JPH0549675A - Package for preserving liquid drug containing bicarbonate compound - Google Patents
Package for preserving liquid drug containing bicarbonate compoundInfo
- Publication number
- JPH0549675A JPH0549675A JP3217025A JP21702591A JPH0549675A JP H0549675 A JPH0549675 A JP H0549675A JP 3217025 A JP3217025 A JP 3217025A JP 21702591 A JP21702591 A JP 21702591A JP H0549675 A JPH0549675 A JP H0549675A
- Authority
- JP
- Japan
- Prior art keywords
- carbon dioxide
- package
- synthetic resin
- gas
- container
- 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
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
- A61M1/16—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis with membranes
- A61M1/1654—Dialysates therefor
Landscapes
- Medical Preparation Storing Or Oral Administration Devices (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は、医療用合成樹脂製容器
を用いる場合の炭酸水素ナトリウムのような重炭酸塩化
合物を含有する薬液の溶解・調製方法を簡易化し、かつ
当該薬液の長期間の保存を可能にした包装体に関する。The present invention relates to a method for dissolving / preparing a drug solution containing a bicarbonate compound such as sodium hydrogen carbonate when using a synthetic resin container for medical use, and for a long period of time of the drug solution. The present invention relates to a package that enables preservation of.
【０００２】[0002]
【従来の技術】従来から、炭酸水素ナトリウムなどの重
炭酸塩化合物含有薬液は、薬物中毒の際の排泄促進やア
シドーシスの是正、あるいは急性じん麻疹の治療に広く
用いられている。そして、このものは一般に、１.２６
％または７％〜８.４％の注射液としてガラス製のアン
プルやバイアル瓶に充填されて市販されている。2. Description of the Related Art Conventionally, a drug solution containing a bicarbonate compound such as sodium hydrogen carbonate has been widely used for promoting excretion during drug poisoning, correcting acidosis, or treating acute urticaria. And this one is generally 1.26
% Or 7% to 8.4% injection solution, which is commercially available in glass ampoules and vials.
【０００３】これらの炭酸水素ナトリウム注射液は、ｐ
Ｈが８付近のアルカリ性を呈しているから、ガラス製容
器に充填後、加熱滅菌して保存しておくと経時的にガラ
スフレークスが発生するため、長期間の保存は不可能で
ある。更に、ガラス製容器は重い上に破損し易く、ま
た、使用済容器の廃棄処理にも手間がかかるという欠点
があった。かかる問題点の解決法として、ガラス製容器
に比して軽量で破損の恐れがない医療用の合成樹脂製容
器が提案され、アルカリによるガラスフレークスの発生
防止や使用後の焼却処分は簡易になった。These sodium hydrogen carbonate injection solutions are p
Since H has an alkalinity of around 8, if it is stored in a glass container after heating and sterilization by heating, glass flakes will be generated over time, so that it cannot be stored for a long period of time. Further, the glass container is heavy and easily broken, and it takes time to dispose of the used container. As a solution to this problem, a synthetic resin container for medical use, which is lighter in weight and less likely to be damaged than a glass container, has been proposed, which makes it easy to prevent the glass flakes from being generated by alkali and to incinerate it after use. It was
【０００４】ところで、一般に炭酸水素ナトリウム水溶
液は、分解して炭酸ガスを発生することがよく知られて
いる。この分解反応は炭酸ナトリウムの生成を伴うた
め、反応が進むに従って水溶液のｐＨは経時的に上昇す
る。特に、当該水溶液を医療目的で使用する場合、加熱
滅菌が必須であり、この加熱滅菌時の加温のために反応
が促進され、ｐＨは著しく上昇する。また、この反応は
可逆反応であるから、炭酸ガスが反応系外に放出される
と進行するが、炭酸水素ナトリウム含有薬液を、前記し
たようなガス非透過性のガラス製容器内に充填した場合
には、分解生成した炭酸ガスが反応系外に出ることがな
く再び薬液中に吸収されるため、ｐＨは安定しており問
題はなかった。By the way, it is well known that an aqueous solution of sodium hydrogencarbonate is generally decomposed to generate carbon dioxide gas. Since this decomposition reaction involves the production of sodium carbonate, the pH of the aqueous solution increases with time as the reaction proceeds. In particular, when the aqueous solution is used for medical purposes, heat sterilization is essential, and the heating during the heat sterilization accelerates the reaction, resulting in a marked increase in pH. Further, since this reaction is a reversible reaction, it progresses when carbon dioxide gas is released to the outside of the reaction system, but when the sodium hydrogencarbonate-containing chemical liquid is filled in the gas impermeable glass container as described above. Since the carbon dioxide gas generated by decomposition did not go out of the reaction system and was absorbed again into the chemical solution, the pH was stable and there was no problem.
【０００５】これに対し、近年採用された医療用合成樹
脂製容器は、高いガス透過性を有するため、この容器内
に充填すると、加熱滅菌時や長期保存時に発生した炭酸
ガスは薬液中に再吸収されることなく、容易に容器壁を
透過して外部に放出され、その結果、分解反応が進行
し、内容液のｐＨは経時的に上昇する。このため、実際
には、炭酸水素ナトリウムを常温よりも低い温度で炭酸
ガスを混入しながら溶解・調製して、加熱滅菌時に上昇
しうる溶液のｐＨを予め強制的に低下させた後、医療用
合成樹脂製容器に充填して加熱滅菌し、更にガス非透過
性の包装体内に収容後、真空包装することにより炭酸ガ
スが外部へ放出するのを防いでいたのである。On the other hand, since the synthetic resin container for medical use which has been adopted in recent years has a high gas permeability, when filled in this container, carbon dioxide gas generated during heat sterilization or during long-term storage is regenerated into the chemical solution. It is not absorbed and easily permeates the container wall and is released to the outside. As a result, the decomposition reaction proceeds and the pH of the content liquid increases with time. Therefore, in practice, sodium hydrogen carbonate is dissolved / prepared at a temperature lower than normal temperature while mixing carbon dioxide gas, and the pH of the solution that can rise during heat sterilization is forcibly lowered in advance for medical use. The carbon dioxide gas was prevented from being released to the outside by filling it in a synthetic resin container, sterilizing it by heating, and further storing it in a gas-impermeable package and then vacuum packaging.
【０００６】[0006]
【発明が解決しようとする課題】しかしながら、かかる
医療用合成樹脂製容器による従来法は、溶解・調製時に
炭酸ガスの混入や薬液を低温に保つための操作が必要な
うえに、たとえ炭酸水素ナトリウム含有薬液を充填した
医療用合成樹脂製容器を更にガス非透過性の包装体内に
収容後、真空包装しても、長期間保存した場合、炭酸ガ
スが反応系外に放出されて炭酸水素ナトリウムの分解反
応が進行する形となり、内容液のｐＨは上昇する。従っ
て、重く破損し易い上に、ガラスフレークスが発生する
というガラス製容器の欠点は解消されるものの、ｐＨの
経時的な上昇を防ぐことはできず、長期間の保存には依
然、適していないという問題点があったのである。ま
た、真空包装工程には、通常の製造ラインの他に特別の
製造装置を必要とする欠点もある。However, the conventional method using such a synthetic resin container for medical use requires the operation of mixing carbon dioxide gas and keeping the chemical solution at a low temperature during dissolution / preparation, and even if sodium hydrogencarbonate is used. Even if the medical synthetic resin container filled with the contained drug solution is further packaged in a gas impermeable package and then vacuum packaged, if it is stored for a long period of time, carbon dioxide gas will be released out of the reaction system to cause sodium hydrogen carbonate The decomposition reaction proceeds and the pH of the content liquid rises. Therefore, although the drawback of the glass container that the glass flakes are generated in addition to being heavy and easily broken is solved, it is not possible to prevent the pH from increasing with time, and it is still not suitable for long-term storage. There was a problem. In addition, the vacuum packaging process has a drawback that it requires a special manufacturing apparatus in addition to the normal manufacturing line.
【０００７】以上のように、これまではガラス製容器ま
たは医療用合成樹脂製容器のいずれを使用しても炭酸水
素ナトリウム含有薬液を長期間安定に保存することは不
可能であり、他の医薬品が一般に３年程度の有効期間を
有するのに対し、炭酸水素ナトリウム含有薬液の有効期
間は１〜１.５年と非常に短く設定せざるを得ないのが
現状だったのである。As described above, it has been impossible to stably store a sodium hydrogencarbonate-containing drug solution for a long period of time using either a glass container or a medical-use synthetic resin container, so that other pharmaceutical products cannot be used. Has a shelf life of about 3 years in general, whereas the shelf life of a sodium hydrogencarbonate-containing drug solution is 1 to 1.5 years, which is very short.
【０００８】[0008]
【問題点を解決するための手段】本発明者らによれば、
上記課題を解決すべく鋭意研究した結果、炭酸水素ナト
リウムなどの重炭酸塩化合物含有薬液を密封した医療用
合成樹脂製容器を包含するガス非透過性の包装体におい
て、当該包装体の内部空間に対し炭酸ガス雰囲気形成手
段を施すことにより、溶解・調製時の炭酸ガス混入や薬
液を低温に保つための操作並びに真空包装するための特
別の装置を要することなく、加熱滅菌時に上昇したｐＨ
を低下させ、かつ、長期間安定した包装体が得られるこ
とを見出だし、この知見に基づき本発明が完成するに至
ったのである。本発明は、第１態様として、上記手段と
して炭酸ガス発生型の脱酸素剤を選択し、かつ、当該脱
酸素剤を上記内部空間に配置させることにより炭酸ガス
雰囲気を形成するもので、重炭酸塩化合物含有薬液を密
封した医療用合成樹脂製容器と、炭酸ガス発生型脱酸素
剤を包含するガス非透過性の包装体を提供するものであ
る。また本発明は、第２態様として、上記手段として炭
酸ガス充填装置を選択し、かつ、当該装置により予め包
装体内の空間中の空気を炭酸ガスで置換することにより
炭酸ガス雰囲気を形成するもので、重炭酸塩化合物含有
薬液を密封した医療用合成樹脂製容器と、炭酸ガスを包
含するガス非透過性の包装体を提供するものである。According to the present inventors,
As a result of intensive research to solve the above problems, in a gas-impermeable package including a medical synthetic resin container sealed with a bicarbonate compound-containing drug solution such as sodium hydrogencarbonate, the internal space of the package is On the other hand, by adding a carbon dioxide atmosphere forming means, the pH increased during heat sterilization without the need for a carbon dioxide mixture during dissolution / preparation or a special device for keeping the chemical solution at a low temperature and vacuum packaging.
It has been found that the package can be reduced and a stable package can be obtained for a long time, and the present invention has been completed based on this finding. As a first aspect of the present invention, a carbon dioxide generating oxygen absorber is selected as the above means, and a carbon dioxide atmosphere is formed by disposing the oxygen absorber in the internal space. The present invention provides a medical synthetic resin container in which a salt compound-containing liquid medicine is sealed, and a gas-impermeable package containing a carbon dioxide-generating oxygen scavenger. In a second aspect of the present invention, a carbon dioxide gas filling device is selected as the above means, and a carbon dioxide gas atmosphere is formed by previously replacing air in the space inside the package with carbon dioxide gas by the device. The present invention provides a medical synthetic resin container in which a chemical solution containing a bicarbonate compound is sealed, and a gas-impermeable package containing carbon dioxide gas.
【０００９】本発明の第１態様によれば、ガス非透過性
の包装体内に封入された炭酸ガス発生型脱酸素剤の作用
で、医療用合成樹脂製容器とガス非透過性包装体の間に
存在する空気中の酸素が、次いで当該容器内に存在する
空気中の酸素が炭素ガスに急速に置換される。これによ
り、医療用合成樹脂製容器の周囲に存在する炭酸ガス
が、医療用合成樹脂製容器の容器壁を通過して薬液中に
溶け込むため、加熱滅菌時に上昇したｐＨを低下させる
ことができる。また、長期保存時において、炭酸水素ナ
トリウムの分解により炭酸ガスが生成しても、医療用合
成樹脂製容器壁を透過して当該容器から出て行く炭酸ガ
スと、当該容器と当該包装体の間の空間から医療用合成
樹脂製容器壁を透過して再び薬液中に吸収される炭酸ガ
スとが速やかに平衡状態となる。その結果、炭酸水素ナ
トリウムの分解反応が抑制され、ｐＨの変動が防止で
き、長期間の保存が可能となったのである。また、本発
明の第２態様によれば、重炭酸塩化合物含有薬液を密封
した医療用合成樹脂製容器の周囲の環境を炭酸ガス雰囲
気とすることにより、加熱滅菌時に上昇したｐＨを低下
させることができ、更に、炭酸水素ナトリウムの分解に
より炭酸ガスが生成しても、上記と同様に速やかに平衡
状態となり、その結果炭酸水素ナトリウムの分解反応が
抑制され、ｐＨの変動が防止でき、長期間の保存が可能
となったのである。According to the first aspect of the present invention, due to the action of the carbon dioxide-generating oxygen scavenger enclosed in the gas impermeable package, the space between the medical synthetic resin container and the gas impermeable package is increased. The oxygen in the air present in the container, and then the oxygen in the air present in the container is rapidly replaced by carbon gas. As a result, the carbon dioxide gas existing around the medical synthetic resin container passes through the container wall of the medical synthetic resin container and dissolves in the drug solution, so that the pH increased during heat sterilization can be lowered. In addition, even if carbon dioxide gas is generated by decomposition of sodium hydrogen carbonate during long-term storage, carbon dioxide gas that permeates the wall of the medical synthetic resin container and exits from the container, and between the container and the packaging body. The carbon dioxide gas that has permeated the wall of the synthetic resin container for medical use and is absorbed again into the chemical solution from the space of 2 is quickly brought into an equilibrium state. As a result, the decomposition reaction of sodium hydrogen carbonate was suppressed, the fluctuation of pH was prevented, and it became possible to store for a long period of time. Moreover, according to the second aspect of the present invention, the environment around the medical synthetic resin container in which the bicarbonate compound-containing drug solution is sealed is set to a carbon dioxide gas atmosphere to reduce the pH that has increased during heat sterilization. In addition, even if carbon dioxide gas is generated by the decomposition of sodium hydrogen carbonate, the equilibrium state is quickly established as described above, and as a result, the decomposition reaction of sodium hydrogen carbonate is suppressed, and the fluctuation of pH can be prevented, and the long-term It is now possible to save.
【００１０】本発明に使用される重炭酸塩化合物は、と
くに炭酸水素ナトリウムである。この化合物を含有する
薬液（とくに水溶液）の化合物濃度は、用途・用法によ
り適宜求められ、また、他の電解質や薬剤を配合してい
てもよい。当該薬液を密封するための医療用合成樹脂製
容器の材質は、医薬品収納用という性格から安全性が高
いものであって、かつ、液体を通さないガス透過性の容
器であれば特に制限はないが、好ましくは、一般にポリ
エチレン、ポリプロピレン、ポリ塩化ビニルなどの熱可
塑性合成樹脂である。かかる医療用合成樹脂製容器を包
み込むためのガス非透過性の包装体は、ガスバリヤー特
性を示し、かつ、液体非透過性であれば、いずれのもの
でもよい。例えば、内層／低密度ポリエチレン、中間層
／エチレン・ビニルアルコール共重合体および外層／二
軸延伸ナイロンからなる積層体が包含され、内容物の確
認ができる程度の透明性を有することが望ましい。The bicarbonate compound used in the present invention is especially sodium hydrogen carbonate. The compound concentration of a chemical solution (particularly an aqueous solution) containing this compound is appropriately determined depending on the application and usage, and other electrolytes or agents may be blended. There is no particular limitation on the material of the medical synthetic resin container for sealing the drug solution, as long as it is a highly safe container due to the nature of storing pharmaceuticals and is a gas permeable container that does not pass liquid. However, it is generally a thermoplastic synthetic resin such as polyethylene, polypropylene or polyvinyl chloride. The gas impermeable package for enclosing such a medical synthetic resin container may be any as long as it exhibits gas barrier properties and is liquid impermeable. For example, a laminate comprising an inner layer / low-density polyethylene, an intermediate layer / ethylene / vinyl alcohol copolymer and an outer layer / biaxially stretched nylon is included, and it is desirable that the laminate has transparency to the extent that the contents can be confirmed.
【００１１】次に、本発明の第１態様において用いられ
る炭酸ガス発生型の脱酸素剤は、脱酸素作用と炭酸ガス
発生作用を併有するものであればいずれのものでもよい
が、包装体の内部空間の酸素を速やかに除去し、かつ炭
酸ガス発生量が多いものが好ましい。当該脱酸素剤に
は、例えば当該主成分として、アスコルビン酸またはエ
リソルビン酸およびそれらの塩などの還元性の多価アル
コール類；ヒドロキノンまたはカテコールなどのポリフ
ェノール類；鉄粉または亜二チオン酸塩、亜硫酸塩、第
一鉄塩などの無機塩類を含み、任意の触媒を含むものが
包含される。脱酸素剤、例えば、亜二チオン酸塩は、水
の存在下で酸素を吸収する一方、重炭酸塩または炭酸塩
と反応して炭酸ガスを発生する。市販のものとして、エ
ージレスＧ(登録商標) (三菱瓦斯化学(株）製）などが
挙げられ、エージレスＧを用いた場合、当該脱酸素剤の
量は、例えば当該空間内の酸素量１００ｍｌあたり２０
ｇ以上、好ましくは３０ｇ以上である。なお、特開昭６
２−２２１３５２号などでは、脱酸素剤を包材内に使用
して、酸素によるアミノ酸輸液などの変質を防止してい
るが、かかる脱酸素剤は、本発明のような炭酸ガス発生
型のものでない。事実、この脱酸素剤を本発明に用いれ
ば無酸素状態となって当該内部空間が陰圧となり、炭酸
水素ナトリウムの分解が促進されるのである。また、本
発明に用いられる炭酸ガス発生型脱酸素剤は、これまで
は、単に、おかきなどの食品収納用缶の内部圧力を均一
に保持するためにのみ使用されていたのであって、炭酸
ガス雰囲気の形成が必須である本発明とは、基本的に異
なったものである。Next, the carbon dioxide generating oxygen scavenger used in the first embodiment of the present invention may be any as long as it has both a deoxidizing action and a carbon dioxide generating action. It is preferable that the oxygen in the internal space is quickly removed and the amount of carbon dioxide gas generated is large. Examples of the oxygen scavenger include, as the main component, reducing polyhydric alcohols such as ascorbic acid or erythorbic acid and salts thereof; polyphenols such as hydroquinone or catechol; iron powder or dithionite salt and sulfite. It includes salts, inorganic salts such as ferrous salts, and includes any catalyst. Oxygen scavengers, such as dithionite, absorb oxygen in the presence of water while reacting with bicarbonate or carbonate to generate carbon dioxide. Examples of commercially available products include Ageless G (registered trademark) (manufactured by Mitsubishi Gas Chemical Co., Inc.). When Ageless G is used, the amount of the oxygen scavenger is, for example, 20 per 100 ml of oxygen in the space.
It is at least g, preferably at least 30 g. Incidentally, JP-A-6
In No. 2-221352 and the like, a deoxidant is used in the packaging material to prevent alteration of amino acid infusion by oxygen and the like. Not. In fact, if this oxygen scavenger is used in the present invention, it becomes anoxic and the internal space becomes negative pressure, and the decomposition of sodium hydrogen carbonate is promoted. Further, the carbon dioxide-generating oxygen scavenger used in the present invention has hitherto been used only for uniformly maintaining the internal pressure of a food storage can such as an oyster. The present invention is fundamentally different from the present invention in which the formation of an atmosphere is essential.
【００１２】他方、本発明の第２態様で用いられる炭酸
ガス充填装置は、包装体の内部空間の空気を炭酸ガスで
置換できるものであればいずれのものでもよく、この目
的に市販されているものを使用することができる。本発
明の包装体は、常法により炭酸水素ナトリウムなどの化
合物薬液を調製し、この薬液を例えば医療用合成樹脂製
バッグ中に充填し、次いで当該脱酸素剤と共にガス非透
過性の積層体内に収納するかまたは収納後に炭酸ガスを
充填して製造することができる。On the other hand, the carbon dioxide gas filling device used in the second aspect of the present invention may be any device as long as it can replace the air in the inner space of the package with carbon dioxide gas, and is commercially available for this purpose. Things can be used. The package of the present invention, a compound drug solution such as sodium hydrogen carbonate is prepared by a conventional method, this drug solution is filled in, for example, a medical synthetic resin bag, and then, together with the oxygen scavenger, in a gas-impermeable laminate. It can be manufactured by storing it or filling it with carbon dioxide after storing.
【００１３】[0013]
【実施例】つぎに、実施例、比較例および試験例を挙げ
て本発明をさらに詳しく説明するが、これらに限定され
るものではない。EXAMPLES Next, the present invention will be described in more detail with reference to Examples, Comparative Examples and Test Examples, but the present invention is not limited to these.
【００１４】実施例１ 炭酸水素ナトリウム１２．６ｇを常温で注射用水に溶解
して１ｌとし、ミリポア−フィルターでろ過した。ろ液
を内容２００ｍｌのポリエチレン製輸液バッグに分注
し、密封した後、高圧蒸気滅菌した。常温に冷却後、こ
の輸液バッグを内層／低密度ポリエチレン、中間層／エ
チレン・ビニルアルコール共重合体および外層／二軸延
伸ナイロンの積層体からなるガス非透過性包装体内に炭
酸ガス発生型脱酸素剤( 「エージレスＧ(登録商標)」三
菱瓦斯化学(株）製）とともに、収納し、密封した。 Example 1 12.6 g of sodium hydrogen carbonate was dissolved in water for injection at room temperature to make 1 l, and the mixture was filtered with a Millipore filter. The filtrate was dispensed into a polyethylene infusion bag having a content of 200 ml, sealed, and then sterilized under high pressure steam. After cooling to room temperature, this infusion bag was deoxygenated with carbon dioxide gas in a gas impermeable package consisting of a laminate of inner layer / low density polyethylene, middle layer / ethylene vinyl alcohol copolymer and outer layer / biaxially stretched nylon. It was stored and sealed together with the agent ("Ageless G (registered trademark)" manufactured by Mitsubishi Gas Chemical Co., Inc.).
【００１５】実施例２ 炭酸水素ナトリウムを７０ｇとした点を除き、実施例１
と同様にして包装体を製造した。 Example 2 Example 1 except that the amount of sodium hydrogen carbonate was 70 g.
A package was manufactured in the same manner as in.
【００１６】比較例１ 薬液の溶解・調製において冷却下に炭酸ガスを混入した
点、並びに炭酸ガス発生型脱酸素剤を用いず、ガス非透
過性包装体内に収納後、真空包装した点を除き、実施例
１と同様にして包装体を製造した。比較例２ 炭酸水素ナトリウムを７０ｇとした点を除き、比較例１
と同様にして包装体を製造した。比較例３ 炭酸水素ナトリウム１２．６ｇを注射用水に溶解して１
ｌとし、ミリポア−フィルターでろ過した。ろ液を内容
２００ｍｌのガラス製バイアル瓶に分注し、密封した
後、高圧蒸気滅菌した。比較例４ 炭酸水素ナトリウムを７０ｇとした点を除き、比較例３
と同様にして製造した。 Comparative Example 1 Except that carbon dioxide was mixed under cooling in the dissolution / preparation of the chemical solution, and that the carbon dioxide-generating oxygen absorber was not used and the product was vacuum packaged after being housed in a gas impermeable package. A package was manufactured in the same manner as in Example 1. Comparative Example 2 Comparative Example 1 except that sodium hydrogencarbonate was 70 g.
A package was manufactured in the same manner as in. Comparative Example 3 12.6 g of sodium hydrogen carbonate was dissolved in water for injection to prepare 1
1 and filtered with a Millipore filter. The filtrate was dispensed into a glass vial having a content of 200 ml, sealed, and then sterilized by high pressure steam. Comparative Example 4 Comparative Example 3 except that 70 g of sodium hydrogen carbonate was used.
It was manufactured in the same manner as.
【００１７】実施例３ 実施例１と同様にして、ポリエチレン製輸液バッグを積
層体からなるガス非透過性包装体内に収納した。その
後、炭酸ガスを充填し、当該包装体を、密封した。 Example 3 In the same manner as in Example 1, a polyethylene infusion bag was placed in a gas-impermeable package made of a laminate. Then, carbon dioxide was filled and the package was sealed.
【００１８】実施例４ 炭酸水素ナトリウムを７０ｇとした点を除き、実施例３
と同様にして包装体を製造した。 Example 4 Example 3 except that 70 g of sodium hydrogen carbonate was used.
A package was manufactured in the same manner as in.
【００１９】ｐＨ試験及び異物試験 以上のようにして得られた包装体を種々の条件下で保存
した後、ｐＨの変動およびガラスフレークスのような異
物の発生を調べる目的で、日本薬局方一般試験法ｐＨ測
定法および日本薬局方製剤総則注射剤による注射剤の不
溶性異物検査法第１法により試験を行った。その結果を
以下の表１に示す。 PH Test and Foreign Substance Test After the packaging obtained as described above is stored under various conditions, the Japanese Pharmacopoeia general test is conducted for the purpose of investigating fluctuations in pH and generation of foreign substances such as glass flakes. The test was carried out by the pH measurement method and the Japanese Pharmacopoeia General Regulations No. 1 method for insoluble foreign matter inspection of injections by injection. The results are shown in Table 1 below.
【００２０】[0020]
【表１】 [Table 1]
【００２１】表１の結果によれば、包装体内の薬物のｐ
Ｈの安定性および異物発生に関し、本発明の包装体であ
る炭酸ガス発生型脱酸素剤使用の実施例１,２および予
め炭酸ガスを充填した実施例３,４が、従来法である真
空包装処理の比較例１，２およびガラス製容器使用の比
較例３，４と比較して、大幅に改善されることが証明さ
れた。According to the results shown in Table 1, p of the drug in the package is
Regarding the stability of H and the generation of foreign matter, Examples 1 and 2 using a carbon dioxide generating oxygen absorber, which are the packages of the present invention, and Examples 3 and 4 in which carbon dioxide is pre-filled are vacuum packaging methods which are conventional methods. It was proved to be significantly improved as compared with Comparative Examples 1 and 2 of the treatment and Comparative Examples 3 and 4 using the glass container.
【００２２】[0022]
【発明の効果】以上の説明から明らかなように、本発明
によれば、重炭酸塩化合物含有薬液を通常の方法により
常温で調製し充填・密封した医療用合成樹脂製容器周囲
の環境を、炭酸ガス発生型脱酸素剤を配置するか (実施
例１,２）または予め炭酸ガスを充填する (実施例３,
４）ことにより、炭酸ガス雰囲気を形成することがで
き、この炭酸ガス雰囲気の形成により、第１に、従来法
のような常温よりも低い温度で炭酸ガスを吹き込みなが
ら溶液を溶解・調製する工程を大幅に簡易化することが
でき、第２に、従来法のような真空包装プロセスに要す
るような特殊な装置が不要なため経済的であり、第３
に、重炭酸塩化合物含有薬液の加熱滅菌時に上昇したｐ
Ｈを急速に低下させると共に長期保存時におけるｐＨの
変動を防止して、従来法では不可能であった長期間にわ
たる保存に成功することができたのである。また、本発
明によれば、合成樹脂製容器を用いているので、ガラス
フレークスのような異物の発生がなく、かつ、軽量で破
損の恐れも少なくしかも取り扱いに便利であるという、
利点もある。As is apparent from the above description, according to the present invention, the environment around the medical synthetic resin container in which the bicarbonate compound-containing drug solution is prepared and filled and sealed at room temperature by the usual method, A carbon dioxide-generating oxygen scavenger is placed (Examples 1 and 2) or prefilled with carbon dioxide (Examples 3, 2).
By 4), a carbon dioxide gas atmosphere can be formed, and by the formation of this carbon dioxide gas atmosphere, firstly, a step of dissolving and preparing a solution while blowing carbon dioxide gas at a temperature lower than room temperature as in the conventional method. Secondly, it is economical because it does not require a special device required for the vacuum packaging process such as the conventional method.
P increased during heat sterilization of a bicarbonate compound-containing drug solution
By rapidly lowering H and preventing fluctuations in pH during long-term storage, it was possible to succeed in long-term storage, which was not possible with conventional methods. Further, according to the present invention, since a synthetic resin container is used, there is no occurrence of foreign matter such as glass flakes, and it is lightweight and less likely to be damaged, and is convenient to handle.
There are also advantages.
【図１】 本発明の第１態様に係る包装体の正面図であ
る。FIG. 1 is a front view of a package according to a first aspect of the present invention.
１ 重炭酸化合物薬液含有医療用合成樹脂製容器 ２ 炭酸ガス発生型脱酸素剤 ３ ガス非透過性包装体 ４ 密封部 1 Container made of medical synthetic resin containing bicarbonate compound 2 Carbon dioxide generating oxygen scavenger 3 Gas impermeable package 4 Sealed part
───────────────────────────────────────────────────── フロントページの続き (72)発明者 山本 恵 大阪府大阪市城東区森之宮２丁目３番30号 扶桑薬品工業株式会社研究開発センター 内 ─────────────────────────────────────────────────── ─── Continuation of front page (72) Megumi Yamamoto 2-3-3 Morinomiya Morinomiya, Joto-ku, Osaka City, Osaka Prefecture Fuso Yakuhin Kogyo Co., Ltd. Research and Development Center
Claims (4)
脂製容器により密封し、この容器を包含するガス非透過
性の包装体であって、 当該包装体内における上記医療用合成樹脂製容器周囲の
空間に対し炭酸ガス雰囲気形成手段を施すことを特徴と
する包装体。1. A gas-impermeable package in which a bicarbonate compound-containing drug solution is sealed in a medical synthetic resin container, and the container is a gas-impermeable package surrounding the medical synthetic resin container. A packaging body characterized by applying a carbon dioxide atmosphere forming means to the space.
あって、当該脱酸素剤を上記空間に配置させる請求項１
記載の包装体。2. The carbon dioxide generating oxygen scavenger, and the oxygen scavenger is disposed in the space.
The package described.
て、当該装置により上記空間に存在する空気を予め炭酸
ガスで置換することからなる請求項１記載の包装体。3. The package according to claim 1, wherein the means is a carbon dioxide gas filling device, and the air existing in the space is replaced with carbon dioxide gas in advance by the device.
ある請求項１記載の包装体。4. The package according to claim 1, wherein the bicarbonate compound is sodium hydrogen carbonate.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3217025A JP2505329B2 (en) | 1991-08-28 | 1991-08-28 | Package for storing chemical solutions containing bicarbonate compounds |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP3217025A JP2505329B2 (en) | 1991-08-28 | 1991-08-28 | Package for storing chemical solutions containing bicarbonate compounds |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP6086208A Division JP2527532B2 (en) | 1994-04-25 | 1994-04-25 | New application of carbon dioxide generating oxygen absorber |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0549675A true JPH0549675A (en) | 1993-03-02 |
| JP2505329B2 JP2505329B2 (en) | 1996-06-05 |
Family
ID=16697660
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP3217025A Expired - Lifetime JP2505329B2 (en) | 1991-08-28 | 1991-08-28 | Package for storing chemical solutions containing bicarbonate compounds |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP2505329B2 (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994016663A1 (en) * | 1993-01-22 | 1994-08-04 | Otsuka Pharmaceutical Factory, Inc. | Bicarbonate-containing powdered medicine storage container and method of stabilizing the same medicine |
| JPH06339512A (en) * | 1994-04-25 | 1994-12-13 | Fuso Yakuhin Kogyo Kk | Novel use of carbon dioxide generation type deoxidation scavenger |
| WO1996017578A1 (en) * | 1994-12-08 | 1996-06-13 | Otsuka Pharmaceutical Factory, Inc. | Method of suppressing adsorption of substances derived from container material on drugs and container |
| WO2020204170A1 (en) | 2019-04-04 | 2020-10-08 | 扶桑薬品工業株式会社 | Reservoir for cardioplegic solution containing bicarbonate ion, and method for manufacturing same |
| CN113116921A (en) * | 2019-12-30 | 2021-07-16 | 石药集团恩必普药业有限公司 | Sodium bicarbonate injection and preparation method thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS56166853A (en) * | 1980-05-26 | 1981-12-22 | Nikkiso Co Ltd | Method of preserving and using bicarbonate undiluted solution |
| JPS6068856A (en) * | 1983-09-26 | 1985-04-19 | エーザイ株式会社 | Prevention of increase in internal pressure of container |
| JPS61355A (en) * | 1984-04-06 | 1986-01-06 | フレゼニウス アクチエンゲゼルシヤフト | Container for bicarbonate-containing solution |
| JPS61115050A (en) * | 1984-11-09 | 1986-06-02 | Daigo Eiyou Kagaku Kk | Production of alkali metal salt of lactic acid in high concentration |
| JPS62221352A (en) * | 1986-03-22 | 1987-09-29 | 株式会社新素材総合研究所 | Liquid drug containing container preventing deterioratioan of liquid drug by oxygen and its production |
| JPS63107932A (en) * | 1986-10-24 | 1988-05-12 | Keizo Fukunaga | High concentration complex electrolyte injection solution |
-
1991
- 1991-08-28 JP JP3217025A patent/JP2505329B2/en not_active Expired - Lifetime
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS56166853A (en) * | 1980-05-26 | 1981-12-22 | Nikkiso Co Ltd | Method of preserving and using bicarbonate undiluted solution |
| JPS6068856A (en) * | 1983-09-26 | 1985-04-19 | エーザイ株式会社 | Prevention of increase in internal pressure of container |
| JPS61355A (en) * | 1984-04-06 | 1986-01-06 | フレゼニウス アクチエンゲゼルシヤフト | Container for bicarbonate-containing solution |
| JPS61115050A (en) * | 1984-11-09 | 1986-06-02 | Daigo Eiyou Kagaku Kk | Production of alkali metal salt of lactic acid in high concentration |
| JPS62221352A (en) * | 1986-03-22 | 1987-09-29 | 株式会社新素材総合研究所 | Liquid drug containing container preventing deterioratioan of liquid drug by oxygen and its production |
| JPS63107932A (en) * | 1986-10-24 | 1988-05-12 | Keizo Fukunaga | High concentration complex electrolyte injection solution |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994016663A1 (en) * | 1993-01-22 | 1994-08-04 | Otsuka Pharmaceutical Factory, Inc. | Bicarbonate-containing powdered medicine storage container and method of stabilizing the same medicine |
| AU669773B2 (en) * | 1993-01-22 | 1996-06-20 | Otsuka Pharmaceutical Factory, Inc. | Bicarbonate-containing powdered medicine storage container and method of stabilizing the same medicine |
| JPH06339512A (en) * | 1994-04-25 | 1994-12-13 | Fuso Yakuhin Kogyo Kk | Novel use of carbon dioxide generation type deoxidation scavenger |
| JP2527532B2 (en) * | 1994-04-25 | 1996-08-28 | 扶桑薬品工業株式会社 | New application of carbon dioxide generating oxygen absorber |
| WO1996017578A1 (en) * | 1994-12-08 | 1996-06-13 | Otsuka Pharmaceutical Factory, Inc. | Method of suppressing adsorption of substances derived from container material on drugs and container |
| AU687276B2 (en) * | 1994-12-08 | 1998-02-19 | Otsuka Pharmaceutical Factory, Inc. | Method of suppressing adsorption of substances derived from container material on drugs and container |
| WO2020204170A1 (en) | 2019-04-04 | 2020-10-08 | 扶桑薬品工業株式会社 | Reservoir for cardioplegic solution containing bicarbonate ion, and method for manufacturing same |
| CN113116921A (en) * | 2019-12-30 | 2021-07-16 | 石药集团恩必普药业有限公司 | Sodium bicarbonate injection and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2505329B2 (en) | 1996-06-05 |
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