JPS60130519A - Fat transfusion solution - Google Patents

Abstract

PURPOSE:A fat transfusion solution, containing an ester derivative of alpha-linolenic acid, having more balanced nutriment than the conventional fat transfusion solution consisting essentially of linoleic acid and antithrombotic action, and useful as a remedial transfusion solution for arteriosclerosis. CONSTITUTION:A fat transfusion solution containing an ester derivative of alpha- linolenic acid, preferably a triglyceride containing the alpha-linolenic acid as a component, e.g. linseed oil, or ethyl linolenate. The transfusion solution is prepared preferably by dispersing 5-20wt./vol.% fat, 1-2wt./vol.% purified egg yolk lecithin and 2-3wt./vol.% glycerol in distilled water for injection, and emulsifying the components under pressure. Soybean oil and safflower oil in a mixture are used as the fat, and the content of the alpha-linolenic acid in the fat is preferably 10-50wt./vol.%. The conventional fat transfusion made from soybean oil, etc. as a raw material has no antithrombotic action, but this transfusion solution is useful also as an antithrombotic pharmaceutical.

Description

DETAILED DESCRIPTION OF THE INVENTION (1) Background Technical Field of the Invention The present invention relates to a fat infusion preparation. More specifically, the present invention relates to a fat infusion containing an ester derivative of α-lylunic acid.

Prior art and problems A variety of 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-linuric acid accounting for only about 7% at most. do not have.

Linoleic acid is converted to arachidonic acid in the human body. Unlike eicosapencitric acid, which is produced in the human body from α-lylunic 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-lylunic acid cannot be said to be well-balanced infusion preparations.

(1) Purpose of the Invention The purpose of the present invention is to provide a fat infusion containing an ester derivative of α-lylunic acid.

As a result of repeated efforts, the present inventors succeeded in preparing a fat infusion preparation suitable as an intravenous nutritional supplement containing an ester derivative of α-lylunic acid. They discovered that it has antithrombotic properties and completed the present invention.

(1) Detailed Description of the Invention That is, the present invention is a fat infusion agent characterized by containing an ester derivative of α-lylunic acid. Further, as the ester derivative of α-lylphinic acid, triglyceride or α-lylinic acid ethyl ester containing α-lyllunic acid as a component is preferable. Furthermore, the fat infusion preparation of the present invention is useful as an antithrombotic preparation.

The fat containing the ester derivative of α-lylunic acid used in the present invention includes triglycerides (eg, linseed oil) containing α-lylunic acid as a component. α
- Rirunic acid ethyl ester is also preferred as a fat for use in the present invention. α-Lilunic acid ethyl ester can be easily obtained by carrying out an esterification reaction between α-lylunic 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 soybean oil is as follows: 20 to 95 W/V% is preferred.

The fat infusion preparation of the present invention can be prepared by dispersing distilled water for injection, fat, purified egg yolk lecithin, and glycerin and emulsifying the mixture under pressure.

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. α-Lilunic acid content in fat is 10-50
W/V% is preferred.

(1)9 Specific effects of the invention The fat infusion preparation of the invention contains an ester derivative of α-lylunic acid, and was confirmed to have 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 an infusion for the treatment of arterial sclerosis (TS□).

Next, the present invention will be explained in more detail with reference to Examples and Test Examples.

Example-1 50 g of α-lylunic acid ether ester, 1 ljff soybean oil 450.9 g, purified egg yolk lecithin 60 g 1 oleic acid 2
．． 5I, 125 g of concentrated glycerin, and 50 g of 0.1N caustic soda were added and dispersed using a homomixer, and then distilled water for injection was added to bring the total liquid volume to 5 tons. This is emulsified using a high-pressure injection emulsifier to prepare a fat infusion. After dispensing 200 Tnt of the fat infusion into plastic bags, it is sterilized using high-pressure steam at 118° C. for 122 minutes to obtain a fat infusion. After sterilization, vacuum packaging is performed using 0■-film (manufactured by Unitika).

Example-2 100 g of α-lylunic acid triglyceride, 300 g of purified soybean oil, 48 Il of purified egg yolk lecithin, 2.0 g of oleic acid.
0g, concentrated glycerin 100#10.1N-caustic soda 4
Disperse 0 with a homomixer* and add distilled water for injection to make a total volume of 4 tons. Thereafter, a fat infusion preparation is produced by processing in the same manner as in Example-1.

Example-3 α-lylunic acid ethyl ester soI! , Refined safflower oil 320.91 Refined egg yolk lecithin 48g, Oleic acid 2
．． 100 g of concentrated glycerin and 40 g of 0.1N caustic soda were dispersed using a homomixer, and distilled water for injection was added to bring the total volume to 4 tons. Thereafter, the same procedure as in Example 1 was carried out to produce a fat infusion.

Test Example Platelet aggregation inhibitory effect Sprague Dawley
) (S, D, ) 18 animals around 20019 were used. Six animals each were divided into three groups. That is, the first group received daily administration of commercially available fat infusion agent 18- containing 10 W/V% soybean oil via the tail vein for 8 consecutive days, and in addition to this, solid powdered feed (CE-2 Nippon Talea ■ (manufactured by the company) was given orally ad libitum. In the second group, fat infusion preparation 18- produced by the method shown in Example-1 was similarly administered for 8 days, and in addition to this, the same solid powdered feed was orally ad libitum. In the third group, solid powdered feed was freely ingested orally. 12 days from the time of final tail vein administration for each group.
After fasting for an hour, under 5% Nembutal anesthesia, heparin (4O Units) 7 was injected into the abdominal aorta using a 20G needle.
m) Collect 4.5 ml of blood into a syringe containing 0.54,
PRP with a platelet count of 300,000/μt was prepared according to a conventional method. Dispense 225 μt of PRP from each rat into a guvette, warm it to 37°C for 5 minutes, add 25 μt of collagen, an aggregation-inducing agent, to a final concentration of 50 μI/me, and measure platelet aggregation using an alibometer. did.

As shown in Table 1, the average platelet aggregation rate was 60.5% in the group to which the second group of fat infusions containing α-lylunic acid ethyl ester was administered, and the commercially available fat infusion containing soybean oil It became clear that the effect was significantly suppressed compared to the first group administered with the same amount of food and the third group given only the normal powdered feed.

Acute toxicity was tested using S, D, male rats weighing around 230 g, and the results showed that the α-
It was found that the fat infusion containing ethyl lyrunic acid ester is extremely safe, as is the commercially available soybean oil fat infusion. The results are shown in Table 2.

Table 1 Table 2 In addition, it was confirmed that the sword fat infusion preparations obtained in Examples 2 and 3 had similar platelet suppressing effects and safety.

Patent applicant: Terumo Corporation

Claims (2)

[Claims] (1) A fat infusion agent characterized by containing an ester derivative of α-lylunic acid. (2) The fat infusion preparation according to claim 1, wherein the ester derivative of α-lyllunic acid is a triglyceride containing α-lyllunic acid or ethyl α-lyllunate.