WO2004039389A1

WO2004039389A1 - SELECTIVE HUMAN β3 ADRENALIN RECEPTOR AGONIST AGENT

Info

Publication number: WO2004039389A1
Application number: PCT/JP2003/013985
Authority: WO
Inventors: Tatsumasa Mae; Misuzu Tsukagawa; Eisaku Konishi; Teruo Kawata
Original assignee: Kaneka Corporation
Priority date: 2002-10-31
Filing date: 2003-10-31
Publication date: 2004-05-13
Also published as: AU2003280675A1; JP2006096666A

Abstract

It is intended to provide a selective human β3 adrenalin receptor agonist agent comprising as the active ingredient a zanthoxylum extract which originates in a highly safe food material. This selective human β3 adrenalin receptor agonist agent is useful as a preventive and/or an improving agent for life style-related diseases such as fatness, obesity, diabetes, hyperlipemia, hypertension and gout.

Description

Specification

Selective human 3-adrenergic receptor agonist

The present invention relates to a selective human 133 adrenergic receptor agonist agent, and a method for preventing lifestyle-related diseases such as obesity, obesity, diabetes, hyperlipidemia, hypertension, and gout, comprising the agent. Or related to an improving agent. Background art

Due to overeating, overnutrition and lack of exercise, the obese population is steadily increasing. Obese people, especially those with visceral fat obesity in which visceral fat has accumulated, are com- bined with lifestyle-related diseases such as diabetes, hyperlipidemia, hypertension, and gout, which is a major social problem. In addition, if an obese person loses 5 to 10% of their body weight, the symptoms of the comorbid lifestyle-related diseases can be reduced or ameliorated. Prevention of obesity and prevention or improvement of lifestyle-related diseases can be prevented. And / or improvement.

Adrenoceptors are receptors that bind to catecholamine agonists such as adrenergic-noradrenaline released from sympathetic nerves, and are classified into two types, α receptors and 0 receptors, depending on the sensitivity to catecholamine agonists. That is, α-adrenergic receptors are sensitive in the order of noradrenaline ≥ adrenerin> dopamine> isoproterenol, and] 3 adrenergic receptors are sensitive in the order of isoproterenol> adrenaline ≥ noradrenaline> dopamine.

Adrenergic receptors include ΐ, 2, and 3 receptors, and in recent years, the existence of 4 receptors has been suggested. The effects of agonists (agonists) on each receptor are as follows: β1 adrenergic receptor agonist increases heart rate, 2 adrenergic receptor agonist relaxes bronchial smooth muscle, 3 adrenergic receptor agonist produces heat It is known that it has an activating action and a lipolytic promoting action. From this, there is a concern that those that activate the sympathetic nerve and promote secretion of catecholamine agonists, or non-selective 13-adrenergic receptor agonists, may have side effects due to j31 and] 32 actions. Suitable for preventing and / or improving lifestyle-related diseases such as obesity Not. Therefore, selective] 33 adrenergic receptor agonists are effective in preventing and / or improving lifestyle-related diseases such as obesity.

] 33 The adrenergic receptor agonist was first discovered in 1984, and its antiobesity and antidiabetic effects due to thermogenesis and lipolysis were observed in animal experiments. However, these effects were weak in humans. In 1989, it was clarified that this difference in effect was due to species differences in the chemical structure of the 3-adrenergic receptor between rodents such as mice and rats and humans (Yasuhito Takakura, Toshihide Yoshida) , Japan Pharmacology Magazine, 118, 315-320, 2001 and C. Weyer, eta 1., Diabetes & Metabo 1 ism, 25, 11-21, 199 99). From these results, agonists with higher selectivity for the j3 3 adrenergic receptor than for j31 and j32 and higher selectivity for the human 3 adrenergic receptor, that is, the selective human / 33 adrenergic receptor Agonists are effective in preventing and / or ameliorating lifestyle-related diseases such as obesity and diabetes, and their development is desired. Recently, several compounds have been known as selective human] 33 adrenergic receptor agonists (Yasuhito Takakura, Toshihide Yoshida, Nippon Pharmacological Journal, 118, 315-320, 2001), and anti-obesity in clinical trials Its effect as a drug or antidiabetic has been confirmed. And selective humans derived from natural food ingredients] 33 The adrestine receptor agogoest is not yet known.

On the other hand, citrus plants are known as lipolysis accelerators derived from natural food materials, and citrus plants and Citrus plants are used as citrus plants. ), Genus Zanthoxy 1 urn, genus Goshu (Evodia) and the like (Japanese Patent Application Laid-Open No. 8-81382). JP-A-9-1241127 and JP-A-9-295932 disclose that a skin extract obtained by drying the pericarp of Citrus unshiu Marcov is used as a cosmetic for slimming. It is also disclosed. However, in these examples, the effect of promoting lipolysis was confirmed using rat adipose tissue, and it is unclear whether it is effective in humans.

It is also known that a citrus plant extract is supplemented with another lipolysis accelerator as a lipolysis accelerator (JP-A-11-269079, JP-A-269079). 000-63227, JP-A-2000-63259 and JP-A-2000-63260).

Sansho is a plant of the genus Rutaceae (Zanthoxylum), and is used as one of spices and crude drugs. Japanese Patent Application Laid-Open No. 8-81382 discloses that the only species of the genus Sancho (Zanthoy 1 urn piperit urn DC) as a genus of the genus Santo has the action of promoting lipolysis. It is indicated that it is preferable to use fruit peels and leaves that use immature fruits because the effect of promoting decomposition is small.

WO 97/47209 also discloses a lipid metabolism improving agent or an antiobesity agent containing an epoxidamine compound as an active ingredient, and a plant containing the epodiamine compound as a plant of the genus Goshu (Rutaceae). Evodia), Fagara, Zanthoxylum and Araliopsis are listed. In addition, Zanthoxylmrheetsa, Z.budruunga, Z.f1avum, Zlimiiiella, and ZintiegliolioLlolium are exemplified as the genus Sanyo. Examples thereof include evodiamine content in ethanol extract (dry extract) of Goshu (Ev odiarutaecarpa), Nozarea (Fagararhetza), and Zantoxylam retza (Zanthoxylum rhetsa), respectively, at 1.13 ° / . , 2.94% and 0.014% (w / w), and their effects have been confirmed in mice or rats. For this reason, the ethanol extract of the plant of the genus Sancho is not practical because it has a much lower epodiamine content than the plant of the genus Goshu. It is unknown whether it is effective in humans.

Further, Japanese Patent Application Laid-Open No. 2002-179586 discloses the use of Sansho as a lipase inhibitor. However, lipase inhibitors inhibit the activity of lipase, which is responsible for in vivo lipid digestion and absorption, and are not considered to exhibit an anti-obesity effect by activating heat production or promoting lipolysis.

Based on the above, Sansho, which is used as a spice and food material, has a selective human | 33 adrenergic receptor agonist effect, and Is not known to be effective in preventing and / or improving lifestyle-related diseases such as obesity and diabetes. Summary of the Invention

The present invention relates to a selective human β3 adrenergic receptor agonist derived from a safe food material, and obesity, obesity, diabetes, hyperlipidemia, and hypertension characterized by containing the agent. An object of the present invention is to provide an agent for preventing and / or improving lifestyle-related diseases such as gout.

The present inventors have conducted intensive studies in order to solve the above-mentioned problems, and as a result, found that pepper was dissolved in a water-soluble organic solvent, preferably ethanol, more preferably 60 ° / ₀ or more ethanol, and further preferably 70% or more. The present inventors have found that a pepper extract, which is an extract obtained by extraction with ethanol, has a selective human 3 adrenergic receptor agonist action, thereby completing the present invention.

That is, the present invention relates to a selective human β3 adrenergic receptor agonist comprising, as an active ingredient, a pepper extract obtained by extraction with an extraction solvent comprising a water-soluble organic solvent.

Further, the present invention provides a method for preventing lifestyle-related diseases such as obesity, obesity, diabetes, hyperlipidemia, hypertension, and gout, which comprises the selective human 03 adrenergic receptor agonist. Or an improving agent. Detailed Disclosure of the Invention

Hereinafter, embodiments of the present invention will be described in detail.

The selective human β 3 -adrenergic receptor agonist 1j of the present invention contains, as an active ingredient, a pepper extract obtained by extraction with an extraction solvent comprising a water-soluble organic solvent. The selective human β3 adrenergic receptor agonist of the present invention may be an extract itself, or may be added with known carriers, auxiliaries, food and drink materials, other pharmaceutically acceptable formulation materials, and the like. A composition may be used.

Sansho is a plant of the genus Zanthoxylum in the Rutaceae family, and there are many varieties. Sansho used in the present invention has sufficient eating experience and is safe. For this reason, varieties commonly used as spices and crude drugs are preferable. For example, Japanese pepper (Zanthoxyl um piperit um DC) and Asakurazansho (Z. piperit urn DC formaine rme Makino: Grape Zansho), etc .; Chinese pepper, Zoku bun gean um Ma xi m .; Crude drug names: Chinese shochu, pepper, safflower pepper, and Zin schinifo 1 i um S ie b. et Zuc c .; crude drug name: green pepper, green pepper) and the like. However, Japanese pepper is classified as a luxury product as a Japanese pepper and is expensive as a raw material. Therefore, Chinese pepper, which is relatively inexpensive and distributed in large quantities, namely, potato pepper and pink pepper, is preferred. Is most preferred.

The portion of the pepper used in the present invention is preferably a portion generally used as a spice or crude drug, for example, fruits, pericarp, seeds and the like.

The pepper extract used in the present invention is obtained from the above pepper by solvent extraction. In addition, the extract can be used in the present invention as an extract, or as a crude extract or a semi-purified extract as long as it does not contain impurities unsuitable for foods and drinks and pharmaceuticals.

The solvent extraction can be performed as follows. For example, the original form, ground or powder of the above pepper is usually immersed in 1 to 20 times, preferably 2 to 10 times, the following extraction solvent on a weight basis, and extracted by stirring and Z or standing, filtration, and centrifugation. An extract can be obtained by separation or the like. Next, the solvent can be removed from the obtained extract by concentration, freeze-drying, or the like, to obtain the extract.

The Japanese pepper extract used in the present invention is obtained by extracting Japanese pepper using an extraction solvent comprising a water-soluble organic solvent. The extraction solvent only needs to contain a water-soluble organic solvent, and may be composed of only a water-soluble organic solvent or a mixture of a water-soluble organic solvent and water.

In the present invention, the above-mentioned water-soluble organic solvent means alcohols, ketones and the like, and does not include esters such as ethyl acetate. As the water-soluble organic solvent, a lower alcohol having 1 to 3 carbon atoms and acetone are preferable. The lower alcohols having 1 to 3 carbon atoms include methanol, ethanol, 1-propanol and 2 Monopropanol. As the water-soluble organic solvent, ethanol is more preferable from the viewpoint of the safety of the residual solvent.

As the above-mentioned extraction solvent, it is preferable to use 60% or more of a water-soluble organic solvent, and it is more preferable to use 70% or more of a water-soluble organic solvent. Further, it is more preferable to use ethanol of 60 ° / ₀ or more, and it is particularly preferable to use ethanol of 70% or more. When a mixture of a water-soluble organic solvent and water is used as the extraction solvent, the upper limit of the ratio of the water-soluble organic solvent in the extraction solvent is not particularly limited, but is preferably 99.5%, more preferably 99%. %, More preferably 95%, particularly preferably 90%.

In the present invention, the “60% or more water-soluble organic solvent” means that the proportion of the water-soluble organic solvent in the extraction solvent is 60% or more on a volume basis, and the other is water. The same applies to the above “70% or more water-soluble organic solvent” and the like. The extraction temperature is not particularly limited, and is usually −20 to 100 ° (preferably 1 to 80 ° C., more preferably 20 to 60 ° C.).

The extraction time is not particularly limited, and is usually 0.1 hour to 1 month, preferably 0.5 hour to 7 days.

The method for evaluating the action of the human j33 adrenergic receptor agonist of the pepper extract used in the present invention is not particularly limited, and can be evaluated, for example, by using cells expressing the human] 33 adrenergic receptor. That is, in an invitro experimental system, animal cells such as cultured cells (CHO cells) derived from Chinese hamster ovaries are stably expressed in human] 33-adrenergic receptor, and the extract is added to the cells, and the cells are caloried. It can be evaluated by measuring the increase in the cyclic adenosine 3 ', 5' monomonophosphate (cyclic AMP) concentration (AA Konkar, eta 1., J. Pharmacol. E. Ther. , 291, 875-883, 1999; T. K iso, eta 1., Biol. Pharm. Bull., 22, 1073-1078, 1999). In addition, it can be evaluated by transfection of the CRE-LUC reporter gene into cells stably expressing the above human 03 adrenergic receptor, followed by adding the extract and measuring luciferase activity. (W. Zheng, eta 1., J. Med. Chem., 42, 2287-2294, 1999; SS Vansal & D. R. Feller, Biochem. Pharmacol., 58, 807-810, 1999). CRE-LUC is a reporter gene in which a luciferase (LUC) gene is linked to a cyclic AMP response element (CRE), and luciferase is expressed by an increase in intracellular cyclic AMP concentration.

Furthermore, in the above experimental system, if cells expressing human 1 or / 32 adrenergic receptor were used instead of human 3 adrenergic receptor, You can compare the differences and evaluate their selectivity.

In the present invention, selective human 133 adrenergic receptor agonism refers to a selective agonist action on human / 33 adrenergic receptor, and a weak effect on human / 31 // 32 adrenergic receptor. Or what does not exist.

In addition, the selective human β3 adrenergic receptor agonist agent of the present invention can selectively be used as a preventive and / or ameliorating agent for lifestyle-related diseases, because it selectively exhibits an agonist effect on human | 33 adrenergic receptor.

The agent for preventing and / or improving lifestyle-related diseases of the present invention contains the above-mentioned selective human] 33 adrenergic receptor agonist. The above preventive and / or ameliorating agent can be preferably used for at least one disease selected from the group consisting of obesity, obesity, diabetes, hyperlipidemia, hypertension and gout among lifestyle-related diseases. Here, obesity and obesity follow obesity diagnostic criteria of the Japan Obesity Society. That is, obesity is defined as having a BMI (Body Mass Index: body mass index: weight (kg) / height (m) ² ) of 25 or more. Obesity is defined as obesity and health impairment or visceral fat obesity due to Mitsuru Tsukiba. Judgment of visceral fat obesity is based on a waist (diameter around the navel) of 85 cm or more for men, 90 cm or more for women, or a visceral fat area of 100 cm ² or more by abdominal CT.

In addition, health disorders due to obesity include 1) type 2 diabetes mellitus, impaired glucose tolerance, 2) abnormal lipid metabolism, 3) hypertension, 4) hyperuricemia / gout, 5) coronary artery disease (myocardial infarction, angina pectoris) , 6) Cerebral infarction (cerebral thrombosis / transient ischemic attack), 7) Sleep apnea syndrome ■ Pic kwick syndrome, 8) Fatty liver, 9) Orthopedic diseases (osteoarthritis · lumbar spondylopathy) ) And 10) abnormal menstruation, at least one selected from the group consisting of: The present invention also comprises a selective human] 33 adrenergic receptor agonist as described above, characterized by high body fat percentage, hyperglycemia, hyperinsulinemia, hypercholesterolemia, and hypercholesterolemia. An agent for preventing and / or ameliorating at least one symptom selected from the group consisting of triglyceridemia, hypertension and hyperuricemia. The preventive and / or ameliorating agent of the present invention may be the selective human 133 adrenergic receptor agonist itself, or may be the one to which a known additive is added.

An agent for preventing and / or improving lifestyle-related diseases such as obesity, obesity, diabetes, hyperlipidemia, hypertension, and gout, comprising the selective human 3 adrenergic receptor agonist agent of the present invention, And a selective human of the present invention] 33 adrenergic receptor agonist, characterized by high body fat percentage, hyperglycemia, hyperinsulinemia, hypercholesterolemia, and hypertriglyceridemia. The preventive and / or ameliorating agent for at least one symptom selected from the group consisting of hypertension and hyperuricemia (hereinafter referred to as the preventive / ameliorating agent of the present invention) can be used for eating and drinking and for medicine. However, the form is not limited. For example, health foods (specified health foods, nutritional foods), health foods, foods and drinks such as dietary supplements, over-the-counter drugs, over-the-counter drugs (over t h e- c o u n t e r d r u g: O T C), etc. can be used as such readily available pharmaceutical or quasi drug.

When used as a food or drink, the prophylactic / ameliorating agent of the present invention can be taken directly as it is, and can be easily taken using known additives such as carriers and auxiliaries such as capsules, tablets, and granules. It can be ingested in a molded form.

The content of prophylactic improving agent of the present invention in these molding agent is preferably from 0.1 to 1 0 0 wt ^_0/0, more preferably 1 0-9 0 weight ^_0/0.

Furthermore, the prophylactic / ameliorating agent of the present invention is mixed with food and drink materials to produce confectionery such as chewing gum, chocolate, candy, jelly, biscuit, and crackers; ice confectionery such as ice cream and ice confection; tea and soft drinks Beverages such as udon, Chinese food, spaghetti, instant meal; kneaded products such as kama, bamboo rings, halves; seasonings such as dressings, mayonnaise, sauces; margarine, butter, salad oil Oils and fats such as bread, ham, soup, retort food, frozen food, etc. can be used for all food and drink. When the prophylactic / ameliorating agent of the present invention is ingested for food or drink, the amount of the extract is preferably 0.01 to 100 OmgZkg body weight per adult per day in terms of the extract, more preferably 0.1 to: L 0 Omg / kg body weight.

When used as a pharmaceutical, the dosage form is not particularly limited, and examples thereof include capsules, tablets, granules, injections, suppositories, and patches. In the formulation, other pharmaceutically acceptable formulation materials, such as excipients, disintegrants, lubricants, binders, antioxidants, coloring agents, anti-agglomeration agents, absorption enhancers, It can be prepared by appropriately adding a solubilizing agent, a stabilizer and the like. -The dosage of these preparations is preferably 0.1 O OO OO OmgZkg body weight, more preferably 0.1 ~: LO OmgZ kg body weight once or several times per adult per S in terms of the extract. It can be administered in divided doses.

When used as a quasi-drug, add other additives as needed, for example, ointments, liniments, aerosols, creams, stones, facial cleansers, body wash, lotion It can be used for lotions, bath salts, etc., and can be used topically. BEST MODE FOR CARRYING OUT THE INVENTION

Hereinafter, the present invention will be described more specifically with reference to examples, but the present invention is not limited to these examples.

(Example 1)

Extract 2 g of Chinese pepper powder (Chinese power Hokuzansho powder: Kanerik Sun Spice Co., Ltd.) with 10 ml of ethanol (99.5%) (room temperature (25 ° C), dark place, leave for 1 week), After filtration and concentration to dryness, 345 mg of a pepper extract was obtained.

(Comparative Example 1)

202 mg of a pepper extract was obtained in the same manner as in Example 1 except that ethyl acetate was used instead of ethanol (99.5%). (Comparative Example 2)

Chen skin powder (250 mg) was obtained in the same manner as in Example 1 except that Kanekasa Co., Ltd. was used instead of the pepper powder (Example 2)

HI β 3 adrenergic receptor agonist activity

In a cultured cell (CHO-K1 cell) derived from Chinese hamster ovary, a plasmid for expression of the human β3 adrenergic receptor gene was replaced with ^{ribophenatoamine} ΤΜ ²⁰⁰⁰ (a gene using cationic lipid manufactured by I η V itrogen). The cells were transfected using the transfection reagent) to obtain cells expressing the human 3 adrenergic receptor (hereinafter referred to as j33ZCHO cells). Using / 3 3ZCHO cells for the measurement group and CHO-K1 cells for the control group, the following methods were used to extract the humans of the extracts obtained in Example 1 and Comparative Examples 1 and 2.] 33 Adrenaline Receptor agonist activity was measured.

Day 1: 3 / CHO cells (measurement group) or CHO-K1 cells (control group) were inoculated into a 96-well culture plate at 3 × 10 ⁴ ce 11 s / we 11 and 37 ° C, and cultured for about 24 hours under 5% CO ₂ conditions. The medium used was an MD medium containing 5% FBS (には fetal serum). The MD medium was MCDB 302 (basic synthetic medium manufactured by SIG MA) 5.5 g / L, DMEM (Du 1 becco's Modified Eagle Medium manufactured by GIBCO) 4.75 g / L L _N L-glutamine (manufactured by Wako Pure Chemical Industries, Ltd.) 0. 3 GZL, (manufactured by GIB CO, Ltd.) sodium bicarbonate 1. was prepared with the composition of 27 GZL.

Day 2: For J33 / CHO cells (measurement group) and CHO-K1 cells (control group)! CRE-1 uc (manufactured by STRATAGENE) and Lipofectamine ^™ 2000 (manufactured by Invitrogen) Was used for transfection. Six hours later, the medium was replaced with a fresh medium and cultured. P CRE-1 uc is a reporter plasmid in which the luciferase (luc) gene is linked to the element (CRE) of the cyclic AMP response.

Day 3: Change to the medium containing the extract obtained in Example 1, Comparative Example 1 or 2, The cells were cultured for 6 hours. A medium containing the above extract was prepared by dissolving the above extract in dimethylsulfoxide (DMSO) and adding lZl 000 volumes to the medium. As an untreated control, only DMSO was used, and as a positive control, BRL 37344 (manufactured by TOCRIS), which is a selective 33-adrenergic receptor agonist, was used instead of the above extract. After washing the cells with phosphate buffered saline containing Ca and Mg (PBS +), Looklite ^™ (a reagent for measuring luminescence with Luciferase manufactured by Packard) is added, and TopCount ^™ microplate scintillation / luminescence is performed. The luminescence intensity of luciferase was measured with a counter (Packard). The ratio of the untreated control to the luciferase luminescence intensity was taken as the luciferase specific activity of the sample.

Table 1 shows the measurement results of the extracts obtained in Example 1 and Comparative Examples 1 and 2.

Mean soil standard deviation (η = 4), * (p × 0.05) In the positive control BRL 37344, β3ZCHO cells (measuring group) showed a significant increase in luciferase specific activity, but CHO-K1 cells ( Control group) Luciferase specific activity did not change. In other words, BRL 37344 increases the intracellular citral AMP concentration via human 3 adrenergic receptor and expresses luciferase, confirming the action of BRL 37344 on human] 33 adrenergic receptor agonism. Was.

As in the case of the positive control BRL 37344, the human pepper adrenergic receptor agonist effect was observed in the pepper extract extracted with ethanol in Example 1. However, the extract of ethyl pepper extracted with ethyl acetate in Comparative Example 1 did not show the action of human 3-adrenergic receptor agonist. On the other hand, the ethanol extract of skin skin of Comparative Example 2 was found to have a human / 33-adrenergic receptor agonist action.

(Example 3)

Human 1,] 3 2, 3 binding activity to adrenergic receptor

The binding activity to each of human 1, β2, and 3 adrenergic receptors was determined by a binding inhibition experiment for RI-labeled ligands (MDS Pharmaceuticals: Atssei No. 204010, 2041 10, 204200). Each of the three was evaluated. Table 2 shows the measurement results of the extracts obtained in Example 1 and Comparative Example 2. Table 2

(Average of duplicates) The pepper extract of Example 1 showed almost no inhibition of binding to human J31 and] 32 adrenergic receptors, and only a binding inhibition to human | 33 adrenergic receptor. Thus, it was shown to selectively bind to the human] 33 adrenergic receptor. That is, the pepper extract of Example 1 binds to the human] 33 adrenergic receptor. It has been found that they selectively exhibit agonist action.

On the other hand, the skin extract of Comparative Example 2 showed almost no binding to the human 1-adrenergic receptor because binding inhibition was observed for the human / 32 and / 33 adrenergic receptors, but the human J32 And 3 bind to the adrenergic receptor to the same extent. That is, it was suggested that the skin extract of Comparative Example 2 was not a selective human 3 adrenergic receptor agonist.

(Example 4)

Chinese pepper powder (China power powder): 5 g each of 25 ml ethanol (99.5%), 70% ethanol, 35% ethanol, diluted with water 17. Extraction was performed with 5% ethanol (room temperature, place, left for 1 week). After filtration, the mixture was concentrated to dryness and Z or freeze-dried to obtain 0.75 g, 1.14 g, 1.04 g, and 0.75 g of extracts, respectively.

The human β3 adrenergic receptor agonist activity of these extracts was measured by the method of Example 2. The results are shown in Table 3. Table 3

Average soil standard deviation ( _η = 4), * (ρ-0.05) Regardless of whether the extraction solvent was 17.5% to 99.5% ethanol, the obtained human pepper extract showed human / 33 adrenergic receptor agonist activity. In particular, the extract with 70% ethanol showed the highest activity.

(Example 5)

40 parts by weight of a 70% ethanolic pepper extract obtained in the same manner as in Example 4, 30 parts by weight of carboxymethylcellulose sodium, 20 parts by weight of crystalline cellulose, and 10 parts by weight of vitamin C The composition was mixed, ground, and filled into gelatin capsules to prepare a capsule for eating and drinking containing the pepper extract. Industrial applicability

According to the present invention, a selective human P3 adrenergic receptor agonist derived from a safe food material, and obesity, obesity, diabetes, hyperlipidemia, comprising An agent for preventing and / or improving lifestyle-related diseases such as hypertension and gout can be obtained.

Claims

The scope of the claims

1. A selective human β3 adrenergic receptor agonist comprising, as an active ingredient, a pepper extract obtained by extraction with an extraction solvent comprising a water-soluble organic solvent.

2. The selective human J33 adrenergic receptor agonist according to claim 1, wherein the extraction solvent is a 60% or more water-soluble organic solvent.

3. The selective human β3 adrenergic receptor agonist according to claim 2, wherein the extraction solvent is a water-soluble organic solvent of 70% or more.

4. The selective human] 33 adrenergic receptor agonist according to any one of claims 1 to 3, wherein the water-soluble organic solvent is a lower alcohol having 1 to 3 carbon atoms or acetone.

5. The selective human β3 adrenergic receptor agonist according to any one of claims 1 to 4, wherein the water-soluble organic solvent is ethanol.

6. The extract of claims 1 to 5, wherein the pepper extract is an extract obtained from Zanthο Xy 1 umbungeanum M axi m .: pepper, pepper, safflower pepper. 3. The selective human according to any one of [1] to [33], an adrenergic receptor agonist.

7. The method according to any one of claims 1 to 6, characterized in that it contains a selective human 3 adrenergic receptor agonist agent, preventing and / or preventing lifestyle-related diseases.

8. The lifestyle according to claim 7, wherein the lifestyle-related disease is at least one disease selected from the group consisting of obesity, obesity, diabetes, hyperlipidemia, hypertension, and gout. An agent for preventing and / or ameliorating a common disease.

9. It comprises the selective human 3 adrenergic receptor agonist according to any one of claims 1 to 6, characterized by high body fat percentage, hyperglycemia, hyperinsulinemia, An agent for preventing and / or ameliorating at least one symptom selected from the group consisting of cholesterolemia, hypertriglyceridemia, hypertension and hyperuricemia.