoule preparations may be contaminated with fine debris generated during ampoule cutting or contaminated with bacteria when transferred to a drug solution into a syringe barrel. Furthermore, the complexity of transfer and the possibility of medication errors are also a problem in the medical field.
For example, an ampoule preparation containing a monoammonium glycyrrhizinate aqueous solution can be said to be a preparation for which prefilled syringes are more demanded because of its large dose and administration frequency.
Therefore, when prefilled syringes were studied, it was found that, when stored in a prefilled syringe, sterilized, and shaken vigorously for a long time, a small amount of visible foreign matter was generated. Since pre-filled syringes cannot avoid vibration during transportation and have a long storage period, it is considered that there is a high possibility of foreign matter generation, and this problem is also serious in medicine, and a pre-filled syringe that solves this problem is provided. The current situation is not.
本発明者らは、シリンジとして十分実用的であり、かつ異物が発生する可能性のないグリチルリチン酸又はその塩類を含有する水溶液が充填されているプレフィルドシリンジを提供することを目的とする。 It is an object of the present invention to provide a prefilled syringe filled with an aqueous solution containing glycyrrhizic acid or a salt thereof that is sufficiently practical as a syringe and has no possibility of generating foreign matters.
上記課題は以下の手段により解決される
（１）連通可能に封止された先端及び開口した後端を有する筒状の外筒と該外筒内を液密に摺動可能に設けられたガスケットとを有するシリンジと、該シリンジの外筒とガスケットで形成された空間内に充填されたグリチルリチン酸又はその塩類を含有する水溶液とを備え、シリンジの少なくとも前記水溶液と接触する部分にシリコーンオイルが塗布されていないプレフィルドシリンジ。
（２）前記ガスケットの少なくとも外筒と摺動しかつ前記水溶液と接触する部分にフッ素系樹脂を含有する被覆層が設けられている上記（１）に記載のプレフィルドシリンジ。
（３）前記外筒が合成樹脂からなる上記（１）または（２）に記載のプレフィルドシリンジ。
（４）前記水溶液の液量が１〜１００ｍＬである上記（１）〜（３）のいずれかに記載のプレフィルドシリンジ。
The above-mentioned problems are solved by the following means: (1) A cylindrical outer cylinder having a front end sealed so as to be able to communicate and an open rear end, and a gasket provided so as to be slidable in a liquid-tight manner And an aqueous solution containing glycyrrhizic acid or a salt thereof filled in a space formed by an outer cylinder of the syringe and a gasket, and silicone oil is applied to at least a portion of the syringe that comes into contact with the aqueous solution Not prefilled syringe.
(2) The prefilled syringe according to the above (1), wherein a coating layer containing a fluororesin is provided on a portion that slides at least on the outer cylinder of the gasket and contacts the aqueous solution.
(3) The prefilled syringe according to (1) or (2), wherein the outer cylinder is made of a synthetic resin.
(4) The prefilled syringe according to any one of (1) to (3), wherein the amount of the aqueous solution is 1 to 100 mL.
本発明によれば、異物の発生が起こらず、しかも十分に実用的な液密性と摺動性を有するグリチルリチン酸又はその塩類を含有する水溶液を収納した、シリコーンオイルとの相互作用のないプレフィルドシリンジを提供することができる。さらに、ガスケットとして外筒と摺動しかつ前記水溶液と接触する部分がフッ素系樹脂により被覆されたゴムまたはエラストマーなどの弾性体を用いた場合、従来のシリンジとほぼ同様の構成の使い勝手の良いプレフィルドシリンジ製剤を提供することができる。 According to the present invention, there is no occurrence of foreign matter, and a prefilled solution containing an aqueous solution containing glycyrrhizic acid or salts thereof having sufficiently practical liquid-tightness and sliding property and having no interaction with silicone oil. A syringe can be provided. In addition, when an elastic body such as rubber or elastomer that slides on the outer cylinder and is in contact with the aqueous solution is used as a gasket and is coated with a fluorine-based resin, it is an easy-to-use prefilled configuration that is almost the same as a conventional syringe. A syringe formulation can be provided.
以下、本発明を詳細に説明する。本発明のプレフィルドシリンジは、連通可能に封止された先端及び開口した後端を有する筒状の外筒と外筒内を液密に摺動可能に設けられたガスケットとを有するシリンジと、該シリンジの外筒とガスケットで形成された空間内に充填されたグリチルリチン酸又はその塩類を含有する水溶液とを備え、シリンジの少なくとも前記水溶液と接触する部分にシリコーンオイル等の潤滑剤が塗布されていないプレフィルドシリンジである。すなわち本発明者らは、異物の原因がプレフィルドシリンジにおいて一般的に摺動部の潤滑剤として使用されているシリコーンオイルとグリチルリチン酸又はその塩類等を含有する水溶液に熱、振動などの環境要因が加わることによる相互作用であることを明らかにし、外筒内面あるいはガスケット等のシリンジ接液部に塗布されたシリコーンオイルと薬液とが環境要因により相互作用を起こして、異物を発生させていることをみいだし、本発明を完成させた。
本発明で規定する潤滑剤とは、シリコーンオイル等、グリチルリチン酸又はその塩類と相互作用を起こすものであり、シリコーンオイルの他、エステルオイル、グリース、植物油等があげられる。
また、本発明で規定するグリチルリチン酸とは、グリチルリチン酸そのものだけでなく、その誘導体をも包含する概念である。
Hereinafter, the present invention will be described in detail. A prefilled syringe of the present invention includes a syringe having a cylindrical outer cylinder having a front end sealed so as to be communicated and an open rear end, and a gasket slidably provided in the outer cylinder, It is provided with an aqueous solution containing glycyrrhizic acid or a salt thereof filled in the space formed by the outer cylinder of the syringe and the gasket, and a lubricant such as silicone oil is not applied to at least a portion in contact with the aqueous solution of the syringe It is a prefilled syringe. In other words, the present inventors have environmental factors such as heat and vibration in an aqueous solution containing silicone oil and glycyrrhizic acid or salts thereof, which is generally used as a lubricant for sliding parts in prefilled syringes. It is clarified that the interaction is due to the addition, and it is confirmed that the silicone oil and chemicals applied to the syringe wetted part such as the inner surface of the outer cylinder or gasket cause interaction due to environmental factors and generate foreign matter. The present invention has been completed.
The lubricants defined in the present invention are those that interact with glycyrrhizic acid or salts thereof, such as silicone oil, and include, in addition to silicone oil, ester oil, grease, vegetable oil, and the like.
The glycyrrhizic acid defined in the present invention is a concept including not only glycyrrhizic acid itself but also its derivatives.
本発明においては、潤滑性を有する物質を接液面に塗布しなくとも外筒−ガスケット間の摺動性が付与されていることが望ましく、例えば、少なくともガスケット側面の外筒内面との摺動部のうち充填された水溶液と接触する部分をフッ素系樹脂等の摺動性の高い素材で被覆する被覆層を有するガスケットを使用することができる。なお、摺動部がガスケット側面に設けられた環状リブである場合には少なくとも最先端に位置する環状リブに前記被覆層が設けられている必要があり、他の環状リブ（言い換えれば充填された水溶液と接触しない環状リブ）には、潤滑剤が塗布されていることを妨げない。そして、被覆層と本体部分とから構成されるガスケットの本体部分をゴム又はエラストマー等の弾性体で形成することにより外筒内面との液密性を良好なものとし、少なくともガスケット側面の外筒内面との摺動部のうち充填された水溶液と接触する部分をフッ素系樹脂等の摺動性の高い素材で被覆することにより摺動性が付与されている。このような構成とすることにより、シリンジの外筒およびガスケットなど充填された水溶液が接触する部分への潤滑剤の塗布なしに、十分な摺動性かつ安定した吐出性能を発揮せしめるとともに、シリコーンオイルを塗布した場合に生じていた異物の発生を防止することができる。前記被覆層は、ガスケットの表面をすべて覆っていてもよく、またガスケット先端面からガスケット側面の外筒内面との摺動部のうち充填された水溶液と接触する部分にわたる領域を覆っていてもよい。 In the present invention, it is desirable that the slidability between the outer cylinder and the gasket be imparted without applying a lubricating substance to the wetted surface. For example, at least the gasket side surface slides with the inner surface of the outer cylinder. The gasket which has a coating layer which coat | covers the part which contacts the aqueous solution with which it filled among parts with high raw materials, such as a fluororesin, can be used. In addition, when the sliding part is an annular rib provided on the side surface of the gasket, it is necessary that the coating layer be provided at least on the annular rib located at the forefront, and other annular ribs (in other words, filled) It does not prevent the lubricant from being applied to the annular ribs that do not come into contact with the aqueous solution. And, by forming the main body portion of the gasket composed of the coating layer and the main body portion with an elastic body such as rubber or elastomer, the liquid tightness with the inner surface of the outer cylinder is improved, and at least the inner surface of the outer cylinder on the side surface of the gasket The portion of the sliding portion that comes into contact with the filled aqueous solution is coated with a highly slidable material such as a fluorine-based resin to provide slidability. By adopting such a configuration, it is possible to exhibit sufficient slidability and stable discharge performance without applying a lubricant to a portion in contact with a filled aqueous solution such as a syringe outer cylinder and a gasket, and silicone oil. Generation | occurrence | production of the foreign material which has arisen when apply | coating can be prevented. The coating layer may cover the entire surface of the gasket, or may cover a region extending from the gasket tip surface to a portion in contact with the filled aqueous solution in the sliding portion between the gasket side surface and the outer cylinder inner surface. .
ガスケットがフッ素系樹脂で被覆されたゴム又はエラストマー等の弾性体である場合、被覆するフッ素系樹脂としては、ポリテトラフルオロエチレンまたはその共重合体、エチレン−テトラフルオロエチレン共重合体、四フッ化エチレン、四フッ化エチレン−パーフルオロアルコキシエチレン共重合体（例えば、四フッ化エチレンと、アルコキシル基の炭素数が１〜５のパーフルオロアルコキシエチレンとの共重合体）、ＰＶｄＥ（ポリビニリデンフロライド）、ＰＣＴＦＥ（ポリクロロトリフルオロエチレン）、ＴＦＥ（テトラフルオロエチレン）、ＦＥＰ（フッ化エチレンプロピレン）等のフッ素系樹脂が挙げられ、これらの１種または２種以上を組み合わせて用いることができる。これらフッ素系樹脂により被覆された部分の厚みは、十分な摺動性をガスケットに付与することができ、かつガスケットを構成する弾性体が有する液密性を低下させない程度に設定することが好ましく、選択するフッ素系樹脂の種類にもよるが、概ね５〜２０μｍであることが望ましい。
また、フッ素系樹脂の他に、ケイ素系樹脂やウレタン系樹脂、それらを配合したものも同様の効果が期待できる。
When the gasket is an elastic body such as rubber or elastomer coated with a fluororesin, polytetrafluoroethylene or a copolymer thereof, ethylene-tetrafluoroethylene copolymer, tetrafluoride can be used as the fluororesin to be coated. Ethylene, tetrafluoroethylene-perfluoroalkoxyethylene copolymer (for example, copolymer of tetrafluoroethylene and perfluoroalkoxyethylene whose alkoxyl group has 1 to 5 carbon atoms), PVdE (polyvinylidene fluoride) ), PCTFE (polychlorotrifluoroethylene), TFE (tetrafluoroethylene), FEP (fluorinated ethylene propylene), and the like, and these can be used alone or in combination. The thickness of the portion coated with these fluorine-based resins is preferably set to such an extent that sufficient slidability can be imparted to the gasket, and the liquid-tightness of the elastic body constituting the gasket is not lowered, Although it depends on the type of fluororesin to be selected, it is generally desirable to be 5 to 20 μm.
In addition to fluorine resins, silicon resins and urethane resins, and those blended with them can be expected to have the same effect.
本発明に係るプレフィルドシリンジのガスケット本体を構成する材料については、ゴム又はエラストマーの弾性体であることが望ましい。通常のシリンジ用ガスケットとして使用されうるものであれば特に制限されないがスチレン−ブチレンエチレン−スチレンブロック共重合体、スチレン−ブタジエン共重合体あるいはその水添物等のスチレン系エラストマーや、エチレン−α−オレフィン共重合体等のエチレン系エラストマーを用いることが好ましく、これらの１種または２種以上を組み合わせて用いることができる。また、物性の改善を目的として、これにポリエチレン、ポリプロピレン、ポリブテン、α−オレフィン共重合体などのポリオレフィンや流動パラフィン、プロセスオイルなどのオイルやタルク、キャスト、マイカなどの粉体無機物を本発明の目的に合致する範囲において混合することができる。さらにポリ塩化ビニル系エラストマー、オレフィン系エラストマー、ポリエステル系エラストマー、ポリアミド系エラストマー、ポリウレタン系エラストマーや天然ゴム、イソプレンゴム、ブチルゴム、クロロプレンゴム、ニトリル−ブタジエンゴム、スチレン−ブタジエンゴム、シリコーンゴムのような各種ゴム材料(特に加流処理したもの)や、それらの混合物等を用いることもできる。中でも、弾性特性、耐蒸気滅菌性などの観点からスチレン系エラストマー、ブチルゴム、シリコーンゴムなどが望ましい。 About the material which comprises the gasket main body of the prefilled syringe which concerns on this invention, it is desirable that it is a rubber | gum or an elastomer elastic body. Any styrene elastomer such as styrene-butylene ethylene-styrene block copolymer, styrene-butadiene copolymer or hydrogenated product thereof, or ethylene-α It is preferable to use an ethylene-based elastomer such as an olefin copolymer, and these can be used alone or in combination. For the purpose of improving physical properties, polyolefins such as polyethylene, polypropylene, polybutene, and α-olefin copolymers, oils such as liquid paraffin, process oil, and powdered inorganic substances such as talc, cast, and mica are used in the present invention. It is possible to mix within a range that meets the purpose. In addition, various types such as polyvinyl chloride elastomer, olefin elastomer, polyester elastomer, polyamide elastomer, polyurethane elastomer, natural rubber, isoprene rubber, butyl rubber, chloroprene rubber, nitrile-butadiene rubber, styrene-butadiene rubber, silicone rubber Rubber materials (especially those subjected to vulcanization treatment), mixtures thereof, and the like can also be used. Of these, styrene-based elastomers, butyl rubber, silicone rubber, and the like are desirable from the viewpoints of elastic properties, steam sterilization resistance, and the like.
なお、本発明におけるガスケットは、外筒内を液密に摺動可能に設けられたものであるが、手指、あるいは機械により外力を加え摺動させるための部分を有していてもよい。例えば、ガスケットの接液面と反対面に硬質プラスチック等で形成した押子を別体に形成し、ネジ嵌合や凹凸嵌合により連結させてもよい。そのほか、外筒内面に接するガスケット本体部分と押子部分とが同一材料から形成されたいわゆるツーパーツシリンジで用いられるガスケットであってもよい。 In addition, although the gasket in this invention is provided so that the inside of an outer cylinder is slidable liquid-tightly, you may have a part for applying external force and sliding with a finger or a machine. For example, a pusher made of hard plastic or the like may be formed separately on the surface opposite to the wetted surface of the gasket and connected by screw fitting or uneven fitting. In addition, it may be a gasket used in a so-called two-part syringe in which the gasket main body portion and the presser portion that are in contact with the inner surface of the outer cylinder are formed of the same material.
本発明に係るプレフィルドシリンジの外筒は、ポリオレフィン系合成樹脂、ポリエステル系合成樹脂等の合成樹脂で形成されている。これらのうち、ポリプロピレン、ポリ (４−メチルペンテン−１)、環状ポリオレフィン等のポリオレフィン、ポリエチレンテレフタレート、ポリエチレンナフタレート、非晶性ポリアリレート等のポリエステル等の光学的に透明でかつ１１０℃以上のガラス転移点又は融点を有する材料で形成されることが好ましい。特にポリプロピレン及び環状ポリオレフィンが、透明性、耐蒸気滅菌性の点で望ましい。 The outer cylinder of the prefilled syringe according to the present invention is formed of a synthetic resin such as a polyolefin-based synthetic resin or a polyester-based synthetic resin. Of these, optically transparent glass such as polypropylene, poly (4-methylpentene-1), polyolefins such as cyclic polyolefin, polyesters such as polyethylene terephthalate, polyethylene naphthalate, and amorphous polyarylate, and a glass at 110 ° C. or higher. It is preferably formed of a material having a transition point or a melting point. In particular, polypropylene and cyclic polyolefin are desirable in terms of transparency and resistance to steam sterilization.
なお、潤滑剤を塗布せずに十分な摺動性をもち、かつガスケットがゴム又はエラストマー等の弾性体ではない例としては、外筒の射出成形時にエンボス加工を施すことで、摺動抵抗を減じ、かつ十分な気密性をもたせているものがある。例えば、ガスケットはポリエチレン、外筒はポリプロピレンで形成されており、外筒内面にエンボス加工を施すことで、ガスケットとの接触面積を減らし、液密性を維持しながら摺動抵抗を小さくするものである。 In addition, as an example that has sufficient slidability without applying a lubricant and the gasket is not an elastic body such as rubber or elastomer, the sliding resistance can be reduced by embossing at the time of injection molding of the outer cylinder. Some of them are reduced and have sufficient airtightness. For example, the gasket is made of polyethylene and the outer cylinder is made of polypropylene. By embossing the inner surface of the outer cylinder, the contact area with the gasket is reduced, and the sliding resistance is reduced while maintaining liquid tightness. is there.
次に、実施例及び試験例を挙げて本発明をさらに詳細に説明するが、本発明はこれらに限定されるわけではない。
（実施例１）グリチルリチン酸モノアンモニウム５．３０ｇ、亜硫酸水素ナトリウム１．０ｇ、グリシン４０．０ｇ、Ｌ−システイン塩酸塩２．４５ｇを溶解した、グリチルリチン酸２ｍｇ/ｍＬ濃度の水溶液を得た（ｐＨ約６．７）。無菌ろ過後、シリコーンオイルを塗布していない２０ｍＬ容量の注射剤容器（ガスケット：ポリテトラフルオロエチレンフィルムより先端面から側面全体にわたる領域を被覆したスチレン−ブタジエンゴム、外筒：ポリプロピレン(日本ポリケム（株）製)）に２０ｍＬずつ充填し、高圧蒸気滅菌をして、プレフィルドシリンジを製した。
EXAMPLES Next, although an Example and a test example are given and this invention is demonstrated further in detail, this invention is not necessarily limited to these.
Example 1 An aqueous solution having a concentration of 2 mg / mL glycyrrhizic acid in which 5.30 g monoammonium glycyrrhizinate, 1.0 g sodium bisulfite, 40.0 g glycine and 2.45 g L-cysteine hydrochloride were dissolved was obtained (pH). About 6.7). After aseptic filtration, 20 mL capacity injection container with no silicone oil applied (gasket: styrene-butadiene rubber coated from the polytetrafluoroethylene film over the entire area from the tip to the side, outer cylinder: polypropylene (Nippon Polychem Corporation )))) Was filled 20 mL at a time, autoclaved and sterilized to produce a prefilled syringe.
（実施例２）グリチルリチン酸モノアンモニウム５．３０ｇ、亜硫酸水素ナトリウム１．０ｇ、グリシン４０．０ｇ、Ｌ−システイン塩酸塩２．４５ｇを溶解した、グリチルリチン酸２ｍｇ/ｍＬ濃度の水溶液を得た（ｐＨ約６．７）。無菌ろ過後、シリコーンオイルを塗布していない２０ｍＬ容量の注射剤容器（ガスケット：フッ素系樹脂により先端面から側面全体にわたる領域を被覆したブチルゴム、外筒：ポリプロピレン(日本ポリケム（株）製) ）に２０ｍＬずつ充填し、高圧蒸気滅菌をして、プレフィルドシリンジを製した。 Example 2 An aqueous solution having a concentration of 2 mg / mL glycyrrhizic acid in which 5.30 g monoammonium glycyrrhizinate, 1.0 g sodium bisulfite, 40.0 g glycine and 2.45 g L-cysteine hydrochloride were dissolved was obtained (pH). About 6.7). After aseptic filtration, in 20 mL capacity injection container without silicone oil applied (gasket: butyl rubber coated with a fluororesin covering the entire area from the tip to the side, outer cylinder: polypropylene (manufactured by Nippon Polychem Co., Ltd.)) Each 20 mL was filled and autoclaved to produce a prefilled syringe.
（比較例１）グリチルリチン酸モノアンモニウム５．３０ｇ、亜硫酸水素ナトリウム１．０ｇ、グリシン４０．０ｇ、Ｌ-システイン塩酸塩２．４５ｇを溶解した、グリチルリチン酸２ｍｇ/ｍＬ濃度の水溶液を得た（ｐＨ約６．７）。無菌ろ過後、シリコーンオイルを塗布した２０ｍＬ容量の注射剤容器（ガスケット：スチレン系エラストマー(三菱化学（株）製)、外筒：ポリプロピレン(日本ポリケム（株）製)）に２０ｍＬずつ充填し、高圧蒸気滅菌をして、プレフィルドシリンジを製した。 (Comparative Example 1) An aqueous solution having a concentration of 2 mg / mL glycyrrhizic acid in which 5.30 g monoammonium glycyrrhizinate, 1.0 g sodium hydrogen sulfite, 40.0 g glycine and 2.45 g L-cysteine hydrochloride were dissolved was obtained (pH). About 6.7). After aseptic filtration, 20 mL capacity injection container (gasket: styrene elastomer (Mitsubishi Chemical Corporation), outer cylinder: polypropylene (Nippon Polychem Co., Ltd.)) filled with silicone oil is filled with 20 mL each. Steam sterilized to produce a prefilled syringe.
（試験例１）実施例１〜２と比較例１で得られたプレフィルドシリンジを２５℃及び６０℃条件下で２６日間保存し、３０分間激しく振とう後の薬液中の異物を目視により観察した結果は、下記の表１に示すとおりであった。 (Test Example 1) The prefilled syringes obtained in Examples 1 and 2 and Comparative Example 1 were stored for 26 days at 25 ° C. and 60 ° C., and the foreign matters in the chemical solution after vigorously shaking for 30 minutes were visually observed. The results were as shown in Table 1 below.
以上の結果から、容器にシリコーンオイルが塗布され、滅菌後、激しく振とう及び長時間放置されると異物は発生し、塗布されていなければ異物は発生しないことが明らかとなった。また、表１の実施例１と２の結果から、シリコーンオイルを塗布せずに、ガスケットにポリテトラフルオロエチレンフィルムより被覆したスチレン−ブタジエンゴムもしくはフッ素系樹脂により被覆したブチルゴムを用いた容器では、異物は発生しないことがわかった。また、実施例１及び２のプレフィルドシリンジは十分な摺動性かつ安定した吐出性能を発揮し、最大摺動抵抗値（初期摺動抵抗値）、平均摺動抵抗値ともにガスケットにシリコーンオイルを塗布した比較例１と同等であり、本発明がグリチルリチン酸水溶液を充填したプレフィルドシリンジとして優れたものであることを確認した。 From the above results, it was clarified that when silicone oil was applied to the container, after sterilization, it was shaken vigorously and left for a long period of time, and foreign matter was generated. In addition, from the results of Examples 1 and 2 in Table 1, in a container using butyl rubber coated with styrene-butadiene rubber or fluorine-based resin coated with a polytetrafluoroethylene film on a gasket without applying silicone oil, It was found that no foreign matter was generated. In addition, the prefilled syringes of Examples 1 and 2 exhibit sufficient slidability and stable discharge performance, and silicone oil is applied to the gasket for both the maximum sliding resistance value (initial sliding resistance value) and the average sliding resistance value. Thus, it was confirmed that the present invention was excellent as a prefilled syringe filled with an aqueous glycyrrhizic acid solution.
Claims (4)
The prefilled syringe according to any one of claims 1 to 3, wherein the amount of the aqueous solution is 1 to 100 mL.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2003307717A JP4430903B2 (en) | 2003-08-29 | 2003-08-29 | Prefilled syringe filled with aqueous glycyrrhizic acid solution |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2003307717A JP4430903B2 (en) | 2003-08-29 | 2003-08-29 | Prefilled syringe filled with aqueous glycyrrhizic acid solution |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2005073930A true JP2005073930A (en) | 2005-03-24 |
| JP4430903B2 JP4430903B2 (en) | 2010-03-10 |
Family
ID=34410425
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2003307717A Expired - Lifetime JP4430903B2 (en) | 2003-08-29 | 2003-08-29 | Prefilled syringe filled with aqueous glycyrrhizic acid solution |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP4430903B2 (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2018535974A (en) * | 2015-11-18 | 2018-12-06 | エスアイオーツー・メディカル・プロダクツ・インコーポレイテッド | Drug package for ophthalmic formulations |
| JP2018537170A (en) * | 2015-11-18 | 2018-12-20 | フォーマイコン アーゲーＦｏｒｍｙｃｏｎ Ａｇ | Prefilled drug package containing liquid formulation of VEGF inhibitor |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6397173A (en) * | 1986-10-15 | 1988-04-27 | 株式会社大協精工 | Slide plug for laminated syringe |
| JPH02152463A (en) * | 1988-12-06 | 1990-06-12 | Terumo Corp | Gasket for syringe and preparation thereof |
| JPH10314305A (en) * | 1997-05-22 | 1998-12-02 | Daikyo Seiko:Kk | Sealing plug for injector and prefilled injector |
| JP2000327539A (en) * | 1999-05-18 | 2000-11-28 | Lion Corp | Composition for shampoo |
-
2003
- 2003-08-29 JP JP2003307717A patent/JP4430903B2/en not_active Expired - Lifetime
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6397173A (en) * | 1986-10-15 | 1988-04-27 | 株式会社大協精工 | Slide plug for laminated syringe |
| JPH02152463A (en) * | 1988-12-06 | 1990-06-12 | Terumo Corp | Gasket for syringe and preparation thereof |
| JPH10314305A (en) * | 1997-05-22 | 1998-12-02 | Daikyo Seiko:Kk | Sealing plug for injector and prefilled injector |
| JP2000327539A (en) * | 1999-05-18 | 2000-11-28 | Lion Corp | Composition for shampoo |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2018535974A (en) * | 2015-11-18 | 2018-12-06 | エスアイオーツー・メディカル・プロダクツ・インコーポレイテッド | Drug package for ophthalmic formulations |
| JP2018537170A (en) * | 2015-11-18 | 2018-12-20 | フォーマイコン アーゲーＦｏｒｍｙｃｏｎ Ａｇ | Prefilled drug package containing liquid formulation of VEGF inhibitor |
| US10925927B2 (en) | 2015-11-18 | 2021-02-23 | Formycon Ag | Pre-filled pharmaceutical package comprising a liquid formulation of a VEGF-antagonist |
| US11298405B2 (en) | 2015-11-18 | 2022-04-12 | Formycon Ag | Pre-filled pharmaceutical package comprising a liquid formulation of a VEGF-antagonist |
| US11654046B2 (en) | 2015-11-18 | 2023-05-23 | Sio2 Medical Products, Inc. | Pharmaceutical package for ophthalmic formulations |
| US11666632B2 (en) | 2015-11-18 | 2023-06-06 | Formycon Ag | Pre-filled pharmaceutical package comprising a liquid formulation of a VEGF-antagonist |
Also Published As
| Publication number | Publication date |
|---|---|
| JP4430903B2 (en) | 2010-03-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2004298220A (en) | Prefilled syringe | |
| JP4460278B2 (en) | Seal plug for syringe and prefilled syringe | |
| JP5003155B2 (en) | Prefilled syringe | |
| US10384008B2 (en) | Syringe with needle, prefilled syringe, and medical liquid administration tool using the same | |
| JP2019531814A (en) | Purification cap for medical connector | |
| US20090149816A1 (en) | Low extractable, thermoplastic syringe and tip cap | |
| US20060106349A1 (en) | Syringe, cap and method of producing prefilled syringe | |
| CN107921221B (en) | Assembly for syringe, prefilled syringe, seal cap for outer cylinder, and assembly package for syringe | |
| CN107377492A (en) | Device Port Cleaner | |
| CN101618384A (en) | Cleaning tool | |
| WO2011117878A1 (en) | Plastic pre-filled syringe | |
| JP2022174188A (en) | Syringe body for prefilled syringe | |
| US8618185B2 (en) | Self-lubricating pharmaceutical syringe stoppers | |
| JP4430903B2 (en) | Prefilled syringe filled with aqueous glycyrrhizic acid solution | |
| JP4717924B2 (en) | Method for preventing loss of active ingredient of radiopharmaceutical in prefilled syringe | |
| JP2016154598A (en) | Prefilled syringe filled with dexmedetomidine injection solution | |
| JPWO2018173925A1 (en) | Female syringe and syringe kit | |
| JP6858561B2 (en) | Syringe assembly, prefilled syringe and syringe assembly packaging | |
| EP1013299A1 (en) | Slide valve for syringes, syringe, and kit preparations | |
| JP2974883B2 (en) | Pharmaceutical container / syringe and stopper | |
| JP3949124B2 (en) | Cap and prefilled chemical container | |
| JP4491215B2 (en) | Prefilled syringe and method for producing prefilled syringe | |
| JP2007029561A (en) | Structure and prefilled syringe | |
| JP5118385B2 (en) | Method for sterilizing chemical solution, prefilled syringe and method for producing the same | |
| JP4355151B2 (en) | Prefilled syringe and prefilled syringe |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20060530 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090424 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090619 |
|
| RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7422 Effective date: 20090619 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20091215 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20091218 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20121225 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 Ref document number: 4430903 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20121225 Year of fee payment: 3 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20131225 Year of fee payment: 4 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| EXPY | Cancellation because of completion of term |