JPH07178151A - Nutrition transfusion formulation in 2-room container - Google Patents
Nutrition transfusion formulation in 2-room containerInfo
- Publication number
- JPH07178151A JPH07178151A JP6239857A JP23985794A JPH07178151A JP H07178151 A JPH07178151 A JP H07178151A JP 6239857 A JP6239857 A JP 6239857A JP 23985794 A JP23985794 A JP 23985794A JP H07178151 A JPH07178151 A JP H07178151A
- Authority
- JP
- Japan
- Prior art keywords
- chamber
- infusion
- amino acid
- sugar
- room
- 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.)
- Pending
Links
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- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 3
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- 235000000193 zinc lactate Nutrition 0.000 description 1
- 229940050168 zinc lactate Drugs 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 229960001763 zinc sulfate Drugs 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 0.000 description 1
- 239000004711 α-olefin Substances 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
- B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
- B65D81/00—Containers, packaging elements, or packages, for contents presenting particular transport or storage problems, or adapted to be used for non-packaging purposes after removal of contents
- B65D81/32—Containers, packaging elements, or packages, for contents presenting particular transport or storage problems, or adapted to be used for non-packaging purposes after removal of contents for packaging two or more different materials which must be maintained separate prior to use in admixture
- B65D81/3261—Flexible containers having several compartments
- B65D81/3266—Flexible containers having several compartments separated by a common rupturable seal, a clip or other removable fastening device
Landscapes
- Engineering & Computer Science (AREA)
- Mechanical Engineering (AREA)
- Package Specialized In Special Use (AREA)
- Non-Alcoholic Beverages (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
Abstract
Description
【０００１】[0001]
【産業上の利用分野】本発明は２室容器入り栄養輸液製
剤、より詳しくは隔離手段により２つの個室が形成され
たプラスチック製２室容器の第１室に特定の乳化剤を用
いた脂肪乳剤とアミノ酸とを収容し且つ第２室に糖と電
解質とを収容した上記栄養輸液製剤に関する。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a nutritional infusion preparation in a two-chamber container, and more specifically, a fat emulsion using a specific emulsifier in the first chamber of a plastic two-chamber container having two individual chambers formed by a separating means. The present invention relates to the above-mentioned nutritional infusion preparation containing an amino acid and a sugar and an electrolyte in the second chamber.
【０００２】[0002]
【従来技術とその課題】従来から術前、術後の栄養補給
や経口的に栄養摂取が不可能か困難な患者には、例えば
糖輸液、アミノ酸輸液、脂肪乳剤、電解質輸液等の各種
栄養輸液が適宜混合された後、経静脈的に投与されてい
る。しかしながら、之等輸液製剤の混合には繁雑な操作
が必要であり、しかも混合時には雑菌汚染等の問題が生
じることは避けられない。このような問題点より、上記
各種の輸液を事前に混合した混合輸液製剤の研究開発が
進められているが、上記各種輸液は、その組合わせによ
って以下に示すような弊害が認められ、いずれにしても
栄養補給のために必要な輸液を全て同時に混合し且つこ
れを加熱滅菌してなる製剤の調製は不可能な現状にあ
る。2. Description of the Related Art Conventionally, various nutritional infusions such as sugar infusion, amino acid infusion, fat emulsion, electrolyte infusion, etc. are used for patients who have been unable or unable to take nutritional supplementation orally before or after surgery. Are mixed appropriately and then administered intravenously. However, a complicated operation is required to mix the infusion preparations, and it is unavoidable that problems such as contamination of various bacteria occur during mixing. Due to such problems, research and development of mixed infusion preparations in which the above various infusions are mixed in advance have been advanced, but the above various infusions have the following adverse effects due to their combination, and in any case, However, it is not possible at present to prepare a preparation in which all infusion solutions necessary for nutritional supplementation are simultaneously mixed and heat-sterilized.
【０００３】 糖輸液とアミノ酸輸液とを混合して加
熱滅菌すれば、メイラード反応により著しい着色が生
じ、また該反応による成分の損失が起こる。When a sugar infusion solution and an amino acid infusion solution are mixed and sterilized by heating, remarkable coloration occurs due to the Maillard reaction and loss of components due to the reaction occurs.
【０００４】 脂肪乳剤と電解質輸液とを混合すると
乳化粒子の粗大化、相分離（クリーミング）が起こりや
すい。特に電解質輸液にカルシウム、マグネシウム等の
２価の陽イオンを含む場合、乳化粒子の凝集・合一が起
こり、乳化破壊に至る。When a fat emulsion and an electrolyte infusion solution are mixed, coarsening of emulsified particles and phase separation (creaming) easily occur. In particular, when the electrolyte infusion contains divalent cations such as calcium and magnesium, the emulsified particles aggregate and coalesce, resulting in emulsion destruction.
【０００５】 脂肪乳剤とアミノ酸輸液とを混合して
加熱滅菌すると、上記と同様に乳化破壊が起こる。特
に、アミノ酸輸液にＬ−アルギニン、Ｌ−リジン、Ｌ−
アスパラギン酸、Ｌ−グルタミン酸等を含む場合、この
乳化破壊は著しく促進される。When a fat emulsion and an amino acid infusion solution are mixed and sterilized by heating, emulsion destruction occurs in the same manner as above. In particular, amino acid infusions include L-arginine, L-lysine, L-
When aspartic acid, L-glutamic acid, etc. are contained, this emulsion destruction is significantly promoted.
【０００６】最近、上記点より、各種の栄養輸液成分を
２つ又はそれ以上の組合わせに適宜振り分け、用時に之
等を混合可能な２室以上の室に収容する技術及びそのた
めの容器が提案、開発されている。その例としては、例
えば（１）アミノ酸輸液、脂肪乳剤、糖電解質輸液を３
つの室に振り分けて収容する方法（特開昭６３−３１７
４８１号公報参照）、（２）糖と脂肪乳剤を含む輸液を
第１室に収容し、第２室にアミノ酸と電解質を含む輸液
を収容する容器（特開平５−３１１５１号公報参照）等
がある。In view of the above points, recently, there has been proposed a technique for appropriately distributing various nutritional infusion components into a combination of two or more and storing them in two or more chambers that can be mixed at the time of use, and a container therefor. Is being developed. Examples include (1) amino acid infusion, fat emulsion, glycoelectrolyte infusion
A method of distributing and accommodating two rooms (Japanese Patent Laid-Open No. 63-317)
(See Japanese Patent Application Laid-Open No. 5-31151), (2) A container (2) containing an infusion solution containing sugar and a fat emulsion in the first chamber, and an infusion solution containing an amino acid and an electrolyte in the second chamber (see JP-A-5-31151). is there.
【０００７】しかしながら、上記（１）の方法では、用
時、３室に収容した脂肪乳剤、糖電解質液輸液及びアミ
ノ酸輸液を均一に混合するための手間がかかる。また、
之等各液を混合すると、短時間で乳化粒子の粗大化、相
分離（クリーミング）が起こりやすい等の不利がある。However, in the above method (1), it takes time and effort to uniformly mix the fat emulsion, sugar electrolyte solution infusion solution and amino acid infusion solution housed in the three chambers during use. Also,
Mixing these liquids has disadvantages such as coarsening of emulsified particles and easy phase separation (creaming) in a short time.
【０００８】上記（２）では、糖と脂肪乳剤を含む輸液
を滅菌すると、それぞれの分解物によりｐＨが低下し、
このｐＨ低下を押さえるために緩衝剤が必要となるが、
リン酸等の緩衝剤は乳化を破壊するため使用できない。
また、該公開公報に示されたＬ−ヒスチジンの使用で
は、これが糖と反応してメラノイジンを生成する不利が
ある。更にこの技術では脂肪乳剤の安定化のために高い
ｐＨが設定されるが、かかる高ｐＨでは糖の分解が起こ
る弊害があり、その防止のために安定化剤の添加を要す
る不利もある。In the above (2), when an infusion solution containing sugar and a fat emulsion is sterilized, the pH is lowered by each decomposed product,
A buffer is required to suppress this pH drop,
Buffering agents such as phosphoric acid cannot be used as they destroy the emulsification.
Further, the use of L-histidine shown in the publication has a disadvantage that it reacts with sugar to produce melanoidin. Further, in this technique, a high pH is set in order to stabilize the fat emulsion, but at such a high pH, there is an adverse effect that sugar decomposition occurs, and there is also a disadvantage that a stabilizer must be added to prevent this.
【０００９】以上のように、従来の２室又はそれ以上の
室を設けた容器を利用する技術でも、尚改善されるべき
各種の弊害があり、現在満足できるものは開発されてい
ない現状にある。As described above, even the conventional technique utilizing a container having two or more chambers has various harmful effects to be improved, and a satisfactory one is not currently developed. .
【００１０】従って、本発明の目的は、従来技術に見ら
れる各種の弊害を全て解消して、用時簡単な操作で無菌
的に且つ容易に混合でき、加熱滅菌しても乳化破壊が起
こらず、均一で経時的に安定な所望の乳液を提供可能な
新しい製剤を提供する点にある。Therefore, the object of the present invention is to eliminate all of the various disadvantages found in the prior art, to enable aseptic and easy mixing by a simple operation at the time of use, and to avoid emulsion destruction even by heat sterilization. The point is to provide a new preparation capable of providing a desired emulsion that is uniform and stable over time.
【００１１】本発明者らは上記目的より鋭意研究を重ね
た結果、乳化剤としてホスファチジルグリセロールを用
いた脂肪乳剤及びアミノ酸を含む輸液を第１室に収容
し、第２室に糖及び電解質を含む輸液を収容する時に
は、上記目的に合致する２室容器入り栄養輸液製剤が提
供できることを見出しここに本発明を完成するに至っ
た。As a result of intensive studies conducted by the present inventors for the above purpose, an infusion solution containing a fat emulsion and an amino acid using phosphatidylglycerol as an emulsifier is contained in the first chamber, and an infusion solution containing sugar and electrolyte is contained in the second chamber. The present invention has been completed here by discovering that a nutritional infusion preparation can be provided in a two-chamber container that accommodates the above-mentioned purpose when storing the above.
【００１２】[0012]
【課題を解決するための手段】本発明によれば、隔離手
段により２つの個室が形成されたプラスチック製２室容
器の第１室に乳化剤としてホスファチジルグリセロール
を用いた脂肪乳剤及びアミノ酸を含む輸液を収容し且つ
上記容器の第２室に糖及び電解質を含む輸液を収容した
ことを特徴とする２室容器入り栄養輸液製剤が提供され
る。According to the present invention, an infusion solution containing an amino acid and a fat emulsion using phosphatidylglycerol as an emulsifier is provided in the first chamber of a plastic two-chamber container in which two individual chambers are formed by an isolation means. There is provided a nutritional infusion preparation in a two-chamber container, which is contained and contains an infusion solution containing sugar and an electrolyte in the second chamber of the container.
【００１３】殊に、本発明によれば、（１）第１室に収
容されている輸液が油脂０．５〜３０ｗ／ｖ％、乳化剤
０．０１５〜１５ｗ／ｖ％及び遊離アミノ酸総量１〜１
５ｗ／ｖ％を含有するものである上記製剤、（２）第２
室に収容されている輸液が糖５〜６０ｗ／ｖ％と共に、
電解質としてナトリウム０〜２５０ｍＥｑ／ｌ、カリウ
ム０〜２００ｍＥｑ／ｌ、カルシウム０〜５０ｍＥｑ／
ｌ、マグネシウム０〜５０ｍＥｑ／ｌ、塩素０〜２５０
ｍＥｑ／ｌ、リン０〜６０ｍｍｏｌ／ｌ及び亜鉛０〜１
００μｍｏｌ／ｌを含有するものである上記製剤、
（３）電解質成分のうち、ナトリウム塩及び／又はカリ
ウム塩の一部又は全部が第１室に収容されている上記製
剤、及び（４）第１室及び第２室に収容されている輸液
が、混合時に油脂、糖、アミノ酸（遊離アミノ酸換算と
して）及び電解質として前記表１記載の組成範囲を有す
るものとなる上記製剤が提供される。In particular, according to the present invention, (1) the infusion solution contained in the first chamber contains 0.5 to 30 w / v% of oil and fat, 0.015 to 15 w / v% of emulsifier, and 1 to 1 total amount of free amino acids. 1
The above-mentioned formulation containing 5 w / v%, (2) second
The infusion solution contained in the chamber is 5-60 w / v% sugar,
As electrolyte, sodium 0-250 mEq / l, potassium 0-200 mEq / l, calcium 0-50 mEq /
1, magnesium 0 to 50 mEq / l, chlorine 0 to 250
mEq / l, phosphorus 0-60 mmol / l and zinc 0-1
The above formulation containing 00 μmol / l,
(3) Among the electrolyte components, the above-mentioned preparation in which a part or all of sodium salt and / or potassium salt is contained in the first chamber, and (4) the infusion solution contained in the first chamber and the second chamber The above-mentioned preparation is provided which, when mixed, has the composition range shown in the above Table 1 as fats and oils, sugars, amino acids (as free amino acid equivalent) and electrolytes.
【００１４】本発明製剤は、上記構成としたことに基づ
いて、用時無菌的且つ容易に混合でき、第１室に収容さ
れた脂肪乳剤及びアミノ酸を含む輸液は、乳化粒子の粗
大化、相分離（クリーミング）が起こり難く、均一で経
時的に安定な特徴を有していると共に、加熱滅菌しても
乳化破壊が起こらない特徴を有している。Based on the above-mentioned constitution, the preparation of the present invention can be mixed aseptically and easily at the time of use, and the infusion solution containing the fat emulsion and the amino acid housed in the first chamber becomes coarse and the phase of the emulsified particles increases. It has a characteristic that separation (creaming) is hard to occur, is uniform and stable over time, and has a characteristic that emulsion destruction does not occur even if it is sterilized by heating.
【００１５】以下、本発明製剤の調製方法につき詳述す
れば、まず本発明製剤において第１室に収容する乳化剤
としてホスファチジルグリセロールを用いた脂肪乳剤及
びアミノ酸を含む輸液（以下、「アミノ酸加脂肪乳剤」
という）は、一般的方法に従い油脂を上記特定乳化剤を
用いて乳化分散させた水中油型乳剤とアミノ酸水溶液と
を混合することにより好適に調製される。The method for preparing the preparation of the present invention will be described in detail below. First, in the preparation of the present invention, a fat emulsion using phosphatidylglycerol as an emulsifying agent to be stored in the first chamber and an infusion solution containing an amino acid (hereinafter, referred to as “amino acid-added fat emulsion”). "
Is preferably prepared by mixing an oil-in-water emulsion in which fats and oils are emulsified and dispersed using the above-mentioned specific emulsifier and an amino acid aqueous solution according to a general method.
【００１６】本アミノ酸加脂肪乳剤を構成するアミノ酸
は、従来より医療分野で栄養補給を主目的として利用さ
れてきている各種のアミノ酸製剤と同様の組成のもので
よい。その具体例としては、必須アミノ酸であるＬ−イ
ソロイシン、Ｌ−ロイシン、Ｌ−リジン、Ｌ−メチオニ
ン、Ｌ−フェニルアラニン、Ｌ−トレオニン、Ｌ−トリ
プトファン及びＬ−バリンの８種を含有し、之等に更に
Ｌ−アルギニン、Ｌ−ヒスチジン、アミノ酢酸、Ｌ−ア
ラニン、Ｌ−アスパラギン酸、Ｌ−システイン、Ｌ−グ
ルタミン酸、Ｌ−プロリン、Ｌ−セリン、Ｌ−チロジン
等の準必須アミノ酸及び非必須アミノ酸から選択される
少なくとも１種を配合したものを例示できる。特に本発
明では上記アミノ酸として、Ｌ−リジン、Ｌ−アルギニ
ン等の塩基性アミノ酸を配合した栄養学的にバランスの
とれたものを用い得、しかもその配合によっても得られ
るアミノ酸加脂肪乳剤は乳化粒子の粗大化、相分離（ク
リーミング）等が起こらない特徴がある。之等のアミノ
酸は、通常総遊離アミノ酸濃度が１〜１５ｗ／ｖ％程
度、好ましくは２〜１３ｗ／ｖ％程度、より好ましくは
３〜１０ｗ／ｖ％程度となる範囲で用いられるのが適当
である。The amino acids constituting the present amino acid fat emulsion may have the same composition as various amino acid preparations which have been conventionally used mainly for nutritional supplementation in the medical field. Specific examples thereof include eight kinds of essential amino acids L-isoleucine, L-leucine, L-lysine, L-methionine, L-phenylalanine, L-threonine, L-tryptophan and L-valine. Furthermore, semi-essential amino acids and non-essential amino acids such as L-arginine, L-histidine, aminoacetic acid, L-alanine, L-aspartic acid, L-cysteine, L-glutamic acid, L-proline, L-serine and L-tyrosine. Examples thereof include a mixture of at least one selected from Particularly in the present invention, as the above-mentioned amino acid, a nutritionally balanced one containing a basic amino acid such as L-lysine and L-arginine can be used, and the amino acid fat emulsion obtained by the addition is also an emulsion particle. The feature is that coarsening and phase separation (creaming) do not occur. It is suitable that these amino acids are usually used in a range where the total free amino acid concentration is about 1 to 15 w / v%, preferably about 2 to 13 w / v%, more preferably about 3 to 10 w / v%. is there.
【００１７】上記アミノ酸加脂肪乳剤を構成するアミノ
酸は、純粋結晶状アミノ酸であるのが好ましく、之等は
通常遊離アミノ酸形態で用いられるが、特に遊離形態で
ある必要はなく、水溶性の各種形態、例えばナトリウム
塩、カリウム塩等の金属塩、塩酸塩、硫酸塩等の鉱酸
塩、酢酸塩、乳酸塩、リンゴ酸塩等の有機酸塩等の薬理
学的に許容される塩の形態でも、生体内で加水分解され
て遊離アミノ酸に変換されるエステルの形態でもよい。
更に上記アミノ酸はそれ等の一部又は全部を、例えばＮ
−アセチル−Ｌ−トリプトファン、Ｎ−アセチル−Ｌ−
システイン、Ｎ−アセチル−Ｌ−プロリン等のＮ−アシ
ル誘導体の形態としてもよく、また、例えばＬ−アルギ
ニン・Ｌ−グルタミン酸塩、Ｌ−リジン・Ｌ−アスパラ
ギン酸塩等や、Ｌ−チロジル−Ｌ−チロジン、Ｌ−アラ
ニル−Ｌ−グルタミン、Ｌ−アラニル−Ｌ−チロジン、
Ｌ−アルギニル−Ｌ−チロジン、Ｌ−チロジル−Ｌ−ア
ルギニン等の２種のアミノ酸の塩やペプチドの形態とす
ることもできる。The amino acids constituting the above-mentioned amino acid fat emulsion are preferably pure crystalline amino acids, and although they are usually used in the free amino acid form, they are not necessarily in the free form and various water-soluble forms are preferred. In the form of a pharmacologically acceptable salt such as a metal salt such as sodium salt and potassium salt, a mineral acid salt such as hydrochloride and sulfate, an organic acid salt such as acetate, lactate and malate. Alternatively, it may be in the form of an ester that is hydrolyzed in vivo and converted into a free amino acid.
Further, the above-mentioned amino acids include some or all of them, for example N
-Acetyl-L-tryptophan, N-acetyl-L-
It may be in the form of an N-acyl derivative such as cysteine or N-acetyl-L-proline, and may be in the form of, for example, L-arginine.L-glutamate, L-lysine.L-aspartate, or L-tyrosyl-L. -Tyrosine, L-alanyl-L-glutamine, L-alanyl-L-tyrosine,
It may also be in the form of a salt or peptide of two kinds of amino acids such as L-arginyl-L-tyrosine and L-tyrosyl-L-arginine.
【００１８】本アミノ酸加脂肪乳剤は、必要に応じて、
例えば、亜硫酸ナトリウム、亜硫酸水素ナトリウム、ピ
ロ亜硫酸ナトリウム、チオ硫酸ナトリウム等の安定化
剤、塩酸、酢酸、乳酸、リンゴ酸、クエン酸、水酸化ナ
トリウム、水酸化カリウム等のｐＨ調整剤、グリセリン
等を加えることもできる。This amino acid-added fat emulsion is, if necessary,
For example, stabilizers such as sodium sulfite, sodium hydrogen sulfite, sodium pyrosulfite, sodium thiosulfate, pH adjusting agents such as hydrochloric acid, acetic acid, lactic acid, malic acid, citric acid, sodium hydroxide, potassium hydroxide, glycerin, etc. It can also be added.
【００１９】また、油脂を特定乳化剤を用いて乳化分散
させた水中油型乳剤に用いられる油脂は、通常栄養補給
等を目的とした熱源（エネルギー源）として用いられて
いる各種のものでよく、例えば大豆油、綿実油、サフラ
ワー油、トウモロコシ油、ヤシ油、シソ油、エゴマ油、
アマニ油等の植物油やイワシ油、タラ肝油等の魚油等
の、必須脂肪酸源としての長鎖脂肪酸トリグリセリド
（ＬＣＴ）、及び易吸収性、易燃焼性、難蓄積性を特徴
とする、例えば商品名パナセート（日本油脂社製）、商
品名ＯＤＯ（日清製油社製）等の通常炭素数８〜１０の
トリグリセリドである中鎖脂肪酸トリグリセリド（ＭＣ
Ｔ）をその代表例として例示できる。更に上記油脂とし
ては、例えば２−リノレオイル−１，３−ジオクタノイ
ルグリセロール等の化学合成トリグリセリドも使用でき
る。之等は１種を単独で用いてもよく２種以上を併用す
ることもできる。上記油脂は、通常調製される水中油型
乳剤中に油脂濃度として０．５〜３０ｗ／ｖ％程度、好
ましくは０．５〜２０ｗ／ｖ％、より好ましくは０．５
〜１０ｗ／ｖ％となる範囲で配合されるのが好適であ
る。The oils and fats used in the oil-in-water emulsion in which the oils and fats are emulsified and dispersed by using a specific emulsifier may be various ones which are usually used as a heat source (energy source) for the purpose of supplementing nutrition, Soybean oil, cottonseed oil, safflower oil, corn oil, coconut oil, perilla oil, perilla oil,
A long-chain fatty acid triglyceride (LCT) as an essential fatty acid source such as vegetable oil such as linseed oil, sardine oil, fish oil such as cod liver oil, etc., and is characterized by easy absorption, easy burning, and poor accumulation, for example, trade name Medium chain fatty acid triglyceride (MC), which is usually a triglyceride having 8 to 10 carbon atoms, such as Panacet (manufactured by NOF CORPORATION) and trade name ODO (manufactured by Nisshin Oil Co., Ltd.)
T) can be illustrated as a representative example. Further, as the above-mentioned fats and oils, for example, chemically synthesized triglycerides such as 2-linoleoyl-1,3-dioctanoylglycerol can be used. These may be used alone or in combination of two or more. The above-mentioned fats and oils have a concentration of fats and oils of about 0.5 to 30 w / v%, preferably 0.5 to 20 w / v%, more preferably 0.5 in an oil-in-water emulsion that is usually prepared.
It is suitable to be blended in the range of 10 to 10 w / v%.
【００２０】上記油脂を乳化分散させるための特定乳化
剤としては、ホスファチジルグリセロールを用いること
が重要である。該ホスファチジルグリセロールとして
は、天然からの抽出物を使用することもでき、また別途
合成品を用いることもできる。本発明に利用される乳化
剤は、上記ホスファチジルグリセロールを主要成分とし
て、これと他の乳化剤とを併用したものであってもよい
が、その場合も、全乳化剤中に上記ホスファチジルグリ
セロールが好ましくは少なくとも５０ｗ／ｖ％、より好
ましくは６０ｗ／ｖ％以上含まれている必要がある。It is important to use phosphatidyl glycerol as a specific emulsifier for emulsifying and dispersing the above fats and oils. As the phosphatidylglycerol, an extract from nature can be used, or a synthetic product can be used separately. The emulsifier used in the present invention may be a combination of the above phosphatidylglycerol as a main component and another emulsifier, but in that case, the phosphatidylglycerol is preferably contained in the total amount of at least 50 w. / V%, more preferably 60 w / v% or more.
【００２１】上記ホスファチジルグリセロールと併用で
きる他の乳化剤としては、例えばホスファチジルポリグ
リセロール、ホスファチジルエチレングリコール、ホス
ファチジルポリエチレングリコール、ジホスファチジル
ポリエチレングリコール等の他のホスファチジル化多価
アルコール類や、大豆レシチン、卵黄レシチン、大豆水
添レシチン、卵黄水添レシチン、例えば商品名ＨＣＯ−
６０（日光ケミカルズ社製）等の非イオン性界面活性剤
等を例示できる。之等はその１種を単独で用いてもよく
２種以上を併用することもできる。Other emulsifiers that can be used in combination with the above phosphatidylglycerol include, for example, other phosphatidylated polyhydric alcohols such as phosphatidylpolyglycerol, phosphatidylethylene glycol, phosphatidylpolyethylene glycol, diphosphatidylpolyethylene glycol, soybean lecithin, egg yolk lecithin, Soybean hydrogenated lecithin, egg yolk hydrogenated lecithin, for example, trade name HCO-
Examples thereof include nonionic surfactants such as 60 (manufactured by Nikko Chemicals Co., Ltd.). These may be used alone or in combination of two or more.
【００２２】上記乳化剤の使用量は、油脂成分１０重量
部に対して０．１〜１０重量部程度、好ましくは０．３
〜５重量部程度、より好ましくは０．５〜３重量部程度
から選ばれるのがよく、これにより優れた乳化安定性を
有する微細な脂肪粒子を水中に均一に分散させた所望の
乳剤を調製できる。The amount of the emulsifier used is about 0.1 to 10 parts by weight, preferably 0.3, based on 10 parts by weight of the oil and fat component.
It is preferable to select from about 5 to 5 parts by weight, more preferably about 0.5 to 3 parts by weight, whereby a desired emulsion in which fine fat particles having excellent emulsion stability are uniformly dispersed in water is prepared. it can.
【００２３】上記水中油型乳剤の調製は、一般には注射
用水に乳化剤及び油脂を分散して粗乳化後、高圧乳化機
等を用いて精乳化することにより実施される。上記粗乳
化は、例えば、特殊機化工業社製Ｔ．Ｋ．ホモミクサー
等のホモミキサーを用いて、通常５０００ｒｐｍ以上で
５分間以上を要して実施できる。精乳化は、例えばマン
トンゴウリンホモジナイザー（ゴウリン社製）等の高圧
ホモジナイザー又は超音波ホモジナイザーを用いて実施
でき、高圧ホモジナイザーを用いる場合、一般には約２
００ｋｇ／ｃｍ2 以上の圧力条件下に、２〜５０回程
度、好ましくは５〜２０回程度の通過で実施することが
できる。之等の混合乳化操作は常温下に実施してもよい
が、若干の加温操作（通常約５５℃〜８０℃前後）を採
用して実施するのが好適である。かくして、本発明の第
１室に収容される所望のアミノ酸加脂肪乳剤を調製でき
る。The above-mentioned oil-in-water emulsion is generally prepared by dispersing an emulsifier and fats and oils in water for injection, followed by rough emulsification and then fine emulsification using a high-pressure emulsifying machine or the like. The above-mentioned rough emulsification is carried out, for example, by T.K. K. It can be carried out using a homomixer such as a homomixer, usually at 5000 rpm or more and for 5 minutes or more. The fine emulsification can be carried out using a high-pressure homogenizer such as Manton Goulin homogenizer (manufactured by Gorin Co.) or an ultrasonic homogenizer. When a high-pressure homogenizer is used, it is generally about 2
It can be carried out under a pressure condition of 00 kg / cm 2 or more by passing about 2 to 50 times, preferably about 5 to 20 times. The above-mentioned mixed emulsification operation may be carried out at room temperature, but it is preferable to carry out a slight heating operation (usually around 55 ° C to 80 ° C). Thus, the desired amino acid fat emulsion contained in the first chamber of the present invention can be prepared.
【００２４】本発明において、容器の第２室に収容され
る糖及び電解質を含む輸液（以下「糖加電解質液」とい
う）を構成する糖としては、従来よりこの種輸液に慣用
されている各種のものでよく、その代表例としては、還
元糖としてのブドウ糖、果糖、マルトース等や、キシリ
トール、ソルビトール等を例示できる。之等糖成分の輸
液への配合量は通常５〜６０ｗ／ｖ％程度、好ましくは
１０〜６０ｗ／ｖ％程度とすることができる。In the present invention, as the sugar constituting the infusion solution containing the sugar and the electrolyte (hereinafter referred to as "sugar-added electrolyte solution") contained in the second chamber of the container, various sugars conventionally used in this kind of infusion solution have been conventionally used. Glucose, fructose, maltose and the like as reducing sugars, xylitol, sorbitol and the like can be exemplified. The amount of the monosaccharide component to be added to the infusion solution is usually about 5 to 60 w / v%, preferably about 10 to 60 w / v%.
【００２５】また電解質としても、従来よりこの種輸液
に慣用されている各種の水溶性塩類を使用できる。その
具体例としては、例えば塩化ナトリウム、酢酸ナトリウ
ム、乳酸ナトリウム、硫酸ナトリウム、グリセロリン酸
ナトリウム、リン酸水素ナトリウム、リン酸二水素ナト
リウム等のナトリウム源；塩化カリウム、グリセロリン
酸カリウム、硫酸カリウム、酢酸カリウム、乳酸カリウ
ム、リン酸二水素カリウム、リン酸二カリウム等のカリ
ウム源；グルコン酸カルシウム、塩化カルシウム、グリ
セロリン酸カルシウム、乳酸カルシウム、パントテン酸
カルシウム、酢酸カルシウム等のカルシウム源；硫酸マ
グネシウム、塩化マグネシウム、グリセロリン酸マグネ
シウム、酢酸マグネシウム、乳酸マグネシウム等のマグ
ネシウム源；グリセロリン酸カリウム、グリセロリン酸
ナトリウム、グリセロリン酸マグネシウム、グリセロリ
ン酸カルシウム、リン酸水素ナトリウム、リン酸二水素
ナトリウム、リン酸二水素カリウム、リン酸二カリウム
等のリン源；硫酸亜鉛、塩化亜鉛、グルコン酸亜鉛、乳
酸亜鉛、酢酸亜鉛等の亜鉛源等をそれぞれ例示できる。As the electrolyte, various water-soluble salts conventionally used for this kind of infusion can be used. Specific examples thereof include sodium sources such as sodium chloride, sodium acetate, sodium lactate, sodium sulfate, sodium glycerophosphate, sodium hydrogenphosphate, sodium dihydrogenphosphate; potassium chloride, potassium glycerophosphate, potassium sulfate, potassium acetate. , Potassium sources such as potassium lactate, potassium dihydrogen phosphate, dipotassium phosphate; calcium sources such as calcium gluconate, calcium chloride, calcium glycerophosphate, calcium lactate, calcium pantothenate, calcium acetate; magnesium sulfate, magnesium chloride, glyceroline Magnesium sources such as magnesium acidate, magnesium acetate and magnesium lactate; potassium glycerophosphate, sodium glycerophosphate, magnesium glycerophosphate, calcium glycerophosphate , Phosphorus sources such as sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate, dipotassium phosphate; zinc sources such as zinc sulfate, zinc chloride, zinc gluconate, zinc lactate, zinc acetate, etc. it can.
【００２６】之等の配合量は、通常のそれらと同様でよ
く、これを投与される患者の要求量に応じて適宜決定で
きる。上記電解質の具体的配合量は、例えば以下の通り
とするのが好ましい。The compounding amount of these substances may be the same as the usual one, and can be appropriately determined according to the required amount of the patient to whom this is administered. The specific blending amount of the electrolyte is preferably, for example, as follows.
【００２７】ナトリウム：０〜２５０ｍＥｑ／ｌ カリウム：０〜２００ｍＥｑ／ｌ カルシウム：０〜５０ｍＥｑ／ｌ マグネシウム：０〜５０ｍＥｑ／ｌ 塩素：０〜２５０ｍＥｑ／ｌ リン：０〜６０ｍｍｏｌ／ｌ 亜鉛：０〜１００μｍｏｌ／ｌ 尚、上記電解質のうち、ナトリウム塩及び／又はカリウ
ム塩の一部又は全部は、第１室に収容することもでき
る。Sodium: 0 to 250 mEq / l Potassium: 0 to 200 mEq / l Calcium: 0 to 50 mEq / l Magnesium: 0 to 50 mEq / l Chlorine: 0 to 250 mEq / l Phosphorus: 0 to 60 mmol / l Zinc: 0 to 100 μmol / L Incidentally, a part or all of the sodium salt and / or the potassium salt in the above-mentioned electrolyte may be housed in the first chamber.
【００２８】上記のような場合や、上記第１室に収容さ
れるアミノ酸のいくつかがナトリウム塩やカリウム塩の
形態で配合される場合は、第２室に上記ナトリウムやカ
リウムを配合しなくてもよい場合がある。In the above case or when some of the amino acids contained in the first chamber are mixed in the form of sodium salt or potassium salt, the sodium or potassium is not mixed in the second chamber. May be good.
【００２９】本糖加電解質液は、通常の糖加電解質液と
同様にして、必要に応じて、例えば、亜硫酸ナトリウ
ム、亜硫酸水素ナトリウム、ピロ亜硫酸ナトリウム、チ
オ硫酸ナトリウム等の安定化剤、塩酸、酢酸、乳酸、リ
ンゴ酸、クエン酸、水酸化ナトリウム、水酸化カリウム
等のｐＨ調整剤等を加えることもできる。The sugar-added electrolyte solution of the present invention is, as in the case of a normal sugar-added electrolyte solution, if necessary, for example, a stabilizer such as sodium sulfite, sodium hydrogen sulfite, sodium pyrosulfite, sodium thiosulfate, hydrochloric acid, A pH adjusting agent such as acetic acid, lactic acid, malic acid, citric acid, sodium hydroxide or potassium hydroxide can also be added.
【００３０】本発明栄養輸液製剤における油脂、アミノ
酸、糖及び電解質の好ましい組成（混合後の組成）の例
は、前記表１に示した通りであり、より好ましくは下記
表２に示す通りである。Examples of preferable compositions (compositions after mixing) of oils and fats, amino acids, sugars and electrolytes in the nutritional infusion preparation of the present invention are as shown in Table 1 above, and more preferably as shown in Table 2 below. .
【００３１】[0031]
【表２】 [Table 2]
【００３２】但し、Ｌ−システインの一部又は全部はＬ
−シスチンで代替できる。However, part or all of L-cysteine is L
-Can be replaced by cystine.
【００３３】また、本発明の２室容器入り栄養輸液製剤
における、各室への各成分の充填、収容は、常法に従
い、例えば予め加熱滅菌された各液を各室に無菌的に行
なうこともできるが、より好ましくは各室にそれぞれの
輸液を、窒素ガス、ヘリウムガス等の不活性ガス雰囲気
下で収容後、施栓し、加熱滅菌するのが好ましい。上記
加熱滅菌操作は、例えば高圧蒸気滅菌、熱水浸漬滅菌、
シャワー滅菌等により行ない得、これは実質的に酸素を
含まない雰囲気下で行なわれるのが好ましい。Further, in the nutritional infusion preparation in a two-chamber container of the present invention, each component is filled and stored in each chamber according to a conventional method, for example, each liquid which has been previously heat-sterilized is aseptically applied to each chamber. However, it is more preferable to store the infusion solution in each chamber in an atmosphere of an inert gas such as nitrogen gas or helium gas, and then cap and sterilize by heating. The heat sterilization operation, for example, high-pressure steam sterilization, hot water immersion sterilization,
It may be carried out by shower sterilization or the like, which is preferably carried out in a substantially oxygen-free atmosphere.
【００３４】かくして本発明製剤を収得できる。これ
は、アミノ酸加脂肪乳剤において通常ｐＨ５．０〜８．
５程度、好ましくは５．５〜８．０程度、糖添加電解質
液においては通常ｐＨ３．５〜６．５程度、好ましくは
４．０〜５．５程度となるように調整され、製剤的に安
定であることは勿論のこと、アミノ酸加脂肪乳剤の乳化
安定性も非常に優れており、乳化粒子の粒度も小さく均
一で、長期間に亘って初期の乳剤形態を保持する優れた
安定性を有している。Thus, the preparation of the present invention can be obtained. This is usually pH 5.0 to 8 in an amino acid fat emulsion.
About 5, preferably about 5.5 to 8.0, and in the sugar-added electrolyte solution, the pH is usually adjusted to about 3.5 to 6.5, and preferably adjusted to about 4.0 to 5.5. Not only is it stable, but the emulsion stability of the amino acid fat emulsion is also very good, the particle size of the emulsion particles is small and uniform, and the excellent stability of maintaining the initial emulsion morphology for a long period of time is achieved. Have
【００３５】本発明製剤の投与量は、これを投与する患
者の状態に応じて適宜決定できるが、通常成人１人１日
当り約１０００〜２０００ｍｌ程度の量とさるのがよ
い。また本発明製剤は、その用時に必要に応じて、第１
室及び第２室のいずれか少なくとも１方に、他の配合
薬、例えば各種ビタミン類、微量元素（ミネラル）等を
任意に添加配合することもできる。該ビタミン類として
は、水溶性及び脂溶性を問わず各種のもの、例えばパル
ミチン酸レチノール、塩酸チアミン、リボフラビン、塩
酸ピリドキシン、シアノコバラミン、アスコルビン酸、
コレカシフェロール、酢酸トコフェロール、ニコチン酸
アミド、パントテン酸カルシウム、葉酸、ビオチン、フ
ィトナジオン等を例示できる。The dose of the preparation of the present invention can be appropriately determined depending on the condition of the patient to which it is administered, but it is usually about 1000 to 2000 ml per adult per day. In addition, the preparation of the present invention is
At least one of the chamber and the second chamber may be optionally mixed with other combination drugs, such as various vitamins and trace elements (minerals). As the vitamins, various ones regardless of water solubility and fat solubility, for example, retinol palmitate, thiamine hydrochloride, riboflavin, pyridoxine hydrochloride, cyanocobalamin, ascorbic acid,
Examples thereof include cholecasiferol, tocopherol acetate, nicotinamide, calcium pantothenate, folic acid, biotin, phytonadione and the like.
【００３６】尚、本発明製剤を収容すべき隔離手段によ
り２つの個室が形成されたプラスチック製２室容器自体
としては、公知の各種のものをいずれも利用できる。そ
の具体例としては、例えば連通部を剥離可能な弱シー
ル部（イージーピールシール）によって区画した２室容
器（特開平２−４６７１号公報、実開平５−５１３８号
公報等参照）、連通部をクリップで区画した２室容器
（特開昭６３−３０９２６３号公報等参照）、連通部
を開封可能な種々の連通手段により区画した２室容器
（特公昭６３−２０５５０号公報等参照）等を例示でき
る。上記に記載の２室容器の例を添付図面（図１）に
示す。As the plastic two-chamber container itself in which two individual chambers are formed by the isolation means for accommodating the preparation of the present invention, various known ones can be used. Specific examples thereof include, for example, a two-chamber container (see Japanese Patent Application Laid-Open No. 2-4671 and Japanese Utility Model Laid-Open No. 5-5138) in which a communication portion is divided by a peelable weak seal portion (easy peel seal) and a communication portion. Examples include a two-chamber container partitioned by clips (see JP-A-63-309263, etc.), a two-chamber container partitioned by various communication means capable of opening the communication part (see Japanese Patent Publication No. 63-20550, etc.), etc. it can. An example of the two-chamber container described above is shown in the attached drawing (FIG. 1).
【００３７】また、上記各室を形成する容器の材質（構
成プラスチックの種類）も、従来より医療用容器等に慣
用されている各種の樹脂と異ならない。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、ポリ塩化
ビニル、架橋されたエチレン酢酸ビニル共重合体、エチ
レンとα−オレフィンとの共重合体、之等各ポリマーの
ブレンド、之等各ポリマーの多層フィルム（積層フィル
ム）等のいずれであってもよい。The material (type of constituent plastic) of the container forming each chamber is not different from various resins conventionally used for medical containers and the like. Specific examples thereof include, for example, polyethylene, polypropylene, polyvinyl chloride, a cross-linked ethylene vinyl acetate copolymer, a copolymer of ethylene and α-olefin, a blend of each polymer, and a multilayer film of each polymer. It may be any of (laminated film) and the like.
【００３８】更に、本発明の２室容器入り製剤は、該容
器中に収容充填した輸液の変質、殊に酸素による変質を
確実に防止するために、より好ましくは該容器を脱酸素
剤と共にガスバリアー性の包装材で包装することがで
き、また、真空包装や不活性ガス充填包装等を行なうこ
ともできる。之等の包装方法はそれ自体公知の各種操作
に従うことができる。Furthermore, the two-chambered preparation of the present invention is more preferably a gas containing an oxygen scavenger, in order to reliably prevent the deterioration of the infusion solution contained and filled in the container, especially the deterioration due to oxygen. It can be packaged with a barrier packaging material, and vacuum packaging, inert gas filling packaging, and the like can also be performed. The packaging method of these can follow various operations known per se.
【００３９】上記包装に適したガスバリアー性を有する
包装材料としては、一般に汎用されている各種材質のフ
ィルム乃至シートを使用できる。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、ポリ塩化
ビニリデン、ポリアクリロニトリル、ポリビニルアルコ
ール、ナイロン、ポリエステル等及び之等の少なくとも
１種を含むシート乃至フィルムを例示できる。As the packaging material having a gas barrier property suitable for the above packaging, generally used films or sheets of various materials can be used. As a concrete example,
For example, a sheet or film containing at least one of ethylene / vinyl alcohol copolymer, polyvinylidene chloride, polyacrylonitrile, polyvinyl alcohol, nylon, polyester and the like can be exemplified.
【００４０】また上記包装剤により、本発明２室容器と
共に包装され得る脱酸素剤としても、従来公知の各種の
もの、例えば水酸化鉄、酸化鉄、炭化鉄等の鉄化合物を
有効成分とするものを利用できる。その代表的市販品と
しては、例えば「エージレス」（三菱瓦斯化学社製）、
「モジュラン」（日本化薬社製）、「セキュール」（日
本曹達社製）等を例示できる。之等脱酸素剤の利用の態
様は、これが輸液を収容充填したプラスチック容器と、
上記ガスバリアー性を有する包装材との空間部に存在す
る限り特に限定はないが、例えば粉末形態を有する脱酸
素剤では、その必要量を通気性のある小袋等に入れ、該
袋入り形態で上記空間部に存在させるのが好ましい。Also, as the oxygen scavenger which can be packaged together with the two-chamber container of the present invention by the above packaging agent, various conventionally known deoxidants, for example, iron compounds such as iron hydroxide, iron oxide and iron carbide are used as active ingredients. Stuff available. As a typical commercial product thereof, for example, "Ageless" (manufactured by Mitsubishi Gas Chemical Co., Inc.),
Examples thereof include "Modulan" (manufactured by Nippon Kayaku Co., Ltd.) and "Secur" (manufactured by Nippon Soda Co., Ltd.). The use of the oxygen scavenger is a plastic container filled with infusion solution.
It is not particularly limited as long as it exists in the space with the packaging material having the gas barrier property, but for example, in the case of an oxygen scavenger having a powder form, the necessary amount thereof is put in a breathable pouch or the like, and in the bag form. It is preferable to allow it to exist in the space.
【００４１】[0041]
【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.
【００４２】[0042]
【実施例１】 （１）アミノ酸加脂肪乳剤の調製 大豆油１００ｇ及びホスファチジルグリセロール１２ｇ
を注射用水に加えて粗乳化した後、水で全量を１０００
ｍｌとした。得られた粗乳化液を、マントンゴウリンホ
モジナイザー（ゴウリン社製、１５Ｍ−８ＴＡ型）を用
いて、５５０ｋｇ／ｃｍ2 の圧力下に１５回通過して精
乳化した。かくして得られた乳化液２００ｍｌに、下記
表３に示す組成のアミノ酸溶液４００ｍｌを加えてアミ
ノ酸加脂肪乳剤を得た。Example 1 (1) Preparation of Amino Acid Added Fat Emulsion 100 g of soybean oil and 12 g of phosphatidylglycerol
Is added to water for injection to roughly emulsify, then add 1000 to
ml. The obtained crude emulsion was passed through 15 times under a pressure of 550 kg / cm 2 using a Manton Goulin homogenizer (manufactured by Goulin Co., 15M-8TA type) to be finely emulsified. To 200 ml of the emulsion thus obtained, 400 ml of an amino acid solution having the composition shown in Table 3 below was added to obtain an amino acid fat emulsion.
【００４３】[0043]
【表３】 [Table 3]
【００４４】（２）糖加電解質液の調製 約６０℃に加温した注射用水に下記表４に示すブドウ糖
及び電解質を所定濃度になるように添加溶解し、クエン
酸を用いてｐＨを４．９に調整して、糖加電解質液を得
た。(2) Preparation of Sugar-added Electrolyte Solution Glucose and electrolytes shown in Table 4 below were added and dissolved in water for injection heated to about 60 ° C. to a predetermined concentration, and the pH was adjusted to 4. with citric acid. It adjusted to 9 and the sugar addition electrolyte solution was obtained.
【００４５】[0045]
【表４】 [Table 4]
【００４６】（３）２室バッグへの充填 図１に示すイージーピールシールによって２室に区画さ
れた輸液バッグの第１室に、上記（１）で調製したアミ
ノ酸加脂肪乳剤４００ｍｌを、窒素ガス気流下に充填
し、施栓した。また第２室に、上記（２）で調製した糖
加電解質液６００ｍｌを封入した。(3) Filling in a two-chamber bag In the first chamber of the infusion bag divided into two chambers by the easy peel seal shown in FIG. 1, 400 ml of the amino acid fat emulsion prepared in (1) above was charged with nitrogen gas. It was filled under an air stream and stoppered. Further, 600 ml of the sugar-added electrolyte solution prepared in (2) above was enclosed in the second chamber.
【００４７】上記各液の収容後の容器を、高圧蒸気滅菌
（１０５℃、４０分間）して、本発明の２室容器入り栄
養輸液製剤を得た。The container after containing each of the above liquids was subjected to high-pressure steam sterilization (105 ° C., 40 minutes) to obtain the nutritional infusion preparation in a two-chamber container of the present invention.
【００４８】[0048]
【試験例１】 （１）安定性試験 上記実施例で調製した本発明の２室容器入り栄養輸液製
剤の輸液バッグのイージーピールシールを剥離し、各室
の輸液を混合して、アミノ酸、脂肪乳剤、糖及び電解質
を含有する輸液を調製した。[Test Example 1] (1) Stability test The easy peel seal of the infusion bag of the nutrition infusion preparation containing the two-chamber container of the present invention prepared in the above Examples was peeled off, and the infusion fluid of each room was mixed to prepare amino acid and fat. An infusion solution containing an emulsion, sugar and electrolyte was prepared.
【００４９】この輸液を室温で３日間保存し、経時的に
液の外観、乳化粒子の平均粒子径を調べた。得られた結
果を表５に示す。尚、上記外観は目視で判定し、平均粒
子径は、ＬＰＡ−３０００／３１００（大塚電子社製）
を用いて測定した。This infusion solution was stored at room temperature for 3 days, and the appearance of the solution and the average particle size of emulsified particles were examined with time. The results obtained are shown in Table 5. The appearance is visually determined, and the average particle size is LPA-3000 / 3100 (Otsuka Electronics Co., Ltd.).
Was measured using.
【００５０】[0050]
【表５】 [Table 5]
【００５１】表５より、本例により得られた輸液は、乳
化粒子の平均粒子径が小さく、また優れた保存安定性を
有するものであることが判った。From Table 5, it was found that the infusion solution obtained in this example had a small average particle size of emulsified particles and had excellent storage stability.
【００５２】[0052]
【実施例２】 （１）アミノ酸加脂肪乳剤の調製 大豆油１００ｇ及びホスファチジルグリセロール１２ｇ
を注射用水に加えて粗乳化した後、水で全量を１０００
ｍｌとした。得られた粗乳化液を、マントンゴウリンホ
モジナイザー（ゴウリン社製、１５Ｍ−８ＴＡ型）を用
いて、５５０ｋｇ／ｃｍ2 の圧力下に１５回通過して精
乳化した。かくして得られた乳化液４００ｍｌに、下記
表６に示す組成のカリウム塩を含むアミノ酸溶液４００
ｍｌを加えてアミノ酸加脂肪乳剤を得た。Example 2 (1) Preparation of Amino Acid Added Fat Emulsion 100 g of soybean oil and 12 g of phosphatidylglycerol
Is added to water for injection to roughly emulsify, then add 1000 to
ml. The obtained crude emulsion was passed through 15 times under a pressure of 550 kg / cm 2 using a Manton Goulin homogenizer (manufactured by Goulin Co., 15M-8TA type) to be finely emulsified. 400 ml of the emulsion thus obtained was added with an amino acid solution 400 containing a potassium salt having the composition shown in Table 6 below.
The amino acid-added fat emulsion was obtained by adding ml.
【００５３】[0053]
【表６】 [Table 6]
【００５４】（２）糖加電解質液の調製 約６０℃に加温した注射用水に下記表７に示すブドウ糖
及び電解質を所定濃度になるように添加溶解し、酢酸を
用いてｐＨを４．９に調整して、糖加電解質液を得た。(2) Preparation of sugar-added electrolyte solution Glucose and electrolytes shown in Table 7 below were added and dissolved in water for injection heated to about 60 ° C. to a predetermined concentration, and the pH was adjusted to 4.9 with acetic acid. Was adjusted to obtain a sugar-added electrolyte solution.
【００５５】[0055]
【表７】 [Table 7]
【００５６】（３）２室バッグへの充填 図１に示すイージーピールシールによって２室に区画さ
れた輸液バッグの第１室に、上記（１）で調製したアミ
ノ酸加脂肪乳剤８００ｍｌを、窒素ガス気流下に充填
し、施栓した。また第２室に、上記（２）で調製した糖
加電解質液２００ｍｌを封入した。(3) Filling in a two-chamber bag In the first chamber of the infusion bag divided into two chambers by the easy peel seal shown in FIG. 1, 800 ml of the amino acid fat emulsion prepared in (1) above was charged with nitrogen gas. It was filled under an air stream and stoppered. In the second chamber, 200 ml of the sugar-added electrolyte solution prepared in (2) above was sealed.
【００５７】上記各液の収容後の容器を、高圧蒸気滅菌
（１０５℃、４０分間）して、本発明の２室容器入り栄
養輸液製剤を得た。The container after containing each of the above liquids was sterilized under high pressure steam (105 ° C., 40 minutes) to obtain the nutritional infusion preparation in a two-chamber container of the present invention.
【００５８】[0058]
【試験例２】上記実施例２で調製した本発明の２室容器
入り栄養輸液製剤につき、試験例１と同様にして安定性
試験を行なった。[Test Example 2] The stability test was conducted on the nutritional infusion preparation in a two-chamber container of the present invention prepared in Example 2 in the same manner as in Test Example 1.
【００５９】その結果、本例により得られた輸液は、実
施例１で得た輸液と同様に、乳化粒子の平均粒子径が１
８０ｎｍ前後で一定しており、外観の変化も全く認めら
れず、優れた保存安定性を有するものであることが判っ
た。As a result, the infusion solution obtained in this example had an average particle size of emulsified particles of 1 as in the infusion solution obtained in Example 1.
It was constant at around 80 nm, no change in appearance was observed, and it was found to have excellent storage stability.
【図１】本発明２室容器入り栄養輸液製剤を収容するに
適したプラスチック製イージーピールシール式輸液バッ
グの一例を示す図である。FIG. 1 is a view showing an example of a plastic easy peel seal type infusion bag suitable for containing a nutritional infusion formulation in a two-chamber container of the present invention.
───────────────────────────────────────────────────── 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 // Ａ２３Ｌ 2/52 Ａ２３Ｌ 2/00 Ｆ ─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. 6 Identification code Office reference number FI technical display area // A23L 2/52 A23L 2/00 F
Claims (5)
ラスチック製２室容器の第１室に乳化剤としてホスファ
チジルグリセロールを用いた脂肪乳剤及びアミノ酸を含
む輸液を収容し且つ上記容器の第２室に糖及び電解質を
含む輸液を収容したことを特徴とする２室容器入り栄養
輸液製剤。1. A plastic two-chamber container in which two individual chambers are formed by an isolation means contains a lipid emulsion using phosphatidylglycerol as an emulsifier and an infusion solution containing an amino acid, and the second chamber of the container is used. A two-chamber nutritional infusion preparation containing an infusion solution containing sugar and an electrolyte.
〜３０ｗ／ｖ％、乳化剤０．０１５〜１５ｗ／ｖ％及び
遊離アミノ酸総量１〜１５ｗ／ｖ％を含有するものであ
る請求項１に記載の製剤。2. The infusion liquid contained in the first chamber is oil / fat 0.5.
The formulation according to claim 1, which comprises -30 w / v%, an emulsifier 0.015-15 w / v% and a total amount of free amino acids 1-15 w / v%.
ｗ／ｖ％と共に、電解質としてナトリウム０〜２５０ｍ
Ｅｑ／ｌ、カリウム０〜２００ｍＥｑ／ｌ、カルシウム
０〜５０ｍＥｑ／ｌ、マグネシウム０〜５０ｍＥｑ／
ｌ、塩素０〜２５０ｍＥｑ／ｌ、リン０〜６０ｍｍｏｌ
／ｌ及び亜鉛０〜１００μｍｏｌ／ｌを含有するもので
ある請求項１に記載の製剤。3. The infusion solution contained in the second chamber is sugar 5 to 60.
0-250m sodium as electrolyte with w / v%
Eq / l, potassium 0-200 mEq / l, calcium 0-50 mEq / l, magnesium 0-50 mEq /
1, chlorine 0 to 250 mEq / l, phosphorus 0 to 60 mmol
/ L and 0-100 μmol / l of zinc, The formulation according to claim 1.
はカリウム塩の一部又は全部が第１室に収容されている
請求項１に記載の製剤。4. The preparation according to claim 1, wherein a part or all of sodium salt and / or potassium salt in the electrolyte component is contained in the first chamber.
が、混合時に油脂、糖、アミノ酸（遊離アミノ酸換算と
して）及び電解質として下記表１記載の組成範囲を有す
るものとなる請求項１乃至４のいずれかに記載の製剤。 【表１】 但し、Ｌ−システインの一部又は全部はＬ−シスチンで
代替できる。5. The infusion solution contained in the first chamber and the second chamber, when mixed, has a composition range shown in the following Table 1 as fats and oils, sugars, amino acids (as free amino acids) and electrolytes. The formulation according to any one of 1 to 4. [Table 1] However, part or all of L-cysteine can be replaced with L-cystine.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP25595693 | 1993-10-13 | ||
| JP5-255956 | 1993-10-13 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH07178151A true JPH07178151A (en) | 1995-07-18 |
Family
ID=17285920
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP6239857A Pending JPH07178151A (en) | 1993-10-13 | 1994-10-04 | Nutrition transfusion formulation in 2-room container |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH07178151A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH09164184A (en) * | 1995-12-13 | 1997-06-24 | Nissho Corp | Drink container for infant |
| JP2009022763A (en) * | 2008-08-08 | 2009-02-05 | Ajinomoto Co Inc | Preliminary preparation method of chemical |
-
1994
- 1994-10-04 JP JP6239857A patent/JPH07178151A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH09164184A (en) * | 1995-12-13 | 1997-06-24 | Nissho Corp | Drink container for infant |
| JP2009022763A (en) * | 2008-08-08 | 2009-02-05 | Ajinomoto Co Inc | Preliminary preparation method of chemical |
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