JP2011178796A - Fat absorption depressant - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a fat absorption depressant originated from a natural product, which has mild behavior, and high safety even if ingested over a long term. <P>SOLUTION: A fat absorption depressant, a lipase inhibitor, a prophylaxis or amelioration agent of adiposis, and a prophylaxis or amelioration agent of serum hypertriglyceridemia are characterized by compounding Biota orientalis which is obtained by removing skin from a seed of oriental arborvitae of the family Cupressaceae to get a core of the seed, and drying. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

The present invention relates to a fat absorption inhibitor derived from a natural product that is effective for preventing and improving obesity and hypertriglyceridemia, and for preventing diseases such as diabetes, hyperlipidemia, hypertension and arteriosclerosis caused by obesity.

Traditionally, Japanese meals have been mainly carbohydrates, but in recent years, Western-style meals such as fast food have become widespread and fat intake has increased. One citizen of 2002 1
Looking at the daily intake of nutrients, etc., the ratio of lipid energy to the amount of energy intake is in a situation where it exceeds the upper limit of 25%, which is the upper limit of the appropriate ratio in the 20-40s (Non-patent Document 1).

Fat overdose is the cause of obesity and serum hypertriglyceridemia. In obesity, insulin resistance is induced, and it is known that the incidence of diabetes, hyperlipidemia, hypertension, and arteriosclerotic diseases is high. Therefore, drugs that suppress the absorption of fat in foods are not only effective in preventing or improving obesity and serum hypertriglyceridemia, but also in diabetes, hyperlipidemia, hypertension, arteries caused by obesity. It is thought to contribute to improving the quality of life by preventing the onset of diseases such as sclerotic diseases.

In fact, orlistat, an ethical drug marketed in Europe and the United States, is known to suppress fat absorption during meals and to exhibit an anti-obesity effect and an effect of improving serum hypertriglyceridemia. However, orlistat has many reports of side effects such as gastrointestinal disorders and fatty stool,
There is a need for a fat absorption inhibitor derived from a natural product that has a mild effect and is highly safe even when ingested over a long period of time.

Triglycerides, which account for most of the fat in food, are broken down into fatty acids and monoglycerides by lipases secreted from the stomach and pancreas and absorbed in the small intestine. Therefore, in order to suppress the absorption of fat, two mechanisms of inhibition of lipase or inhibition of fatty acid and monoglyceride absorption in the small intestine can be considered. At present, it is lipase inhibitors that actually have an action of suppressing fat absorption, and the action has been reported in many lipase inhibitors including the aforementioned orlistat.

Conventionally, as a material derived from natural products that suppress fat absorption, defatted cocoa mass (Patent Document 1)
)It has been known. Moreover, as a natural product which shows a lipase inhibitory action, it is a dokatsu, a ryekyo, a betel palm, a bay bean, a sun pens, and a ketsumeishi (patent document 2), lemongrass, allspice, cinnamon or clove (patent document 3), alfalfa extract,
Bitter tea extract, gold and silver flower extract, peppermint extract, clove extract, horseshoe extract, olive extract and raffma tea extract (Patent Document 4), walrus, western primrose, bodaiju, asparagus, ginkgo, Uanalpomacho, Ooawadachiso, Linden, Castorba, Eucalyptus, Koki, Cascara Sagrada, Onis, Muyuju, Senega plants and royal jelly (Patent Document 5) are disclosed.

Bald eagle is a plant of the family Ranunculaceae (Pulsatilla chinens)
is), the root of which is dried. As pharmacological actions, cardiotonic action, peripheral vasodilatory action, vasoconstriction action governed by visceral nervous system, anti-amoeboid protozoa action, anti-vaginal trichomonas action, and antibacterial action are known. In Kampo, it is used for cleansing and detoxification purposes.

Buddleia officinalis M
axim) buds were collected before the flowers opened and dried. Although there are few reports on pharmacological effects, it is used for antipyretic, anti-inflammatory and ophthalmic treatments.

Kite spruce (sea paulownia) is a lego (Erythrina indica L. = E. variegata L. va)
r. orientalis (L.) Merr.) bark. Also, citrus (Zanthoxylum ailanthoides Sieb. Et zucc.) And scallion (Kalopanax)
pictus (thumb.) Nakagi) and Panyaceae (Bombax malabaricum DC) are also called sea paulownia. As a pharmacological action, an inhibitory action against skin fungi and Staphylococcus aureus has been reported. As a drug, it is used for analgesics such as rheumatoid arthritis, skin scabies and toothache.

Hakushijin is a cypress family plant, Thuja orientalis L. = Biota o
rientalis (L) ENDL.) The seeds obtained by removing the skin from the seeds are dried. Although there are few reports on pharmacological effects, it is used for nourishment, tonic, insomnia, and constipation. Note that the branches and leaves of Konotegasiwa are known as Sakuhakuyo (acupuncture leaves), but their main components and uses are different from those of Hakushidin.

Capsicum (Winter Lion) is a cucumber of the Cucurbitaceae (Benincasa cerifera Savi = B. hi)
spida (Thumb.) Cogn.) is a dried mature seed. Although there are almost no reports on pharmacological action, it is used as an auxiliary agent for cough due to visceral suppuration (internal hemorrhoids) or fever as an antitussive, expectorant, drainage, anti-inflammatory diuretic (Non-patent Documents 2 and 3 ). In addition, although the fruit part of a chili pepper is known as a chili (winter basket) and is widely known as a diet food, the chili pepper which is the seed is different from a main component and a use.

JP-A-6-321796 JP 5-255100 A JP2001-120237 JP2003-26585 JP2003-192605 Current state of national nutrition / 2002 National Nutrition Survey, Ministry of Health, Labor and Welfare, Health and Nutrition Information Study Group Namba Tsuneo, Encyclopedia of Japanese and Chinese Medicine [I], Childcare, p.57-58, p.286-287, p.219-220 Namba Tsuneo, Encyclopedia of Japanese and Chinese Medicine [II], Yoikusha, p.112-113, p.154-156

  An object of the present invention is to provide a fat absorption inhibitor derived from a natural product.

As a result of intensive studies to solve the above problems, the present inventors have found that certain herbal medicines or extracts thereof have an excellent fat absorption inhibitory action, and that the action is attributable to a lipase inhibitory action, The present invention has been completed.

That is, the present invention
1) A fat absorption inhibitor characterized by blending hacidine.
2) A lipase inhibitor characterized by containing hacidine.
3) A prophylactic or ameliorating agent for obesity characterized by containing hakudin.
4) A preventive or ameliorating agent for serum hypertriglyceridemia, characterized by containing hacidine.
It is.

Since the present invention has an action of inhibiting lipid absorption, it is effective in preventing or improving obesity and serum hypertriglyceridemia, and preventing diseases such as diabetes, hyperlipidemia, hypertension and arteriosclerosis caused by obesity. Also effective.

The huccidin according to the present invention can be used as a crude drug powder as it is, or as an extract extracted with water, a polar solvent, a mixed solvent thereof or the like, but an extract extracted with a solvent in which water and alcohol are mixed in equal amounts. Is preferred. Moreover, a dry extract, a flow extract, etc. can also be used for an extract.

  The herbal medicine components used in the present invention can be used alone or in combination.

The dose of the fat absorption inhibitor of the present invention can be appropriately increased or decreased in consideration of age, sex, etc., but can be used in the range of 100 mg to 50 g as a drug substance equivalent per day for normal adults,
Preferably, it is 500 mg to 5 g.

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, etc. are blended, and liquids, tablets, Oral or parenteral preparations such as granules, powders, capsules, dry syrups, chewable tablets and transmucosal agents can be used.

It was revealed that the herbal medicine component of the present invention has an excellent fat absorption inhibitory action and lipase inhibitory action.

  The present invention will be specifically described below with reference to examples and test examples.

Shredded bald eagle, add 10 times 50% ethanol, heat extract at about 80 ° C,
After filtration, ethanol was distilled off under reduced pressure, and further concentrated to obtain an extract.

In addition, the extract was manufactured by extracting with the same extraction method also about mitsumouka, a spruce, a cabbage, and a red pepper.

Test Example 1 (Measurement of fat absorption inhibitory effect in rats)
SD rats (male) were divided into 2 groups with 7 rats per group and fasted for 16-20 hours from the day before the test. In one group, herbal extract was orally administered at a dose of 10 mL / kg, and immediately after that, ³ H-labeled triolein was orally administered at a dose of 1 mL / animal. Another group is the control group and purified water instead of herbal extract.
10 mL / kg was orally administered, and immediately after that, ³ H-labeled triolein was orally administered. In addition, the crude drug extract used what was diluted with purified water so that it might become 1g / 10mL as an extract. ^{For 3} H-labeled triolein, 0.25 nmol as triolein (486.55 kBq as radioactivity) is dispensed into a glass tube, the solvent is evaporated with nitrogen gas, and 1 mL of 0.5% Tween-80 solution is added and sonicated for 10 minutes. What was dispersed by using was used. 30, 60, 90, from administration of ³ H-labeled triolein
120 minutes later, blood was collected from the tail vein without anesthesia, and blood was collected in a tube containing heparin. Plasma was separated by centrifugation, 50 μL of which was mixed well with 10 mL of scintillator solution, and radioactivity was measured using a liquid scintillation counter.

The time course of 50 μL of plasma radioactivity in the control group and the crude drug extract administration group is shown in FIG. Furthermore, the area under the blood concentration curve (AUC) was calculated, and the AUC of the crude drug extract administration group relative to the AUC of the control group
The rate of decrease in fat was shown as fat absorption inhibition rate (%) and shown in Table 1.

As is clear from FIG. 1 and Table 1, a fat absorption inhibitory effect was observed in the herbal extract extract group.

Test Example 2 (Measurement of lipase inhibitory action)
25 μL of each herbal extract (dissolved in 2.5% DMSO) obtained in Example 1 in 50 μL of a substrate solution (0.2 mM 4-methylumbelliferyl oleate) and an enzyme solution (100 U / mL pancreatic lipase, TypeVI-S fro
m porcine pancreas) 25 μL was added. After reacting at 37 ° C. for 15 minutes, 150 μL of 0.1M hydrochloric acid and 25 μL of 0.1M sodium citrate were added, and fluorescence absorption at an excitation wavelength of 320 nm and a fluorescence wavelength of 450 nm was measured. Each crude drug extract was added so as to have final concentrations of 12.5, 25, 50, and 100 μg / mL.

When the herbal extract-free group is defined as 100%, the fluorescence of the herbal extract combination group is expressed as the lipase inhibition rate (%
) And the 50% activity inhibitory concentration are shown in Table 2.

As apparent from FIG. 2 and Table 2, the lipase inhibitory action was observed in the herbal extract administration group that suppressed fat absorption in rats.

Since the herbal medicine of the present invention has an excellent fat absorption inhibitory effect, diseases such as obesity, serum hypertriglyceridemia, and other diseases derived from accumulation of fat, diabetes caused by obesity, hyperlipidemia, hypertension, arteriosclerosis, etc. It can be used for pharmaceuticals, foods, functional foods, etc. for treatment or prevention of diseases.

A view showing the fat absorption inhibiting action of the herbal extract of the present invention, the radioactivity of rat plasma 50μL each vertical axis shows the elapsed time from administration of ³ H-labeled Triolein each horizontal axis. It is the figure which showed the lipase activity inhibition rate about each crude drug extract of this invention, and showed the inhibition rate on each vertical axis | shaft, and the extract density | concentration on each horizontal axis.

Claims (4)

A fat absorption inhibitor characterized by containing hacidine. A lipase inhibitor characterized by containing hacidine. A prophylactic or ameliorating agent for obesity, characterized by containing haxidine. A preventive or ameliorating agent for serum hypertriglyceridemia, characterized by containing hakuzin.

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