JPH0789856A - Amino acid transfusion preparation packed in plastic container - Google Patents
Amino acid transfusion preparation packed in plastic containerInfo
- Publication number
- JPH0789856A JPH0789856A JP5233047A JP23304793A JPH0789856A JP H0789856 A JPH0789856 A JP H0789856A JP 5233047 A JP5233047 A JP 5233047A JP 23304793 A JP23304793 A JP 23304793A JP H0789856 A JPH0789856 A JP H0789856A
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- JP
- Japan
- Prior art keywords
- amino acid
- plastic container
- preparation
- present
- acid infusion
- 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.)
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- Medical Preparation Storing Or Oral Administration Devices (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明はアミノ酸輸液製剤、詳し
くはシステイン、システイン塩酸塩及び之等の誘導体並
びに亜硫酸塩もしくは重亜硫酸塩は含有しないがトリプ
トファンを含有するアミノ酸輸液を、プラスチック容器
に充填し、これをガスバリア性包材で二重包装したアミ
ノ酸輸液製剤に関する。BACKGROUND OF THE INVENTION The present invention relates to an amino acid infusion preparation, more specifically, a plastic container filled with an amino acid infusion containing cysteine, cysteine hydrochloride and its derivatives and sulfite or bisulfite but containing tryptophan. The present invention relates to an amino acid transfusion preparation which is double-packed with a gas barrier packaging material.
【０００２】[0002]
【従来の技術】従来より、経静脈投与等により使用され
るアミノ酸輸液は、各種の必須アミノ酸及び非必須アミ
ノ酸が配合され、経口的に栄養源を摂取することが不可
能であるかもしくは困難である患者に投与適用されてい
る。2. Description of the Related Art Conventionally, amino acid infusions used by intravenous administration and the like have been mixed with various essential amino acids and non-essential amino acids, and it has been impossible or difficult to orally take nutritional sources. It is applied to certain patients.
【０００３】かかるアミノ酸輸液の処方としては、従来
より例えば必須アミノ酸処方としてのＶｕｊ−Ｎ処方や
ＦＡＯ処方を基本とする各種のものが知られており、ま
た病態別アミノ酸処方として、例えば腎不全用アミノ酸
輸液として商品名「アミュー」（森下ルセル株式会社
製）等がすでに市販されている。Various amino acid infusion formulations based on the Vuj-N formulation and FAO formulation, which are essential amino acid formulations, have been known in the past, and as amino acid formulations according to disease states, for example, renal failure. As the amino acid infusion, the trade name "Amu" (made by Morishita Roussel Co., Ltd.) and the like are already on the market.
【０００４】之等のアミノ酸輸液は、いずれも必須アミ
ノ酸としてのトリプトファンもしくはその誘導体と共に
各種のアミノ酸を含むアミノ酸組成を有するに加えて、
下記１〜３に大別できる処方上の特徴を有している。In addition to the amino acid infusions described above, each has an amino acid composition containing various amino acids together with tryptophan or its derivative as an essential amino acid.
It has prescription characteristics that can be roughly classified into the following 1 to 3.
【０００５】１）抗酸化剤としてのＮａＨＳＯ3 、Ｎａ
2 ＳＯ3 等の亜硫酸塩もしくは重亜硫酸塩を含み、また
システイン等をアミノ酸成分のひとつとして又は上記亜
硫酸塩等と同様の抗酸化剤（安定化剤）として含む、 ２）抗酸化剤としてのＮａＨＳＯ3 等の亜硫酸塩もしく
は重亜硫酸塩は含むが、システイン等は含まない、 ３）システイン等は含むが、ＮａＨＳＯ3 等の抗酸化剤
は含まない。1) NaHSO 3 and Na as antioxidants
2 Sulfite such as SO 3 or bisulfite, and cysteine or the like as one of the amino acid components or as an antioxidant (stabilizer) similar to the above sulfite, 2) NaHSO as an antioxidant Sulfites or bisulfites such as 3 are included but cysteine or the like is not included. 3) Cysteines or the like are included, but antioxidants such as NaHSO 3 are not included.
【０００６】しかしながら、上記従来のこの種アミノ酸
輸液処方において、抗酸化剤として利用されるＮａＨＳ
Ｏ3 、Ｎａ2 ＳＯ3 等は、食品や飲料水、医薬品等にそ
の添加配合の認められているものではあるが、近年、喘
息患者やアトピー性非喘息患者等の一部の感受性の高い
患者について、気管支痙攣やアナフィラキシーショック
等の副作用が報告されるに至り、かかる副作用を伴うお
それのある抗酸化剤の使用回避が叫ばれている現状にあ
る。However, NaHS used as an antioxidant in the above conventional amino acid infusion formulation of this kind.
O 3 , Na 2 SO 3 and the like are admitted to be added to food, drinking water, pharmaceuticals, etc., but in recent years, some highly susceptible patients such as asthma patients and atopic non-asthma patients As for the above, side effects such as bronchospasm and anaphylactic shock have been reported, and the avoidance of the use of antioxidants that may cause such side effects is being sought.
【０００７】また、上記アミノ酸輸液は、ビタミン製剤
と混注して投与されることも多く、この場合でも該輸液
中に亜硫酸イオンや亜硫酸水素イオンが共存すれば、ビ
タミン製剤中のチアミンが分解することが知られてお
り、かかるチアミンを含むビタミン製剤の混注において
は、投与量、投与速度等に充分に注意しなければならな
い不利がある。Further, the above amino acid infusion solution is often administered as a mixed injection with a vitamin preparation, and even in this case, if sulfite ion or bisulfite ion coexists in the infusion solution, thiamine in the vitamin preparation is decomposed. Is known, and in such mixed injection of a vitamin preparation containing thiamine, there is a disadvantage that attention must be paid to the dose and the administration speed.
【０００８】更に、システイン等は、酸化されると分解
して、硫化水素（Ｈ2 Ｓ）を発生し、これが悪臭の原因
となる。この悪臭の発生は、アミノ酸輸液の製造時の加
熱滅菌工程のみならず、例えば輸液製品の保存中にもし
ばしば認められる。また高カロリー輸液では、一般に上
記のごときアミノ酸輸液に更にミネラルや微量元素製剤
が配合されるが、この場合には、上記発生する硫化水素
が亜鉛、鉄、銅、マンガン等と反応して硫化物の着色沈
殿を生成させる不利も認められる。上記システイン等の
酸化分解乃至これに伴われる硫化水素発生の問題は、殊
に製剤中に抗酸化剤としての亜硫酸塩や重亜硫酸塩を配
合しない製剤の場合に重大である。Further, cysteine and the like are decomposed when they are oxidized to generate hydrogen sulfide (H 2 S), which causes a bad odor. The generation of this malodor is often observed not only during the heat sterilization step in the production of the amino acid infusion solution but also during the storage of the infusion solution product. In the case of high calorie infusion, generally, the amino acid infusion as described above is further blended with a mineral or trace element preparation. In this case, the hydrogen sulfide generated reacts with zinc, iron, copper, manganese, etc. to form a sulfide. The disadvantage of producing colored precipitates of is also observed. The above-mentioned problem of oxidative decomposition of cysteine and the like and generation of hydrogen sulfide associated therewith is particularly serious in the case of a preparation in which sulfite or bisulfite as an antioxidant is not added.
【０００９】一方、この種アミノ酸輸液製剤に添加配合
されているトリプトファンも、一般に酸化されやすい物
質であり、これが酸化されると液が着色し、また水不溶
性のインドール化合物を生成する問題がある。On the other hand, tryptophan, which is added to and mixed with this kind of amino acid transfusion preparation, is also a substance which is generally easily oxidized, and when it is oxidized, the liquid is colored and there is a problem that a water-insoluble indole compound is produced.
【００１０】[0010]
【発明が解決しようとする課題】従って、本発明の目的
は、上記アミノ酸輸液製剤に見られる各種の問題を悉く
解決した新しいアミノ酸製剤、特に気管支痙攣やアナフ
ィラキシーショック等の副作用の心配のある抗酸化剤と
してのＮａＨＳＯ3 等の亜硫酸塩もしくは重亜硫酸塩を
含まず、ｐＨがより生理的であり、また抗酸化剤でもあ
るが、酸化分解により硫化水素を発生するシステイン等
のアミノ酸も含まず、しかもトリプトファンは含むがそ
の酸化による液の着色や不溶性微粒子の発生等の問題を
見事に解消した、斯界で要望されている安定な高張のア
ミノ酸製剤を提供する点にある。SUMMARY OF THE INVENTION Therefore, the object of the present invention is to provide a new amino acid preparation that solves various problems found in the above amino acid infusion preparations, especially antioxidants which may cause side effects such as bronchospasm and anaphylactic shock. It does not contain sulfites or bisulfites such as NaHSO 3 as an agent, has a more physiological pH, and is also an antioxidant, but does not contain amino acids such as cysteine that generate hydrogen sulfide by oxidative decomposition, and An object of the present invention is to provide a stable hypertonic amino acid preparation which is required in the art, which contains tryptophan, but has solved the problems such as coloring of the liquid due to its oxidation and generation of insoluble fine particles.
【００１１】[0011]
【課題を解決するための手段】本発明者等は上記目的よ
り鋭意研究を重ねた結果、プラスチック容器と脱酸素剤
とを併用し且つ之等をガスバリヤー性包材で包装する時
には、上記目的に合致する効果を奏し得る新しいアミノ
酸輸液製剤が得られることを見出だし、ここに本発明を
完成するに至った。Means for Solving the Problems As a result of intensive studies conducted by the present inventors from the above objects, when the plastic container and the oxygen scavenger are used in combination and they are packed with a gas barrier packaging material, It was found that a new amino acid infusion preparation capable of exhibiting an effect conforming to the above can be obtained, and the present invention has been completed here.
【００１２】即ち本発明は、抗酸化剤である亜硫酸塩も
しくは重亜硫酸塩並びにシステイン、システイン塩酸塩
及び之等の誘導体を含有せず、トリプトファン又はその
誘導体を必須成分として含有し且つ遊離アミノ酸換算で
総アミノ酸含量が少なくとも４重量％であるアミノ酸輸
液がプラスチック容器に充填され、該容器が脱酸素剤と
共にガスバリヤー性包材により封入されていることを特
徴とするプラスチック容器入りアミノ酸輸液製剤に係わ
る。That is, the present invention does not contain sulfite or bisulfite as an antioxidant and derivatives such as cysteine, cysteine hydrochloride, and the like, but contains tryptophan or its derivative as an essential component and in terms of free amino acid. The present invention relates to an amino acid infusion preparation in a plastic container, wherein an amino acid infusion solution having a total amino acid content of at least 4% by weight is filled in a plastic container, and the container is enclosed together with a deoxidizer by a gas barrier packaging material.
【００１３】本発明のアミノ酸輸液製剤は、亜硫酸塩や
重亜硫酸塩等の抗酸化剤（安定化剤）を配合していない
ことに基いて、之等の配合に起因する気管支痙攣やアナ
フィラキシーショック等の副作用のおそれが完全に回避
されていることは勿論のこと、抗酸化剤でもあるシステ
イン、システイン塩酸塩及び之等の誘導体を含有しない
ために、加熱滅菌時や保存時における硫化水素による悪
臭発生の問題もなく、これをビタミン製剤やミネラル微
量元素製剤と混注して併用する際にも、従来のこの種輸
液製剤に見られる如きビタミンの分解や着色、沈殿、沈
殿発生等の不利はない。The amino acid infusion preparation of the present invention does not contain antioxidants (stabilizers) such as sulfite and bisulfite. Not to mention the complete avoidance of the side effects of, it does not contain cysteine, which is also an antioxidant, cysteine hydrochloride, and other derivatives, so it produces an offensive odor due to hydrogen sulfide during heat sterilization and storage. Also, when this is mixed with a vitamin preparation or a mineral trace element preparation and used in combination, there is no disadvantage such as decomposition, coloring, precipitation, or precipitation of the vitamin as seen in the conventional infusion preparation of this kind.
【００１４】更に本発明製剤は、上記抗酸化剤の無添加
にもかかわらず、トリプトファンの酸化による液の着色
や不溶性微粒子の発生が見事に防止される特徴を有して
いる。Further, the preparation of the present invention has a characteristic that the coloring of the liquid and the generation of insoluble fine particles due to the oxidation of tryptophan are excellently prevented, even though the above antioxidant is not added.
【００１５】以下、本発明アミノ酸輸液製剤に利用され
るアミノ酸輸液につき詳述すれば、その処方は、含硫ア
ミノ酸であるシステイン、システイン塩酸塩、之等のア
セチル置換体等の誘導体のいずれも含まないこと及びト
リプトファン及びその誘導体から選ばれる成分を必須成
分として含むことを除いて他は、通常公知の各種のもの
と同様のものとすることができる。即ちこれはアミノ酸
輸液に適した各種の必須及び非必須アミノ酸を含むこと
ができ、その処方は、例えばＶｕｊ−Ｎ処方やＦＡＯ処
方に準じることができ、特に上記アミノ酸輸液は、遊離
アミノ酸換算で総アミノ酸含量が少なくとも４重量％の
高張（高濃度）の上記各処方であるのが好ましい。The amino acid infusion solution used in the amino acid infusion preparation of the present invention will be described in detail below. The formulation contains any of the sulfur-containing amino acids such as cysteine, cysteine hydrochloride, and derivatives such as acetyl substitution products. It can be the same as various conventionally known ones except that it does not exist and contains a component selected from tryptophan and its derivative as an essential component. That is, it can contain various essential and non-essential amino acids suitable for amino acid infusion, and its formulation can be based on, for example, Vuj-N formulation or FAO formulation. It is preferable that each of the above formulations is hypertonic (high concentration) having an amino acid content of at least 4% by weight.
【００１６】また、本発明に用いるアミノ酸輸液は、あ
る種の特定の病態用に調製された高張アミノ酸輸液、例
えば癌用（特公昭６１−５４００７号公報参照）、腎不
全用（森下ルセル社製市販品、商品名「アミュー」）、
肝性脳症用（森下ルセル社製市販品、商品名「モリヘパ
ミン」）であってもよく、之等と同様の処方に調製され
たものであってもよい。The amino acid infusion solution used in the present invention is a hypertonic amino acid infusion solution prepared for a certain specific pathological condition, for example, for cancer (see Japanese Examined Patent Publication No. 61-54007), for renal failure (made by Morishita Roussel). Commercial item, trade name "Amu"),
It may be for hepatic encephalopathy (commercial item manufactured by Morishita Roussel Co., Ltd., trade name “Molihepamine”), or may be prepared according to the same formulation as described above.
【００１７】之等のアミノ酸輸液の調製は、常法に従う
ことができ、得られる輸液のｐＨは、一般には５．５〜
７．５、好ましくは６．０〜７．３程度に調整されるの
が好適であり、かかるｐＨ調整は、通常のｐＨ調整剤、
例えば塩酸、酢酸、乳酸、リンゴ酸、クエン酸等の酸類
や水酸化ナトリウム等のアルカリを用いて行なうことが
できる。The preparation of the amino acid infusion solution described above can be carried out according to a conventional method, and the pH of the obtained infusion solution is generally 5.5 to 5.
It is preferable that the pH is adjusted to about 7.5, preferably about 6.0 to 7.3.
For example, it can be carried out using an acid such as hydrochloric acid, acetic acid, lactic acid, malic acid or citric acid, or an alkali such as sodium hydroxide.
【００１８】更に上記アミノ酸輸液には、通常この種輸
液に添加配合されることのよく知られている各種の添加
剤、例えば糖類、電解質、ビタミン、脂肪、ミネラル、
微量元素等を任意に添加配合させることができる。Further, various additives well known to be usually added to and mixed with this type of infusion solution, such as sugars, electrolytes, vitamins, fats and minerals, are added to the above amino acid infusion solution.
Trace elements and the like can be arbitrarily added and mixed.
【００１９】尚、本発明に利用するアミノ酸輸液と同一
の高張処方のアミノ酸輸液を、バイアル瓶に充填する場
合は、可及的脱酸素状態であっても、加熱滅菌により不
溶性粒子が増加して、また投与時の濾過フィルター上を
着色させる酸化分解物の生成が顕著に認められる場合が
あるが、本発明に従ってプラスチック容器に充填し、脱
酸素剤と共に特定の二重包装を行なう場合には、上記容
器内アミノ酸輸液は滅菌時の酸化ダメージをより受けや
すいと考えられるにもかかわらず、実際の加熱滅菌時に
は、上記バイアル瓶に充填する場合に認められる問題を
伴わないことが、本発明者らにより確認されている。従
って、本発明によれば、注射液として適合したアミノ酸
輸液を提供できる利点がある。When the vial is filled with an amino acid infusion solution of the same hypertonic formulation as the amino acid infusion solution used in the present invention, the insoluble particles increase due to heat sterilization even in the deoxidized state as much as possible. In some cases, the production of oxidative decomposition products that color the filtration filter during administration may be remarkably observed. However, when a plastic container is filled in accordance with the present invention and a specific double packaging is performed with an oxygen scavenger, Although the amino acid infusion in the container is considered to be more susceptible to oxidative damage during sterilization, the present inventors have found that during actual heat sterilization, the problem observed when filling the vial bottle is not involved. Have been confirmed by. Therefore, according to the present invention, there is an advantage that an amino acid transfusion suitable as an injection can be provided.
【００２０】本発明において、上記アミノ酸輸液を充填
するプラスチック容器は、従来より一般に用いられてい
る各種の材質のもののいずれでもよい、その具体例とし
ては、例えばポリエチレン、ポリプロピレン等のポリオ
レフィンや之等の共重合体や、ポリ塩化ビニル、エチレ
ン酢酸ビニル共重合体、ポリエステル、ナイロン等の各
種ポリマーを例示できる。上記容器は、之等ポリマーの
単層から構成される必要はなく、同一もしくは異なる２
種以上のポリマーの複合多層構造をとるものであっても
よく、その厚さは、一般に約５０〜１０００μｍ、好ま
しくは約１５０〜５００μｍであるのがよく、またその
形状、大きさ等は通常のアミノ酸輸液を収容できる限り
任意であり、特にバッグ形状やボトル形状であるのが好
ましい。In the present invention, the plastic container filled with the amino acid infusion may be made of any of various materials that have been generally used in the past. Specific examples thereof include polyolefins such as polyethylene and polypropylene, and the like. Examples thereof include copolymers, polyvinyl chloride, ethylene-vinyl acetate copolymers, various polymers such as polyester and nylon. The containers need not consist of a single layer of the same polymer, but can be the same or different.
It may have a composite multilayer structure of one or more polymers, and its thickness is generally about 50 to 1000 μm, preferably about 150 to 500 μm, and its shape, size, etc. It is optional as long as it can contain an amino acid infusion solution, and particularly preferably in the shape of a bag or bottle.
【００２１】本発明で利用される脱酸素剤としては、例
えば代表的には、水酸化鉄、酸化鉄、炭化鉄等の鉄化合
物を有効成分として含有するもの等を例示できる。その
具体的市販品としては、例えば商品名「エージレス」
（三菱瓦斯化学社製）、商品名「モジュラン」（日本化
薬社製）、商品名「セキュール」（日本曹達社製）等を
例示できる。また、例えば「タモツ」（王子化工社製）
や鮮度保持剤Ｃ（凸版印刷社製）等の有機系脱酸素剤を
利用することも可能である。上記脱酸素剤の利用形態は
特に限定はないが、通常市販品として入手される脱酸素
剤は粉末状形態を有しており、かかる粉末形態の場合
は、その必要量を通気性のある小袋等に収容して、これ
を前記アミノ酸輸液を収容したプラスチック容器と共
に、後記するガスバリヤー性包材で包装して該包材中に
封入すればよい。Typical examples of the oxygen scavenger used in the present invention include those containing iron compounds such as iron hydroxide, iron oxide and iron carbide as an active ingredient. Specific examples of the commercially available product include, for example, the product name “Ageless”
(Made by Mitsubishi Gas Chemical Co., Inc.), trade name “Modulan” (manufactured by Nippon Kayaku Co., Ltd.), trade name “Secur” (manufactured by Nippon Soda Co., Ltd.) and the like. Also, for example, "Tamotsu" (Oji Kako Co., Ltd.)
It is also possible to use an organic oxygen scavenger such as a freshness-retaining agent C (manufactured by Toppan Printing Co., Ltd.). The use form of the oxygen absorber is not particularly limited, but the oxygen absorber that is usually obtained as a commercial product has a powder form, and in the case of such a powder form, the necessary amount thereof is a breathable sachet. And the like, and this may be packaged with a plastic container containing the amino acid transfusion in a gas barrier packaging material described later and sealed in the packaging material.
【００２２】本発明アミノ酸輸液製剤における上記脱酸
素剤とアミノ酸輸液収容プラスチック容器との、ガスバ
リヤー性包材中への封入は、常法に従うことができ、特
に空間部を窒素ガス置換包装するのがより好ましい。Encapsulation of the oxygen scavenger and the amino acid transfusion-containing plastic container in the amino acid transfusion preparation of the present invention into a gas barrier packaging material can be carried out in accordance with a conventional method, and in particular, the space is subjected to nitrogen gas substitution packaging. Is more preferable.
【００２３】上記において用いられるガスバリヤー性包
材としては、酸素透過量が約０．１ｍｌ／ｍ2 ・hr・at
m 以下のバリヤー性を有するフィルムが好適である。そ
の具体例としては、例えばエチレン・ビニルアルコール
共重合体樹脂、塩化ビニリデン樹脂、ポリアクリロニト
リル、ポリビニルアルコール、ナイロン樹脂、ポリエス
テル等のガスバリヤー素材を少なくとも１種含む多層フ
ィルム、シリカ蒸着フィルム、アルミ蒸着フィルム及び
之等を複合した高分子フィルム等を例示できる。The gas barrier packaging material used in the above has an oxygen transmission rate of about 0.1 ml / m 2 · hr · at.
A film having a barrier property of m or less is suitable. Specific examples thereof include a multilayer film containing at least one gas barrier material such as ethylene / vinyl alcohol copolymer resin, vinylidene chloride resin, polyacrylonitrile, polyvinyl alcohol, nylon resin, polyester, silica vapor deposition film, aluminum vapor deposition film. A polymer film or the like, which is a composite of the above, can be exemplified.
【００２４】かくして、本発明アミノ酸輸液製剤を収得
できる。このものは亜硫酸塩や重亜硫酸塩等の安定化剤
の配合による気管支痙攣やアナフィラキシーショック等
の副作用のおそれを完全に回避して、しかもシステイ
ン、システイン塩酸塩及び之等の誘導体を含有しないこ
とにより、加熱滅菌時や保存時における硫化水素の発生
もなく、これに伴われる着色や悪臭発生等の不利もな
く、またトリプトファンの酸化による着色や不溶性微粒
子の発生も認められず、優れた保存安定性を有してい
る。Thus, the amino acid infusion preparation of the present invention can be obtained. This product completely avoids the risk of side effects such as bronchospasm and anaphylactic shock due to the addition of stabilizers such as sulfite and bisulfite, and does not contain cysteine, cysteine hydrochloride, and other derivatives. Excellent storage stability, no generation of hydrogen sulfide during heat sterilization or storage, no disadvantages such as coloring and bad odor associated with it, no coloring due to oxidation of tryptophan and generation of insoluble fine particles have.
【００２５】[0025]
【実施例】以下、本発明を更に詳しく説明するため実施
例を挙げる。EXAMPLES Examples will be given below to explain the present invention in more detail.
【００２６】[0026]
【実施例１】下記表１に示した組成のアミノ酸原料を注
射用水に溶解し、氷酢酸でｐＨを６．０に調整した後、
全量を１０リットルとした液を、０．２μｍのメンブラ
ンフィルターで濾過し、その２００ｍｌを窒素雰囲気下
でポリプロピレン製バッグ（大塚製薬工場社製）に充填
密封し、高圧蒸気滅菌した。Example 1 Amino acid raw materials having the compositions shown in Table 1 below were dissolved in water for injection, and the pH was adjusted to 6.0 with glacial acetic acid.
A liquid having a total volume of 10 liters was filtered through a 0.2 μm membrane filter, and 200 ml thereof was filled and sealed in a polypropylene bag (manufactured by Otsuka Pharmaceutical Factory Co., Ltd.) under a nitrogen atmosphere and sterilized under high pressure steam.
【００２７】このアミノ酸輸液入り容器を、脱酸素剤
（「エージレス」、三菱瓦斯化学社製）と共に、ガスバ
リヤー性フィルム（「ボブロン」、日本合成化学社製）
で二次包装して、本発明アミノ酸輸液製剤を調製した。A gas barrier film (“Bovlon”, manufactured by Nippon Synthetic Chemical Co., Ltd.) was used together with an oxygen scavenger (“Ageless” manufactured by Mitsubishi Gas Chemical Co., Inc.) in a container containing this amino acid infusion solution.
Then, the amino acid infusion preparation of the present invention was prepared by secondary packaging.
【００２８】[0028]
【実施例２】表１に示す組成のアミノ酸原料（ｐＨを氷
酢酸で６．３に調整）を用い、これをポリプロピレン製
バッグ（大塚製薬工場社製）に充填する以外は、実施例
１と同様にして、本発明アミノ酸輸液製剤を調製した。Example 2 Example 1 was repeated except that the amino acid raw material having the composition shown in Table 1 (pH adjusted to 6.3 with glacial acetic acid) was filled in a polypropylene bag (Otsuka Pharmaceutical Factory). Similarly, the amino acid infusion preparation of the present invention was prepared.
【００２９】[0029]
【実施例３】表１に示す組成のアミノ酸原料（ｐＨを氷
酢酸で７．３に調整）を用い、これを３層のポリエチレ
ン製バッグ（大塚製薬工場社製）に充填する以外は、実
施例１と同様にして、本発明アミノ酸輸液製剤を調製し
た。Example 3 Amino acid raw material having the composition shown in Table 1 (pH adjusted to 7.3 with glacial acetic acid) was used, except that a polyethylene bag of three layers (manufactured by Otsuka Pharmaceutical Factory Co., Ltd.) was filled. In the same manner as in Example 1, the amino acid infusion preparation of the present invention was prepared.
【００３０】[0030]
【実施例４】表１に示す組成のアミノ酸原料（ｐＨを氷
酢酸で５．９に調整）を用い、これをポリエチレン製バ
ッグ（大塚製薬工場社製）に充填する以外は、実施例１
と同様にして、本発明アミノ酸輸液製剤を調製した。Example 4 Example 1 was repeated except that the amino acid raw material having the composition shown in Table 1 (pH was adjusted to 5.9 with glacial acetic acid) was filled in a polyethylene bag (Otsuka Pharmaceutical Factory).
The amino acid infusion preparation of the present invention was prepared in the same manner as in.
【００３１】[0031]
【実施例５】表１に示す組成のアミノ酸原料（ｐＨを氷
酢酸で５．９に調整）を用い、これをポリプロピレン製
ボトル（大塚製薬工場社製）に充填する以外は、実施例
１と同様にして、本発明アミノ酸輸液製剤を調製した。Example 5 Example 1 was repeated except that an amino acid raw material having the composition shown in Table 1 (pH adjusted to 5.9 with glacial acetic acid) was filled in a polypropylene bottle (Otsuka Pharmaceutical Factory). Similarly, the amino acid infusion preparation of the present invention was prepared.
【００３２】[0032]
【実施例６】表１に示す組成のアミノ酸原料（ｐＨを氷
酢酸で６．０に調整）を用い、これをポリプロピレン製
ボトル（大塚製薬工場社製）に充填する以外は、実施例
１と同様にして、本発明アミノ酸輸液製剤を調製した。Example 6 Example 1 was repeated except that an amino acid raw material having the composition shown in Table 1 (pH adjusted to 6.0 with glacial acetic acid) was filled in a polypropylene bottle (Otsuka Pharmaceutical Factory). Similarly, the amino acid infusion preparation of the present invention was prepared.
【００３３】[0033]
【比較例１】実施例１と同一処方のアミノ酸輸液をバイ
アル瓶に充填した後、加熱滅菌して、比較アミノ酸輸液
製剤を調製した。Comparative Example 1 Amino acid infusion solution having the same formulation as in Example 1 was filled in a vial and sterilized by heating to prepare a comparative amino acid infusion formulation.
【００３４】[0034]
【表１】 [Table 1]
【００３５】[0035]
【試験例１】上記各実施例及び比較例で調製した本発明
アミノ酸輸液製剤及び比較アミノ酸輸液製剤のそれぞれ
につき、それらの加熱滅菌後の光透過の程度を肉眼観察
すると共に、英国薬局方（ＢＰ）１９８８年による不溶
性微粒子試験（コールターマチルサイザー (COULTER EL
ECTRONICS)社製を使用）及び日本薬局方（ＪＰ）第１２
改正による不溶性微粒子試験に供した。Test Example 1 For each of the amino acid infusion preparation of the present invention and the comparative amino acid infusion preparation prepared in the above Examples and Comparative Examples, the degree of light transmission after heat sterilization was visually observed, and the British Pharmacopoeia (BP) was used. ) Insoluble fine particle test according to 1988 (COULTER EL
Made by ECTRONICS) and Japanese Pharmacopoeia (JP) No. 12
It was subjected to the insoluble fine particle test according to the revision.
【００３６】得られた結果を表２に示す。The results obtained are shown in Table 2.
【００３７】[0037]
【表２】 [Table 2]
【００３８】表２より、本発明アミノ酸輸液製剤は、い
ずれの試験結果も優れたものであり、注射剤として適合
する品質を有することが明らかであったが、比較アミノ
酸輸液製剤は、不溶性微粒子試験において不適であり、
外観的にも注射剤としての利用には好ましくないもので
あった。From Table 2, it was clear that the amino acid infusion preparation of the present invention was excellent in all the test results and had a quality suitable as an injection, but the comparative amino acid infusion preparation was tested in the insoluble fine particle test. Is unsuitable for
The appearance was not preferable for use as an injection.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.6 識別記号 庁内整理番号 ＦＩ 技術表示箇所 //(Ａ６１Ｋ 31/405 31:195） ─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. 6 Identification number Office reference number FI technical display area // (A61K 31/405 31: 195)
Claims (1)
塩並びにシステイン、システイン塩酸塩及び之等の誘導
体を含有せず、トリプトファン又はその誘導体を必須成
分として含有し且つ遊離アミノ酸換算で総アミノ酸含量
が少なくとも４重量％であるアミノ酸輸液がプラスチッ
ク容器に充填され、該容器が脱酸素剤と共にガスバリヤ
ー性包材により封入されていることを特徴とするプラス
チック容器入りアミノ酸輸液製剤。1. A total amino acid content of tryptophan or a derivative thereof as an essential component, which does not contain sulfite or bisulfite as an antioxidant and derivatives of cysteine, cysteine hydrochloride, and the like as an essential component. Amino acid infusion preparation in a plastic container, characterized in that an amino acid infusion solution containing at least 4% by weight is filled in a plastic container, and the container is enclosed together with a deoxidizer by a gas barrier packaging material.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5233047A JPH0789856A (en) | 1993-09-20 | 1993-09-20 | Amino acid transfusion preparation packed in plastic container |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5233047A JPH0789856A (en) | 1993-09-20 | 1993-09-20 | Amino acid transfusion preparation packed in plastic container |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH0789856A true JPH0789856A (en) | 1995-04-04 |
Family
ID=16948971
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP5233047A Pending JPH0789856A (en) | 1993-09-20 | 1993-09-20 | Amino acid transfusion preparation packed in plastic container |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0789856A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006136490A (en) * | 2004-11-11 | 2006-06-01 | Terumo Corp | Ritodrine hydrochloride injection preparation |
| JP2014513543A (en) * | 2011-05-13 | 2014-06-05 | バイオジェン・アイデック・エムエイ・インコーポレイテッド | Methods for preventing and removing trisulfide bonds |
| CN106727523A (en) * | 2016-12-02 | 2017-05-31 | 北京哈三联科技有限责任公司 | A kind of preparation method of 18 Amino Acid Compound Injections without antioxidant and pH adjusting agent and products thereof |
| US10308706B2 (en) | 2009-10-02 | 2019-06-04 | Biogen Ma Inc. | Methods of preventing and removing trisulfide bonds |
-
1993
- 1993-09-20 JP JP5233047A patent/JPH0789856A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006136490A (en) * | 2004-11-11 | 2006-06-01 | Terumo Corp | Ritodrine hydrochloride injection preparation |
| JP4598484B2 (en) * | 2004-11-11 | 2010-12-15 | テルモ株式会社 | Ritodrine hydrochloride injection solution |
| US10308706B2 (en) | 2009-10-02 | 2019-06-04 | Biogen Ma Inc. | Methods of preventing and removing trisulfide bonds |
| JP2014513543A (en) * | 2011-05-13 | 2014-06-05 | バイオジェン・アイデック・エムエイ・インコーポレイテッド | Methods for preventing and removing trisulfide bonds |
| US9562252B2 (en) | 2011-05-13 | 2017-02-07 | Biogen Ma Inc. | Methods of preventing and removing trisulfide bonds |
| US9790533B2 (en) | 2011-05-13 | 2017-10-17 | Biogen Ma Inc. | Methods of preventing and removing trisulfide bonds |
| US10590454B2 (en) | 2011-05-13 | 2020-03-17 | Biogen Ma Inc. | Methods of preventing and removing trisulfide bonds |
| CN106727523A (en) * | 2016-12-02 | 2017-05-31 | 北京哈三联科技有限责任公司 | A kind of preparation method of 18 Amino Acid Compound Injections without antioxidant and pH adjusting agent and products thereof |
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