JP2003040780A - Hyperlipemia inhibitor, hypercholesterolaemia inhibitor or antiobestic agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a hyperlipemia inhibitor, a hypercholesterolaemia inhibitor or an antiobestic agent having high safety. SOLUTION: This hyperlipemia inhibitor, this hypercholesterolaemia inhibitor or this antiobestic agent contains a carthamin having a structure represented by the formula (wherein Gl is glucose residue) and being a red dye extracted from petal of safflower as a main ingredient.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to an agent for suppressing hyperlipidemia, an agent for suppressing hypercholesterolemia or an antiobesity agent, which is used for prevention and treatment of arteriosclerosis, cerebral infarction and heart disease.

[0002]

2. Description of the Related Art Conventionally, prevention of hyperlipidemia and other diseases associated with arteriosclerosis by directly removing the risk factors,
Alternatively, a drug to be treated is known, but a drug to be prevented by improving lifestyle such as eating habit is not well known.

The cholesterol level lowered by drug therapy is generally about 20%, but the effect of the drug tends to decrease with long-term drug therapy, and the cholesterol level further increases with age. However, the effects of obesity cannot be ignored. Currently, EPA, DHA, etc., which are currently marketed as health food materials, have an effect of lowering neutral fat and LDL cholesterol in blood and HDL.
It is said to have a cholesterol-increasing effect, but it is also considered that there is a problem of excessive calories due to ingestion in the state of being mixed with high-calorie oils and fats, and the risk of oxidation of oils and fats. Monacholine obtained from Aspergillus niger also has a neutral fat and cholesterol lowering action, but a purification method for increasing the purity is difficult. On the other hand, recent findings suggest that plant anthocyanins also have a cholesterol-lowering and HDL-cholesterol-increasing action, but they have the drawback that a purification method for increasing the purity is difficult and a large amount must be ingested.

[0004]

The present invention is directed to hyperlipidemia,
It is intended to provide a drug for preventing or treating hyperlipidemia, hypercholesterolemia and obesity by lowering lipid peroxide and LDL cholesterol in an initial state in which symptoms associated with hypercholesterolemia and the like are prominent. To aim.

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention relates to a hyperlipidemia inhibitor, a hypercholesterolemia inhibitor or an antiobesity agent containing cartamine. Furthermore, the present invention relates to a hyperlipidemia inhibitor, a hypercholesterolemia inhibitor or an antiobesity agent containing a red pigment extracted from safflower petals.
Carthamin used in the present invention is the main component of the red pigment of safflower petal extract. The safflower (Safflower: Carthamus tinctorius LINNE) used in the present invention is an annual or perennial year of the Asteraceae native to Egypt, the plant height grows to 0.4 to 1.3 m, and each stem grows at the top and becomes early summer. A flower resembling a yellow-orange thistle is attached to the top, and changes to red over time. In the present invention, cartamine is obtained from the safflower flower or one obtained by fermenting or enzymatically treating the safflower, after removing yellow pigment with water, extracting caltamine with a weak alkaline aqueous solution at room temperature, and neutralizing it. is there. As an old method of fermentation, the safflower is picked, washed with water several times, the yellow water is removed, and lightly sprinkled to form a mochi. The upper and lower parts are sandwiched by rather than wet, and water is added to ferment every one to two days. If this unevenness is an important step and takes on a black tint, over-fermentation will occur and the pigment will decompose. Today, if you remove the yellow water and knead it with a machine like a meat grinder, it will turn into cartamine in a short time and turn red. This method has the advantage of not over-fermenting and of constant quality. Enzyme treatment means glucose oxidase 100,000u
nit / g about 10ppm, peroxidase 150,000 unit / g about 1
Safflowerye out of safflower yellow by using 00ppm
Convert llowB to cartamine. The origin of the enzyme may be any of plants, animals and microorganisms. To extract cartamine from safflower, for example, dried safflower petals are refluxed with water for 1 hour, left to stand overnight, and then dehydrated. The safflower yellow pigment is removed by repeating this operation twice.
The residue is refluxed with a 1.0% sodium carbonate solution for 1 hour to perform an extraction operation. Next, powdered cellulose is added to the extract, and the pH is adjusted to 5.0 to 6.0 with an organic acid such as citric acid.
Adjust to. The crude cartamine adsorbed on the cellulose by water addition and decantation is dehydrated with a screw decanter, the cartamine is extracted again with a 1.0% sodium carbonate solution, and the extract is filtered. An organic acid such as citric acid is added to the filtrate to adjust the pH to 5.0 to 6.0 and precipitate. 2 mmol / L Mcllvaine bu
The decantation is repeated with FFer (pH 5.0), the precipitate is collected by centrifugation, dried, sterilized and crushed to obtain cartamine. The specific structure of cartamine is shown below.

[Chemical 1] (In the formula, Gl represents a glucose residue.) In the present invention, red dye extracted from cartamine or safflower petals is a dosage form such as tablets, granules, powders, fine granules, dry syrups, hard capsules, and soft capsules. Can be

The dose of the hyperlipidemia-suppressing agent, the hypercholesterolemia-suppressing agent or the antiobesity agent of the present invention varies depending on the symptoms, age, body weight, etc., but is usually 1 mg to 30 mg of cartamine per adult per day. The amount is 5000 mg, preferably about 10 mg to 2000 mg. Hereinafter, the present invention will be specifically described with reference to examples.

[0007]

EXAMPLES The present invention will be described in more detail below with reference to reference examples and experimental examples. Reference Example 1 (Adjustment of Cartamine) 90 kg of dried safflower petals were refluxed with 900 L of water for 1 hour, left to stand overnight, and then dehydrated. The safflower yellow pigment was removed by repeating this operation twice. 1.0 for residue
An extraction operation was performed by refluxing with 900 L of a sodium carbonate solution of 1% for 1 hour. 25 kg of powdered cellulose was added to the extract, and the pH was adjusted to 5.0 to 6.0 with 15 kg of citric acid. The water addition and decantation were repeated three times. The crude cartamine adsorbed on the cellulose was dehydrated with a screw decanter, and cartamine was extracted again with 900 L of 1.0% sodium carbonate solution. The extract was filtered, citric acid was added to the filtrate, and the pH was adjusted to 5.0 to 6.0. 2 mmol / L Mcllvaine bu
The decantation was repeated three times with the fffer (pH 5.0). The precipitate is collected by centrifugation and separated by Sepha
The dex LH-20 column chromatography was repeatedly purified twice. The thus obtained cartamine was dark red to dark green, and was well dissolved in dimethylformamide, dissolved in propylene glycol and methanol, partially dissolved in water-containing ethanol and water, but not dissolved in fats and oils. The purity was confirmed by HPLC and was 99%.

(Activation) 4-week-old Wist manufactured by CLEA Japan
Using ar male rats, 6 rats as a group, normal diet,
The animals were bred on a vitamin E deficient diet and a diet containing 0.5% cholesterol and 0.25% cholic acid. The administration period of cartamine was 4 weeks. Using a sonde oral administration method, total cholesterol in serum, neutral fat (triglyceride), HDL, determiner LPO, lipid peroxides such as TBA, etc. were measured. As a control, 1 ml of purified water was administered, and in the cartamine test group, 1 mg of the above sample was dissolved in 1 ml of purified water and then administered. In the diet containing 0.5% cholesterol + 0.25% cholic acid, the medicinal DHA ethyl ester (purity 95%
%, Manufactured by Harima Kasei Co., Ltd.) was dissolved in 1 ml of purified water and administered.

Test results 1. Effects on serum total cholesterol, neutral fat (triglyceride), HDL, LDL, arteriosclerosis index, lipid peroxide, etc. in normal diet As shown in Table 1, in the normal diet control and cartamine administration groups, total cholesterol Although the values are almost unchanged, neutral fat tends to decrease in the cartamine-administered group, and HDL-cholesterol concentration is increased, LDL-cholesterol concentration is decreased, arteriosclerosis index is decreased, and lipid peroxide is decreased. It was

[Table 1]

2. Serum total cholesterol, triglyceride, HDL, LD in a vitamin E deficient diet
Effects on L, arteriosclerosis index, lipid peroxides, etc. As shown in Table 2, in the control of the vitamin E deficient diet and the cartamine-administered group, the total cholesterol level was almost unchanged, and the triglyceride level was not changed. In the group, an increase in HDL-cholesterol concentration, a decrease in LDL-cholesterol concentration, a decrease in arteriosclerosis index, and a decrease in lipid peroxide were observed.

[Table 2]

3. Cholesterol 0.5% + Cholic acid 0.25%
Effects on serum total cholesterol, triglyceride (triglyceride), HDL, LDL, arteriosclerosis index, lipid peroxides, etc. in the added diet As shown in Table 3, control and carthamin administration in the cholesterol + cholic acid added diet The total cholesterol level decreased in both the group and the DHA ethyl ester administration group. Neutral fat increased in the DHA ethyl ester administration group, but decreased in the cartamine administration group. The HDL-cholesterol concentration decreases in the DHA ethyl ester-administered group, whereas the cartamine-administered group gradually decreases. L
The DL-cholesterol concentration is lower in the cartamine administration group than in the DHA ethyl ester administration group. The arteriosclerosis index increased in the DHA ethyl ester administration group, but decreased in the cartamine administration group. The lipid peroxide concentration increased in the DHA ethyl ester administration group, but decreased in the cartamine administration group.

[Table 3]

From these results, the total cholesterol level remained almost unchanged in all cases, the neutral fat tended to decrease, the HDL-cholesterol concentration increased, and the LDL level increased.
-A decrease in cholesterol concentration, an arteriosclerosis index, and a decrease in lipid peroxide were observed, and it was found to be effective in improving hyperlipidemia and hypercholesterolemia.

INDUSTRIAL APPLICABILITY The hyperlipidemia-suppressing agent, hypercholesterolemia-suppressing agent or antiobesity agent of the present invention has a simple purification method for increasing the purity of the main component, cartamine. In addition, safflower extract is a red pigment that has been used for a long time in food additive colorants and cosmetic raw materials.
Excellent in safety.

   ─────────────────────────────────────────────────── ─── Continued front page    (72) Inventor Shigeru Matsuba             Yamagata Prefecture Yonezawa City Higashi 2-chome 7-139-414 (72) Inventor Toshio Kashiwagi             2-33 Kyobashi, Chuo-ku, Tokyo Toyoe             FCC Corporation F-term (reference) 4C057 BB02 DD01 JJ25 JJ34                 4C086 AA01 AA02 EA09 MA01 MA04                       NA14 ZA70 ZC33                 4C088 AB26 AC03 BA08 NA14 ZA70                       ZC33

Claims (2)

[Claims] 1. A hyperlipidemia inhibitor, a hypercholesterolemia inhibitor or an antiobesity agent containing cartamine. 2. A hyperlipidemia inhibitor, a hypercholesterolemia inhibitor or an antiobesity agent comprising a red pigment extracted from safflower petals.