JPS60197621A - Hypocholesterolemic - Google Patents

Abstract

PURPOSE:A hypocholesterolemic containing delta-tocopherol as an active ingredient. CONSTITUTION:The objective hypocholesterolemic is obtained by using an effective amount of delta-tocopherol (a tocopherol mixture in which the concentration has been increased more than 50% in composition proportion, containing alpha-, beta-, gamma-, delta-tocopherols), when needed additionally an appropriate carrier and diluents are combined. The drug reduced remarkably serum cholesterol and can be effectively used as a preventive for arteriosclerosis, hypertension, thrombosis, stenocardia, cerebral hemorrhage and myocardiac infarction. There is no axiety of side-effect and toxicity, because a kind of vitamin E is used as an active ingredient.

Description

DETAILED DESCRIPTION OF THE INVENTION This invention relates to a novel cholesterol-lowering agent containing δ-tocopherol as an active ingredient.

[Prior art]

Hypercholesterolemia is considered to be one of the three major risk factors for arteriosclerosis, along with hypertension and smoking. Therefore, many studies have been conducted on the relationship between hypercholesterolemia and arteriosclerosis, and serum cholesterol levels have a very high position as a risk factor for coronary atherosclerosis. It is recognized that there is a close relationship6.

Drugs that suppress cholesterol synthesis, such as clofibrate, are mainly used to lower serum cholesterol levels, but these drugs generally take large doses and are taken for long periods of time, which can cause gastrointestinal disorders. It also has drawbacks such as side effects such as liver damage and difficulty in taking it.

[Purpose of the invention]

The present invention aims to provide a drug that effectively lowers cholesterol without causing side effects such as gastrointestinal disorders or liver disorders even when taken over a long period of time.

[Structure of the invention]

The cholesterol-lowering agent of the present invention is characterized by containing 6-) core tocopherol as an active ingredient.
) is known as vitamin E, and its actions can be broadly divided into biological activity and antioxidant action against fats and oils, but it is thought that there are still unknown actions.

It is known that there are four homologs of tocopherol, α-1β-, r-, and δ, and the biological activity is α-9.
It is said that it decreases in the order of β-9r-9δ=. Non-α
It has been reported that even if α-unit is administered, its absorption and utilization is low, so it is thought that α-unit is selectively utilized in humans as well. For these reasons, only α monomers are currently used for pharmaceutical purposes.

The present inventor obtained the new knowledge that μ, δ-tocopherol has an extremely superior effect on lowering blood cholesterol, even though its betavitamin E activity is 1/100 that of α-tocopherol. completed.

In the present invention, δ-tocopherol may be separated from other tocopherols and used alone, or a mixture of δ-tocopherol in an effective amount, e.g., 50% or more in composition ratio, may be used. -1β-91-
A mixture of eδ-tocopherol may be used, or 6-tocopherol may be used together with other suitable pharmaceutical carriers and diluents.

The δ-tocopherol used in the present invention is known to be contained in vegetable oils such as soybean oil, wheat germ oil, sesame oil, and rice bran oil, and can be produced using known manufacturing methods such as the above-mentioned deodorizing process of the vegetable oil. The deodorized distillate (so-called deodorized scum) obtained is subjected to molecular distillation, or dissolved in an organic solvent and adsorbed on an ion exchange resin or adsorption chromatography, and then an organic solvent is used to separate each of the seven tocopherols. It can be obtained by a method of fractionating lacquerware, a synthesis method, etc., but its production method and origin are not particularly limited.

Note that the isolated δ-tocopherol is already commercially available for use as an antioxidant, so it is possible to use this commercially available product.

In addition, by adding isolated J-) copherol to mixed tocopherol or selectively concentrating δ-tocopherol in mixed tocopherol, J-) core i
The effects of the present invention can be obtained even when mixed tocopherols with a roll composition ratio of 50% or more are used.

Although the cholesterol-lowering agent of the present invention can be in any form, it is mainly used in the form of tablets, granules, powders, liquids, capsules, and the like.

〔Effect of the invention〕

The cholesterol-lowering agent of the present invention has a remarkable effect of lowering blood cholesterol, and is effective against diseases such as arteriosclerosis, high blood pressure, blood clots, angina pectoris, stroke, myocardial infarction, etc., which have been increasing in recent years. It is extremely effective in preventing adult diseases. The cholesterol-lowering agent of the present invention contains one type of vitamin E as an active ingredient and does not cause problems such as drug damage that have conventionally tended to occur even when administered continuously for a relatively long period of time, and there is no fear of toxicity.

Next, an experimental example will be explained in order to further clarify the effects of the present invention.

Experimental Example Confirmation of the effect of lowering plasma cholesterol and triglyceride in rats by administration of α-tocopherol and J-)co7erol Four-week-old SD male rats were divided into 5 groups of 6 rats per group.

Feed includes cholesterol α5%, cole rice sodium (
As a control, those that are likely to develop hypercholesterolemia loaded with 125% α-α-tocopherol α
5% and 15% d-δ-tocopherol were added.

After feeding these feeds for 2 weeks on average for 91 days, blood was collected from the tails of the rats in each group, and plasma cholesterol and triglyceride as triglycerides were measured by an enzymatic method. The results are shown in Table 1.

Table 1 Total cholesterol - HDL cholesterol Expressed as HDL cholesterol.

As can be seen from the results in the table above, there was no significant difference in plasma total cholesterol in the α-tocopherol group, which is considered to be lower than the control in Group 1, but in the δ-tocopherol group in Group 5.
- In the tocopherol group, the increase was clearly suppressed. There was no significant difference between the three groups regarding HDL cholesterol, which is usually said to be good cholesterol and the higher the value, the better.
The tocopherol group clearly showed significantly lower values. Furthermore, regarding triglycerides, for which lower values are considered better, a significant increase in triglycerides was observed in the second group.

From the above results, α-tocopherol cannot suppress the rise in blood cholesterol as per conventional knowledge, while δ-tocopherol, which is said to have only 1/100 of the physiological activity of α-tocopherol, It was observed that the use of the same amount of alpha monomer showed a significant reduction in blood cholesterol.

〔Example〕

Some examples of formulations are shown below in Examples. Note that the preparations are not limited to these. In the examples, parts indicate parts by weight unless otherwise specified.

Example 1 Soft capsule δ-tocopherol (manufactured by Eisai ■, (-Mix D1)
(purity 94.8%) was mixed with 70 parts of wheat germ oil,
The mixture was heated to about 60° C. and stirred to uniformly dissolve it.

Separately, 60 parts of gelatin, 30 parts of glycerin, and 10 parts of water were uniformly mixed and formed into a film, which was then injection molded into a capsule having a capacity of 500 square meters to produce a gelatin container.

The above-mentioned liquid mixture was poured into this container, and then the injection port was sealed by heating to obtain the cholesterol-lowering agent of the present invention.

Example 2 Tablet 11) δ-tococoa o -A/... Old... Mountain...
...River...5o part (11) Lactose...
・・・・・・・・・・・・・・・・・・・・・・・・
・・・・・・・・・・・・・・・・・・・・・・suitable
Amount (ml) Crystalline Cellulose・・・・・・・・・・・・・
・・・・・・・・・・・・・・・・・・・・・60
Part IVI Potato powder・・・・・・・・・・・・・・・
・・・・・・・・・・・・・・・・・・・・・・・・
・54 parts (v) Magnesium stearate...
・・・・・・・・・ Part 2 Of the above, (I) ~ (:V
) and a portion of (1v) that had been separated in advance was added to 10
% starch paste and form into granules. After drying the granules and removing the powder that did not become granules with a sieve, M was added and mixed, and the tablets were compressed using a tablet machine to give 200 tablets per tablet.
■Tablets. The tablets may be coated with commonly used sugar coating, if necessary.

Example 3 Capsule (1) δ-tocopherol・・・・・・・・・・・・
・・・・・・・・・50 parts (11) Calcium hydrogen phosphate・・・・・・・・・・・・・・・・・・50 parts (lit) Aluminum silicate...・・・・・・・・・
・・・・・・・・・・・・・・・・・・411(iV) Crystalline cellulose・・・・・・・・・・・・・・・・・・・
・・・・・・・・・・・・・・・60 parts M magnesium stearate・・・・・・・・・・・・・・・ 2 parts Mix the above (1) to (v), After passing through a sieve and mixing thoroughly, make 200 capsules per capsule according to a conventional method.

Example 4 Soft capsules Total tocopherol (vitamin E) 340 parts (δ-tocopherol 200 parts) Soybean lecithin 500 parts Liel Yabu, Rirun #R (vitamin F) 320 parts A uniform mixture of the above was prepared as in Example 1. One capsule is 300 W.

゛Patent applicant Hounen Oil Co., Ltd.

Claims (1)

[Claims] (1) A cholesterol-lowering agent containing δ-tocopherol as an active ingredient. (The cholesterol-lowering agent according to claim 1, which comprises mixed tocopherols containing δ-tocopherol in a composition ratio of 2150% or more.