JPH0733672A - Arteriosclerosis inhibitor and composition containing the same - Google Patents

Abstract

PURPOSE:To obtain an arteriosclerosis inhibitor having sufficiently improving action on imbalance of lipid amount in blood, excellently inhibitory effect on arteriosclerosis and high safety. CONSTITUTION:An arteriosclerosis inhibitor is mixed with an extract of a plant of the genus Ligustrum of the family Olaceae. Otherwise, the arteriosclerosis inhibitor is added to a composition such as a food or a medicine.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an arteriosclerosis inhibitor and a composition containing the same, and more specifically, an arteriosclerosis inhibitor containing an extract of a plant of the genus Iridaceae as an active ingredient and the arteriosclerosis inhibitor. A composition containing an agent.

[0002]

2. Description of the Related Art In recent years, as westernization of eating habits has advanced,
The amount of fat intake per capita has continued to increase, and in particular, the increase in total fat intake in young people and the increase in animal fat intake in all age groups are particularly remarkable. For this reason, excessive intake of fat causes an imbalance of blood lipid levels to cause hyperlipidemia, and many people suffer from circulatory adult diseases such as arteriosclerosis. Is becoming a youthful social problem and is one of the social problems.

In order to suppress such adult diseases of the circulatory system, as a method for improving pathological conditions in which the lipid content in blood is out of balance, such as hyperlipidemia which causes arteriosclerosis, etc. Methods such as ingesting polyunsaturated fatty acids such as linoleic acid and methods such as using clofibrate and nicotinic acid have been taken.

However, polyunsaturated fatty acids have a problem of excessive intake in addition to long-term continuous use, and clofibrate has side effects such as muscle cramps, and nicotinic acid also has side effects such as systemic flushing and gastric disorders. There was a problem that there was.

By the way, plants belonging to the genus Iridaceae of the family Oleaceae include, for example, ligustrum purpurasens and ligustrum pedonclare. These plants are said to have anti-inflammatory and anti-fatigue effects in China and have been used since ancient times.

However, it is not known that the extracts of these plants have the effect of improving the balance of blood lipid levels, and attempts to suppress arteriosclerosis by utilizing these are still reported. It has not been.

[0007]

The present invention has been made from the above point of view, has an effect of sufficiently improving the balance of blood lipid levels, and has an excellent effect of suppressing arteriosclerosis,
An object of the present invention is to provide an arteriosclerosis inhibitor with high safety and a composition containing the same.

[0008]

[Means for Solving the Problems] In order to solve the above problems, the present inventor has eagerly searched for a component having an action to improve the imbalance in the blood lipid level, and as a result, extracted the plant of the genus Iridaceae from the family Oleaceae. It was found that there is a component having an excellent blood lipid amount balance improving action in the product, and the present invention has been completed.

That is, the present invention is an arteriosclerosis inhibitor containing an extract of the plant of the genus Iridaceae as an active ingredient, and a composition such as a food or a drug containing the arteriosclerosis inhibitor.

The present invention will be described in detail below.

<1> Inhibitor of Arteriosclerosis of the Present Invention (1) Extract of Botanical Plant of the Family Oleaceae The arteriosclerosis inhibitor of the present invention contains an extract of the plant of Genus Botanaceae of the family Oleaceae as an active ingredient.

[0012] First, the plant of the genus Iridaceae, which is used in the present invention, means, for example, Ligustrum purpense (Ligustrum purpense), which is often collected in the Yunnan region of China.
urascens YCYang), a Ligustrum pedunc (Ligustrum pedunc) that is also often collected in Sichuan, China.
ulare Rhed.), Ligustrum lucidumAi
t.), mugwort (Ligustrum japonicum Thumb.), and the like. Among them, ligustrum purpurasens and ligustrum pedonclare are particularly preferably used in the present invention.

The above-mentioned plant of the genus Iridaceae contains a component having an action of improving the balance of blood lipid level, and it is possible to use crushed leaves as they are, but an extract containing the above component by extraction. It is preferable to take out and use as an active ingredient of the arteriosclerosis inhibitor of the present invention. In the present invention, the extract may be any of such a pulverized product and an extract, a fraction described below, or a concentrate thereof, or a mixture thereof.

The extraction treatment of the plant of the genus Iridaceae of the family Asteraceae is carried out by a continuous method, a batch method or the like by a conventional method such as cold soaking or warm soaking for an arbitrary time. For example, leaves of the plant of the genus Iridaceae are minced and immersed in an extraction solvent at room temperature for 1 to 3 days or at the boiling temperature of the extraction solvent for 1 to 5 hours for extraction. Then, remove the extraction residue from the extract,
The extract is concentrated by performing vacuum or ultrafiltration. further,
If necessary, the organic solvent is completely distilled off to dryness or freeze-drying.

The solvent used for extraction is preferably water and / or a polar organic solvent. Examples of the polar organic solvent include methanol, ethanol, and acetone. These may be used alone or in combination of two or more, or may be a mixed solvent of these and water.

The extract thus obtained may be used for formulation, but a fraction containing a high concentration of a component having an action of improving the balance of blood lipid level in the extract May be used. In order to obtain the fractionated product, a method such as column chromatography in which the above extract is passed through a column packed with an adsorption distribution type packing material, a gel filtration agent, or the like is used.

For example, the above extract is dissolved in purified water,
When passed through Amberlite XAD-2 (porous styrene-divinylbenzene copolymer, manufactured by Organo Co., Ltd.), components having an action of improving the balance of blood lipid content are adsorbed by Amberlite XAD-2. By eluting this adsorbate with ethanol, acetone, or the like, a fraction containing the above components in a high concentration can be obtained as a solution of the solvent. Further, if necessary, the solvent may be completely distilled off from the solution to dry it. Further, as a modification of this method, fractionation processing can be performed by a batch method.

If necessary, the extract may be degreased by a conventional method using a non-polar solvent such as n-hexane or petroleum ether before the fractionation.

(2) Arteriosclerosis Inhibitor The arteriosclerosis inhibitor of the present invention contains an extract of the plant of the genus Iridaceae, as described above. Further, these extracts may be directly used as a preparation, or may be mixed with various bases to give a preparation.

The compounding amount and the kind of the base are not particularly limited and may be appropriately set. As the base, for example, oral bases such as tablets, capsules and drinks are preferable.

<2> Composition Containing Arteriosclerosis Inhibitor of the Present Invention The composition of the present invention is a composition in which the above arteriosclerosis inhibitor is blended according to a conventional method, and examples thereof include foods and pharmaceuticals. .

When the above-mentioned arteriosclerosis inhibitor is used in food, as a general food, the required amount of the extract is added to each food material, and the food is processed and manufactured by a usual manufacturing method. As a functional food, a plant, an extract, or a fractionated product can be used as it is or in an easily eatable state.

The dosage form of the pharmaceutical composition of the present invention is not particularly limited, but is generally one or more kinds of vehicles, carriers, excipients, excipients, integrators, preservatives, stabilizers, which are generally harmless in terms of formulation, It is preferable to mix it with a flavoring agent or the like to prepare an oral dosage form such as tablets, granules, capsules and drenches. These can be manufactured using a conventionally known technique.

The content of the above-mentioned arteriosclerosis inhibitor in these compositions is usually 10 to 2000 mg / kg per day for an adult as an extract of the plant of the genus Iridaceae of the family Oleaceae.
Preferably, 30 to 100 mg / kg, 5 in the fraction.
~ 1000 mg / kg, preferably 15-50 mg /
It is kg.

[0025] Many plants of the genus Iridaceae belonging to the family Oleaceae are widely used for drinking as tea in China, and there is no problem in terms of safety.

[0026]

EXAMPLES Examples of the present invention will be described below. First, examples of the arteriosclerosis inhibitor of the present invention will be shown.

[0027]

[Example 1] Dried rigs trim Purpurasense leaves finely chopped into 5 to 10 mm length 100 g of purified water 1
000 ml was added and reflux extraction was performed at 105 ° C. for 3 hours.
Then, this was filtered, and the obtained filtrate was concentrated by a rotary evaporator under reduced pressure. This concentrated solution was freeze-dried to obtain 30.5 g of Ligustrim purpurense extract. This extract was a brown amorphous solid having a characteristic odor and was hygroscopic. This was directly used as an arteriosclerosis inhibitor.

[0028]

Example 2 By the same method as in Example 1 above, 34.3 g of an extract was obtained from the leaves of Ligustri pedonclare. Similar to the extract of Example 1, this extract was a brown amorphous solid having a unique odor and having hygroscopicity. This was directly used as an arteriosclerosis inhibitor.

[0029]

Example 3 6.0 g of the Ligustrim purpurense extract obtained in the above Example 1 was dissolved in 30 ml of purified water, passed through a column filled with 120 ml of Amberlite XAD-2, and then passed through 500 ml of purified water. ,
The obtained elution part was used as a non-adsorbed fraction. Next, in order to obtain an adsorption part, a 99.5% ethanol aqueous solution 5 was added to the above column.
The eluate was distilled off with a rotary evaporator. Thus, 3.3 g of a 99.5% ethanol-eluted fraction was obtained.

Of the fractions obtained as described above,
Only the 99.5% ethanol-eluted fraction was found to have an effect of improving blood lipids. The fraction is a light brown amorphous solid having a unique odor and hygroscopicity, and is soluble in water, methanol, ethanol, etc., but insoluble in n-hexane, diethyl ether, etc. , The ferric chloride reaction was positive.

TLC (PSC-Frtigplatten Kieselgel 60
: MERCK), 50% sulfuric acid was sprayed with a developing solvent of chloroform: methanol = 10: 1, and then R was developed by heating and coloring.
_It was confirmed as several spots with an _f value of 0.00 to 0.27. Under the same conditions, when the developing solvent was chloroform: methanol: water = 45: 15: 2, several spots were confirmed at R _f values of 0.03 to 0.62. This was directly used as an arteriosclerosis inhibitor.

[0032]

Example 4 In exactly the same manner as in Example 3, 3.4 g of 99.5% ethanol-eluted fraction was obtained from the extract of ligustrim pedon-clare obtained in Example 2.

Like the fraction of Example 3, this is a light brown amorphous solid having a characteristic odor and having a hygroscopic property.
It was soluble in water, methanol, ethanol, etc., but insoluble in n-hexane, diethyl ether, etc., and was positive for the ferric chloride reaction.

TLC (PSC-Frtigplatten Kieselgel 60
: MERCK), 50% sulfuric acid was sprayed with a developing solvent of chloroform: methanol = 10: 1, and then R was developed by heating and coloring.
_It was confirmed as several spots with an _f value of 0.00 to 0.27. Under the same conditions, when the developing solvent was chloroform: methanol: water = 45: 15: 2, several spots were confirmed at R _f values of 0.03 to 0.62. This was directly used as an arteriosclerosis inhibitor.

<Evaluation of Arteriosclerosis Inhibitor of the Present Invention> The arteriosclerosis inhibitory effect of the arteriosclerosis inhibitor obtained in each of the above Examples was evaluated.

1 in a breeding room adjusted to a room temperature of 22 ± 1 ° C.
Five groups of 10-week-old male ICR mice of each group were preliminarily bred for 4 weeks by allowing them to freely take a mixed solid feed of CE-2 (80%) and cellulose powder (20%) manufactured by CLEA Japan, Inc. and water. did.

Thereafter, the blank group was mixed with the mixed solid feed having the same composition as the mixed solid feed and water, and the control group and the test groups 1 and 2 were CE-2 (8 manufactured by CLEA Japan, Inc.).
0%) and lard (20%) mixed solid feed and water were freely taken, while 1% by weight sodium carboxymethylcellulose aqueous solution was used for the blank group and the control group, and the test groups 1 and 2 were used for the above. Examples 1, 2
The 1% by weight sodium carboxymethyl cellulose aqueous solution containing 10% by weight of the arteriosclerosis inhibitor obtained in each was orally administered at a dose of 0.5 ml / animal / day for 2 weeks.

After the administration, all mice were fasted for 16 hours and blood was collected. Serum was collected from the obtained blood by an ordinary method, and the total cholesterol amount was measured by the enzyme method, and the HDL-cholesterol amount was measured by the heparin-Mn precipitation enzyme method.

In addition to the total cholesterol amount and the HDL cholesterol amount, the value obtained by subtracting the HDL cholesterol amount from the total cholesterol amount and dividing by the HDL cholesterol amount was used as an arteriosclerosis index. The result
The average value of 10 mice in each group is shown in Table 1 together with the standard deviation. Incidentally, * in the table is 5 with respect to the control group.
% Of risk, ** 1 against control group
A risk rate of less than% indicates that there are significant differences.

[0040]

[Table 1] Next, the same test was performed for the arteriosclerosis inhibitors of Examples 3 and 4. However, the dose of the arteriosclerosis inhibitor was 3.3 g for the arteriosclerosis inhibitor of Example 3, and
For the arteriosclerosis inhibitor of 3
It was dissolved in 1 ml of a 1% by weight sodium carboxymethyl cellulose aqueous solution, and the ratio was 0.5 ml per animal per day. The results are shown in Table 2 as the average value of 10 mice in each group together with the standard deviation. In the table, * indicates a risk rate of less than 5% with respect to the control group, and ** indicates a risk rate of less than 1% with respect to the control group, each showing a significant difference.

[0041]

[Table 2] As shown in Tables 1 and 2, the mice to which the arteriosclerosis inhibitor of the present invention was administered have an action of significantly suppressing the increase in arteriosclerosis index, as compared with the mice to which only the sodium carboxymethylcellulose solution was administered, Furthermore, it is clear that it increases the proportion of HDL cholesterol in the total cholesterol.

<Acute toxicity test> dd with a body weight of 13 to 19 g
An acute toxicity test was conducted by oral administration using 10 mice per group of mice. As a sample, an aqueous solution containing 30% by weight of the arteriosclerosis inhibitor obtained in Example 1 was used, and 12.0 g / kg was used.
After 72 hours from oral administration, life or death was determined. As a result, none died and no difference from the normal animal group was observed in the subsequent observation for 1 week.

Next, examples of the composition containing the arteriosclerosis inhibitor of the present invention will be described. In addition, all compounding amounts used below are parts by weight.

[0044]

Example 5 Candy The component A in Table 3 was heated and dissolved at 150 ° C., cooled to 120 ° C., the component B was added, and the mixture was stirred and molded into a uniform product.
Cooled into candy.

[0045]

[Table 3]

[0046]

Example 6 Gummies In Table 4, component A was heated and dissolved at 110 ° C., component B separately swollen and dissolved was added, component C was further added, and the mixture was poured into a mold, left for one day and night, and then removed from the mold to produce a gummy. .

[0047]

[Table 4]

[0048]

Example 7 Capsule A component in Table 5 was mixed and stirred to make it uniform, and B component was added thereto and kneaded sufficiently by a kneader. This was encapsulated by a capsule filling machine to obtain a product.

[0049]

[Table 5]

[0050]

Example 8 Tablet The ingredients shown in Table 6 were uniformly mixed, granulated by a flow method and then dried. This was tableted with a tableting machine to obtain a product.

[0051]

[Table 6]

[0052]

[Examples 9 and 10] Granules A component in Table 7 was sieved with No. 60 sieve and uniformly mixed, and then put into a kneader, and 5% aqueous solution of B component was added to knead the mixture. did. Then, after sieving with 18 combined sieves, air drying was performed at 50 ° C. for 24 hours. It granulates after drying and the granules of Examples 9 and 10 were manufactured.

[0053]

[Table 7]

[0054]

The arteriosclerosis-inhibiting agent of the present invention and the composition containing the same have the effect of sufficiently improving the imbalance of the blood lipid content, and are excellent in the effect of suppressing arteriosclerosis.
Moreover, it is highly safe.

 ─────────────────────────────────────────────────── ─── Continuation of front page (72) Inventor Chen Xinmin, 4th Section, Chengdu South People's Road, Chengdu, Sichuan, China 4th Section, Chengdu Institute of Biological Research, Chinese Academy (72) In Yang Yang, 4th Section, Chengdu South Road, Chengdu, Sichuan, China Chengdu Institute of Biological Research, Chinese Academy

Claims (4)

[Claims] 1. An arteriosclerosis inhibitor containing as an active ingredient an extract of a plant of the genus Ibotanaceae of the family Oleaceae. 2. The arteriosclerosis inhibitor according to claim 1, wherein the plant of the genus Ignatia of the family Oleaceae is selected from Ligustrum purpurasens and Ligustrum pedonclare. 3. The arteriosclerosis inhibitor according to claim 1 or 2, wherein the extract is extracted with water and / or a polar organic solvent. 4. A composition containing the arteriosclerosis inhibitor according to claim 1.