JP3204348B2 - Arteriosclerosis inhibitor and food or medicine containing it - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to an arteriosclerosis inhibitor, a food containing the same, and a pharmaceutical composition containing the same for treating cardiovascular diseases.

[0002]

2. Description of the Related Art In recent years, as eating habits have become westernized,
The per capita fat intake continues to increase, with a marked increase in total fat intake among young people and animal fat intake among all ages. For this reason, excessively ingested fat may cause an imbalance in blood lipids or hyperlipidemia. These trigger many people to suffer from adult diseases of the circulatory system such as arteriosclerosis, and also cause a younger phenomenon of adult diseases of the circulatory system, which is one of the major social problems.

[0003] In order to prevent such an increase in cardiovascular adult diseases, it is necessary to improve the balance of blood lipids such as hyperlipidemia which causes arteriosclerosis. Thus, a method of ingesting a polyunsaturated fatty acid such as linoleic acid and a method of using chlorofibrate, nicotinic acid, and the like have been known.

However, ingestion of polyunsaturated fatty acids requires long-term continuous use, and there is a problem of excessive intake. Chlorofibrate has side effects such as muscle spasm. There was a problem that there were side effects.

[0005]

Accordingly, the present invention provides a highly safe arteriosclerosis inhibitor which has an effect of improving the balance of blood lipid content, has an excellent effect of suppressing arteriosclerosis, and is highly safe. It is intended to provide a food or a pharmaceutical composition for treating a circulatory disease containing the same.

[0006]

Means for Solving the Problems In view of the above situation, the present inventors have selected a Chinese herbal medicine which has been used since ancient times and is considered safe for its use, As a result of extensive screening using the arteriosclerosis inhibitory action as an index, the inventors found that an extract of licorice had an excellent arteriosclerosis inhibitory action and completed the invention.

Accordingly, the present invention relates to an arteriosclerosis inhibitor comprising an extract of licorice.

[0008] The present invention also relates to a food containing the above-mentioned arteriosclerosis inhibitor.

Further, the present invention relates to a pharmaceutical composition for treating cardiovascular diseases, comprising the above-mentioned arteriosclerosis inhibitor.

By the way, the licorice used in the present invention,
This is a generic term for plants belonging to the genus Glycirridae,
abra L.), Nankin licorice (G.glabra L.var glandu)
rifera Regel et Herder, G.uralen
sis Fisch.et DC), Chinese elephant (G. echinata L.),
Dog liquorice (G. pallidiflora Maxim), Maruti licorice (G.
infrata BAT), which has been widely used as a herbal medicine in China and in Japan since ancient times. Its medicinal properties in Chinese medicine are analgesia, antipyretic, antitussive, etc., and no improvement in blood lipid balance or arteriosclerosis inhibitory action was known at all.

[0011] The licorice contains a substance having an effect of improving the balance of the amount of lipids in blood, and it is possible to use whole pulverized plants. It is preferable to use it as an active ingredient of the arteriosclerosis inhibitor of the present invention. The whole plant can be used as a plant part to be used, but a root or rhizome rich in medicinal ingredients is preferable. In the present invention, the extract refers to one or more selected from such a pulverized product and an extract, a fractionated product described below, or a concentrate thereof.

The licorice extraction process is carried out by a conventional method, such as a continuous method or a batch method, by cold or hot digestion for an arbitrary time. For example, after drying the roots and rhizomes of licorice, shred,
It may be immersed in the extraction solvent at room temperature for 1 to 3 days or at the boiling temperature of the extraction solvent for 1 to 5 hours. At this time, as the extraction solvent to be used, water and polar organic solvents such as alcohols and acetones are preferable, and these may be used alone or in combination of two or more. Thereafter, if necessary, the solvent may be removed by filtration, or concentrated by reduced pressure or ultrafiltration to dry the solvent. A preferred product is a product obtained by extracting the hot water, followed by filtration and freeze-drying. This product is a brown hygroscopic amorphous material.

[0013] The extract thus obtained may be used in the preparation of a pharmaceutical preparation, and a fraction containing a high concentration of a component having an effect of improving the balance of blood lipid content in the extract may be used. May be. In order to obtain a fraction, it is preferable to remove a portion having a small effect and a remarkably high polarity from the extract, and the method includes a liquid-liquid extraction method, an adsorption column chromatography method, and a partition column chromatography method. , GPC column chromatography and the like. Among them, the distribution column chromatography method using a porous styrene divinylbenzene copolymer as a carrier is the simplest and preferable.

To obtain a fraction using a porous styrene-divinylbenzene copolymer, for example, the following procedure may be performed. That is, a solution obtained by dissolving the above extract in purified water is passed through Amberlite XAD-2 (manufactured by Organo Corporation), washed sufficiently with purified water, and eluted with a polar organic solvent such as alcohol. Further, it may be carried out by a batch method, or may be subjected to a degreasing treatment with normal hexane or petroleum ether in advance.

Both the extract and the fraction thus obtained can be used as an arteriosclerosis inhibitor. The arteriosclerosis inhibitor may be used as a preparation as it is, or may be mixed with various bases to prepare a preparation.

The compounding amount and the type of base are not particularly limited, and may be appropriately set according to the dosage form. For example, as pharmaceuticals, tablets, powders, granules, capsules, suppositories And injections, liquid preparations, etc., which may be formulated in a usual manner together with bulking agents, excipients, lubricants, disintegrants, binders, flavoring agents and the like.

As foods, general foods can be prepared by adding the required amount of extract to various food ingredients and processing them by a usual production method. The fraction can be used as it is or in a state where it is easy to eat.

The daily dose of the above-mentioned arteriosclerosis inhibitor in these compositions varies depending on symptoms, height, weight, age, etc., but it is 1 to 2000 mg / adult per adult.
Kg, preferably 3 to 100 mg / Kg, may be administered once or several times.

It is clear that the safety of the arteriosclerosis inhibitor of the present invention is superior to that of licorice, which has been widely used as a Chinese herbal medicine since ancient times.

[0020]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples, but it goes without saying that the present invention is not limited to these Examples.

Embodiment 1 Production Example 1. 1000 ml of purified water was added to 100 g of the licorice root and rhizome chopped to a length of 5 to 10 mm, and the mixture was extracted by refluxing at 105 ° C. for 3 hours. After cooling, the filtrate was collected by filtration, concentrated under reduced pressure, and freeze-dried to obtain 21.9 g of an arteriosclerosis inhibitor as a brown amorphous.

Embodiment 2 FIG. Production Example 2. 6 g of the arteriosclerosis inhibitor of Production Example 1 was dissolved in 30 ml of purified water, passed through a column filled with Amberlite XAD-2, and further washed with 500 ml of purified water. This was eluted with 500 ml of 99.5% ethanol, and concentrated under reduced pressure to obtain 2.0 g of an arteriosclerosis inhibitor.

Embodiment 3 FIG. Production Example 3 5-10 mm for roots and rhizomes of Uralkan elephant
1000 g of purified water was added to 100 g of the mixture cut into lengths, and the mixture was refluxed at 105 ° C. for 3 hours and extracted. After cooling, the filtrate was collected by filtration, concentrated under reduced pressure, lyophilized, and dried.
7.8 g of arteriosclerosis inhibitor was obtained as brown amorphous.

Embodiment 4 FIG. Production Example 4. 5-10 m of roots and rhizomes of licorice
500 g of purified water and 500 ml of ethanol were added to 100 g of the m-sized pieces, and the mixture was extracted by refluxing at 105 ° C. for 3 hours. After cooling, the filtrate was collected by filtration, concentrated under reduced pressure, and freeze-dried to obtain 18.4 g of an arteriosclerosis inhibitor.

Embodiment 5 FIG. Acute toxicity toxicity test An acute toxicity test by oral administration was performed using ten ddy mice weighing 15 to 25 g per group. The samples were from Examples 1 to
The arteriosclerosis inhibitor of No. 4 was used. 30% of each sample
It was made into a physiological saline solution and orally administered at a dose of 12 g / Kg. No deaths were found in any of the groups. This clearly shows that the arteriosclerosis inhibitor of the present invention has high safety.

Embodiment 6 FIG. Evaluation of Arteriosclerosis Inhibiting Action 1 The arteriosclerosis inhibitor of Examples 1, 3, and 4 was evaluated for its arteriosclerosis inhibitory effect. That is, 5 of 10 animals per group
Week-old ICR mice were pre-fed for 4 weeks with free access to water and a mixed solid feed of CE-2 (80%) and cellulose powder (20%) manufactured by CLEA Japan. Thereafter, the blank group received the mixed solid feed and water, and the control group, the administration group of Example 1, the administration group of Example 3, and the administration group of Example 4 exhibited CE-2 (80%) and lard (20%) high fat. A 1% by weight aqueous solution of sodium carboxymethylcellulose was added to the control group and the blank group at the same time while the mixed solid feed and water were freely ingested.
In the administration group of Example 4, 0.5 ml / mouse of a 1% by weight aqueous solution of sodium carboxymethylcellulose containing 10% by weight of the arteriosclerosis inhibitor of Examples 1, 3, and 4 was used.
Oral administration was performed at a daily dose for 2 weeks. After completion of the administration, all mice were fasted for 16 hours and blood was collected. Serum was separated from the obtained blood by an ordinary method, and the total cholesterol amount was measured by an enzyme method, and the HDL cholesterol amount was measured by a heparin-Mn precipitation enzyme method. The value obtained by subtracting the HDL cholesterol amount from the total cholesterol amount and dividing the HDL cholesterol amount by the HDL cholesterol amount was used as an arteriosclerosis index, and this value was used as an index of the arteriosclerosis inhibitory action. Table 1 shows the results. Note that * is a risk factor of less than 5% and ** is 1
Indicates that there was a significant difference from the control group at a risk rate of less than 10%. This indicates that the arteriosclerosis inhibitor of the present invention has an excellent arteriosclerosis inhibitory action.

[0027]

[Table 1]

Embodiment 7 FIG. Evaluation 2 of Arteriosclerosis Inhibitory Effect The arteriosclerosis inhibitor of Example 2 was evaluated in the same manner as in Example 6 for its arteriosclerosis inhibitory effect. Table 2 shows the results. This clearly shows that the arteriosclerosis inhibitor of the present invention has an excellent arteriosclerosis inhibitory action.

[0029]

[Table 2]

Embodiment 8 FIG. Formulation Example 1 to Candy The following component (A) is heated and melted at 150 ° C., cooled to 120 ° C., added with component (B), stirred to form a uniform product, and cooled to obtain a candy. Obtained. (A) sugar 58 syrup 30 (B) citric acid 1 arteriosclerosis inhibitor of Example 1 10 fragrance 1

Embodiment 9 FIG. Formulation Example 2 to Candy The following component (A) is heated and dissolved at 150 ° C., cooled to 120 ° C., and the component (B) is added. Obtained. (A) sugar 67 syrup 30 (B) citric acid 1 arteriosclerosis inhibitor of Example 2 1 fragrance 1

Embodiment 10 FIG. Example of formulation to gummy The following component (A) is heated and dissolved at 110 ° C., and the separately swelled and dissolved component (B) is added. The component (C) is further added and poured into a mold. Obtained. (A) sugar 40 starch syrup 45 (B) gelatin 8 (C) citric acid 2 arteriosclerosis inhibitor of Example 3 5

Embodiment 11 FIG. Example of formulation to gummies 2. The following component (A) is heated and dissolved at 110 ° C., and the separately swelled and dissolved component (B) is added. The component (C) is further added and poured into a mold. Obtained. (A) sugar 40 starch syrup 45 (B) gelatin 8 (C) citric acid 2 arteriosclerosis inhibitor of Example 4 5

Embodiment 12 FIG. Capsule The following component (A) is uniformly mixed and stirred, and then mixed with (B)
The ingredients were added and kneaded well with a kneader. This was encapsulated by a capsule filling machine to prepare a capsule. (A) squalene 15 linolenic triglyceride 15 wheat germ oil 10 purified sardine oil 20 α-d-tocopherol 0.2 (B) defatted soybean powder 39.8 Arteriosclerosis inhibitor 10 of Example 2

Embodiment 13 FIG. Tablets The following ingredients are mixed uniformly and granulated by a fluid bed granulation method.
Let dry. This was tableted with a tableting machine to obtain tablets. Dextrin 15 Lactose 5 Palatinose 15 Potato starch 40 Magnesium stearate 5 Arteriosclerosis inhibitor of Example 3 20

Embodiment 14 FIG. Granules The following component (A) is placed in a grading machine and granulated while dropping a 5% aqueous solution of component (B), and dried at 40 ° C.
The granules were sized to obtain granules. (A) Lactose 67.5 Corn starch 10 Arteriosclerosis inhibitor of Example 4 20 (B) Hydroxypropylcellulose 2.5

[0037]

EFFECTS OF THE INVENTION The arterial effect inhibitor of the present invention is highly useful in preventing and treating cardiovascular diseases, because it is highly safe and has an excellent inhibitory effect on arterial effect.

Continued on the front page (58) Fields surveyed (Int. Cl. ⁷ , DB name) A61K 35/78 A23G 3/00 101 A23L 1/30 BIOSIS (DIALOG) CA (STN)

Claims (3)

(57) [Claims] 1. An arteriosclerosis inhibitor comprising water and / or a polar organic solvent extract of licorice. 2. An oral composition comprising the arteriosclerosis inhibitor according to claim 1. 3. A pharmaceutical composition for treating cardiovascular disease, comprising the arteriosclerosis inhibitor according to claim 1.