RU2291707C2 - Compositions for prophylaxis or relief of multiple risk factor syndromes - Google Patents

Abstract

FIELD: medicine, pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates to preparing agent used in prophylaxis or relief of syndrome of the multiply risk factors. The agent used for prophylaxis or relief of syndrome of the multiple risk factors comprises at least one component taken in the definite amount and chosen from the group consisting of licorice hydrophobic extract, yellow radix extract (turmeric), clove extract and cinnamon extract. The above describes agent promotes to effective prophylaxis and relief of syndrome of multiple risk factors.

EFFECT: valuable medicinal properties of composition.

9 cl, 18 tbl, 35 ex

Description

TECHNICAL AREA

The present invention relates to compositions for preventing or alleviating the syndrome of multiple risk factors, including obesity by type of visceral fat deposition, diabetes mellitus, hyperlipidemia and hypertension.

BACKGROUND OF THE INVENTION

A lifestyle-related disease resulting from a deterioration in habitual household behavior, such as excessive food intake and lack of mobility, is currently a major social problem. Lifestyle-related disease includes various conditions of the disease, such as obesity, diabetes mellitus, hyperlipidemia and hypertension, and these conditions of the disease attract significant attention as a syndrome of multiple risk factors that may underlie arteriosclerosis. Moreover, it is a problem not only for humans, but also for pets such as dogs and cats.

Obesity is broadly classified into obesity by type of subcutaneous fat deposition resulting from accumulation of subcutaneous fat, and by obesity by type of subcutaneous fat deposition resulting from accumulation of intra-abdominal fat. Obesity by type of visceral fat deposition is a disease that is accompanied with high frequency by hyperlipidemia, impaired glucose tolerance and hypertension, and is also characterized by strong resistance to insulin, which is why it is known as multiple risk factor syndrome. In addition, the accumulation of visceral fat is found not only in obese individuals, but also in people with body weights within the normal range, and it may be accompanied by the multiple risks mentioned above (BIO Clinica, September 2000, Extended Section 16 -55). Thus, the accumulation of visceral fat serves as a trigger factor, triggering the mechanism of the emergence of insulin resistance, diabetes mellitus, hyperlipidemia, hypertension, etc. Matsuzawa et al. proposed the term “visceral fat syndrome” for the disease in general (Diabetes / Metabolism Reviews, 13, 3-13, 1997). "Syndrome X," as suggested by G.M. Reaven (Diabetes, 37, 1595-1607, 1988), a “deadly quartet,” as suggested by N.M. Kaplan (Archives of Internal Medicine, 149, 1514-1520, 1989), and “insulin-resistant syndrome,” as suggested by R.A. DeFronzo (Diabetes Care, 14, 173-194, 1991) refer to the same disease as a whole.

Treatment for obesity usually consists in the appointment of a diet and exercise, and drug treatment is indicated in cases of severe obesity. However, these treatment regimens are recommended or prescribed to patients in medical institutions, and are not intended for so-called candidate patients in reserve. In addition, anti-obesity agents include appetite suppressants, carbohydrate and fat digestion and absorption inhibitors as energy sources, and energy-consuming agents. However, appetite suppressants and digestion and absorption inhibitors do not have a positive effect on reducing the amount of visceral fat, and agents that promote energy consumption do not specifically affect the decrease in visceral fat.

Japanese publication Kokai Hei-11-187843 indicates that the administration of Cassia nomame extract, which has an inhibitory effect on fat absorption, and Morus bombycus extract, which has an inhibitory effect on carbohydrate absorption, in combination leads to suppression of weight gain and a decrease in the amount of subcutaneous fat and visceral fat. As for other substances of natural origin, it is known that substances derived from oils with a high degree of unsaturation, such as fish oil and vegetable oil, such as linseed oil and perilla oil, perennial (Japanese publication Kokai Hei-10-231495), or conjugated isomerized fatty acids with a high degree of unsaturation (Japanese publication Kokai 2000-144170) have an effect that reduces the amount of accumulated visceral fat; that an amylase inhibitor derived from wheat (Japanese publication Kokai Hei-09-194390) inhibits the accumulation of visceral fat, and that D-xylose and / or L-arabinose (Japanese publication Kokai Hei-07-309765 and Japanese publication Kokai Hei-07 -242551) inhibit the accumulation of body fat (subcutaneous fat and visceral fat).

Diabetes mellitus is a disease whose main manifestation is chronic hyperglycemia as a result of a deficiency in insulin activity, and at least 90% of people with diabetes have type II diabetes (non-insulin-dependent diabetes mellitus; NIDDM). The number of patients with diabetes in Japan has risen sharply from 1.57 million in 1993 to 2.18 million in 1996 (according to the Ministry of Health). In addition, according to the diabetes qualification of the Ministry of Health, adopted in November 1997, the number of persons with respect to whom there are strong suspicions of diabetes (including those undergoing treatment) is 6.9 million, and the sum of this number and the number of persons , in which the presence of diabetes cannot be ruled out, was estimated at 13.7 million. Thus, in addition to the sharp increase in the number of people with diabetes, the number of people on standby and not being treated in medical facilities is much larger, and this is a matter of serious concern.

Treatment for diabetes includes diet and exercise therapy, and in cases that are not sufficiently resistant to these types of treatment, drug treatment is added. Medication includes insulin treatment and the administration of oral hypoglycemic drugs. As oral hypoglycemic drugs, sulfonylurea derivatives such as tolbutamide and glibenclamide can be mentioned; biguanides such as buformin and metformin; α-glucosidase inhibitors such as acarbose and voglibose; and drugs that correct insulin resistance, such as troglitazone and pioglitazone.

When treated with a diet, the patient is advised to avoid overeating and develop a habit of limited calorie intake, and if the patient is obese, they recommend trying to lose weight to a standard body weight. As dietetic foods, dietary kits of diabetic people are known, which are special products approved by the Ministry of Health. However, these are nothing more than the so-called low-calorie, balanced foods, and one cannot assume that they have inherent therapeutic efficacy for diabetes.

In addition, these treatments are prescribed for people with diabetes in health facilities, and they are not intended for so-called backup diabetics, whose number is much higher than the number of people already suffering from diabetes. Accordingly, there is a need for a composition effective for preventing or alleviating diabetes mellitus in the form of a food / drink product, such as a food product that meets the requirements of a healthy diet (a product for the indicated health application and a product that meets certain nutritional function requirements), or healthy food, or a drug (including a quasi-drug) that will be readily available to anyone unrelated to medical facilities.

The prevalence of diabetes is also constantly increasing among farm animals or pets, and it is desirable to develop a composition effective to prevent or alleviate diabetes in farm animals or pets.

Japanese publication Kokai Hei-01-233217 describes an antidiabetic composition comprising curcumenon, Curcuma aromatica extract, the Zingiberaceae family, as an active ingredient. Japan Patent Hei-06-192086 describes an antidiabetic composition comprising (4S, 5S) - (+) - germacron-4,5-epoxide, Curcuma aromatica extract, as an active ingredient. Curcuma aromatica is known to be an untreated drug, but it has not been purified for use as a dietary supplement.

Licorice and its aqueous extract are used as untreated drugs and are used as untreated drugs with analgesic / anticonvulsant and expectorant action, or as food products. Since the main component of glycyrrhizin (glycyrrhizic acid) is approximately 200 times sweeter than sucrose, the “licorice extract”, which can be obtained by extracting the licorice with water or an alkaline aqueous medium, is a food supplement for use also as a sweetener (Annotated List of Additives in Available Books, page 163, Japan Food Additives Association, 1999). Its physiological properties, known to date, are adrenocortical electrolyte or glucocorticoid-like action, estrogen-like effect, inhibitory testosterone production effect, antitussive effect, anti-inflammatory effect, antiallergic effect, detoxifying effect, action that improves hyperlipidemia, the effect of increasing cell count lining of the stomach, an action that prevents or attenuates liver damage in an expert cops, antiviral action, interferon-inducing action, anticaries action, tumor growth inhibitory action, the effect of lowering the content of cytosolic Ca ^2+, action, phospholipase A ₂ inhibitory action, LTB ₄ and inhibiting PGE ₂ production, the action of inhibiting production of Factor, activating platelets, etc. In addition, licorice is one of the components of the traditional Chinese medicine Byakko-ka-Ninjin-To, which is prescribed for diabetes associated with intense dry mouth, polyposis and polyuria, and like gypsum, anemarren, and ginseng, which are also included in the composition of a medicinal product, an aqueous licorice extract has been reported to have a hypoglycemic effect (I. Kimura, et al. Phytotherapy Research, 13, 484-488, 1999).

It is known that the residues that remain after extraction of glycyrrhizin from licorice with water or an aqueous alkaline medium have a hepatotonic (hepatoprotective) effect and / or anti-infective effect (Japanese publication Kokai Hei-09-143085), immunopotentiation effect (Japanese publication Kokai Hei-05- 05- 262658) and antiviral effect (Japanese publication Kokai Hei-01-175942). In addition, “licorice oil extract”, which can be obtained by extracting, after washing them with water, licorice residues with ethanol, acetone or hexane, is an antioxidant for use as a dietary supplement (Annotated Lists of Additives in Available Books, page 164, Food Association additives of Japan, 1999). Licorice oil extract is known to have antibacterial activity against Helicobacter pylori (Japanese publication Kokai Hei-10-130161, Japanese publication Kokai Hei-08-119872). However, it is not known whether the indicated residue after glycyrrhizin extraction from licorice or the indicated licorice oil extract has an effect on reducing the amount of visceral fat, a hypoglycemic effect, an effect improving lipid metabolism, or an effect inhibiting an increase in blood pressure.

Meanwhile, it has long been known that excessive intake or prolonged use of licorice induces pseudoaldosteronism, including hypertension, edema, and hypokalemia. This condition is caused by glycyrrhizin, which is the main component of licorice. It is also reported that hypertension can cause glycyrrhetinic acid, which is a product of the hydrolysis of glycyrrhizin (H. Siguruonsdottir, et al .: Journal of Human Hypertension, 15, 549-552, 2001). Thus, an aqueous licorice extract, which contains a hydrophilic licorice fraction and consists mainly of glycyrrhizin, induces hypertension.

As tropical plants belonging to the genus Curcuma, the Zingiberaceae family (originating from tropical Asia) has several varieties known, such as Curcuma longa, Curcuma aromatica, Curcuma zedoaria and Curcuma xanthorrhiza. Among them, Curcuma longa is often called the "yellow root", and it is known as one of the components of curry spices. It is used not only as a food product, since the main component of Curcuma longa curcumin is a yellow dye (natural dye); this plant or its extract (turmeric dye) is used as a dye or coloring agent (food supplement). In herbal medicine using traditional medicines such as Kampo (a traditional Chinese medicine) in China, Ayur-Veda in India and Jama in Indonesia, it has long been known that Curcuma longa has a hemostatic, increases the functional activity of the stomach, antibacterial and anti-inflammatory effect, and Currently, this plant is still used as a medicine. In addition, the effectiveness of the yellow root (Curcuma longa) and its main component, curcumin, attracts attention and it has been found that it has various physiological effects, such as antioxidant action, choleretic effect, an effect that enhances the function of internal organs (liver, pancreas glands), antitumor effect, action that improves lipid metabolism, and skin softening effect.

However, it is not known whether the yellow root or its extract has an effect on reducing the amount of visceral fat, a hypoglycemic effect or an action that inhibits an increase in blood pressure.

Clove is a flower bud, leaf, or flower of the Syzygium aromaticum or Eugenia caryophyllata of the Myrtaceae family and is known as a type of spice. Due to its antibacterial / bactericidal effect and analgesic / anesthetic effect, many generations have used cloves not only for breath freshening or as a remedy for toothache, but also as a means of increasing the functional activity of the stomach, in the field of untreated drugs and in herbal medicine (Campo drug ) In addition, clove extract is used as an antioxidant for use as a dietary supplement. However, it is not known whether clove or its extract has an effect on reducing the amount of visceral fat, a hypoglycemic effect, an effect improving lipid metabolism, or an action inhibiting an increase in blood pressure.

Cinnamon or cassia is the bark of Cinnamomum cassia, C. zeylanicum or C. loureirii of the family Lauraceae. Cinnamon has antibacterial and antioxidant effects, and has long been used as a type of spice, and its bark has been used for medicinal purposes. However, it is not known whether cinnamon or its extract has an effect on reducing the amount of visceral fat, a hypoglycemic effect, an effect improving lipid metabolism, or an action inhibiting an increase in blood pressure.

SUMMARY OF THE INVENTION

The present invention relates to compositions for the prevention or alleviation of multiple risk factor syndrome, including visceral fat deposition obesity, diabetes mellitus, hyperlipidemia and hypertension, without the risk of side effects or other safety concerns.

The authors of the present invention, putting forward the postulate that the cause of the syndrome of multiple risk factors is obesity by type of visceral fat deposition, believe that the syndrome of multiple risk factors can be prevented or alleviated by reducing the amount of accumulated visceral fat.

Thus, the applicants used all means available to them to study the aforementioned goal and found that hydrophobic licorice extract, yellow root extract, clove extract and cinnamon extract each have the property of decreasing the amount of visceral fat accumulated, an effect that inhibits the increase in blood glucose, hypoglycemic an action, an action that improves lipid metabolism, and an action that inhibits an increase in blood pressure. The present invention was developed based on the above discovery.

The present invention therefore relates to a composition for the prevention or alleviation of multiple risk factor syndrome, which includes at least one component selected from the group consisting of a hydrophobic licorice extract, yellow root extract, clove extract and cinnamon extract. This composition for the prevention or alleviation of the syndrome of multiple risk factors of the present invention may be a composition for the prevention or alleviation of obesity by type of visceral fat deposition, a composition for the prevention or alleviation of diabetes mellitus, a composition for the prevention or alleviation of hyperlipidemia or a composition for the prevention or relief of hypertension.

The present invention also relates to a method for preventing or alleviating a multiple risk factor syndrome, which comprises administering or administering a composition comprising at least one component selected from the group consisting of a hydrophobic licorice extract, yellow root extract (Curcuma longa), clove extract and extract cinnamon, human, farm animal or pet.

In addition, the present invention relates to the use of at least one component selected from the group consisting of a hydrophobic licorice extract, yellow root extract, clove extract and cinnamon extract for the manufacture of a composition for the prevention or alleviation of multiple risk factor syndrome.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is further described in detail.

The composition of the present invention includes at least one component selected from the group consisting of a hydrophobic licorice extract, yellow root extract, clove extract and cinnamon extract. These extracts are food products and, in addition, are purified for use as food additives, thus having no side effects and other safety problems.

The composition of the present invention has the property of reducing the amount of accumulated visceral fat and, as such, is able to prevent or alleviate the syndrome of multiple risk factors, therefore, obesity by type of visceral fat deposition, diabetes mellitus, hyperlipidemia and hypertension. Thus, in addition to the indicated property of reducing the amount of accumulated visceral fat, it has an action that inhibits an increase in blood glucose, a hypoglycemic effect, an action that improves lipid metabolism, and an action that inhibits an increase in blood pressure. The lipid metabolism improving action mentioned above is a property of lowering total cholesterol, a property of lowering triglycerides, or a property of lowering free serum fatty acids.

Diabetes mellitus in the syndrome of multiple risk factors is type II diabetes (non-insulin-dependent diabetes mellitus) resulting from impaired glucose tolerance. Moreover, hyperlipidemia in the syndrome of multiple risk factors is a condition of the disease, which is characterized by an increase in serum levels of total cholesterol, triglycerides or free fatty acids, which is caused by impaired lipid metabolism.

The effect of reducing the amount of accumulated visceral fat can be determined by weighing the accumulated intra-abdominal fat, for example, fat around the penis (epididymis, uterus), perirenal fat, mesenteric fat, omentum fat, etc., in experimental animals. The experimental animals for use in this technique are preferably animals with a nutritional model of obesity receiving a high fat diet (M. Rebuffe-Scrive, et al., Metabolism, 42, 1405-1409, 1993), or experimental animals with hereditary obesity such as KK mice, KK-Au mice, ob / ob mice, db / db mice, Zucker obese rats and OLETF rats. The effect of decreasing the amount of visceral fat accumulated can be evaluated by reducing the area occupied by visceral fat on a CT scan in experimental animals (CS Hun, et al. Biochemical and Biophysical Research Communications, 259, 85-90, 1999) and in humans (K . Tokunaga, et al. International Journal of Obesity, 7, 437-445, 1983), but more appropriate for measuring the decrease in girth.

In addition, since the composition of the present invention has the property of reducing the amount of accumulated visceral fat, it is able to prevent or alleviate the syndrome of multiple risk factors, including obesity by type of visceral fat deposition, diabetes mellitus, hyperlipidemia and hypertension. Thus, by reducing the amount of visceral fat, the percentage of fat in the body can be reduced in order to prevent or reduce obesity. In addition, as the amount of visceral fat decreases, adipocyte secretion of various physiologically active substances (adipocytokines) decreases, such as leptin, TNF-α (tumor necrosis factor-α), free fatty acids, apoprotein E, angiotensinogen, PAI-1 (activator inhibitor plasminogen-1), etc. Thus, as the amount of visceral fat decreases, the amount of TNF-α involved in insulin resistance decreases, and the blood glucose level decreases due to the improvement in insulin resistance and remission of impaired glucose tolerance, which contributes to the prevention or relief diabetes mellitus. In addition, as the amount of free fatty acids and apoprotein E, which is associated with lipid transport, decreases, there is an improvement in lipid metabolism disorders, which leads to a decrease in blood lipids, which contributes to the prevention or reduction of hyperlipidemia. The amount of angiotensinogen that is involved in the regulation of blood pressure and PAI-1, which is involved in the formation of blood clots, also decreases, and blood pressure decreases, which contributes to the prevention or relief of hypertension or arteriosclerosis.

Licorice, a raw material for a hydrophobic licorice extract for use in the present invention includes Clycyrrhiza glabra, G. uralensis and G. inflata, genus Clycyrrhiza, family Leguminosae. Licorice has been used for centuries, and is used as a dietary supplement, as well as medicinal raw materials.

The hydrophobic licorice extract for use in the present invention can be obtained by extracting the active component from the licorice or from its powder with an organic solvent. An alternative production method involves first extracting the hydrophilic component from the licorice with water or an alkaline aqueous solution and extracting the remainder of the licorice in its natural form or after drying with an organic solvent. The organic solvent for use in this method is preferably a solvent that has been purified for use in the manufacture and processing of pharmaceutical products, food products and food additives, including, thus, inter alia, acetone, ethanol, glycerin, ethyl acetate, diethyl ether, cyclohexane , butanol, propanol, propylene glycol, hexane and methanol. Oils such as edible oils may also be used. You can also use a mixture of two or more types of these solvents or a mixture of any of them with water. In addition, in order to extract the hydrophobic fraction of licorice using a single solvent with good efficiency, it is preferable to use ethyl acetate, acetone or ethanol. The extract obtained by extraction of the hydrophobic licorice fraction, or the extract from which the solvent used for extraction was removed, is referred to herein as the hydrophobic licorice extract. In addition, a crude extract or a semi-purified extract can also be used in the present invention if it does not contain impurities that are unacceptable to pharmaceutical products and food products.

Yellow root, the raw material for the yellow root extract for use in the present invention, is the root or rhizome of Curcuma longa, which is a perennial plant of the genus Curcuma, family Zingiberaceae. The yellow root is a food product that has been eaten for centuries as a spice called “yellow root”, and the dye of the yellow root, which can be obtained by extracting the yellow root with an organic solvent such as ethanol, hexane or acetone, has been purified for use as food additives to color food, and is highly safe.

The yellow root extract for use in the present invention can be obtained by extracting the active component from the yellow root or from its powder with water or an organic solvent. The organic solvent for use in this method is preferably a solvent that has been purified for use in the manufacture and processing of pharmaceutical products, food products and food additives, including, thus, inter alia, acetone, ethanol, glycerin, ethyl acetate, diethyl ether, cyclohexane , butanol, propanol, propylene glycol, hexane and methanol. Oils such as edible oils may also be used. You can also use a mixture of two or more types of these solvents or a mixture of any of them with water. An extract obtained using the extraction procedure described above, or an extract from which the solvent used for extraction was removed, is referred to herein as yellow root extract. In addition, a crude extract or a semi-purified extract can also be used in the present invention if it does not contain impurities that are unacceptable to pharmaceutical products and food products.

Clove, a raw material for clove extract for use in the present invention, is a flower bud, leaf or flower of Syzygium aromaticum or Eugenia caryophyllata of the Myrtaceae family. Cloves have been eaten for centuries as a spice, and clove extract has been purified for use as a dietary supplement acting as an antioxidant and is highly safe.

The clove extract for use in the present invention can be obtained by extracting the active component from the clove or from its powder with water or an organic solvent. The organic solvent for use in this method is preferably a solvent that has been purified for use in the manufacture and processing of pharmaceutical products, food products and food additives, including, thus, inter alia, acetone, ethanol, glycerin, ethyl acetate, diethyl ether, cyclohexane , butanol, propanol, propylene glycol, hexane and methanol. Oils such as edible oils may also be used. You can also use a mixture of two or more types of these solvents or a mixture of any of them with water. An extract obtained using the extraction procedure described above, or an extract from which the solvent used for extraction was removed, is referred to herein as a clove extract. In addition, a crude extract or a semi-purified extract can also be used in the present invention if it does not contain impurities that are unacceptable to pharmaceutical products and food products.

Cinnamon, the raw material for the cinnamon extract of the present invention, is Cinnamomum cassia, C. zeylanicum or C. loureirii of the genus Cinnamomum of the family Lauraceae. Cinnamon has been eaten as a spice for centuries, and it has no side effects or other safety concerns.

Cinnamon extract for use in the present invention can be obtained by extracting the active ingredient from cinnamon or from its powder with water or an organic solvent. The organic solvent for use in this method is preferably a solvent that has been purified for use in the manufacture and processing of pharmaceutical products, food products and food additives, including, thus, inter alia, acetone, ethanol, glycerin, ethyl acetate, diethyl ether, cyclohexane , butanol, propanol, propylene glycol, hexane and methanol. Oils such as edible oils may also be used. You can also use a mixture of two or more types of these solvents or a mixture of any of them with water. An extract obtained using the extraction procedure described above, or an extract from which the solvent used for extraction was removed, is referred to herein as a cinnamon extract. In addition, a crude extract or a semi-purified extract can also be used in the present invention if it does not contain impurities that are unacceptable to pharmaceutical products and food products.

The composition of the present invention is a composition for preventing or alleviating the syndrome of multiple risk factors, and provided that it contains at least one component selected from the group consisting of said hydrophobic licorice extract, yellow root extract, clove extract and cinnamon extract , it is not limited in form and can be used as a food / drink, such as a food product that meets the requirements of a healthy diet (product for the indicated example neniya health and product according to specific requirements for nutrient function), or health food, or as a pharmaceutical product, a cosmetic product or a quasi.

For use as a food / drink, it can be taken orally, or it can be made in the form of easily swallowed products, such as capsules, tablets, granules and the like, using a known carrier, adjuvant or the like, for swallowing. The amount of each extract in such a manufactured product may be from 0.1 to 100 wt.%, Preferably from 10 to 90 wt.%. In addition, it can be mixed in raw materials for all types of food and drinks, for example, for confectionery such as chewing gum, chocolate, sweets, jellies, cookies, crackers, etc .; for frozen sweets such as ice cream, ice candies, etc .; for beverages such as tea, soft drinks, nutritious drinks, beauty drinks, etc .; for noodles such as Japanese wheat noodles, Chinese noodles, spaghetti, instant noodles, and the like; for minced fish products such as steamed minced fish (kamaboko), fish sausage (chikuwa), minced meat (hannpen), etc .; for seasonings such as gravy, mayonnaise, sauces, etc .; for oily products such as margarine, butter, lettuce oil and the like; for bakery products, ham products, soups, distilled foods, frozen foods and so on. When taking such a composition in the form of a food product or a drink, daily intake for an adult of 0.1 to 1000 mg / kg, more preferably 1 to 100 mg / kg, based on the extract content, is recommended. Similar compositions can also be used as feed for farm animals and pets or as food for pets, and the recommended daily intake for the indicated use is preferably from 0.1 to 1000 mg / kg, based on the content of the extract.

For use as a pharmaceutical product, the dosage form is not particularly limited, but includes capsules, tablets, granules, injectables, suppositories and plasters. Said dosage forms can be prepared using a suitable pharmaceutical material for the manufacture of pharmaceutical compositions, such as an excipient, a disintegrant, a lubricant, a binding agent, an antioxidant, a coloring agent, an aggregation inhibitor, an absorption promoting agent, a solubilizing agent, a stabilizer, and the like. The daily dose of this drug for an adult is from 0.1 to 1000 mg / kg, preferably from 1 to 100 mg / kg, based on the content of the extract; the indicated dose should be administered once a day or in several divided doses per day. This composition can also be used as a pharmaceutical product for farm animals and pets, and the daily dose for said use is preferably from 0.1 to 1000 mg / kg, based on the content of the extract.

For use as a cosmetic agent or quasi-drug, the composition can be used in such forms as, among others, ointments, liniments, sprays, creams, soaps, face cleansers, body cleansers, toilet water, lotions and bath agents .

The composition of the present invention can be administered or administered to all animals, including fish, reptiles, amphibians, birds and mammals. The mammal mentioned above is not limited in a special way, but includes, among others, humans, monkeys, dogs, cats, cattle, horse species, pigs, sheep, mice, rats and guinea pigs.

BEST MODE FOR CARRYING OUT THE PRESENT INVENTION

The following examples illustrate the present invention in more detail without limiting its scope.

Hydrophobic licorice extract

(Production Example 1) Production of a hydrophobic licorice extract 1

Using a glass vessel, 500 g of licorice powder (Kaneka Sun Spice Co., Ltd.) was soaked (immersed) in 5 volumes of ethyl acetate and allowed to stand at room temperature, protected from light, for 1 week with periodic stirring. The mixture was filtered twice through filter paper (ADVANTEC No. 2) to remove the powder and obtain an extract solution. The extract solution was concentrated under reduced pressure to remove the solvent, after which 33.91 g of a hydrophobic licorice extract was obtained.

(Production Example 2) The content of glycyrrhizin in the hydrophobic licorice extract

The glycyrrhizin content in the hydrophobic licorice extract obtained in Production Example 1 was quantified by HPLC according to M.A. Raggi, et al. (Boll. Chim. Farmaceutico., 133, 704-708, 1994). As an analytical column, COSMOSIL 5C18-AR, 4.6 x 250 mm (Nacalai Tesque, Inc.) was used at 40 ° C. Using a mixture of acetonitrile: distilled water: acetic acid (35: 65: 0.5, v / v) as the mobile phase with a flow rate of 1 ml / min, a peak at 251 nm was detected. Using ammonium glycyrrhizinate (Wako Pure Chemical Industries, Ltd .; product that meets the requirements for food additives) as the standard glycyrrhizin, a calibration curve was constructed within the concentration range from 1 to 20 μg / ml and analysis was performed.

As a result, the amount of glycyrrhizin in 1 mg / ml hydrophobic licorice extract was 4 μg / ml, i.e. the glycyrrhizin content in the extract was 0.4%. Since glycyrrhizin content is usually not less than 2.5% in licorice powders, not less than 4.5% in aqueous extracts, or not less than 6.0% in hot water extracts, the glycyrrhizin content in the hydrophobic licorice extract was considered extremely small.

(Experimental example 1) The effect of reducing the amount of visceral fat

C57BL / 6J mice (females, 10 weeks old) were given plenty of fats and carbohydrates (product of Oriental Yeast Co .; Table 1) for 4-8 weeks to obtain nutritional obesity. The mice were then divided into groups of 6-8 animals, and using a normal diet (Oriental Yeast Co. product; table 1) as the main diet, the untreated group (control group) and the diet supplemented group were formed hydrophobic licorice extract obtained in manufacturing example 1. In both groups, the mice had free access to food for 4 weeks. After an overnight abstinence from food, the animals underwent laparotomy under ether anesthesia, and the mice were sacrificed by bleeding from the abdominal aorta. Then, para-fat and perinephric fat were excised and weighed. The sum of the mass of perinatal fat and perineal fat was recorded as the mass of intra-abdominal fat. The data are presented in table 2.

Table 1 High feed
fat and carbohydrate content Normal food
(modified AIN-93G) Cleavage Percentage Fats 53% 22% Carbohydrates 27% 58.5% Squirrels twenty% 19.5% Total energy 5100 kcal / kg 4100 kcal / kg Structure Casein 25,000% 20,000% Corn
starch 14.869% 49.948% Sucrose 20,000% 10,000% Soybean oil 2,000% 10,000% Lard 14,000% 0,000% Beef fat 14,000% 0,000% Powder
pulp 5,000% 5,000% A mixture of mine-
rails AIN-93 3,500% 3,500% Mixture of vita
mines AIN-93 1,000% 1,000% Bitartrate
choline 0.250% 0.250% Tert-butyl
hydroquinone 0.006% 0.002% L-cysteine 0.375% 0.300% table 2 (n = 6) group,
mean ± WITH Food intake
(g / day / mouse) Body weight after
feeding (g) Mass inside
abdominal
fat / mass
body (%) Group without
treatment
(control
Group) 2.92 ± 0.39 23.0 ± 1.1 1.08 ± 0.24 Group,
received 1%
hydrophobic
extract
licorice 2.81 ± 0.50 22.2 ± 0.5 0.82 ± 0.15

From the data given in table 2, it is obvious that, compared with the untreated group (control group), the group receiving the diet supplemented with hydrophobic licorice extract showed significantly lower weight of intra-abdominal fat, although there were differences in food intake or body weight was not observed. Therefore, it is clear that the amount of visceral fat accumulated by consuming foods high in fats and carbohydrates decreased with food containing hydrophobic licorice extract.

(Experimental example 2) Preventive effect-1 in relation to diabetes in mice with a model of type II diabetes

Using KK-Ay mice, which are model animals that have hereditary obesity and the development of type II diabetes, the prophylactic effect of the hydrophobic licorice extract obtained in Production Example 1 against the diabetes was evaluated. The antidiabetic agent troglitazone was used as a positive control.

KK-Ay mice (females, 6 weeks old) were divided into 3 groups (5 per group), and using a normal diet (Oriental Yeast Co product; table 1) as the main diet, the untreated group was formed ( control group), a group receiving troglitazone, and a group receiving a hydrophobic licorice extract. In all groups, mice had free access to food for 4 weeks. For troglitazone, a Noscal 200 tablet (200 mg troglitazone in each tablet; Sankyo Co., Ltd.) was ground into powder in an agate mortar and added to normal feed to a final concentration of 0.2%. As for the hydrophobic licorice extract, the extract obtained in Production Example 1 was added to normal feed to a final concentration of 0.15%.

During the feeding period, small blood samples were taken from the tail vein weekly from mice and blood glucose was determined using a simple blood glucose test Novo Assist Plus (Novo Nordisk Pharma Ltd.).

At the end of the feeding period, the mice were deprived of food for one night, after which a laparotomy was performed under ether anesthesia. Blood was removed from the abdominal aorta and the liver was excised and weighed. In addition, Sogo Ikagaku Kenkyusho Co. Ltd. charged with testing for total serum cholesterol (T-CHO), triglycerides (TG), free fatty acids (NEFA), GOT, GPT, LAP, cholinesterase (ChoE), total protein (TP-S), albumin (ALB-S) and A / G ratio.

Table 3 Mouse body mass (g) Group without treatment (control group) Group
troglitazone Hydrophobic group
licorice extract Start 27.3 ± 1.0 28.0 ± 0.8 27.7 ± 0.9 1 Week 33.7 ± 1.3 34.5 ± 1.9 32.9 ± 0.7 2 week 39.2 ± 0.9 40.7 ± 3.5 39.4 ± 1.7 3 week 42.1 ± 1.5 43.0 ± 5.3 41.9 ± 2.1 4 week 46.0 ± 1.6 48.6 ± 1.6 * 43.9 ± 1.7 * (p <0.05)

The body weights of the mice are shown in Table 3. The average body weight of the mice in the troglitazone group slightly exceeded the indicated value in the untreated group (control group), and significantly after 4 weeks. In the group receiving hydrophobic licorice extract, there was no significant difference compared with the group not receiving treatment (control group).

Table 4 Blood Glucose (mg / dl) Group without treatment (control group) Group
troglitazone Hydrophobic group
licorice extract Start 151 ± 12 145 ± 11 157 ± 18 1 Week 391 ± 95 217 ± 74 ** 358 ± 59 2 week 417 ± 71 173 ± 40 ** 290 ± 78 * 3 week 471 ± 43 304 ± 77 ** 342 ± 72 ** 4 week 441 ± 67 246 ± 51 ** 272 ± 48 ** * (p <0.05), ** (p <0.01)

Data on blood glucose are presented in table 4. The level of glucose in the blood at the beginning of feeding ranged from 145 to 157 mg / dl; hyperglycemia was not observed in any of the groups. After 1 week, the blood glucose in the untreated group (control group) exceeded 390 mg / dl, which indicates the onset of diabetes. In contrast to this untreated group (control group), the troglitazone-treated group showed significant inhibition of an increase in blood glucose, indicating that this drug inhibits an increase in blood glucose. The dosage of troglitazone at the indicated point in time, according to the calculation taking into account the body weight of the mice and their food intake, was about 270 mg / kg per day. On the other hand, in the hydrophobic licorice extract group, there was a significant inhibition of an increase in blood glucose after 2 weeks, indicating that the extract inhibits an increase in blood glucose. The dosage of hydrophobic licorice extract at the indicated time, calculated taking into account the body weight of the mice and their food intake, was about 190 mg / kg per day.

Table 5 Group without treatment (control group) Group
troglitazone Group
hydrophobic extract
licorice Liver mass
(g / 100 g body weight) 4.23 ± 0.27 6.84 ± 1.30 ** 3.26 ± 0.51 T-CHO (mg / dl) 161 ± 12 163 ± 7 131 ± 13 ** TG (mg / dl) 127 ± 57 39 ± 14 * 82 ± 26 NEFA (μEq / L) 3299 ± 600 1750 ± 302 ** 2285 ± 175 * GOT (ME / L) 107 ± 22 121 ± 26 83 ± 17 GPT (IU / L) 37.4 ± 13.7 70.5 ± 26.2 * 28.2 ± 6.3 LAP (ME / L) 63.4 ± 8.4 60.8 ± 6.1 57.4 ± 5.7 ChoE (ME / L) 145 ± 13 153 ± 9 145 ± 10 TP-S (g / dl) 5.00 ± 0.21 5.13 ± 0.17 4.90 ± 0.10 ALB-S (g / dl) 2.56 ± 0.13 2,50 ± 0,12 2.40 ± 0.07 A / G ratio 1,04 ± 0,05 0.98 ± 0.05 0.98 ± 0.08 * (p <0.05), ** (p <0.01)

Data on liver mass and blood test data are presented in table 5. Compared with the untreated group (control group), in the troglitazone group, a significant decrease in TG and NEFA was observed, which indicates the effect of this drug improving lipid metabolism. However, in the troglitazone-treated group, there was a significant increase in liver mass, a significant increase in GPT and a 13% increase in GOT, which, however, was not statistically significant, which indicates impaired liver function. On the other hand, in the hydrophobic licorice extract group, there was a significant decrease in T-CHO and NEFA and a 35% decrease in TG, which, however, was not statistically significant, which indicates the effect of the extract improving lipid metabolism. In addition, in the hydrophobic licorice extract group, there were significant changes in markers of liver function, such as liver mass, GOT and GPT, indicating that the extract was not hepatotoxic.

From the above results it is clear that, like the positive control with troglitazone, the hydrophobic licorice extract has an inhibitory effect on blood glucose and improves lipid metabolism.

(Production Example 2) Production of a hydrophobic licorice extract 2

Using a glass jar, 300 g of licorice powder (Kaneka Sun Spice Co., Ltd.) was soaked in 10 volumes of warm water (about 40 ° C) and stirred, protecting from light, overnight (approximately 18 hours). The mixture was then filtered through filter paper (ADVANTEC No.2) and the resulting residue was dried (about 60 ° C) to give 265 g of an aqueous extract residue. The specified residue was soaked in 5 volumes of ethanol and left to stand at room temperature, protecting from light, for 1 week with periodic stirring. The mixture was filtered twice through filter paper (ADVANTEC No.2) to remove the powder and obtain an extract solution. The specified extract solution was concentrated under reduced pressure to remove the solvent, after which 23.62 g of a hydrophobic licorice extract was obtained.

(Experimental Example 3) Preventive effect-2 on diabetes in mice with a type II diabetes model

The diabetes prophylactic effect of the hydrophobic licorice extract obtained in Production Example 2 was evaluated using the same procedure as used in Experimental Example 2. In the group receiving the hydrophobic licorice extract, the extract made in Production Example 2 was added to normal food until final concentration of 0.2%. An antidiabetic agent pioglitazone was used as a positive control. For pioglitazone, an Actos 30 tablet (30 mg of pioglitazone in each tablet; Takeda Chemical Industries, Ltd.) was ground into powder in an agate mortar and added to normal feed to a final concentration of 0.04%. A simple blood glucose test, Glutest Ace (Sanwa Kagaku Kenkyusho Co., Ltd.), was used to determine blood glucose.

Table 6 Mouse body mass (g) Group
without treatment (control group) Group
pioglitazone Hydrophobic group
licorice extract Start 27.3 ± 0.3 26.9 ± 1.0 26.4 ± 0.9 1 Week 34.5 ± 0.9 36.7 ± 1.0 34.4 ± 1.9 2 week 38.9 ± 1.1 39.9 ± 1.2 38.8 ± 2.1 3 week 42.4 ± 1.5 42.9 ± 1.2 41.7 ± 1.9 4 week 43.5 ± 1.3 43.8 ± 1.4 43.2 ± 1.9

The body mass data of the mice are presented in Table 6. Over time, the body weight of the mice in the pioglitazone group and the hydrophobic licorice extract group were comparable to body weight over time in the untreated group (control group), which indicated lack of significant difference.

Table 7 Blood Glucose (mg / dl) Group
without treatment (control
Group) Group
pioglitazone Hydrophobic group
licorice extract Start 142 ± 12 151 ± 9 143 ± 8 1 Week 322 ± 70 163 ± 23 ** 180 ± 4 ** 2 week 427 ± 70 182 ± 9 ** 257 ± 73 ** 3 week 455 ± 66 167 ± 18 ** 206 ± 26 ** 4 week 479 ± 71 153 ± 21 ** 231 ± 59 ** ** (p <0.01)

Data on blood glucose are presented in table 7. After 1 week, the blood glucose level in the untreated group (control group) increased, which indicates the onset of diabetes. In contrast, in the pioglitazone group, a significant inhibition of an increase in blood glucose was observed, which indicates the inhibitory effect of this drug on an increase in blood glucose. The dosage of pioglitazone at a specified point in time, calculated taking into account the body weight of the mice and their food intake, was about 50 mg / kg per day. In the group receiving the hydrophobic licorice extract, a significant inhibition of an increase in blood glucose was also observed, which indicates the inhibitory effect of this extract on an increase in blood glucose. The dosage of the hydrophobic licorice extract at the indicated point in time, calculated taking into account the body weight of the mice and their food intake, was about 260 mg / kg per day.

From the above results it is clear that the hydrophobic licorice extract inhibits the increase in blood glucose, as well as the positive control pioglitazone, which indicates the presence of the preventive effect of this extract on diabetes.

(Experimental Example 4) Effect Relieving Diabetes in Mice with Type II Diabetes Model

Using KK-Ay mice, the diabetes-alleviating effect of the hydrophobic licorice extract obtained in Production Example 2 was evaluated. The antidiabetic agent pioglitazone was used as a positive control.

KK-Ay mice (females, 15 weeks old) were divided into 3 groups (4 per group), and using a normal diet as the main diet, the untreated group (control group), the pioglitazone group, and the group were formed receiving hydrophobic licorice extract. Mice had free access to food for 7 days. Pioglitazone was added to normal feed to a final concentration of 0.02%. As for the hydrophobic licorice extract, the extract obtained in Production Example 2 was added to normal feed to a final concentration of 0.2%. A simple blood glucose test, Glutest Ace (Sanwa Kagaku Kenkyusho Co., Ltd.), was used to determine blood glucose.

Table 8 Blood Glucose (mg / dl) Group
without treatment (control
Group) Group
pioglitazone Hydrophobic group
licorice extract Start 391 ± 45 378 ± 36 389 ± 63 Day 4 528 ± 52 168 ± 49 ** 192 ± 61 ** Day 7 534 ± 44 143 ± 16 ** 272 ± 61 ** ** (p <0.01)

Data on blood glucose are presented in table 8. The blood glucose level at the beginning of feeding ranged from 378 to 391 mg / dl, which indicated the presence of hyperglycemia in mice in all groups. The blood glucose in the untreated group (control group) was approximately 530 mg / dl on day 4 and day 7, indicating an exacerbation of the disease. In contrast, in the pioglitazone group and the hydrophobic licorice extract group, the blood glucose level was significantly reduced on day 4 and day 7, indicating that this drug and this extract had a hypoglycemic effect.

From the above results it is clear that the hydrophobic licorice extract has a hypoglycemic effect, causing the effect of alleviating diabetes, as well as the positive control pioglitazone.

(Production Example 3) Production of a hydrophobic licorice extract 3

Using a stainless steel vessel, 1.5 kg of licorice powder (Kaneka Sun Spice Co., Ltd.) was soaked in 10 volumes of water and stirred at room temperature, protected from light, for approximately 24 hours. The mixture was centrifuged (5000 g, 20 min), and the resulting residue was dried (about 55 ° C) to obtain a residue of the aqueous extract. The specified residue was soaked in 5 volumes of ethanol and left to stand at room temperature, protecting from light, for 1 week with periodic stirring. The mixture was then filtered twice through filter paper (ADVANTEC No. 2) to remove the powder and obtain an extract solution. The specified extract solution was concentrated under reduced pressure to remove the solvent, after which 141.5 g of a hydrophobic licorice extract was obtained.

(Experimental example 5) Efficacy in rats with spontaneous hypertension

Using rats with spontaneous hypertension (SHR), which are animals with a model of essential hypertension, in which hypertension develops with age, the effectiveness of the hydrophobic licorice extract obtained in Production Example 3 was evaluated. The antihypertensive agent enalapril maleate was used as a positive control.

SHR (males, 5 weeks old) were divided into 3 groups (8 per group) to form the control group receiving the vehicle, the group receiving the hydrophobic licorice extract, and the group receiving enalapril maleate. In the control group receiving the carrier, the animals were injected with propylene glycol at doses of 3 ml / kg per day, in the group receiving the hydrophobic licorice extract, the animals were injected with a solution of hydrophobic licorice extract in propylene glycol at doses of 300 mg / 3 ml / kg per day, and in the group treated with enalapril maleate, animals were injected with a solution of enalapril maleate in 0.5% methylcellulose (aqueous solution) at doses of 20 mg / 10 ml / kg per day, orally for 3 consecutive weeks. During this period of time, the mice had free access to food (CRF-1, Oriental Yeast Co.) and water.

On the day immediately preceding the start of treatment, and on day 7, day 14 and day 21 of treatment, the blood pressure in the caudal artery was measured using a non-invasive automatic blood pressure monitor (BP-97A, Softron Co., Ltd.). Measurement of blood pressure was carried out before each injection of the sample.

Table 9 Body weight (g) Control
group (carrier) Hydrophobic group
licorice extract Group
enalapril maleate To start 76 ± 2.1 76 ± 1,7 77 ± 1.7 1 Week 114 ± 2.9 118 ± 1.8 115 ± 1.0 2 week 156 ± 4.1 161 ± 2.8 151 ± 1.2 3 week 192 ± 4.3 200 ± 3.1 187 ± 1.4

Body mass data for SHR are presented in Table 9. Over time, body mass was almost comparable in all groups, indicating a lack of significant difference.

Table 10 Blood pressure (mmHg) Control
group (carrier) Hydrophobic group
licorice extract Enalapril maleate group To start 113 ± 2.2 112 ± 2.5 111 ± 2.5 Day 7 137 ± 4.0 125 ± 3.3 118 ± 3.2 ** Day 14 156 ± 3.3 143 ± 5.2 119 ± 3.4 ** Day 21 166 ± 2.9 153 ± 2.8 ** 134 ± 3.1 ** * (p <0.05), ** (p <0.01)

Data on blood pressure are presented in table 10. Blood pressure prior to administration ranged from 111 to 113 mm Hg; thus, no hypertension was detected in any group. In the control group receiving the carrier, blood pressure began to rise on day 7, which indicated the onset of hypertension. Compared with the control group receiving the carrier, the increase in blood pressure in the group receiving the hydrophobic licorice extract was inhibited, with a significant difference observed on day 7 and day 21. In the group receiving the antihypertensive agent enalapril maleate, the increase in blood pressure was significantly inhibited on day 7 and thereafter.

From the above results it is clear that the hydrophobic licorice extract is effective in the prevention or relief of hypertension.

(Example 1) Production of tablets containing hydrophobic licorice extract

Hydrophobic licorice extract 45 parts by weight Lactose 35 parts by weight Crystalline cellulose 15 parts by weight Sucrose and fatty acid ester 5 mass parts

According to the above recipe, tablets containing a hydrophobic licorice extract were prepared using the usual procedure for use in food / drinks or for medical purposes.

(Example 2) Production of soft capsules containing hydrophobic licorice extract

Hydrophobic licorice extract 40 parts by weight Sesame oil 55 parts by weight Glycerol and fatty acid ester 5 mass parts

According to the above recipe, a soft capsule containing a hydrophobic licorice extract was made using the usual procedure for use in food / drinks or for medical purposes.

(Example 3) Production of crackers containing hydrophobic licorice extract

Hydrophobic licorice extract 1 mass part Soft wheat flour 120 parts by weight Edible salt 1 mass part Baking powder 2 mass parts Oil 30 parts by weight Water 40 parts by weight

According to the above recipe, crackers containing a hydrophobic licorice extract were made using the usual procedure.

(Example 4) Making noodles containing hydrophobic licorice extract

Hydrophobic licorice extract 1 mass part Durum wheat flour 100 parts by weight Soft wheat flour 100 parts by weight Edible salt 10 parts by weight Water 100 parts by weight

According to the above recipe, a noodle containing a hydrophobic licorice extract was made using the usual procedure.

(Example 5) Production of a seasoning containing a hydrophobic licorice extract

Hydrophobic licorice extract 10 parts by weight Olive oil 80 parts by weight Wine vinegar 60 parts by weight Edible salt 3 mass parts Pepper 1 mass part Lemon juice 5 mass parts

According to the above recipe, a seasoning containing a hydrophobic licorice extract was made using the usual procedure.

Yellow root extract

(Production Example 4) Production of Yellow Root Extract 1

Using a glass vessel, 400 g of yellow root powder (Kaneka Sun Spice Co., Ltd.) was soaked in 5 volumes of ethanol and allowed to stand at room temperature, protected from light, for 1 week with periodic stirring. The mixture was filtered twice through filter paper (ADVANTEC No. 2) to remove the powder and obtain an extract solution. This extract solution was concentrated under reduced pressure to remove the solvent, after which 43.71 g of yellow root extract was obtained.

(Experimental example 6) The effect of reducing the amount of visceral fat

C57BL / 6J mice (females, 10 weeks old) were given plenty of fats and carbohydrates (product of Oriental Yeast Co .; Table 1) for 4-8 weeks to obtain nutritional obesity. The mice were then divided into groups of 6-8 animals, and using a normal diet (Oriental Yeast Co. product; table 1) as the main diet, the untreated group (control group) and the diet supplemented group were formed yellow root extract obtained in manufacturing example 4. In both groups, the mice had free access to food for 4 weeks. After an overnight abstinence from food, the animals underwent laparotomy under ether anesthesia and the mice were killed by bleeding from the abdominal aorta. Then, para-fat and perinephric fat were excised and weighed. The sum of the mass of perinatal fat and perineal fat was recorded as the mass of intra-abdominal fat. The data are presented in tables 11 and 12.

Table 11 (n = 8) group,
mean ± WITH Food intake
(g / day / mouse) Body weight after
feeding (g) Intra-abdominal fat mass / mass
body (%) Group without
treatment
(control
Group) 3.17 ± 0.43 22.9 ± 1.5 1.76 ± 0.73 Group,
received
1% extract
yellow root 2.92 ± 0.62 21.7 ± 1.1 0.71 ± 0.20 Table 12 (n = 6 / group,
mean ± WITH Food intake
(g / day / mouse) Body weight after
feeding (g) Mass inside
abdominal
fat / mass
body (%) Group without
treatment
(control
Group) 2.92 ± 0.39 23.0 ± 1.1 1.08 ± 0.24 Group,
treated with 0.5% extract
yellow root 2.53 ± 0.59 22.6 ± 0.9 0.90 ± 0.50

From the data given in tables 11 and 12, it is obvious that in comparison with the untreated group (control group), in the group receiving the diet with the addition of yellow root extract, there was no difference in food intake or body weight, but was noted significantly lower mass of abdominal fat. It was obvious that the amount of visceral fat accumulated by consuming foods high in fats and carbohydrates decreased with food containing yellow root extract.

(Production Example 5) Production of Yellow Root Extract 2

Using a glass jar, 793 g of yellow root powder (Kaneka Sun Spice Co., Ltd.) was soaked in 4000 ml of ethanol and allowed to stand at room temperature, protected from light, for 1 week with periodic stirring. The mixture was filtered twice through filter paper (ADVANTEC No. 2) to remove the powder and obtain an extract solution. This extract solution was concentrated under reduced pressure to remove the solvent, after which 79.48 g of yellow root extract was obtained.

(Experimental Example 7) Efficacy in Mice with Type II Diabetes Model

Using KK-Ay mice, which are model animals that have hereditary obesity and the development of type II diabetes, the effect of yellow root extract was evaluated. An antidiabetic agent pioglitazone was used as a positive control.

KK-Ay mice (females, 6 weeks old) were divided into 3 groups (5 per group), and using normal food (Oriental Yeast Co product; table 1) as the main diet, animals in the untreated group (control group), in the group receiving pioglitazone, and in the group receiving yellow root extract, they were fed ad libitum for 4 weeks. For pioglitazone, an Actos 30 tablet (30 mg of pioglitazone in each tablet; Takeda Chemical Industries, Ltd.) was ground into powder in an agate mortar and added to normal feed to a final concentration of 0.04%. As for the yellow root extract, the extract obtained in Production Example 5 was added to normal feed to a final concentration of 0.5%.

During the weekly feeding period, small blood samples were taken from the tail vein mice weekly and blood glucose was determined using a simple blood glucose test Glutest Ace (Sanwa Kagaku Kenkyusho Co., Ltd.).

Table 13 Mouse body mass (g) Group
without treatment (control group) Group
pioglitazone Extract group
yellow root Start 27.3 ± 0.3 26.9 ± 1.0 27.1 ± 0.8 1 Week 34.5 ± 0.9 36.7 ± 1.0 35.3 ± 1.1 2 week 38.9 ± 1.1 39.9 ± 1.2 39.4 ± 1.2 3 week 41.0 ± 1.3 42.3 ± 1.2 41.8 ± 1.3 4 week 43.5 ± 1.3 43.8 ± 1.4 44.4 ± 1.6

The body weights of the mice are shown in Table 13. In the pioglitazone group and the yellow root extract group, almost the same body masses were observed over time as in the untreated group (control group), which indicates the absence of statistically significant difference.

Table 14 Blood Glucose (mg / dl) Group
without treatment (control
Group) Group
pioglitazone Extract group
yellow root Start 142 ± 12 151 ± 9 142 ± 6 1 Week 322 ± 70 163 ± 23 ** 193 ± 28 ** 2 week 427 ± 70 182 ± 9 ** 201 ± 50 ** 3 week 455 ± 66 166 ± 18 ** 244 ± 47 ** 4 week 479 ± 71 153 ± 21 ** 270 ± 37 ** ** (p <0.01)

Data on blood glucose are presented in table 14. The level of glucose in the blood at the beginning of feeding ranged from 142 to 151 mg / dl; hyperglycemia was not observed in any of the groups. After 1 week, the blood glucose level in the untreated group (control group) increased, indicating the onset of diabetes. Compared with the untreated group (control group), in the group receiving the yellow root extract, there was a significant inhibition of the increase in blood glucose, as in the group receiving the antidiabetic agent pioglitazone, indicating that this extract has the property of lowering blood glucose. The dosage of the yellow root extract at the indicated point in time, according to the calculation taking into account the body weight of the mice and their food intake, was about 670 mg / kg per day. From the above results, it is clear that yellow root extract is effective in preventing or alleviating diabetes mellitus.

(Example 6) Production of tablets containing yellow root extract

Yellow root extract 45 parts by weight Lactose 35 parts by weight Crystalline cellulose 15 parts by weight Sucrose and fatty acid ester 5 mass parts

According to the above recipe, tablets containing the yellow root extract were made using the usual procedure for use in food / drink or for medical purposes.

(Example 7) Production of soft capsules containing yellow root extract

Yellow root extract 40 parts by weight Sesame oil 55 parts by weight Glycerol and fatty acid ester 5 mass parts

According to the above recipe, soft capsules containing yellow root extract were made using the usual procedure for use in foods / drinks or for medical purposes.

(Example 8) Production of crackers containing yellow root extract

Yellow root extract 1 mass part Soft wheat flour 120 parts by weight Edible salt 1 mass part Baking powder 2 mass parts Oil 30 parts by weight Water 40 parts by weight

According to the above recipe, crackers containing yellow root extract were made using the usual procedure.

(Example 9) Making noodles containing yellow root extract

Yellow root extract 1 mass part Durum wheat flour 100 parts by weight Soft wheat flour 100 parts by weight Edible salt 10 parts by weight Water 100 parts by weight

According to the above recipe, a noodle containing yellow root extract was made using the usual procedure.

(Example 10) Production of seasoning containing yellow root extract

Yellow root extract 10 parts by weight Olive oil 80 parts by weight Wine vinegar 60 parts by weight Edible salt 3 mass parts Pepper 1 mass part Lemon juice 5 mass parts

According to the above recipe, a seasoning containing yellow root extract was made using the usual procedure.

Clove extract

(Production Example 6) Production of clove extract 1

Using a glass vessel, 600 g of clove powder (Kaneka Sun Spice Co., Ltd.) was soaked in 5 volumes of ethyl acetate and allowed to stand at room temperature, protected from light, for 1 week with periodic stirring. The mixture was filtered twice through filter paper (ADVANTEC No. 2) to remove the powder and obtain an extract solution. This extract solution was concentrated under reduced pressure to remove the solvent, after which 47.59 g of clove extract was obtained.

(Experimental example 8) The effect of reducing the amount of visceral fat

C57BL / 6J mice (females, 10 weeks old) were given plenty of fats and carbohydrates (product of Oriental Yeast Co .; Table 1) for 4-8 weeks to obtain nutritional obesity. The mice were then divided into groups of 6-8 animals and, using normal food (product of Oriental Yeast Co .; table 1) as the main diet, the untreated group (control group) and the diet-supplemented group were formed cloves obtained in manufacturing example 6. In both groups, mice had free access to food for 4 weeks. After an overnight abstinence from food, the animals underwent laparotomy under ether anesthesia, and the mice were sacrificed by bleeding from the abdominal aorta. Then, para-fat and perinephric fat were excised and weighed. The sum of the mass of perinatal fat and perineal fat was recorded as the mass of intra-abdominal fat. The data are presented in table 15.

Table 15 (n = 8) group,
mean ± WITH Food intake
(g / day / mouse) Body weight after
feeding (g) Mass of abdominal
fat / mass
body (%) Group without
treatment
(control
Group) 3.17 ± 0.43 22.9 ± 1.5 1.76 ± 0.73 Group,
received 1%
extract
carnations 2.55 ± 0.53 21.7 ± 0.6 0.79 ± 0.15

From the data given in table 15, it is obvious that in comparison with the untreated group (control group), in the group receiving the diet with the addition of clove extract, there was no difference in food intake or body weight, but significantly lower mass of abdominal fat. It was obvious that the amount of visceral fat accumulated by eating foods high in fats and carbohydrates decreased with food containing clove extract.

(Production Example 7) Production of clove extract 2

Using a glass jar, 2 kg of clove powder (Kaneka Sun Spice Co., Ltd.) was soaked in 10 L of ethanol and allowed to stand at room temperature, protected from light, for 1 week with occasional stirring. The mixture was filtered twice through filter paper (ADVANTEC No. 2) to remove the powder and obtain an extract solution. This extract solution was concentrated under reduced pressure to remove the solvent, after which 217 g of clove extract was obtained.

(Experimental Example 9) Efficacy in Mice with Type II Diabetes Model

Using KK-Ay mice, which are model animals that have hereditary obesity and the development of type II diabetes, the effect of clove extract was evaluated. An antidiabetic agent pioglitazone was used as a positive control.

KK-Ay mice (females, 6 weeks old) were divided into 3 groups (5 per group), and using normal food (Oriental Yeast Co product; table 1) as the main diet, animals in the untreated group (control group), in the group receiving pioglitazone, and in the group receiving clove extract, fed ad libitum for 3 weeks. For pioglitazone, an Actos 30 tablet (30 mg of pioglitazone in each tablet; Takeda Chemical Industries, Ltd.) was ground into a powder in an agate mortar and added to normal feed to a final concentration of 0.02%. As for the clove extract, the extract obtained in Production Example 7 was added to normal feed to a final concentration of 0.5%.

During the weekly feeding period, small blood samples were taken from the tail vein mice weekly and blood glucose was determined using a simple blood glucose test Glutest Ace (Sanwa Kagaku Kenkyusho Co., Ltd.).

Table 16 Mouse body mass (g) Group
without treatment (control
Group) Group
pioglitazone Extract group
carnations Start 26.7 ± 1.1 27.4 ± 0.5 27.1 ± 1.1 1 Week 34.2 ± 2.1 35.0 ± 1.1 34.7 ± 1.9 2 week 39.2 ± 2.0 41.0 ± 1.5 39.2 ± 1.4 3 week 42.7 ± 2.5 45.4 ± 1.4 42.5 ± 2.1

The body weights of mice are shown in Table 16. In the group receiving pioglitazone and in the group receiving clove extract, almost the same body masses were observed over time as in the untreated group (control group), which indicates the absence of a statistically significant the difference.

Table 17 Blood Glucose (mg / dl) Group
without treatment (control group) Group
pioglitazone Extract group
carnations Start 163 ± 14 156 ± 16 171 ± 14 1 Week 304 ± 77 208 ± 21 289 ± 63 2 week 457 ± 48 192 ± 17 ** 274 ± 67 ** 3 week 514 ± 60 164 ± 16 ** 311 ± 90 ** * (p <0.05), ** (p <0.01)

Data on blood glucose are presented in table 17. The level of glucose in the blood at the beginning of feeding ranged from 156 to 171 mg / dl; hyperglycemia was not observed in any of the groups. After 1 week, the blood glucose level in the untreated group (control group) increased, indicating the onset of diabetes. Compared with the untreated group (control group), in the group receiving clove extract, there was a significant inhibition of an increase in blood glucose, as in the group receiving the antidiabetic agent pioglitazone, indicating that this extract has the property of lowering blood glucose. The dosage of clove extract at a specified point in time, according to the calculation taking into account the body weight of the mice and their food intake, was about 660 mg / kg per day.

(Example 11) Production of tablets containing clove extract

Clove extract 45 parts by weight Lactose 35 parts by weight Crystalline cellulose 15 parts by weight Sucrose and fatty acid ester 5 mass parts

According to the above recipe, tablets containing clove extract were made using the usual procedure for use in food / drink or for medical purposes.

(Example 12) Production of soft capsules containing clove extract

Clove extract 40 parts by weight Sesame oil 55 parts by weight Glycerol and fatty acid ester 5 mass parts

According to the above recipe, soft capsules containing clove extract were made using the usual procedure for use in food / drinks or for medical purposes.

(Example 13) Making crackers containing clove extract

Clove extract 1 mass part Soft wheat flour 120 parts by weight Edible salt 1 mass part Baking powder 2 mass parts Oil 30 parts by weight Water 40 parts by weight

According to the above recipe, crackers containing clove extract were made using the usual procedure.

(Example 14) Making noodles containing clove extract

Clove extract 1 mass part Durum wheat flour 100 parts by weight Soft wheat flour 100 parts by weight Edible salt 10 parts by weight Water 100 parts by weight

According to the above recipe, a noodle containing clove extract was made using the usual procedure.

(Example 15) Production of seasoning containing clove extract

Clove extract 10 parts by weight Olive oil 80 parts by weight Wine vinegar 60 parts by weight Edible salt 3 mass parts Pepper 1 mass part Lemon juice 5 mass parts

According to the above recipe, a seasoning containing clove extract was made using the usual procedure.

Cinnamon extract

(Production Example 8) Production of Cinnamon Extract

Using a glass vessel, 1000 g of cinnamon powder (Kaneka Sun Spice Co., Ltd.) was soaked in 5 volumes of ethyl acetate and allowed to stand at room temperature, protected from light, for 1 week with periodic stirring. The mixture was filtered twice through filter paper (ADVANTEC No.2) to remove the powder and obtain an extract solution. This extract solution was concentrated under reduced pressure to remove the solvent, after which 59.57 g of cinnamon extract was obtained.

(Experimental example 10) The effect of reducing the amount of visceral fat

C57BL / 6J mice (females, 10 weeks old) were given plenty of fats and carbohydrates (product of Oriental Yeast Co .; Table 1) for 4-8 weeks to obtain nutritional obesity. The mice were then divided into groups of 6-8 animals, and using a normal diet (Oriental Yeast Co. product; table 1) as the main diet, the untreated group (control group) and the diet supplemented group were formed cinnamon extract obtained in manufacturing example 8. In both groups, the mice had free access to food for 4 weeks. After an overnight abstinence from food, the animals underwent laparotomy under ether anesthesia, and the mice were sacrificed by bleeding from the abdominal aorta. Then, para-fat and perinephric fat were excised and weighed. The sum of the mass of perinatal fat and perineal fat was recorded as the mass of intra-abdominal fat. The data are presented in table 18.

Table 18 (n = 8) group,
mean ± WITH Food intake
(g / day / mouse) Body weight after
feeding (g) Mass inside
abdominal
fat / mass
body (%) Group without
treatment
(control
Group) 3.17 ± 0.43 22.9 ± 1.5 1.76 ± 0.73 Group,
treated with 1% extract
cinnamon 2.61 ± 0.38 21.5 ± 1.0 1.00 ± 0.27

From the data given in table 18, it is obvious that in comparison with the untreated group (control group), in the group receiving a diet with the addition of cinnamon extract, there was no difference in food intake or body weight, but significantly lower mass of abdominal fat. It was obvious that the amount of visceral fat accumulated by consuming foods high in fats and carbohydrates decreased with food containing cinnamon extract.

(Example 16) Production of tablets containing cinnamon extract

Cinnamon extract 45 parts by weight Lactose 35 parts by weight Crystalline cellulose 15 parts by weight Sucrose and fatty acid ester 5 mass parts

According to the above recipe, tablets containing cinnamon extract were made using the usual procedure for use in food / drink or for medical purposes.

APPLICABILITY IN INDUSTRIAL CONDITIONS

The present invention presented above relates to a composition for preventing or alleviating a syndrome of multiple risk factors, including obesity by type of visceral fat deposition, diabetes mellitus, hyperlipidemia and hypertension. Oral administration of the composition of the present invention reduces the amount of accumulated visceral fat and therefore leads to the prevention or alleviation of lifestyle-related diseases arising from the accumulation of visceral fat, such as obesity, diabetes mellitus, hyperlipidemia and hypertension.

Claims (9)

1. An agent for the prevention or alleviation of the syndrome of multiple risk factors, which includes at least one component in an amount of from 0.1 to 100 wt.%, Selected from the group consisting of a hydrophobic licorice extract, yellow root extract (turmeric), clove extract and cinnamon extract. 2. An agent for the prevention or alleviation of obesity by type of visceral fat deposition, which includes at least one component in an amount of from 0.1 to 100 wt.%, Selected from the group consisting of a hydrophobic licorice extract, yellow root extract (turmeric), clove extract and cinnamon extract. 3. The tool according to claim 1 or 2, which includes at least one component selected from the group consisting of a hydrophobic licorice extract, clove extract and cinnamon extract. 4. The tool according to claim 1 or 2, which includes a hydrophobic licorice extract. 5. The tool according to claim 1 or 2, which includes an extract of yellow root. 6. The tool according to claim 1 or 2, which includes clove extract. 7. The tool according to claim 1 or 2, which includes an extract of cinnamon. 8. The tool according to claim 1 or 2, which is intended for use in food / drinks. 9. The tool according to claim 1, where the specified syndrome of multiple risk factors is a syndrome that accompanies obesity by type of visceral fat deposition, and at least one condition from the group including diabetes mellitus, hyperlipidemia and hypertension.