JP3695499B2

JP3695499B2 - Fat emulsion

Info

Publication number: JP3695499B2
Application number: JP06151798A
Authority: JP
Inventors: 實佐野; 良平難波; 博福田
Original assignee: Nipro Corp
Current assignee: Nipro Corp
Priority date: 1997-03-12
Filing date: 1998-03-12
Publication date: 2005-09-14
Anticipated expiration: 2018-03-12
Also published as: JPH10310517A

Description

【０００１】
【発明の属する技術分野】
本発明は脂肪乳剤に関し、詳しくは極微小粒径の脂肪粒子が水中に乳化されて得られる、室温でも長期間保存可能な安定で澄明な脂肪乳剤に関する。
【０００２】
【従来の技術】
通常、患者への栄養補給は経腸的に摂取させることが自然であり、また最良の方法と考えられている。しかし、腸管からの栄養補給が不十分または不可能な患者への栄養補給は経静脈的に行わざるを得ない。脂肪乳剤はアミノ酸輸液剤、糖質輸液剤等とともに栄養輸液剤の一種であって、単位質量あたりのカロリー量が糖質輸液もしくはアミノ酸輸液と比較して２倍以上と高く、しかも浸透圧をほとんど有さず等張化が容易であるので末梢静脈から脂肪乳剤を投与しても静脈炎を起こしにくい。
【０００３】
脂肪乳剤は、必須脂肪酸の補給、体蛋白質および窒素源の消費抑制といった治療にも使用されるが、主にエネルギ−補給手段として術前、術後、急・慢性消化器疾患、消耗性疾患、熱傷、外傷、長期にわたる意識不明状態等の所見を呈する患者に投与されている。脂肪乳剤は油脂を乳化剤で乳化し、グリセリン、グルコ−ス等を添加して製造された輸液製剤である。日本薬局方では乳濁性注射剤中の粒子径は７μm 以下に規定されているが、一般に市販されている脂肪乳剤は１μm 以下の平均粒子径に調整されている。
【０００４】
すなわち、一般に市販されている脂肪乳剤は、大豆油等の植物油を油脂１重量部に対して乳化剤を0.06〜0.12重量部添加して、高速回転攪拌機で粗乳化した後、ゴ−リンホモジナイザ−、マイクロフルイダイザ−等の高圧乳化機を用い、圧力 350〜1750kgf/cm²の条件下で精乳化して製造されている。このようにして得られた脂肪乳剤の平均粒子径は、0.17〜0.30μm であり、粗大粒子を含む多分散の乳剤であり、孔径0.22μm のフアイナルフイルタ−を通過しないものが多くあった。脂肪乳剤と他の輸液製剤とを同時に投与する場合、脂肪粒子は凝集または粗大化して0.22〜0.45μm のフイルタ−を通過できなかったり、混合後に配合変化を起こしたりすることがあった。
【０００５】
また、特開平5-9111号公報には、油脂をグリセリン、グルコ−スとともに、乳化剤を用いて乳化して平均粒子径が0.17μm 以下の脂肪乳剤が得られることが紹介されている。該公報の実施例によると、脂肪乳剤の最小平均粒子径は0.10μm を超えた値である。そして、かかる脂肪乳剤は、高圧蒸気滅菌の前後においても白色の均質な乳剤であって、良好な乳化状態を長期間維持することができ、安定性が著しく向上し、他の輸液製剤と混合しても相分離が起こりにくくなるといっている。
【０００６】
【発明が解決しようとする課題】
かかる脂肪乳剤は平均粒子径0.10〜0.17μm であるにもかかわらず白濁しているのは、可視光の下限波長360nm 以上の粒子径の脂肪粒子が多数含有された分散度の高い粒度分布をもった系であって入射光が散乱を起こすためである。白濁した脂肪乳剤は、異物の混入、高圧蒸気滅菌あるいは他の輸液製剤との混合による脂肪粒子の凝集、配合変化を目視によって確認することができない問題点を有している。
【０００７】
1994年４月18日に米国食品医薬品局（ＦＤＡ）は、電解質、アミノ酸、糖、脂肪乳剤を混合した輸液を投与中に死亡した症例および呼吸困難に陥った症例が各々２症例ずつあり、その原因が肺の毛細血管にリン酸カルシウムの沈澱物が堆積して塞栓していることであると究明し、医療関係者宛に高カロリ−輸液剤は生命を脅かす危険があるので沈澱物が生じないように細心の注意を払うようにと警告している。そして、脂肪乳剤の配合は沈澱物の確認を不可能にするので電解質、アミノ酸、糖とは別の経路で患者に投与されるべきであると勧告している。
本発明の目的は、かかる従来の脂肪乳剤の問題点を解決するために研究されたものであって、極微小粒径の脂肪粒子が水中に乳化されて得られる室温でも長期間保存可能な安定で澄明な脂肪乳剤を提供することである。
【０００８】
【課題を解決するための手段】
本発明者等は、安定で澄明な脂肪乳剤を得るために鋭意検討した結果、油脂を水中で乳化させる際に、乳化剤の添加量を多くし、少なくとも2000kgf/cm²の高圧噴射ホモジナイザ−を使用して油脂を精乳化することによって、平均粒子径が 0.003〜0.100 μm の脂肪粒子からなる脂肪乳剤が得られることを見出し本発明に到達した。
すなわち、本発明は乳化剤を用いて油脂を水中で乳化させて得られる脂肪粒子の平均粒子径が0.003 〜0.100 μm である脂肪乳剤である。
また、本発明は前記脂肪乳剤において、脂肪乳剤の濁度が200 度未満である脂肪乳剤である。
更に、本発明は前記脂肪乳剤において、乳化剤の添加量が油脂１重量部に対して0.15〜3.00重量部である脂肪乳剤である。
更にまた、本発明は前記脂肪乳剤において、油脂を乳化剤とともに水中に分散させた後、少なくとも2000kgf/cm²の圧力で油脂を乳化させる脂肪乳剤である。また、本発明は前記脂肪乳剤において、グリセリンが脂肪乳剤中に１〜９０重量％含有されてなる脂肪乳剤である。
【０００９】
【発明の実施の形態】
本発明の脂肪乳剤は、乳化剤を用いて油脂を水中で乳化させて得られる極微小粒径の脂肪粒子からなる澄明なものである。油脂としては、植物油、魚油、合成トリグリセリド等が挙げられ、特に大豆油、トウモロコシ油、ヤシ油、サフラワ−油、エゴマ油等の植物油が好ましい。また、乳化剤としては、精製卵黄レシチン、精製ダイズレシチン、水素添加精製卵黄レシチン、水素添加精製ダイズレシチン、セスキオレイン酸ソルビタン、プロピレングリコ−ル、ポリオキシエチレン硬化ヒマシ油、ポリオキシエチレンヒマシ油、ポリオキシエチレンポリオキシプロピレン、ポリソルベ−ト等が挙げられ、特に精製卵黄レシチン、精製ダイズレシチンが好ましい。乳化剤の添加量は、油脂１重量部に対して0.15〜3.00重量部、好ましくは0.2 〜１重量部である。乳化剤の添加量が0.15重量部未満であると、極微小粒径の脂肪粒子が得にくくなる傾向があり、3.00重量部を超えると遊離脂肪酸量が増大して毒性の原因となる傾向がある。
【００１０】
油脂と乳化剤を前記配合量で水相に分散させ、例えば高圧噴射式ホモジナイザ−を用いて粗乳化し、次いで該粗乳化液を高圧噴射式ホモジナイザ−を用いて少なくとも2000kgf/cm²、好ましくは少なくとも3000kgf/cm²の処理圧力で精乳化することによって、平均粒子径が 0.003〜0.100 μm の脂肪粒子の脂肪乳剤が得られる。本発明の脂肪乳剤の脂肪粒子の平均粒子径は 0.003〜0.100 μm 、好ましくは0.003 〜0.050 μm であり、最大粒子径は多くとも0.15μm 、好ましくは多くとも0.10μm である。そして、得られた脂肪乳剤は、透明もしくは半透明の澄明なものであり、40℃の雰囲気中に６ケ月間放置しても脂肪粒子の凝集が認められず、孔径0.22μm の親水性フイルタ−で落差１ｍで自然滴下により濾過しても脂肪乳剤は全量通過した。本発明の脂肪乳剤の濁度は200 度未満、好ましくは１〜150 度、更に好ましくは５〜50度である。
【００１１】
本発明の脂肪乳剤は、孔径0.22μm の親水性フイルタ−を全量通過する極微小粒径の脂肪粒子からなるので、濾過滅菌だけでも充分であるが、必要に応じて脂肪乳剤を容器に充填して密封した後、高圧蒸気滅菌、熱水浸漬滅菌してもよい。本発明の脂肪乳剤は、栄養輸液剤として、そのままの状態あるいは水で希釈して、脂肪乳剤単独、あるいは糖質、電解質、アミノ酸、ビタミン剤等と混合して患者の静脈、経口、経腸等から投与される。
【００１２】
本発明の脂肪乳剤に澄明化剤を添加して水相と油相の屈折率を近づけると、脂肪乳剤は澄明となる。澄明化剤としては、グリセリン、ソルビトール、キシリトール、マンニトール、グルコース、スクロース、リン酸塩等が挙げられ、特にグリセリンが好ましい。脂肪乳剤の澄明性は添加量に比例して良好になるが、好ましくは脂肪乳剤中１〜90重量％、特に30〜60重量％が好ましい。グリセリンの添加量が９０重量％を超えると、脂肪乳剤中の油分の含有量が少なくなり、患者への脂肪乳剤の投与量が増加したり、粘度が高くなりすぎるため、好ましくない。
【００１３】
【実施例】
以下、実施例により本発明の一例を説明する。
【実施例１】
精製卵黄レシチン10g と濃グリセリン25g と精製水900gとを混合し、高速回転攪拌ミキサ−Clearmix(M-Technique社製) で均一に分散させた。この分散液に精製ダイズ油 10gを加え、高圧噴射式ホモジナイザ−DeBEE(BEE INTERNATIONAL 社製）を用い、デユアルフイ−ド法で粗乳化させ粗乳化液を得た。この粗乳化液に精製水を加え全量を1000mlとした後、高圧噴射式ホモジナイザ−DeBEE を用いリバ−ス法で処理圧力3150kgf/cm²で精乳化した。そして調製後の脂肪乳剤のｐＨをｐＨ調整剤を用いて７付近に調整し、高圧蒸気滅菌を行った。このようにして得られた脂肪乳剤の澄明性、吸光度、脂肪粒子の平均粒子径、最大粒子径、最小粒子径を表１に示す。
【００１４】
なお、表１の測定項目の測定方法は次の通りである。
(1) 脂肪粒子の平均粒子径、最大粒子径、最小粒子径
粒子径・粒度分布測定装置 NICOMP Model 380 ZLS(Particle Sizing System 社製）を用いて、脂肪乳剤中の脂肪粒子の粒子径を測定した。
(2) 脂肪乳剤の澄明性
Ｕ3000吸光度測定器（日立製作所製）を使用し、脂肪乳剤の波長６６０ｎｍにおける吸光度を測定し、カオリン１mg／リットルの同一波長における吸光度を１度として濁度を算出した。
(3) 脂肪乳剤の吸光度
Ｕ3000吸光度測定器（日立製作所製）を使用し、波長660nm における脂肪乳剤の吸光度を測定した。
【００１５】
【実施例２】
精製ダイズレシチン10g と濃グリセリン25g と精製水900gとを混合し、高速回転攪拌ミキサ−Clearmixで均一に分散させた。この分散液に精製サフラワ−油５g を加え、高圧噴射式ホモジナイザ−DeBEE を用い、デユアルフイ−ド法で粗乳化させ粗乳化液を得た。この粗乳化液に精製水を加え全量を1000mlとした後、高圧噴射式ホモジナイザ−DeBEE を用いリバ−ス法で処理圧力3150kgf/cm²で精乳化した。そして調製後の脂肪乳剤のｐＨをｐＨ調整剤を用いて７付近に調整し、高圧蒸気滅菌を行った。このようにして得られた脂肪乳剤の澄明性、吸光度、脂肪粒子の平均粒子径、最大粒子径、最小粒子径を表１に示す。
【００１６】
【実施例３】
ポリソルベ−ト80（花王社製）10g と濃グリセリン25g と精製水900gとを混合し、高速回転攪拌ミキサ−Clearmixで均一に分散させた。この分散液に精製ダイズ油10g を加え、高圧噴射式ホモジナイザ−DeBEE を用い、デユアルフイ−ド法で粗乳化させ粗乳化液を得た。この粗乳化液に精製水を加え全量を1000mlとした後、高圧噴射式ホモジナイザ−DeBEE を用いリバ−ス法で処理圧力3150kgf/cm²で精乳化した。そして調製後の脂肪乳剤のｐＨをｐＨ調整剤を用いて７付近に調整し、高圧蒸気滅菌を行った。このようにして得られた脂肪乳剤の澄明性、吸光度、脂肪粒子の平均粒子径、最大粒子径、最小粒子径を表１に示す。
【００１７】
【実施例４】
精製ダイズ油50g と精製卵黄レシチン25g とを均質に混和させた後に、濃グリセリン900 ｇ及び適量の精製水を加え、高速回転攪拌ミキサ−Clearmixを用い粗乳化し粗乳化液を得た。この粗乳化液に精製水を加え全量を1000ｍｌとした後、高圧噴射式ホモジナイザ−DeBEE を用いリバース法で処理圧力3150kgf/cm²で精乳化した。そして調製後の脂肪乳剤のｐＨをｐＨ調整剤を用いて７付近に調整し、高圧蒸気滅菌を行った。このようにして得られた脂肪乳剤の澄明性、吸光度、脂肪粒子の平均粒子径、最大粒子径、最小粒子径を表１に示す。
【００１８】
【比較例１】
精製水900ml に濃グリセリン25g を溶かし、精製卵黄レシチン1.25ｇを分散させた後、高速回転攪拌ミキサ−Clearmixを用いてダイズ油10g を粗乳化させた。粗乳化液に精製水を加え全量を1000mlとした。次いで、高圧ホモジナイザ−「ゴ−リン」（APV 社製）を用い、処理圧力700 kgf/cm²で精乳化した。そして調製後の脂肪乳剤のｐＨをｐＨ調整剤を用いて７付近に調整し、高圧蒸気滅菌を行った。このようにして得られた脂肪乳剤の澄明性、吸光度、脂肪粒子の平均粒子径、最大粒子径、最小粒子径を表１に示す。
【００１９】
【表１】

【００２０】
表１から明らかなように、本発明の実施である実施例１〜４で得られた脂肪乳剤は、脂肪粒子の平均粒子径は0.10μm 以下で最大粒子径でも実施例４の0.1280μm であり、可視光の下限波長360nm 以下であり、澄明性がよく、波長660nm における吸光度も従来の方法に準じて調製した比較例１の脂肪乳剤と比較して著しく低い。
【００２１】
【実施例５】
精製ダイズ油50ｇと精製卵黄レシチン50ｇとを均質に混和させた後に、濃グリセリン100 ｇ及び適量の精製水を加え、高速回転攪拌ミキサーClearmixを用い、粗乳化し粗乳化液を得た。このようにして得られた粗乳化液に精製水を加え全量を1000mlとした後、高圧噴射式ホモジナイザーDeBEE を用い、リバース法にて処理圧力3150kgf/cm²で精乳化処理を行った。そして、調製後の脂肪乳剤のｐＨをｐＨ調整剤を用いて７付近に調整し、高圧蒸気滅菌を行った。このようにして得られた脂肪乳剤の濁度、脂肪粒子の平均粒子径、最大粒子径を表２に示す。
【００２２】
【実施例６】〜
【実施例１０】
実施例５において、脂肪乳剤中のグリセリン添加量を表２に示す重量割合に変更して得られた脂肪乳剤の濁度、脂肪粒子の平均粒子径、最大粒子径を表２に示す。
【００２３】
【表２】

【００２４】
表２から明らかなように、グリセリンの添加量が６０重量％付近まで増加するにつれて濁度が小さくなり、脂肪乳剤の澄明性が向上している。
【００２５】
【実施例１１】
精製ダイズ油50ｇと精製卵黄レシチン50ｇとを均質に混和させた後に、ソルビトール溶液６６７ｇ及び適量の精製水を加え、高速回転攪拌ミキサーClearmixを用いて粗乳化し粗乳化液を得た。このようにして得られた粗乳化液に精製水を加え全量を1000mlとした後、高圧噴射式ホモジナイザーDeBEE を用い、リバース法にて3150kgf/cm²の圧力で精乳化処理を行った。そして、調製後の脂肪乳剤のｐＨをｐＨ調整剤を用いて７付近に調整し、高圧蒸気滅菌を行った。このようにして得られた脂肪乳剤の濁度、脂肪粒子の平均粒子径、最大粒子径を表３に示す。
【００２６】
【実施例１２】
精製ダイズ油50ｇと精製卵黄レシチン50ｇとを均質に混和させた後に、グルコース４００ｇ及び適量の精製水を加え、高速回転攪拌ミキサーClearmixを用いて粗乳化し粗乳化液を得た。このようにして得られた粗乳化液に精製水を加え全量を1000mlとした後、高圧噴射式ホモジナイザーDeBEE を用い、リバース法にて3150kgf/cm²の圧力で精乳化処理を行った。そして、調製後の脂肪乳剤のｐＨをｐＨ調整剤を用いて７付近に調整し、高圧蒸気滅菌を行った。このようにして得られた脂肪乳剤の濁度、脂肪粒子の平均粒子径、最大粒子径を表３に示す。
【００２７】
【実施例１３】
精製ダイズ油50ｇと精製卵黄レシチン50ｇとを均質に混和させた後に、適量の精製水を加え、高速回転攪拌ミキサーClearmixを用いて粗乳化し粗乳化液を得た。このようにして得られた粗乳化液に精製水を加え全量を500 ｍｌとした後、高圧噴射式ホモジナイザーDeBEE を用い、リバース法にて3150kgf/cm²の圧力で精乳化処理を行った。そして、得られた精乳化液に濃グリセリン500 ｇおよび精製水を加えｐＨをｐＨ調整剤を用いて７付近に調整し、全量を1000mlとし高圧蒸気滅菌を行った。このようにして得られた脂肪乳剤の濁度、脂肪粒子の平均粒子径、最大粒子径を表３に示す。
【００２８】
【実施例１４】
精製ダイズ油50ｇと精製卵黄レシチン50ｇとを均質に混和させた後に、適量の精製水を加え、高速回転攪拌ミキサーClearmixを用いて粗乳化し粗乳化液を得た。このようにして得られた粗乳化液に精製水を加え全量を500 ｍｌとした後、高圧噴射式ホモジナイザーDeBEE を用い、リバース法にて3150kgf/cm²の圧力で精乳化処理を行った。そして、得られた精乳化液にソルビトール溶液６６７ｇおよび精製水を加えｐＨをｐＨ調整剤を用いて７付近に調整し、全量を1000mlとし高圧蒸気滅菌を行った。このようにして得られた脂肪乳剤の濁度、脂肪粒子の平均粒子径、最大粒子径を表３に示す。
【００２９】
【表３】

【００３０】
表３から明らかなように、澄明化剤としてグリセリン以外のものを使用しても脂肪乳剤の澄明性は向上した。
【００３１】
【発明の効果】
本発明の脂肪乳剤は、極微小粒径の脂肪粒子が水中に乳化された澄明なものであり、脂肪乳剤中の不溶性異物、凝集した脂肪粒子、配合変化の発見が容易であるので、脂肪乳剤中からかかる不純物を除去することが容易であり、肺の毛細血管が異物で塞栓して患者が死亡したり呼吸困難になることはない。また、本発明の脂肪乳剤は、室温でも長期間保存可能な安定なものである。[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a fat emulsion, and more particularly to a stable and clear fat emulsion obtained by emulsifying fat particles having a very small particle diameter in water and capable of being stored for a long period of time at room temperature.
[0002]
[Prior art]
Usually, it is natural and best practice for patients to be fed enterally. However, nutritional supplementation for patients who are inadequate or impossible to supplement from the intestinal tract must be done intravenously. Fat emulsion is a kind of nutritional infusions along with amino acid infusions, sugar infusions, etc., and the calorie amount per unit mass is more than twice as high as that of sugar infusions or amino acid infusions. It is easy to be isotonic without having phlebitis even if it is administered from a peripheral vein.
[0003]
Fat emulsion is also used for treatments such as supplementation of essential fatty acids, suppression of consumption of body protein and nitrogen source, but mainly as an energy supplementation means before and after surgery, sudden and chronic digestive tract diseases, debilitating diseases, It is administered to patients who have findings such as burns, trauma, and long-term unconsciousness. A fat emulsion is an infusion preparation produced by emulsifying fats and oils with an emulsifier and adding glycerin, glucose or the like. In the Japanese Pharmacopoeia, the particle size in emulsion injections is regulated to 7 μm or less, but generally commercially available fat emulsions are adjusted to an average particle size of 1 μm or less.
[0004]
That is, a commercially available fat emulsion is prepared by adding 0.06 to 0.12 parts by weight of an emulsifier to 1 part by weight of vegetable oil such as soybean oil, roughly emulsifying with a high-speed rotary stirrer, It is manufactured by finely emulsifying under a pressure of 350-1750 kgf / cm ² using a high-pressure emulsifier such as a microfluidizer. The average particle size of the fat emulsion thus obtained was 0.17 to 0.30 μm, and it was a polydisperse emulsion containing coarse particles, and many of them did not pass through a final filter having a pore size of 0.22 μm. When the fat emulsion and other infusion preparations were administered at the same time, the fat particles sometimes aggregated or coarsened and could not pass through a 0.22 to 0.45 μm filter, or caused a change in composition after mixing.
[0005]
Japanese Patent Application Laid-Open No. 5-9111 discloses that fat and oil can be obtained by emulsifying fats and oils with glycerin and glucose using an emulsifier, and having an average particle size of 0.17 μm or less. According to the examples of the publication, the minimum average particle size of the fat emulsion is a value exceeding 0.10 μm. Such a fat emulsion is a white homogeneous emulsion even before and after autoclaving and can maintain a good emulsified state for a long period of time. The stability is remarkably improved and mixed with other infusion preparations. However, phase separation is less likely to occur.
[0006]
[Problems to be solved by the invention]
Such a fat emulsion has an average particle size of 0.10 to 0.17 μm but is cloudy because it has a highly dispersed particle size distribution containing a large number of fat particles having a particle diameter of 360 nm or more, the lower limit wavelength of visible light. This is because the incident light scatters. The white turbid fat emulsion has problems that it cannot visually check for contamination of foreign particles, high-pressure steam sterilization or agglomeration of fat particles due to mixing with other infusion preparations, and changes in the composition.
[0007]
On April 18, 1994, the US Food and Drug Administration (FDA) found that there were 2 cases each of which died during administration of an infusion containing electrolytes, amino acids, sugars, and fat emulsions, and 2 cases of dyspnea. Investigated that the cause is the accumulation of calcium phosphate deposits in the pulmonary capillaries and embolization, and high-calorie infusions for health care workers are potentially life-threatening, so they do not form deposits. Warned to pay close attention. It is recommended that fat emulsions should be administered to patients by a route other than electrolytes, amino acids, and sugars, as it makes it impossible to identify precipitates.
The object of the present invention has been studied to solve the problems of such conventional fat emulsions, and is stable and can be stored for a long period of time even at room temperature obtained by emulsifying ultrafine fat particles in water. And providing a clear fat emulsion.
[0008]
[Means for Solving the Problems]
As a result of intensive studies to obtain a stable and clear fat emulsion, the present inventors have increased the amount of emulsifier added when emulsifying fats and oils in water, and use a high-pressure jet homogenizer of at least 2000 kgf / cm ^2. Thus, the present inventors have found that a fat emulsion composed of fat particles having an average particle size of 0.003 to 0.100 μm can be obtained by finely emulsifying fats and oils.
That is, the present invention is a fat emulsion in which the average particle diameter of fat particles obtained by emulsifying fats and oils in water using an emulsifier is 0.003 to 0.100 μm.
The present invention is the above fat emulsion, wherein the fat emulsion has a turbidity of less than 200 degrees.
Furthermore, the present invention provides the fat emulsion, wherein the amount of emulsifier added is 0.15 to 3.00 parts by weight per part by weight of the fats and oils.
Furthermore, the present invention is the fat emulsion in which the fat is emulsified at a pressure of at least 2000 kgf / cm ² after the fat is dispersed in water together with an emulsifier. Further, the present invention is a fat emulsion wherein the glycerin is contained in the fat emulsion in an amount of 1 to 90% by weight.
[0009]
DETAILED DESCRIPTION OF THE INVENTION
The fat emulsion of the present invention is a clear emulsion composed of fat particles having a very small particle diameter obtained by emulsifying fats and oils in water using an emulsifier. Examples of the oils and fats include vegetable oils, fish oils, synthetic triglycerides and the like, and vegetable oils such as soybean oil, corn oil, coconut oil, safflower oil, and sesame oil are particularly preferable. Further, as an emulsifier, purified egg yolk lecithin, purified soybean lecithin, hydrogenated purified egg yolk lecithin, hydrogenated purified soybean lecithin, sorbitan sesquioleate, propylene glycol, polyoxyethylene hydrogenated castor oil, polyoxyethylene castor oil, poly Examples thereof include oxyethylene polyoxypropylene and polysorbate, and particularly, purified egg yolk lecithin and purified soybean lecithin are preferable. The amount of the emulsifier added is 0.15 to 3.00 parts by weight, preferably 0.2 to 1 part by weight, based on 1 part by weight of the fat. If the added amount of the emulsifier is less than 0.15 parts by weight, it is difficult to obtain fat particles having a very small particle size, and if it exceeds 3.00 parts by weight, the amount of free fatty acid tends to increase and cause toxicity.
[0010]
The fats and oils and the emulsifier are dispersed in the aqueous phase at the above blending amount, and are roughly emulsified using, for example, a high-pressure jet homogenizer, and then the crude emulsion is at least 2000 kgf / cm ² using a high-pressure jet homogenizer, preferably at least By fine emulsification at a processing pressure of 3000 kgf / cm ² , a fat emulsion of fat particles having an average particle size of 0.003 to 0.100 μm is obtained. The average particle size of the fat particles of the fat emulsion of the present invention is 0.003 to 0.100 μm, preferably 0.003 to 0.050 μm, and the maximum particle size is at most 0.15 μm, preferably at most 0.10 μm. The obtained fat emulsion is transparent or translucent and clear, and even when left in a 40 ° C. atmosphere for 6 months, agglomeration of fat particles is not observed, and a hydrophilic filter having a pore size of 0.22 μm. The total amount of the fat emulsion was passed even if it was filtered by natural dropping at a drop of 1 m. The turbidity of the fat emulsion of the present invention is less than 200 degrees, preferably 1 to 150 degrees, more preferably 5 to 50 degrees.
[0011]
Since the fat emulsion of the present invention is composed of ultrafine particles having a very small particle diameter that passes through a hydrophilic filter having a pore size of 0.22 μm, filtration sterilization is sufficient. However, if necessary, the fat emulsion can be filled in a container. After sealing, high pressure steam sterilization or hot water immersion sterilization may be performed. The fat emulsion of the present invention, as a nutritional infusion, is used as it is or diluted with water and mixed with a fat emulsion alone, or a carbohydrate, electrolyte, amino acid, vitamin, etc. Is administered.
[0012]
When a clarifying agent is added to the fat emulsion of the present invention and the refractive indexes of the aqueous phase and the oil phase are made close, the fat emulsion becomes clear. Examples of the clarifying agent include glycerin, sorbitol, xylitol, mannitol, glucose, sucrose, phosphate and the like, and glycerin is particularly preferable. The clarity of the fat emulsion is improved in proportion to the amount added, but it is preferably 1 to 90% by weight, particularly 30 to 60% by weight in the fat emulsion. If the amount of glycerin added exceeds 90% by weight, the content of oil in the fat emulsion is decreased, the dosage of the fat emulsion to the patient is increased, and the viscosity becomes too high.
[0013]
【Example】
Hereinafter, an example of the present invention will be described with reference to examples.
[Example 1]
10 g of purified egg yolk lecithin, 25 g of concentrated glycerin and 900 g of purified water were mixed and dispersed uniformly with a high-speed rotary mixer-Clearmix (manufactured by M-Technique). 10 g of purified soybean oil was added to this dispersion, and a coarse emulsion was obtained by rough emulsification by a dual feed method using a high-pressure jet homogenizer-DeBEE (manufactured by BEE INTERNATIONAL). Purified water was added to the crude emulsified liquid to make the total volume 1000 ml, and then the resulting mixture was finely emulsified with a high pressure jet homogenizer DeBEE at a processing pressure of 3150 kgf / cm ² using a reverse method. Then, the pH of the prepared fat emulsion was adjusted to around 7 using a pH adjuster, and high-pressure steam sterilization was performed. Table 1 shows the clarity, absorbance, average particle size, maximum particle size, and minimum particle size of the fat emulsion thus obtained.
[0014]
In addition, the measuring method of the measurement item of Table 1 is as follows.
(1) Fat particle average particle size, maximum particle size, minimum particle size, minimum particle size, particle size distribution measuring device NICOMP Model 380 ZLS (Particle Sizing System) is used to measure the size of fat particles in fat emulsions. did.
(2) Clarity of fat emulsion Using U3000 absorbance meter (manufactured by Hitachi, Ltd.), the absorbance of fat emulsion was measured at a wavelength of 660 nm, and the turbidity was calculated with the absorbance at the same wavelength of 1 mg / liter of kaolin as 1 degree. .
(3) Absorbance of fat emulsion The absorbance of the fat emulsion at a wavelength of 660 nm was measured using a U3000 absorbance meter (manufactured by Hitachi, Ltd.).
[0015]
[Example 2]
10 g of purified soybean lecithin, 25 g of concentrated glycerin and 900 g of purified water were mixed and dispersed uniformly with a high-speed rotary stirring mixer-Clearmix. To this dispersion, 5 g of refined safflower oil was added and coarsely emulsified by a dual feed method using a high-pressure jet homogenizer-DeBEE to obtain a crude emulsion. Purified water was added to the crude emulsified liquid to make the total volume 1000 ml, and then the resulting mixture was finely emulsified with a high pressure jet homogenizer DeBEE at a processing pressure of 3150 kgf / cm ² using a reverse method. Then, the pH of the prepared fat emulsion was adjusted to around 7 using a pH adjuster, and high-pressure steam sterilization was performed. Table 1 shows the clarity, absorbance, average particle size, maximum particle size, and minimum particle size of the fat emulsion thus obtained.
[0016]
[Example 3]
10 g of polysorbate 80 (manufactured by Kao Corporation), 25 g of concentrated glycerin and 900 g of purified water were mixed and dispersed uniformly with a high-speed rotary mixer-Clearmix. To this dispersion, 10 g of purified soybean oil was added and coarsely emulsified by a dual-feed method using a high-pressure jet homogenizer-DeBEE to obtain a coarse emulsion. Purified water was added to the crude emulsified liquid to make the total volume 1000 ml, and then the resulting mixture was finely emulsified with a high pressure jet homogenizer DeBEE at a processing pressure of 3150 kgf / cm ² using a reverse method. Then, the pH of the prepared fat emulsion was adjusted to around 7 using a pH adjuster, and high-pressure steam sterilization was performed. Table 1 shows the clarity, absorbance, average particle size, maximum particle size, and minimum particle size of the fat emulsion thus obtained.
[0017]
[Example 4]
After 50 g of purified soybean oil and 25 g of purified egg yolk lecithin were homogeneously mixed, 900 g of concentrated glycerin and an appropriate amount of purified water were added and coarsely emulsified using a high-speed rotary mixer-Clearmix to obtain a crude emulsion. Purified water was added to the crude emulsified liquid to make the total volume 1000 ml, and then the resulting mixture was finely emulsified by a reverse method using a high pressure jet homogenizer-DeBEE at a processing pressure of 3150 kgf / cm ² . Then, the pH of the prepared fat emulsion was adjusted to around 7 using a pH adjuster, and high-pressure steam sterilization was performed. Table 1 shows the clarity, absorbance, average particle size, maximum particle size, and minimum particle size of the fat emulsion thus obtained.
[0018]
[Comparative Example 1]
25 g of concentrated glycerin was dissolved in 900 ml of purified water, 1.25 g of purified egg yolk lecithin was dispersed, and then 10 g of soybean oil was roughly emulsified using a high-speed rotary mixer-Clearmix. Purified water was added to the crude emulsion to make a total volume of 1000 ml. Subsequently, the mixture was finely emulsified using a high-pressure homogenizer “Gorin” (APV) at a processing pressure of 700 kgf / cm ² . Then, the pH of the prepared fat emulsion was adjusted to around 7 using a pH adjuster, and high-pressure steam sterilization was performed. Table 1 shows the clarity, absorbance, average particle size, maximum particle size, and minimum particle size of the fat emulsion thus obtained.
[0019]
[Table 1]

[0020]
As is apparent from Table 1, the fat emulsions obtained in Examples 1 to 4 which are the embodiments of the present invention have the average particle size of fat particles of 0.10 μm or less and the maximum particle size of 0.1280 μm of Example 4 as well. The lower limit wavelength of visible light is 360 nm or less, the transparency is good, and the absorbance at a wavelength of 660 nm is significantly lower than that of the fat emulsion of Comparative Example 1 prepared according to the conventional method.
[0021]
[Example 5]
After 50 g of purified soybean oil and 50 g of purified egg yolk lecithin were homogeneously mixed, 100 g of concentrated glycerin and an appropriate amount of purified water were added and coarsely emulsified using a high-speed rotary stirring mixer Clearmix to obtain a crude emulsion. Purified water was added to the crude emulsion thus obtained to make a total volume of 1000 ml, and then a fine emulsification treatment was performed by a reverse method at a treatment pressure of 3150 kgf / cm ² using a high-pressure jet homogenizer DeBEE. Then, the pH of the prepared fat emulsion was adjusted to around 7 using a pH adjuster, and high-pressure steam sterilization was performed. Table 2 shows the turbidity, the average particle size of the fat particles, and the maximum particle size of the fat emulsion thus obtained.
[0022]
Example 6
[Example 10]
Table 2 shows the turbidity, the average particle diameter of fat particles, and the maximum particle diameter of the fat emulsion obtained in Example 5 by changing the glycerin addition amount in the fat emulsion to the weight ratio shown in Table 2.
[0023]
[Table 2]

[0024]
As is apparent from Table 2, the turbidity decreases as the amount of glycerin added increases to around 60% by weight, and the clarity of the fat emulsion is improved.
[0025]
Example 11
After 50 g of purified soybean oil and 50 g of purified egg yolk lecithin were homogeneously mixed, 667 g of a sorbitol solution and an appropriate amount of purified water were added and coarsely emulsified using a high-speed rotary stirring mixer Clearmix to obtain a crude emulsion. Purified water was added to the crude emulsion thus obtained to make a total volume of 1000 ml, and then a fine emulsification treatment was performed by a reverse method at a pressure of 3150 kgf / cm ² using a high-pressure jet homogenizer DeBEE. Then, the pH of the prepared fat emulsion was adjusted to around 7 using a pH adjuster, and high-pressure steam sterilization was performed. Table 3 shows the turbidity, the average particle size of the fat particles, and the maximum particle size of the fat emulsion thus obtained.
[0026]
Example 12
After 50 g of purified soybean oil and 50 g of purified egg yolk lecithin were homogeneously mixed, 400 g of glucose and an appropriate amount of purified water were added and coarsely emulsified using a high-speed rotary stirring mixer Clearmix to obtain a crude emulsion. Purified water was added to the crude emulsion thus obtained to make a total volume of 1000 ml, and then a fine emulsification treatment was performed by a reverse method at a pressure of 3150 kgf / cm ² using a high-pressure jet homogenizer DeBEE. Then, the pH of the prepared fat emulsion was adjusted to around 7 using a pH adjuster, and high-pressure steam sterilization was performed. Table 3 shows the turbidity, the average particle size of the fat particles, and the maximum particle size of the fat emulsion thus obtained.
[0027]
Example 13
After 50 g of purified soybean oil and 50 g of purified egg yolk lecithin were homogeneously mixed, an appropriate amount of purified water was added and coarsely emulsified using a high-speed rotary stirring mixer Clearmix to obtain a crude emulsion. Purified water was added to the crude emulsion thus obtained to make a total volume of 500 ml, and then a fine emulsification treatment was performed by a reverse method at a pressure of 3150 kgf / cm ² using a high-pressure jet homogenizer DeBEE. Then, 500 g of concentrated glycerin and purified water were added to the resulting fine emulsion, the pH was adjusted to around 7 using a pH adjuster, and the total amount was 1000 ml, followed by high-pressure steam sterilization. Table 3 shows the turbidity, the average particle size of the fat particles, and the maximum particle size of the fat emulsion thus obtained.
[0028]
Example 14
After 50 g of purified soybean oil and 50 g of purified egg yolk lecithin were homogeneously mixed, an appropriate amount of purified water was added and coarsely emulsified using a high-speed rotary stirring mixer Clearmix to obtain a crude emulsion. Purified water was added to the crude emulsion thus obtained to make a total volume of 500 ml, and then a fine emulsification treatment was performed by a reverse method at a pressure of 3150 kgf / cm ² using a high-pressure jet homogenizer DeBEE. Then, 667 g of sorbitol solution and purified water were added to the resulting fine emulsion, and the pH was adjusted to around 7 using a pH adjuster, and the total amount was 1000 ml, and high-pressure steam sterilization was performed. Table 3 shows the turbidity, the average particle size of the fat particles, and the maximum particle size of the fat emulsion thus obtained.
[0029]
[Table 3]

[0030]
As is apparent from Table 3, the clarity of the fat emulsion was improved even when a clarifier other than glycerin was used.
[0031]
【The invention's effect】
The fat emulsion of the present invention is a clear emulsion of ultrafine fat particles emulsified in water, and it is easy to find insoluble foreign matter, agglomerated fat particles, and blending changes in the fat emulsion. It is easy to remove such impurities from the inside, and the pulmonary capillaries are not blocked by a foreign substance so that the patient does not die or have difficulty breathing. The fat emulsion of the present invention is stable and can be stored for a long time even at room temperature.

Claims

Oils and emulsifiers and at least one compound selected from the group consisting of glycerin, sorbitol, xylitol, mannitol, glucose, sucrose, and phosphate, and the amount of the emulsifier added is 0.15 to 3.00 with respect to 1 part by weight of the oils and fats. A fat emulsion having an average particle size of fat particles of 0.003 to 0.100 μm, which is obtained by emulsifying fat and oil at a pressure of at least 3150 kgf / cm ² after dispersing the fat and oil in water together with an emulsifier.

2. A fat emulsion according to claim 1, comprising from 10 to 90% by weight of a clarifying agent.

2. A fat emulsion according to claim 1, comprising 20 to 90% by weight of a clarifying agent.

2. A fat emulsion according to claim 1, comprising 30 to 90% by weight of a clarifying agent.