JPH0316922B2 - - Google Patents

Description

〔Technical field〕

The present invention relates to anti-arteriosclerotic formulations. More specifically, the present invention relates to an anti-arteriosclerosis preparation containing an ester of α-linolenic acid as an active ingredient. [Prior Art] The effect of lowering the amount of cholesterol (cholesterin) in the blood of preparations such as fat infusions containing esters of α-linolenic acid is not yet known. Purpose of the Invention The purpose of the present invention is to reduce the amount of cholesterol in the blood, and to reduce arteriosclerosis, which is caused by excessive cholesterol in the blood due to excessive intake of cholesterol or cholesterol metabolic disorder. Provides a blood cholesterol level lowering agent, that is, an anti-arteriosclerosis preparation useful as a therapeutic or preventive agent for aortic and coronary artery sclerosis, myocardial infarction, cerebral thrombosis, aortic aneurysm, peripheral arterial occlusion, hyperlipidemia, diabetes, etc. It's about doing. The present invention, which achieves the above object, is an anti-arteriosclerosis preparation containing an ester of α-linolenic acid as an active ingredient. As the α-linolenic acid ester, triglycerides containing α-linolenic acid or α-linolenic acid ethyl ester are preferred. DETAILED DESCRIPTION OF THE INVENTION As a result of extensive research, the present inventors have discovered that preparations such as fat infusions containing α-linolenic acid esters have the surprising effect of lowering blood cholesterol content. Based on this finding, we have completed this invention. As the α-linolenic acid ester used in the present invention, triglyceride containing α-linolenic acid as a component, α-linolenic acid ethyl ester, etc. are preferably used. Triglycerides containing α-linolenic acid as a component are contained, for example, in linseed oil. Further, 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. α which is the active ingredient of the anti-arteriosclerosis preparation of the present invention
- The dosage of linolenic acid ester varies depending on the symptoms, but is generally 1 to 30 g per day for adults, preferably 4 to 10 g, and 1 to 3 g as necessary depending on the symptoms.
It is best to administer in divided doses. The administration method may be intravenous injection or any other arbitrary method. The α-linolenic acid ester may be administered alone, or may be dissolved or dispersed in a liquid, as a mixture with various other ingredients, or as a combination with other drugs. When used as a mixture or compound with other ingredients,
The amount of the above active ingredients is preferably 1 to 10 W/V%. Forms of preparations include tablets, sugar-coated tablets, powders, capsules, granules, suspensions, emulsions, injections, and the like. Examples of carriers or excipients include calcium carbonate, calcium phosphate, starch, glucose,
Examples include lactose, dextrin, alginic acid, mannitol, talc, and magnesium stearate. When the anti-arteriosclerosis preparation according to the present invention is used in the form of a fat infusion, the above-mentioned α-linolenic acid ester can be further mixed with, for example, purified soybean oil or purified safflower oil. In that case, the blending ratio of refined soybean oil or refined safflower oil is preferably 0 to 95% W/V in the fat. A fat infusion preparation can be prepared by dispersing distilled water for injection, fat, purified egg yolk lecithin, and glycerin, and emulsifying the dispersion under pressure. In this case, it is preferable that the fat be 5 to 20 W/V%, the purified egg yolk lecithin be 1 to 2 W/V%, and the glycerin be 2 to 3 W/V%. The content of the ester derivative of α-linolenic acid in the fat is preferably 10 to 100 W/V%. Next, the present invention will be explained in more detail by showing Examples and Test Examples when formulated as a fat infusion. Example 1 50 g of α-linolenic acid ethyl ester, 450 g of purified soybean oil, 60 g of purified egg yolk lecithin. Oleic acid 2.5
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, the fat infusion is sterilized using high-pressure steam at 118°C for 22 minutes. After sterilization, OV-
Vacuum package with film (manufactured by Unitika). Example 2 100g α-linolenic acid triglyceride, 300g purified soybean oil, 48g purified egg yolk lecithin, 2.0g oleic acid, 100g concentrated glycerin, 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. Test Example Blood Cholesterol Lowering Effect An experiment was conducted using 5-week-old male rats (Sprague Dawley strain) in groups of 5 rats. 15 ml of the fat infusion prepared in the above example was administered to rats through the tail vein for 1 hour each for 4 days. Furthermore, from the day the infusion was started, 10ml of 2W/V% cholesterol suspension, which is made by suspending cholesterol in 0.5W/V% Metrose (trade name, manufactured by Shin-Etsu Chemical Co., Ltd.) aqueous solution, was administered twice a day for 4 days. Administer orally. In addition to the fat infusion, the animals were fed 20 g of non-fat solid feed (manufactured by CLEA Japan Co., Ltd.) per day. As a comparative example, a commercially available fat infusion containing purified soybean oil at 10 W/V% in the fat infusion was administered. After administration for 4 days, the animals were fasted, and on the 5th day, blood was collected from the abdominal aorta, the serum was centrifuged, and cholesterol in the blood was measured by an enzymatic method (measuring kit: V-cholestase, manufactured by Nippon Pharmaceutical Co., Ltd.). The results are shown in Table 1.

[Table] As is clear from Table 1, the anti-arteriosclerotic preparation containing an ester of α-linolenic acid as an active ingredient according to the present invention exhibits a superior effect on lowering the amount of cholesterol in the blood compared to the comparative example. There is. In addition, as a result of performing a t-test, it became clear that both Examples 1 and 2 had a significant difference with respect to the comparative example at a risk rate of 5%. Acute toxicity Male rat (Sprague Dawley)
Dawley system), it was confirmed that the anti-arteriosclerosis preparation according to the present invention is extremely safe, similar to commercially available soybean oil-containing fat infusion preparations.
The results are shown in Table 2.

[Table] Effects of the Invention As described above, according to the present invention, an anti-arteriosclerosis preparation containing an ester of α-linolenic acid as an active ingredient is provided. The anti-arteriosclerosis preparation according to the present invention has a remarkable effect of lowering blood cholesterol level and can be used safely without side effects or other toxicity. Therefore, therapeutic agents for arteriosclerosis, that is, hardening of the aorta and coronary arteries, myocardial infarction, cerebral thrombosis, aortic aneurysm, peripheral artery occlusion, hyperlipidemia, diabetes, etc., caused by excessive cholesterol in the blood. It can be usefully used as a preventive agent.

Claims (1)

[Scope of Claims] 1. An anti-arteriosclerotic preparation containing an ester of α-linolenic acid as an active ingredient. 2. The anti-arteriosclerotic preparation according to claim 1, wherein the ester of α-linolenic acid is a triglyceride containing α-linolenic acid or ethyl α-linolenic acid.