JPH0421645B2 - - Google Patents

Info

Publication number
JPH0421645B2
JPH0421645B2 JP58237517A JP23751783A JPH0421645B2 JP H0421645 B2 JPH0421645 B2 JP H0421645B2 JP 58237517 A JP58237517 A JP 58237517A JP 23751783 A JP23751783 A JP 23751783A JP H0421645 B2 JPH0421645 B2 JP H0421645B2
Authority
JP
Japan
Prior art keywords
fat
linolenic acid
infusion
content
present
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.)
Expired - Lifetime
Application number
JP58237517A
Other languages
Japanese (ja)
Other versions
JPS60130519A (en
Inventor
Megumi Kunimasa
Shinji Ozawa
Toshio Wakabayashi
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Terumo Corp
Original Assignee
Terumo Corp
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Terumo Corp filed Critical Terumo Corp
Priority to JP23751783A priority Critical patent/JPS60130519A/en
Priority to EP84112091A priority patent/EP0145873B1/en
Priority to DE8484112091T priority patent/DE3475870D1/en
Priority to BE0/214110A priority patent/BE901206A/en
Publication of JPS60130519A publication Critical patent/JPS60130519A/en
Publication of JPH0421645B2 publication Critical patent/JPH0421645B2/ja
Granted legal-status Critical Current

Links

Description

【発明の詳細な説明】 発明の背景 技術分野 本発明は、5〜20W/V%の脂肪分を含有する
脂肪輸液剤において、前記脂肪分中のα−リノレ
ン酸エチルエステルまたはα−リノレン酸トリグ
リセライドの含有量が10〜50W/V%であること
を特徴とする脂肪輸液剤に関するものである。 先行技術および問題点 脂肪輸液剤としては種々のものが市販されてお
り、一般的には脂肪成分としては精製大豆油また
は精製サフラワー油が使用され、乳化剤としては
卵黄レシチン、大豆レシチン等が使用され調製さ
れている。 これらの脂肪輸液剤には大豆油またはサフラワ
ー油が原料として用いられているため、含有され
ている脂肪酸はリノール酸が主であり、α−リノ
レン酸は高々約7%程度しか含有されていない。
リノール酸はヒト体内では、アラキシド酸に変換
される。アラキドン酸はα−リノレン酸からヒト
体内で生成するエイコサペンタエン酸とは異な
り、そのもの自体には抗血栓作用はない。アラキ
ドン酸を家兎に投与すると肺塞栓を発症し死に到
ることが知られている。従つてα−リノレン酸の
含有量の少ない大豆油またはサフラワー油から成
る脂肪輸液剤は、バランスのとれた輸液剤とは云
い難い。 発明の目的 本発明の目的は5〜20W/V%の脂肪分を含有
する脂肪輸液剤において、前記脂肪分中のα−リ
ノレン酸エチルエステルまたはα−リノレン酸ト
リグリセライドの含有量が10〜50W/V%である
ことを特徴とする脂肪輸液剤を提供することにあ
る。 本発明者らは、鋭意研究を重ねた結果、α−リ
ノレン酸のエステル誘導体を含有する経静脈栄養
剤として適した脂肪輸液剤の調製に成功すると共
に、該脂肪輸液剤が著明な抗血栓性を有すること
を見い出し本発明を完成するに至つた。 発明の具体的説明 すなわち、本発明は5〜20W/V%の脂肪分を
含有する脂肪輸液剤において、前記脂肪分中のα
−リノレン酸エチルエステルまたはα−リノレン
酸トリグリセライドの含有量が10〜50W/V%で
あることを特徴とする脂肪輸液剤である。また、
本発明の脂肪輸液剤は抗血栓性製剤として有用で
ある。 本発明において使用されるα−リノレン酸のエ
ステル誘導体を含有する脂肪としてはα−リノレ
ン酸を成分とするトリグリセライド(たとえば亜
麻仁油)があげられる。α−リノレン酸エチルエ
ステルも本発明において使用される脂肪としては
好ましいものである。α−リノレン酸エチルエス
テルはα−リノレン酸とエタノールとから常法に
よりエステル化反応させることにより容易に得ら
れる。本発明の脂肪輸液剤は上記の脂肪に精製さ
れた大豆油または精製されたサフラワー油を混合
して用いることができるが、その場合の精製大豆
油または精製サフラワー油の混合比率としては20
〜95W/V%が好ましい。 本発明の脂肪輸液剤は、注射用蒸留水、脂肪、
精製卵黄レシチンおよびグリセリンを分散させ、
加圧乳化することにより調製することが出来る。
この場合、脂肪は5〜20W/V%、精製卵黄レシ
チン1〜2W/V%、グリセリンは2〜3W/V%
が好ましい。脂肪族中のα−リノレン酸のエステ
ル誘導体の含量は10〜50W/V%である。 発明の具体的作用効果 本発明の脂肪輸液剤は、5〜20W/V%の脂肪
分を含有する脂肪輸液剤において、前記脂肪分中
のα−リノレン酸エチルエステルまたはα−リノ
レン酸トリグリセライドの含有量が10〜50W/V
%であり、経静脈投与によつて血小板凝集阻止作
用を有することが確認された。従つて本発明の脂
肪輸液剤は抗血栓性製剤として有用であり、バラ
ンスのとれた栄養輸液剤としてばかりでなく、動
脈硬化の治療輸液剤としても用いることが出来
る。 次に実施例および試験例を示して本発明をさら
に具体的に説明する。 実施例 1 α−リノレン酸エチルエステル50g、精製大豆
油450g、精製卵黄レシチン60g、オレイン酸2.5
g、濃グリセリン125g、0.1N−苛性ソーダ50ml
を加え、ホモミキサーで分散させたのち、注射用
蒸留水を加え、全液量を5とする。これを高圧
噴射式乳化機にて乳化し、脂肪輸液剤を調製す
る。該脂肪輸液剤を200mlずつプラスチツク製バ
ツクに分注したのち、118℃、22分間の高圧蒸気
減菌処理して脂肪輸液剤とする。減菌後、OV−
フイルム(ユニチカ社製)で真空包装する。 実施例 2 α−リノレン酸トリグリセライド100g、精製
大豆油300g、精製卵黄レシチン48g、オレイン
酸2.0g、濃グリセリン100g、0.1N−苛性ソーダ
40mlをホモミキサーで分散させたのち、注射用蒸
留水を加え全液量を4とする。以下実施例−1
と同様に処理して脂肪輸液剤を製造する。 実施例 3 α−リノレン酸エチルエステル80g、精製サフ
ラワー油320g、精製卵黄レシチン48g、オレイ
ン酸2.0g、濃グリセリン100g、0.1N−苛性ソー
ダ40mlをホモミキサーで分散させたのち、注射用
蒸留水を加え全液量を4とする。以下実施例−
1と同様に処理して脂肪輸液剤を製造する。 試験例 血小板凝集抑制作用 スプラグ・ドウリー(Sprague Dawley)(S.
D)系ラツト200g前後のものを18匹用いた。各
6匹を3群に分けた。即ち、第1群は尾静脈より
8日間連日10W/V%大豆油を含有する市販の脂
肪輸液剤18mlを毎日投与し、これに加えて毎日固
型粉末飼料(CE−2日本クレア(株)社製)を自由
に経口摂取せしめた。第2群は、同じように、8
日間実施例−1で示した方法で製造した脂肪輸液
剤18mlを投与し、これに加えて同じく固型粉末飼
料を経口的に自由摂取させた。第3群は固型粉末
飼料を経口的に自由摂取させたものである。各群
とも最終の尾静脈投与時より12時間絶食させた
後、5%ネンブタール麻酔下、腹部大動脈より、
20G注射針を用いヘパリン(40ユニツト/ml)
0.5mlを入れたシリンジに4.5ml採血し、常法に従
つて、血小板数30個/μのPRPを作成した。
各ラツトのPRP225μをキユベツトに分注し、
5分間37℃に加温後、凝集惹起剤であるコラーゲ
ン25μを最終濃度50μg/mlとなるように加え、
アグリゴメーターを用いて血小板凝集を測定し
た。表1に示す如く、α−リノレン酸エチルエス
テルを含有する第2群の脂肪輸液剤を投与した群
では平均の血小板凝集率が60.5%であり、市販の
大豆油を含有する脂肪輸液剤を投与した第1群お
よび通常の粉末飼料のみの第3群よりも有意に抑
制されていることが明らかとなつた。 急性毒性については230g前後のS.D.系ラツト
(雄)を用いて試験した結果、実施例1で製造し
たα−リノレン酸エチルエステルを含有した脂肪
輸液剤は市販大豆油脂肪輸液剤と同じく極めて安
全であることが判明した。結果を表2に示す。
Detailed Description of the Invention Background Technical Field of the Invention The present invention provides a fat infusion preparation containing a fat content of 5 to 20% W/V, in which α-linolenic acid ethyl ester or α-linolenic acid triglyceride in the fat content is The present invention relates to a fat infusion agent characterized by having a content of 10 to 50 W/V%. Prior art and problems Various fat infusion preparations are commercially available, and generally refined soybean oil or refined safflower oil is used as the fat component, and egg yolk lecithin, soybean lecithin, etc. are used as the emulsifier. and prepared. These fat infusions use soybean oil or safflower oil as raw materials, so the fatty acid they contain is mainly linoleic acid, with α-linolenic acid accounting for only about 7% at most. .
Linoleic acid is converted to arachidic acid in the human body. Unlike eicosapentaenoic acid, which is produced in the human body from α-linolenic acid, arachidonic acid itself does not have antithrombotic effects. It is known that when arachidonic acid is administered to domestic rabbits, they develop pulmonary embolism, leading to death. Therefore, fat infusion preparations made of soybean oil or safflower oil with a low content of α-linolenic acid cannot be said to be well-balanced infusion preparations. Purpose of the Invention The purpose of the present invention is to provide a fat infusion preparation containing a fat content of 5 to 20 W/V%, in which the content of α-linolenic acid ethyl ester or α-linolenic acid triglyceride in the fat content is 10 to 50 W/V%. It is an object of the present invention to provide a fat infusion agent characterized by having a concentration of V%. As a result of intensive research, the present inventors succeeded in preparing a fat infusion agent suitable as an intravenous nutritional agent containing an ester derivative of α-linolenic acid, and also found that the fat infusion agent has a marked antithrombotic effect. The present invention was completed based on this discovery. Detailed Description of the Invention That is, the present invention provides a fat infusion preparation containing a fat content of 5 to 20 W/V%, in which α in the fat content is
- A fat infusion preparation characterized in that the content of linolenic acid ethyl ester or α-linolenic acid triglyceride is 10 to 50 W/V%. Also,
The fat infusion preparation of the present invention is useful as an antithrombotic preparation. The fat containing the ester derivative of α-linolenic acid used in the present invention includes triglycerides containing α-linolenic acid (for example, linseed oil). Alpha-linolenic acid ethyl ester is also a preferred fat for use in the present invention. α-Linolenic acid ethyl ester can be easily obtained by carrying out an esterification reaction between α-linolenic acid and ethanol by a conventional method. The fat infusion preparation of the present invention can be used by mixing refined soybean oil or refined safflower oil with the above fat, but in that case, the mixing ratio of refined soybean oil or refined safflower oil is 20%.
~95W/V% is preferred. The fat infusion preparation of the present invention comprises distilled water for injection, fat,
Disperse purified egg yolk lecithin and glycerin,
It can be prepared by pressure emulsification.
In this case, fat is 5-20 W/V%, purified egg yolk lecithin is 1-2 W/V%, and glycerin is 2-3 W/V%.
is preferred. The content of ester derivatives of α-linolenic acid in the aliphatic ranges from 10 to 50% W/V. Specific effects of the invention The fat infusion preparation of the present invention is a fat infusion preparation containing 5 to 20 W/V% fat content, in which the fat content contains α-linolenic acid ethyl ester or α-linolenic acid triglyceride. The amount is 10~50W/V
%, and it was confirmed that it has a platelet aggregation inhibiting effect when administered intravenously. Therefore, the fat infusion of the present invention is useful as an antithrombotic preparation, and can be used not only as a balanced nutritional infusion, but also as a therapeutic infusion for arteriosclerosis. Next, the present invention will be explained in more detail with reference to Examples and Test Examples. Example 1 α-linolenic acid ethyl ester 50g, purified soybean oil 450g, purified egg yolk lecithin 60g, oleic acid 2.5g
g, concentrated glycerin 125g, 0.1N-caustic soda 50ml
After adding and dispersing with a homomixer, add distilled water for injection to make the total liquid volume 5. This is emulsified using a high-pressure injection emulsifier to prepare a fat infusion. After dispensing 200 ml of the fat infusion into plastic bags, it is sterilized with high-pressure steam at 118°C for 22 minutes to obtain a fat infusion. After sterilization, OV-
Vacuum package with film (manufactured by Unitika). Example 2 α-linolenic acid triglyceride 100g, purified soybean oil 300g, purified egg yolk lecithin 48g, oleic acid 2.0g, concentrated glycerin 100g, 0.1N caustic soda
After dispersing 40 ml with a homomixer, add distilled water for injection to make a total volume of 4. Example-1 below
A fat infusion preparation is produced by processing in the same manner as above. Example 3 After dispersing 80 g of α-linolenic acid ethyl ester, 320 g of purified safflower oil, 48 g of purified egg yolk lecithin, 2.0 g of oleic acid, 100 g of concentrated glycerin, and 40 ml of 0.1N caustic soda using a homomixer, distilled water for injection was added. Add to make the total liquid volume 4. Examples below-
A fat infusion preparation is produced by processing in the same manner as in 1. Test example Platelet aggregation inhibitory effect Sprague Dawley (S.
D) 18 rats weighing around 200 g were used. Six animals each were divided into three groups. That is, the first group received 18 ml of a commercially available fat infusion solution containing 10 W/V% soybean oil daily for 8 consecutive days via the tail vein, and in addition to this, they were given a solid powdered feed (CE-2 Nippon CLEA Co., Ltd.) every day. (manufactured by the company) was given orally ad libitum. Similarly, the second group is 8
18 ml of a fat infusion prepared by the method shown in Example 1 was administered daily, and in addition to this, the same solid powdered feed was orally given ad libitum. In the third group, solid powdered feed was freely ingested orally. After fasting for 12 hours from the time of the final tail vein administration in each group, the abdominal aorta was administered under 5% Nembutal anesthesia.
Heparin (40 units/ml) using a 20G needle
4.5 ml of blood was collected into a syringe containing 0.5 ml, and PRP with a platelet count of 30/μ was prepared according to a conventional method.
Dispense 225μ of PRP from each rat into a cuvette.
After heating to 37°C for 5 minutes, 25μ of collagen, an aggregation inducing agent, was added to a final concentration of 50μg/ml.
Platelet aggregation was measured using an aggregometer. As shown in Table 1, the average platelet aggregation rate was 60.5% in the group administered with the second group of fat infusions containing α-linolenic acid ethyl ester, and the group administered with the commercially available fat infusion containing soybean oil. It became clear that the effect was significantly suppressed compared to the first group that received only the normal powdered feed and the third group that received only the normal powdered feed. Regarding acute toxicity, the results of a test using SD rats (male) weighing around 230 g showed that the fat infusion containing α-linolenic acid ethyl ester produced in Example 1 was extremely safe, as was the commercially available soybean oil fat infusion. It turns out that there is something. The results are shown in Table 2.

【表】【table】

【表】【table】

【表】 尚、実施例2および実施例3により得られた脂
肪輸液剤も同様な血小板抑制作用と安全性を有す
ることが確かめられた。
[Table] Furthermore, it was confirmed that the fat infusion preparations obtained in Examples 2 and 3 had similar platelet suppressing effects and safety.

Claims (1)

【特許請求の範囲】[Claims] 1 5〜20W/V%の脂肪分を含有する脂肪輸液
剤において、前記脂肪分中のα−リノレン酸エチ
ルエステルまたはα−リノレン酸トリグリセライ
ドの含有量が10〜50W/V%であることを特徴と
する脂肪輸液剤。
1. A fat infusion preparation containing a fat content of 5 to 20 W/V%, characterized in that the content of α-linolenic acid ethyl ester or α-linolenic acid triglyceride in the fat content is 10 to 50 W/V%. Fat infusion agent.
JP23751783A 1983-12-16 1983-12-16 Fat transfusion solution Granted JPS60130519A (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
JP23751783A JPS60130519A (en) 1983-12-16 1983-12-16 Fat transfusion solution
EP84112091A EP0145873B1 (en) 1983-12-16 1984-10-09 Transfusion emulsion
DE8484112091T DE3475870D1 (en) 1983-12-16 1984-10-09 Transfusion emulsion
BE0/214110A BE901206A (en) 1983-12-16 1984-12-04 EMULSION FOR TRANSFUSION.

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP23751783A JPS60130519A (en) 1983-12-16 1983-12-16 Fat transfusion solution

Publications (2)

Publication Number Publication Date
JPS60130519A JPS60130519A (en) 1985-07-12
JPH0421645B2 true JPH0421645B2 (en) 1992-04-13

Family

ID=17016493

Family Applications (1)

Application Number Title Priority Date Filing Date
JP23751783A Granted JPS60130519A (en) 1983-12-16 1983-12-16 Fat transfusion solution

Country Status (1)

Country Link
JP (1) JPS60130519A (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102005058369A1 (en) * 2005-12-06 2007-06-14 Lts Lohmann Therapie-Systeme Ag Unsaturated fatty acids as thrombin inhibitors

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3169094A (en) * 1960-08-26 1965-02-09 Wretlind Arvid Johannes Method of preparing intravenously injectable fat emulsions free from side reactions or complications
JPS55147228A (en) * 1979-05-07 1980-11-17 Green Cross Corp:The Fat emulsion for intravenous injection
JPS5791915A (en) * 1980-09-24 1982-06-08 Roussel Uclaf Novel lipid composition useful for dietetics, resuscitation and treatment
JPS57198062A (en) * 1981-05-30 1982-12-04 Hideyoshi Kurose Nutrient bean curd and its preparation
JPS58208217A (en) * 1982-02-03 1983-12-03 スコッティア ホウルディングズ ピーエルシー Local medicine composition

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3169094A (en) * 1960-08-26 1965-02-09 Wretlind Arvid Johannes Method of preparing intravenously injectable fat emulsions free from side reactions or complications
JPS55147228A (en) * 1979-05-07 1980-11-17 Green Cross Corp:The Fat emulsion for intravenous injection
JPS5791915A (en) * 1980-09-24 1982-06-08 Roussel Uclaf Novel lipid composition useful for dietetics, resuscitation and treatment
JPS57198062A (en) * 1981-05-30 1982-12-04 Hideyoshi Kurose Nutrient bean curd and its preparation
JPS58208217A (en) * 1982-02-03 1983-12-03 スコッティア ホウルディングズ ピーエルシー Local medicine composition

Also Published As

Publication number Publication date
JPS60130519A (en) 1985-07-12

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