JP2005132835A - Lipid metabolism improving agent - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a treating agent for hyperlipemia, having high safety, having enough efficacy, and derived from a natural product. <P>SOLUTION: A lipid metabolism improving agent (1), the treating or prophylactic agent for the hyperlipemia (2), a treating or prophylactic agent for serum hypercholesterolemia (3), a treating or prophylactic agent for serum hypertriglyceridemia (4), and a treating or prophylactic agent for serum hyper (low density lipoprotein)-LDL-cholesterolemia (5) are provided by mixing Asiasarum therinto, respectively. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a crude drug-derived drug or food effective for the treatment or prevention of lipid metabolism abnormality including hyperlipidemia.

  In recent years, due to changes in diet, hyperlipidemia, which is one of risk factors such as coronary artery disease and cerebral infarction, has been increasing year by year. In particular, serum total cholesterol concentration, serum LDL-cholesterol concentration, and serum triglyceride concentration are all positively correlated with the incidence of coronary artery disease and are known to be independent risk factors (Non-patent Document 1). . Therefore, lowering the serum total cholesterol concentration, serum LDL-cholesterol concentration, and serum triglyceride concentration that are increased beyond the normal range is considered to be effective in reducing the risk of coronary artery disease and cerebral infarction.

  Cholesterol is synthesized mainly in the liver in vivo. That is, suppressing cholesterol synthesis in the liver is thought to enable a reduction in serum cholesterol, and in recent years, cholesterol synthesis inhibitors such as HMG-CoA reductase inhibitors are widely used as antihypercholesterolemia drugs in clinical practice. It is used.

  Acyl CoA: cholesterol acyltransferase (ACAT) is an enzyme that esterifies cholesterol and is involved in the production of lipoproteins in the intestine and liver. Therefore, inhibition of ACAT activity is thought to lead to a decrease in serum cholesterol, and such drugs are being developed every day.

  Until now, various treatments such as HMG-CoA reductase inhibitors and bile acid adsorbents have been used to treat hyperlipidemia. However, the treatment of hyperlipidemia requires continuous administration of the drug, and it is also necessary to take it prophylactically even when serum cholesterol is high before it develops to hyperlipidemia Therefore, a therapeutic or preventive agent for natural hyperlipidemia that can be taken by patients more safely has been demanded.

  Conventionally, as a therapeutic agent for hyperlipidemia derived from a natural material, a technique using Yanagi tea as an active ingredient (Patent Document 1), a technique using Ginkgo leaves, gadgets, or jade yellow as an active ingredient (Patent Document 2) are known. However, it is still not satisfactory.

  Asiasarum, a plant of the Aristolochiaceae family, is incorporated into Kampo formulas for the purpose of antipyretic, analgesic, antitussive, expectorant, diuretic, etc. It has been. Commonly said to be finely spiced are: Usasairum (Asiasarum sieboldii F. MAEKAWA), Keirinsaicin (Asiasarum heterotropoides F. MAEKAWA var. F. MAEKAWA var. Seoulense F. MAEKAWA) is known (Non-patent Document 2).

  Conventionally, a free radical scavenger containing an ingredient obtained from a spicy extract as an active ingredient has been disclosed (Patent Document 3), but the effect of the spicy extract on serum lipids has not been reported.

JP2001-2579 JP-A-11-193240 Japanese Patent Laid-Open No. 4-134092 Japanese Atherosclerosis Society 2002 Encyclopedia of Japanese and Chinese medicines [II] p.14-15 by Namba Tsuneo (Nuryosha)

  An object of the present invention is to provide a therapeutic agent for hyperlipidemia derived from a natural product having high safety and sufficient effect.

  As a result of intensive investigations to solve the problems, the present inventors have found that there is an effect of treating or preventing hyperlipidemia excellent in the fineness of the herbal medicine and completed the present invention.

That is, the present invention
(1) A lipid metabolism improving agent characterized by containing fine spicy.
(2) A therapeutic or prophylactic agent for hyperlipidemia, characterized by blending fine spicy.
(3) A therapeutic or prophylactic agent for serum hypercholesterolemia, characterized by containing fine spicy.
(4) A therapeutic or prophylactic agent for serum hypertriglyceridemia, characterized by blending fine spicy.
(5) A cholesterol synthesis inhibitor characterized by containing fine spicy.
(6) ACAT inhibitor characterized by blending fine spicy.
It is.

  The fine spicy that is an active ingredient of the present invention is a herbal powder or extract obtained by pulverizing the spicy root or rhizome of the urchinaceae. Here, the extract includes a herbal medicine extracted with water, a polar solvent, or a mixture thereof, a dry extract, a flow extract, and the like.

  As for the spiciness used in the present invention, a plant that is generally considered to be spicy can be used. Is preferred.

  The dose of the crude drug component in the present invention varies depending on the patient's age, sex, body weight, and the degree of the disease, but is usually about 10 mg to 30 g per day for an adult drug, preferably 100 mg per day for an adult drug. Administer ~ 3g in 1 to several divided doses.

  As an active ingredient of the present invention, the spicy spice has been used enough as a traditional Chinese medicine and over-the-counter medicine, and no serious side effects have been reported. Can be a functional food for people with a high price.

  The present invention is a qualitative and quantitative range that does not impair the effects of the invention, vitamins, xanthine derivatives, amino acids, excipients, pH adjusting agents, cooling agents, suspending agents, antifoaming agents, viscous agents, Solubilizing agents, disintegrating agents, binders, lubricants, antioxidants, coating agents, coloring agents, flavoring agents, surfactants, plasticizers, fragrances and the like can be blended.

  The therapeutic or preventive agent for hyperlipidemia of the present invention is appropriately added with a spicy extract and an appropriate additive if necessary, and various dosage forms such as powders, granules, It can be formulated into tablets, capsules, dry syrups, drinks, chewable tablets, transmucosal agents, etc., and administered by oral or parenteral routes of administration.

  As a result, it was found that the spicy salt, which is an active ingredient of the present invention, has a serum cholesterol concentration inhibitory effect, a serum triglyceride concentration inhibitory effect, a hepatocyte cholesterol synthesis inhibitory effect, and an ACAT activity inhibitory effect.

  Hereinafter, the present invention will be described in more detail with reference to examples and test examples.

(Prepared spicy extract)
The rhizomes and roots of fine spicy (Kailinsaicin, Asiasarum heterotropoides F. MAEKAWA var. Mandshuricum F. MAEKAWA) were chopped. Ten times the amount of 50% (v / v) ethanol was added, and the mixture was extracted by heating at about 80 ° C. After filtration, the ethanol was distilled off under reduced pressure, and further concentrated to obtain a spicy extract.

(Formulation example 1)
Spicy 30% ethanol extract (dry extract) 1000mg
Powdered sugar 600mg
Erogil 36mg
Aspartame 9mg
Low-substituted hydroxypropylcellulose 54mg
Granules having the above composition were prepared by a conventional method.

Test example 1
Inhibition of serum cholesterol level and serum triglyceride level increase Male golden Syrian hamsters were divided into 4 groups of 6 per group.

  The control group was given a normal diet containing 5% corn oil and no added cholesterol, and 10 mL / kg of water as an administration solution was orally administered once a day for 2 weeks.

  The remaining group was given a high fat + high cholesterol diet containing 10% coconut oil and 1% cholesterol, resulting in hyperlipidemia. One group was water as the administration solution, and the other group was 100 mg / mL or 200 mg / mL suspension of fine 50% ethanol extract as the administration solution. Orally administered for a week.

  The blood of each fasting hamster was collected and the serum was separated, and then the serum total cholesterol concentration and the serum triglyceride concentration were measured. Serum total cholesterol concentration and serum triglyceride concentration were measured using Cholesterol C-II Test Wako (Wako Pure Chemical Industries, Ltd.) and Triglyceride G Test Wako (Wako Pure Chemical Industries, Ltd.), respectively.

  The results are shown in FIG. 1 and FIG.

  As is clear from the figure, increases in serum total cholesterol concentration and serum triglyceride concentration due to a high fat + high cholesterol diet were significantly suppressed by administration of spicy 50% ethanol extract.

Test Example 2 Suppression of hepatocyte cholesterol synthesis by spicy extract The effect of the spicy extract on cholesterol synthesis ability in hepatocytes was examined.

After culturing the human hepatoma cell line HepG2 cells to confluence on a collagen-coated 6-well multiplate, the cells were further cultured in a medium from which lipoproteins were removed. Next, spicy 50% ethanol extract was added to 500 μg / mL, and after 1 hour, ¹⁴ C-labeled acetic acid was added to 0.5 μCi / well and incubated for 24 hours. After removing the culture solution, the cells were collected, and the lipid fraction extracted by the method of Folch et al. Was dissolved in methanol and developed with TLC. The radioactivity of the spot corresponding to cholesterol was measured, and the cholesterol synthesis ability of the spicy 50% ethanol extract treated group when the untreated group was taken as 100% was expressed as a relative value.

  The results are shown in Table 1.

  As is clear from the table, the spicy extract administration group showed excellent cholesterol synthesis inhibitory activity.

Test Example 3 ACAT activity inhibitory action of spicy extract The effect of spicy extract on ACAT activity was examined.

After culturing the human hepatoma cell line HepG2 cells to confluence on a collagen-coated 6-well multiplate, the cells were further cultured in a medium from which lipoproteins were removed. Next, spicy 50% ethanol extract was added to 500 μg / mL, and after 1 hour, ¹⁴ C-labeled oleic acid was added to 1 μCi / well and incubated for 4 hours. After removing the culture solution, the cells were collected, and the lipid fraction obtained by the method of Folch et al. Was dissolved in methanol and developed with TLC. The radioactivity of the spot corresponding to cholesterol ester was measured, and the ACAT activity of the spicy 50% ethanol extract treated group when the untreated group was taken as 100% was expressed as a relative value.

  Table 1 shows the results of the cholesterol synthesis inhibitory action and ACAT activity inhibitory action of the spicy extract in HepG2 cells.

表から明らかなように、細辛エキスを添加した群では優れたACAT活性阻害作用が確認された。

As is clear from the table, an excellent ACAT activity inhibitory action was confirmed in the group to which the spicy extract was added.

  Since the composition for improving lipid metabolism having an excellent effect is obtained by the present invention, it is useful for pharmaceuticals, functional foods and the like.

It is the figure which showed the total cholesterol lowering effect of the spicy plasma, the plasma total cholesterol density | concentration (mg / dL) was shown on the vertical axis | shaft, and each sample was shown on the horizontal axis. In the figure, “HF + HC diet” indicates a high fat + high cholesterol diet, “#” indicates a significant difference from the normal diet group, and “*” indicates a significant difference from the control group. There is a significant difference. It is the figure which showed the triglyceride lowering effect in plasma of a spicy plasma, the plasma triglyceride density | concentration (mg / dL) was shown on the vertical axis | shaft, and each sample was shown on the horizontal axis. In the figure, “HF + HC diet” indicates a high fat + high cholesterol diet, “#” indicates a significant difference from the normal diet group, and “*” indicates a significant difference from the control group. There is a significant difference.

Claims (6)

  A lipid metabolism-improving agent characterized by containing fine spicy.   A therapeutic or prophylactic agent for hyperlipidemia, characterized by blending fine spicy.   A therapeutic or prophylactic agent for serum hypercholesterolemia, characterized by containing fine spicy.   A therapeutic or prophylactic agent for serum hypertriglyceridemia, characterized by containing fine spicy.   A cholesterol synthesis inhibitor characterized by containing fine spicy.   An ACAT inhibitor characterized by containing fine spicy.

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