WO2019225847A1 - Anti-obesity or body fat reduction composition comprising navy bean extract and pleurotus eryngii extract - Google Patents

Anti-obesity or body fat reduction composition comprising navy bean extract and pleurotus eryngii extract Download PDF

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WO2019225847A1
WO2019225847A1 PCT/KR2019/003131 KR2019003131W WO2019225847A1 WO 2019225847 A1 WO2019225847 A1 WO 2019225847A1 KR 2019003131 W KR2019003131 W KR 2019003131W WO 2019225847 A1 WO2019225847 A1 WO 2019225847A1
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extract
composition
obesity
alcohol
water
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PCT/KR2019/003131
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French (fr)
Korean (ko)
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이계완
김도훈
박유화
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동국제약 주식회사
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/07—Basidiomycota, e.g. Cryptococcus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/332—Promoters of weight control and weight loss
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2250/00—Food ingredients
    • A23V2250/20—Natural extracts
    • A23V2250/208—Fungi extracts

Definitions

  • the present invention relates to a composition for reducing obesity or body fat, and more particularly, to a composition for preventing, treating and improving obesity comprising white kidney bean extract and agar mushroom extract as an active ingredient.
  • composition for preventing and treating obesity comprising the white kidney bean extract and the extract of Awi mushrooms may be used as a pharmaceutical composition and / or health functional food composition to include a pharmaceutically acceptable excipient and / or a food acceptable acceptable excipient. Can be used.
  • the World Health Organization has determined that obesity exceeds 30 kg / m 2 of body mass index, with abnormal or excessive fat accumulating in the adipose tissue to the point of harm to health.
  • Obesity is a disease caused by a combination of factors such as environmental, genetic, mental and endocrine factors. Coronary artery disease, hypertension, stroke, type 2 diabetes, dyslipidemia, Sleep apnea, lung disease, and cancer. Obesity is a high socioeconomic cost because it is directly involved in the increased mortality from these diseases.
  • the anti-obesity agents sold in Korea include Belvic (component Lorcaserin), Contrab (component Bupropion / Naltrexone), purimine (component Phentemine), Puring (component Phendimetrazine), and saccharin (Glucagon-Like Peptide 1).
  • Belvic component Lorcaserin
  • Contrab component Bupropion / Naltrexone
  • purimine component Phentemine
  • Puring component Phendimetrazine
  • saccharin Glucagon-Like Peptide 1
  • the ultimate treatment goal of obesity is to go beyond weight loss and to ameliorate and prevent the diseases associated with obesity. Therefore, anti-obesity drugs should be safer in 'long-term use' and have an advantage in managing various comorbid diseases.
  • side effects that are currently on the market, including dizziness, nausea, constipation, dry mouth and depression.
  • a total of 27 raw materials are sold on the market for functional foods related to body fat reduction.
  • Representative raw materials include Garcinia cambogia extract, complex extracts such as seaweed and wild mango seed extract.
  • Garcinia cambogia extract has undergone functional re-evaluation from the Ministry of Food and Drug Safety due to safety issues related to liver disease, and complex extracts such as seaweed are also lacking in human test results to prove their effectiveness.
  • the present invention is to provide a composition having little side effects and safe for the human body, and excellent in preventing obesity or reducing body fat, and a pharmaceutical or functional food containing the same.
  • the present invention provides an anti-obesity or body fat reduction composition containing the extract of white kidney beans and awi mushrooms as an active ingredient used as food ingredients.
  • the present invention also provides an anti-obesity or body fat-reducing medicine or health functional food comprising the anti-obesity or body fat-reducing composition.
  • the present invention provides a use of anti-obesity or body fat reduction by mixing a white kidney bean extract and a mushroom extract.
  • the composition of the present invention and a pharmaceutical or functional food containing the same have an excellent anti-obesity or body fat reduction effect.
  • FIG. 1 is a process chart showing a process for preparing a composition according to the present invention.
  • Figure 2 is a graph showing the ⁇ -amylase inhibition rate by mixing ratio of the anti-obesity composition according to the present invention using the ⁇ -amylase (amylase) inhibition test.
  • Figure 3 is a graph showing the lipase activity rate of the mixing ratio of the anti-obesity composition according to the present invention using a triglyceride lipase activity test.
  • Figure 4 is a graph showing the change in body fat according to the mixing ratio of the anti-obesity composition in a high fat diet-induced obesity model.
  • 5 is a graph showing the weight change according to the mixing ratio of the anti-obesity composition in the high fat diet-induced obesity model.
  • Figure 6 is a graph showing the change in weight measurement according to the dose of the anti-obesity composition after 8 weeks repeated administration in a high fat diet-induced obesity model by date and experimental groups, respectively.
  • Figure 7 is a graph showing the total fat, abdominal fat and subcutaneous fat change with respect to the change in body fat mass according to the dose of the anti-obesity composition after repeated administration for 8 weeks in a high-fat diet obesity model.
  • FIG. 8 is a graph showing the change in carbohydrate content in the feces according to the dose of the anti-obesity composition after 8 weeks repeated administration in a high fat diet-induced obesity model.
  • FIG. 9 is a graph showing triglyceride changes in the liver according to the dose of the anti-obesity composition after repeated 8-week administration in a high fat diet-induced obesity model.
  • the present inventors endeavored to obtain a composition having anti-obesity and body fat reduction effect among natural products which have been used and consumed for a long time, and confirmed that the mixed extract of white kidney beans and awi mushrooms has an excellent anti-obesity and body fat reduction effect.
  • the present invention has been completed.
  • the present invention relates to a composition for preventing, treating or improving obesity, including white kidney bean extract and agar mushroom extract as active ingredients.
  • the present invention relates to a composition for preventing, treating or improving obesity comprising an extract of a mixture of white kidney beans and awi mushroom as an active ingredient.
  • the anti-obesity or body fat reducing composition of the present invention can be obtained through conventional methods such as extraction, concentration and drying.
  • the extract may be obtained by extracting with water, alcohol (preferably 1 to 4 carbon straight chain or branched alcohol), or a mixture of water and alcohol.
  • the extract thus obtained may be obtained by further extraction with a nonpolar solvent such as hexane, dichloromethane, chloroform, or ethyl acetate.
  • the extract may be extracted by applying heat during extraction.
  • the extract is extracted by applying heat when extracting the extract.
  • the content ratio of the white kidney bean extract and the awi mushroom extract is 1: 1 to 1: 5 and 1: 1 to 5: 1, preferably 1: 1 to 5, based on the weight of the solid dried extract. : 1, more preferably 2: 1 to 4: 1.
  • the anti-obesity or body fat reducing composition of the present invention can be prepared in the form of pharmaceuticals and functional foods.
  • Pharmaceuticals and health functional foods may include pharmaceutically or pharmaceutically acceptable excipients or additives.
  • the pharmaceutical or functional food containing the anti-obesity or body fat reducing composition of the present invention may be a solid preparation or a liquid preparation.
  • Solid form preparations include, but are not limited to, tablets, capsules, granules, powders, transdermals, suppositories, and the like.
  • Solid form preparations may include excipients, binders, disintegrants, glidants, coatings and the like.
  • Liquid formulations include, but are not limited to, aqueous solutions, suspensions, emulsions, syrups, aerosols, or sterile injectable solutions, and can be prepared by adding suitable colorants, flavors, stabilizers, and the like.
  • tablets may be mixed with suitable pharmaceutically acceptable excipients (maltodextrin) and pharmaceutically acceptable suitable binders such as D-sorbitol powder, silicon dioxide, and pharmaceutically acceptable suitable glidants such as magnesium stearate. It can be prepared using a tablet press.
  • suitable pharmaceutically acceptable excipients maltodextrin
  • suitable binders such as D-sorbitol powder, silicon dioxide, and pharmaceutically acceptable suitable glidants such as magnesium stearate.
  • the anti-obesity or body fat reducing composition of the present invention may be administered as an oral, injectable, inhalant, etc., depending on the condition to be treated and the condition of the individual, but is not limited thereto. It may be formulated into a suitable formulation including non-toxic, pharmaceutically acceptable carriers, additives, and the like, commonly used according to the route of administration.
  • Oral liquid preparations include suspensions, solvents, emulsions, and syrups.
  • various excipients may be included, such as wetting agents, sweeteners, fragrances, and preservatives. have.
  • Formulations for parenteral administration include sterile aqueous solutions, suspensions, emulsions, and lyophilized preparations.
  • the composition has a daily dose of 1.5 g / day or less of an active ingredient based on animal test results.
  • the composition may be administered in an amount of 0.1 to 300mg / kg daily dose based on the active ingredient.
  • the dosage may vary depending on the patient's condition (age, weight, gender, etc.). If necessary, the total daily dose may be divided into one day for convenience.
  • the extract-containing composition was obtained as follows.
  • Purified water was added 3 to 10 times to 5 kg of white kidney beans dry powder, and extracted with stirring for 24 hours.
  • the extracted extract was filtered (No. 2 whatman, Maidstone, England) and the filtrate was concentrated under reduced pressure (rotary vacuum evaporator) to obtain an extract.
  • the extract was freeze-dried (PVTFD10R, ILSHIN, Daejeon, Korea) to finally obtain 1.07 kg white kidney bean extract powder.
  • Purified water was added 3 to 10-fold to 5 kg of the above-mentioned mushroom dry powder, and extracted with stirring at 80 ° C for 10 hours.
  • the prepared extract was filtered and the filtrate was concentrated under reduced pressure to obtain an extract.
  • Dextrin was added to the extract, followed by spray drying. Finally, 1.01 kg of Awi mushroom extract powder was obtained.
  • White kidney bean extract powder and awi mushroom extract powder were stored in a freezer at -20 ° C., respectively, and the extracts were used alone or in the following experiments.
  • ⁇ -amylase inhibitory activity was evaluated by measuring the amount of soluble starch decreased by the enzymatic reaction by the iodine reaction method.
  • Human saliva-derived ⁇ -amylase was dissolved in PBS (phosphate buffer) at a concentration of 20 units / ml, and soluble starch was used as a substrate of ⁇ -amylase in 1% concentration in PBS (phosphate buffer).
  • ⁇ -amylase inhibitor As a standard of the ⁇ -amylase inhibitor, it was dissolved in DMSO at a concentration of 100 ⁇ g / ml of acarbose, and compared with the extract.
  • test group was evaluated with white kidney bean extract powder, awi mushroom extract powder, mixed extract powder (1: 1 ⁇ 1: 5 and 1: 1 ⁇ 5: 1) group of white kidney bean and awi mushroom (concentration of mixed extract) Maintain 1.0 mg / ml).
  • acarbose was used.
  • Table 1 summarizes the composition and test procedure of the control group, test group, black 1 and 2.
  • composition of the Test Composition Control Extract test group Blank 1 Blank 2 ⁇ -amylase solution (20 units / ml) 10 ⁇ l 10 ⁇ l PBS buffer 290 ⁇ l 290 ⁇ l 300 ⁇ l 300 ⁇ l Inhibitors (White Kidney Bean and Agaric Mushroom Extract) - 50 ⁇ l - 50 ⁇ l Standard (Akaboz) DMSO Solution 50 ⁇ l - 50 ⁇ l - Free incubation (37 °C, 10 minutes) 1% Soluble Starch Solution 350 ⁇ l 350 ⁇ l 350 ⁇ l 350 ⁇ l 350 ⁇ l Incubation (37 °C, 10 minutes) I 2 solution (0.1% KI + 0.01% I 2 /0.05N HCl) 300 ⁇ l 300 ⁇ l 300 ⁇ l 300 ⁇ l 300 ⁇ l OD measurement (620nm)
  • the anti-obesity composition according to the present invention increased the ⁇ -amylase inhibitory activity as the ratio of white kidney beans extract powder increases.
  • Lipase is responsible for breaking down triglycerides.
  • Orlistat a typical obesity treatment, reduces the absorption of triglycerides and cholesterol in the body by irreversibly binding and inactivating lipases that degrade triglycerides. Triglycerides and cholesterol that are not degraded are excreted unchanged in feces.
  • Orlistat as a standard for the evaluation of triglyceride lipase (TGL) activity was dissolved in DMSO at a concentration of 100 ⁇ g / ml and compared with the extract.
  • 16 ⁇ l substrate mixture (5 ⁇ l of 120 mM Tauricholic acid solution + 1 M Enzyme Assay buffer (1 M NaH 2 PO 4 , 1 M NaCl, pH 7.0) 10 ul + 400 mM P-NPB (p-nitrophenyl butyrate) 1 ul) was added to each well (96well). plate). In each well, add 54 ul of standard orlistat-containing DMSO solution or 54 ul of extract (concentration 250 ⁇ g / ml). Absorbance is measured at 405 nm using a plate reader.
  • Enzyme (2 mg / ml TGL solution 10ul + 0.1% BSA buffer 20ul) was added to the wells and mixed, the light is blocked, and incubated at room temperature for 10 minutes. Absorbance is measured at 405 nm using a plate reader.
  • test group was evaluated using a group of white kidney bean extract powder, awi mushroom extract powder, a mixture of white kidney bean extract and awi mushroom extract (1: 1 to 1: 5 and 1: 1 to 5: 1) (single extract and The mixed extract concentrations should all be 250 ⁇ g / ml). Negative control groups do not contain extracts or test substances.
  • the anti-obesity composition according to the present invention increased the activity of triglyceride enzymes as the ratio of agaric mushrooms increased.
  • mice Thirty-three C57BL / 6J male mice, 8 weeks old, were acclimated for a week, followed by feeding a high fat diet (45% HFD (Research diet, D12451) pellet form-free diet) for 2 weeks to induce obesity.
  • a high fat diet 45% HFD (Research diet, D12451) pellet form-free diet
  • Negative and diet were freely fed and body fat mass and body weight were measured during the experiment.
  • the test dose was administered at 200 mg / kg.
  • the anti-obesity composition [Case 3] mixed extract the tendency to reduce the body fat mass and weight at 8 weeks compared to the high-fat diet group [Con (-)] was confirmed in Figures 4 and 5.
  • test group was divided into seven groups. In other words
  • Negative and diet were freely fed during the trial period, including: 1 body weight (measured at the start of anti-obesity composition administration, twice a week thereafter and on autopsy day), and 2 body fat (eight weeks after initiation of anti-obesity composition administration) Body fat mass measured by micro-CT (micro-CT)), 3 Carbohydrate content in feces (measured by ELISA analysis on the 8th week sample after anti-obesity composition administration), 4 TG (triglyceride) in liver tissue Changes were measured (analyzed by blood samples collected at 4, 6, 7, and 8 weeks after the start of the anti-obesity composition administration and at the time of autopsy).
  • composition and dose settings of each test group are shown in Table 2 below:
  • the general symptoms and health status were confirmed, and 84 animals having a weight gain of at least 10% compared to the normal diet were used for the test.
  • Body weights were measured on the day of administration of the anti-obesity composition, afterwards twice a week and on an autopsy day.
  • the induced control group (G2) showed a significant increase in total fat, abdominal fat and subcutaneous fat compared to the non-induced control. The results are shown in FIG. 7 (p ⁇ 0.001).
  • feces were collected by each breeding box once a week. Collected feces were stored in a cryogenic freezer (about -70 °C or less) until analysis, and analyzed by ELISA analysis for the samples 2 and 8 weeks after administration of the anti-obesity composition.
  • the induced control group (G2) showed a significant increase compared to the non-induced control group (G1) (p ⁇ 0.001), and the high dose anti-obesity composition group (G7) compared to the induced control group (G2). Showed a significant decrease. This is shown in FIG. 9 (p ⁇ 0.005).
  • the composition of the present invention is to provide a composition having a low side effect and safe for the human body, excellent in preventing obesity or reducing body fat, and a pharmaceutical or functional food containing the same.

Abstract

Disclosed is a body fat reduction and anti-obesity composition comprising navy bean extract and pleurotus eryngii extract as active ingredients.

Description

흰강낭콩 및 아위버섯 추출물을 함유하는 항비만 또는 체지방 감소용 조성물 Anti-obesity or Body Fat Reducing Composition Containing White Kidney Bean and Awi Mushroom Extract
본 발명은 항비만 또는 체지방 감소용 조성물에 관한 것으로서, 보다 구체적으로는 흰강낭콩 추출물과 아위버섯 추출물을 유효성분으로 포함하는, 비만의 예방, 치료 및 개선용 조성물에 관한 것이다.The present invention relates to a composition for reducing obesity or body fat, and more particularly, to a composition for preventing, treating and improving obesity comprising white kidney bean extract and agar mushroom extract as an active ingredient.
본 발명의 흰강낭콩 추출물과 아위버섯 추출물을 포함하는 비만 예방 및 치료용 조성물은 약학적으로 허용되는 부형제 및/또는 식품학적으로 허용되는 부형제를 포함하도록 하여 약학적 조성물 및/또는 건강기능식품 조성물로 사용할 수 있다.The composition for preventing and treating obesity comprising the white kidney bean extract and the extract of Awi mushrooms may be used as a pharmaceutical composition and / or health functional food composition to include a pharmaceutically acceptable excipient and / or a food acceptable acceptable excipient. Can be used.
세계보건기구(WHO)는 비만에 대해 '건강을 해칠 정도로 지방 조직에 비정상적인 또는 과도한 지방질이 축적되는 상태로 체질량지수 30kg/m2를 초과하는 상태”로 정하였다. 우리나라를 비롯한 아시아 태평양 국가들은 비만에 대하여 25kg/m2를 초과하는 상태로, 고도 비만은 30kg/m2를 초과하는 상태로 정하고 있다.The World Health Organization (WHO) has determined that obesity exceeds 30 kg / m 2 of body mass index, with abnormal or excessive fat accumulating in the adipose tissue to the point of harm to health. The Asia-Pacific countries, including Korea, are over 25kg / m 2 for obesity and high obesity over 30kg / m 2 .
비만은 환경적, 유전적, 정신적, 내분비적 요인 등의 여러 인자가 복합적으로 작용하여 발생되는 질환이며, 비만과 동반되는 질환에는 관상동맥질환, 고혈압, 뇌졸중, 제2형 당뇨병, 이상지질혈증, 수면 무호흡증, 폐질환, 암 등이 있다. 비만은 이들 질환으로 인한 사망률 증가에 직접 관여하므로, 사회 경제적인 비용이 높은 질환이다.Obesity is a disease caused by a combination of factors such as environmental, genetic, mental and endocrine factors. Coronary artery disease, hypertension, stroke, type 2 diabetes, dyslipidemia, Sleep apnea, lung disease, and cancer. Obesity is a high socioeconomic cost because it is directly involved in the increased mortality from these diseases.
지난 20 년간 비만의 유병률은 전 세계적으로 현저하게 증가하였고 지속적으로 상승하는 추세이며, 국내에서도 2015년 국민건강 영양조사에 의하면 성인 인구의 33.2% (남자: 39.7%, 여자 26.5%)가 비만으로 조사되어 성인 3명 중에 1명은 비만인 것으로 밝혀졌다.The prevalence of obesity in the past two decades has risen markedly and continues to rise globally, and in Korea, according to the 2015 National Health and Nutrition Survey, 33.2% (male: 39.7%, female 26.5%) of the adult population were surveyed as obesity. One out of three adults was found to be obese.
2016년 국민건강보험공단에서 발간된 백서에 따르면 비만 유병률이 2002년 29.3%에서 2013년 31.7% 로 가파르게 증가하고 있다. 국민건강보험공단 건강보험정책연구원의 보고서에서 2013년 비만의 사회 경제적 비용은 6조7700억원으로 2005년 3조400억원 대비 2.22배 증가하였고, 1998년 국민건강영양조사 결과인 2,050억~4,225억과 대비하여 약 17배가 증가하였다. 2005년과 비교하여 흡연의 사회경제적 비용이 1.62배 증가하고, 음주의 사회경제적 비용이 1.56배 증가한 것을 고려하면, 비만의 손실 규모가 최근 급증하였다는 것을 알 수 있다. 과체중을 포함한 비만과 관련된 진료비는 2005년 1조7천억원에서 2013년 4조4천억원으로 2.6배 상승하였다.According to a white paper published by the National Health Insurance Corporation in 2016, the prevalence of obesity has increased rapidly from 29.3% in 2002 to 31.7% in 2013. According to the report of the National Institute of Health Insurance, Korea's Health Insurance Policy Research Institute, the socioeconomic cost of obesity in 2013 was 6.77 trillion won, an increase of 2.22 times compared to 3.5 trillion won in 2005. In contrast, about 17 times increase. Considering that the socioeconomic cost of smoking increased by 1.62 times and the socioeconomic cost of drinking increased by 1.56 times compared with 2005, the loss of obesity has recently increased. Medical expenses related to obesity including overweight rose 2.6 times from 1.7 trillion won in 2005 to 4.4 trillion won in 2013.
현재 국내에서 판매되고 있는 비만치료제는 벨빅(성분 Lorcaserin), 콘트라브(성분 Bupropion/Naltrexone), 푸리민(성분 Phentemine), 푸링(성분 Phendimetrazine) 및 삭센다(Glucagon-Like Peptide 1) 등이 있다. 비만의 궁극적인 치료 목표는, 체중 감량을 넘어, 비만과 관련하여 동반되는 질환의 개선과 예방에 있다. 따라서 비만 치료제는 `장기간 사용` 시 보다 안전하고, 여러 동반 질환 관리에 있어서도 이점이 있어야 한다. 하지만 현재 판매되고 있는 의약품은 어지러움, 구역, 변비, 구갈, 우울증 등 다양한 부작용이 보고되고 있다.Currently, the anti-obesity agents sold in Korea include Belvic (component Lorcaserin), Contrab (component Bupropion / Naltrexone), purimine (component Phentemine), Puring (component Phendimetrazine), and saccharin (Glucagon-Like Peptide 1). The ultimate treatment goal of obesity is to go beyond weight loss and to ameliorate and prevent the diseases associated with obesity. Therefore, anti-obesity drugs should be safer in 'long-term use' and have an advantage in managing various comorbid diseases. However, there are a number of side effects that are currently on the market, including dizziness, nausea, constipation, dry mouth and depression.
체지방 감소와 관련한 건강기능식품 기능성 원료로는 총 27가지의 원료가 시중에 판매되고 있다. 대표적인 원료는 가르시니아 캄보지아 추출물, 미역 등 복합추출물, 와일드 망고 종자 추출물 등이 있다. 가르시니아 캄보지아 추출물은 간질환과 관련된 안전성 문제로 식품의약품안전처로부터 기능성 재평가를 받았으며, 미역 등 복합추출물 또한 효력을 입증할 만한 인체 적용시험 결과가 부족한 상황이다.A total of 27 raw materials are sold on the market for functional foods related to body fat reduction. Representative raw materials include Garcinia cambogia extract, complex extracts such as seaweed and wild mango seed extract. Garcinia cambogia extract has undergone functional re-evaluation from the Ministry of Food and Drug Safety due to safety issues related to liver disease, and complex extracts such as seaweed are also lacking in human test results to prove their effectiveness.
국내의 체지방 감소용 건강기능식품으로 판매되고 있는 제품들은 대부분 해외의 효능 원료를 수입하여 판매하고 있다. 따라서 장기 복용 시 안전성 및 유효성이 과학적으로 입증된 체지방 감소용 기능성의 새로운 원료 개발이 절실히 요구되고 있다.Most of the products that are sold as health functional foods for reducing body fat in Korea are imported and sold from overseas. Therefore, there is an urgent need to develop new raw materials for reducing body fat, which have been scientifically proven to be safe and effective during long-term use.
본 발명은 부작용이 적고 인체에 안전하며, 비만의 예방 또는 체지방 감소 효과가 우수한 조성물 및 이를 함유하는 의약품 또는 기능성 식품을 제공하기 위한 것이다.The present invention is to provide a composition having little side effects and safe for the human body, and excellent in preventing obesity or reducing body fat, and a pharmaceutical or functional food containing the same.
상기 기술적 과제를 달성하기 위하여, 본 발명은 식재료로 사용되고 있는 원료들인 흰강낭콩 및 아위버섯의 추출물을 유효성분으로 함유하는 항비만 또는 체지방 감소용 조성물을 제공한다. In order to achieve the above technical problem, the present invention provides an anti-obesity or body fat reduction composition containing the extract of white kidney beans and awi mushrooms as an active ingredient used as food ingredients.
또한, 본 발명은 상기 항비만 또는 체지방 감소용 조성물을 포함하는 항비만 또는 체지방 감소용 의약품 또는 건강기능성 식품을 제공한다.The present invention also provides an anti-obesity or body fat-reducing medicine or health functional food comprising the anti-obesity or body fat-reducing composition.
본 발명은 흰강낭콩 추출물과 아위버섯 추출물을 혼합한 것으로 항비만 또는 체지방 감소의 용도를 제공한다. 본 발명의 조성물 및 이를 포함하는 의약품 또는 건강기능성 식품은 항비만 또는 체지방 감소 효과가 탁월하다.The present invention provides a use of anti-obesity or body fat reduction by mixing a white kidney bean extract and a mushroom extract. The composition of the present invention and a pharmaceutical or functional food containing the same have an excellent anti-obesity or body fat reduction effect.
도 1은 본 발명에 따른 조성물을 제조하는 공정을 도시한 공정도이다.1 is a process chart showing a process for preparing a composition according to the present invention.
도 2는 α-아밀라아제(amylase) 저해 시험을 이용한 본 발명에 따른 항비만 조성물의 혼합 비율별 α-아밀라아제 저해율을 보여주는 그래프이다. Figure 2 is a graph showing the α-amylase inhibition rate by mixing ratio of the anti-obesity composition according to the present invention using the α-amylase (amylase) inhibition test.
도 3은 트리글리세라이드 리파제(triglyceride lipase) 활성 시험을 이용한 본 발명에 따른 항비만 조성물의 혼합 비율별 리파제 활성율을 보여주는 그래프이다.Figure 3 is a graph showing the lipase activity rate of the mixing ratio of the anti-obesity composition according to the present invention using a triglyceride lipase activity test.
도 4는 고지방식이 유도 비만 모델에서 항비만 조성물의 혼합 비율에 따른 체지방 변화를 보여주는 그래프이다.Figure 4 is a graph showing the change in body fat according to the mixing ratio of the anti-obesity composition in a high fat diet-induced obesity model.
도 5는 고지방식이 유도 비만 모델에서 항비만 조성물의 혼합 비율에 따른 체중 변화를 보여주는 그래프이다.5 is a graph showing the weight change according to the mixing ratio of the anti-obesity composition in the high fat diet-induced obesity model.
도 6은 고지방식이 유도 비만 모델에서 8주 반복 투여 후, 항비만 조성물의 용량에 따른 체중 측정 변화를 각각 날짜 별로, 그리고 실험군 별로 보여주는 그래프이다. Figure 6 is a graph showing the change in weight measurement according to the dose of the anti-obesity composition after 8 weeks repeated administration in a high fat diet-induced obesity model by date and experimental groups, respectively.
도 7은 고지방식이 유도 비만 모델에서 8주 반복 투여 후, 항비만 조성물의 용량에 따른 체지방량 변화에 관하여 각각 총지방량, 복부지방량 및 피하지방량 변화를 나타낸 그래프이다.Figure 7 is a graph showing the total fat, abdominal fat and subcutaneous fat change with respect to the change in body fat mass according to the dose of the anti-obesity composition after repeated administration for 8 weeks in a high-fat diet obesity model.
도 8은 고지방식이 유도 비만 모델에서 8주 반복 투여 후, 항비만 조성물의 용량에 따른 분변 내 탄수화물함량 변화를 보여주는 그래프이다.8 is a graph showing the change in carbohydrate content in the feces according to the dose of the anti-obesity composition after 8 weeks repeated administration in a high fat diet-induced obesity model.
도 9는 고지방식이 유도 비만 모델에서 8주 반복 투여 후, 항비만 조성물의 용량에 따른 간에서 트리글레세라이드(triglyceride) 변화를 보여주는 그래프이다.9 is a graph showing triglyceride changes in the liver according to the dose of the anti-obesity composition after repeated 8-week administration in a high fat diet-induced obesity model.
본 발명자들은 오랫동안 사용하고 섭취해온 안전성이 확보된 천연물 중에서 항비만 및 체지방 감소 효과를 가지는 조성물을 얻고자 노력하였고, 흰강낭콩 및 아위버섯의 혼합 추출물이 뛰어난 항비만 및 체지방 감소 효과가 있음을 확인하여 본 발명을 완성하였다.The present inventors endeavored to obtain a composition having anti-obesity and body fat reduction effect among natural products which have been used and consumed for a long time, and confirmed that the mixed extract of white kidney beans and awi mushrooms has an excellent anti-obesity and body fat reduction effect. The present invention has been completed.
따라서, 본 발명은 유효성분으로 흰강낭콩 추출물 및 아위버섯 추출물을 포함하는 비만 예방, 치료 또는 개선용 조성물에 관한 것이다. 또한, 본 발명은 유효성분으로 흰강낭콩과 아위버섯의 혼합물의 추출물을 포함하는 비만 예방, 치료 또는 개선용 조성물에 관한 것이다.Therefore, the present invention relates to a composition for preventing, treating or improving obesity, including white kidney bean extract and agar mushroom extract as active ingredients. In addition, the present invention relates to a composition for preventing, treating or improving obesity comprising an extract of a mixture of white kidney beans and awi mushroom as an active ingredient.
본 발명의 항비만 또는 체지방 감소용 조성물은 추출, 농축 및 건조 등과 같은 통상적인 방법을 통해서 얻을 수 있다. 예를 들어, 본 발명에서 상기 추출물은 물, 알코올(바람직하게는 탄소소 1 내지 4개의 직쇄 또는 분지형 알코올), 또는 물과 알코올의 혼합물로 추출하여 수득할 수 있다. 또한, 이와 같이 수득된 추출물은 헥산, 디클로로메탄, 클로로포름, 또는 에틸아세테이트와 같은 비극성 용매로 더 추출하여 수득할 수 있다. 본 발명에서 상기 추출물은 추출시 열을 가하여 추출할 수도 있다. 바람직하게는 아위버섯 추출물을 추출할 때에 열을 가하여 추출한다.The anti-obesity or body fat reducing composition of the present invention can be obtained through conventional methods such as extraction, concentration and drying. For example, in the present invention, the extract may be obtained by extracting with water, alcohol (preferably 1 to 4 carbon straight chain or branched alcohol), or a mixture of water and alcohol. In addition, the extract thus obtained may be obtained by further extraction with a nonpolar solvent such as hexane, dichloromethane, chloroform, or ethyl acetate. In the present invention, the extract may be extracted by applying heat during extraction. Preferably, the extract is extracted by applying heat when extracting the extract.
본 발명에서 상기 흰강낭콩 추출물 및 상기 아위버섯 추출물의 함량비는 추출물을 건조시킨 고형분의 중량을 기준으로 1:1~1:5 및 1:1~5:1, 바람직하게는 1:1~5:1, 더욱 바람직하게는 2:1~4:1로 한다.In the present invention, the content ratio of the white kidney bean extract and the awi mushroom extract is 1: 1 to 1: 5 and 1: 1 to 5: 1, preferably 1: 1 to 5, based on the weight of the solid dried extract. : 1, more preferably 2: 1 to 4: 1.
본 발명의 항비만 또는 체지방 감소용 조성물은 의약품 및 기능성 식품의 형태로 제조될 수 있다. 의약품 및 건강 기능성 식품은 약제학적 또는 식품학적으로 허용되는 부형제 또는 첨가제를 포함할 수 있다.The anti-obesity or body fat reducing composition of the present invention can be prepared in the form of pharmaceuticals and functional foods. Pharmaceuticals and health functional foods may include pharmaceutically or pharmaceutically acceptable excipients or additives.
본 발명의 항비만 또는 체지방 감소용 조성물을 포함하는 의약품 또는 건강기능성 식품은 고형 제제 또는 액상 제제일 수 있다. 고형 제제는 정제, 캡슐제, 과립제, 산제, 경피제, 좌제 등이 있으나 이에 한정되는 것은 아니다. 고형 제제에는 부형제, 결합제, 붕해제, 활택제, 코팅제 등이 포함될 수 있다. 액상 제제로는 수성 액제, 현탁제, 에멀젼, 시럽, 에어로졸, 또는 멸균 주사용액 등이 있으나, 이에 한정되는 것은 아니며, 적당한 착색제, 착향제, 안정화제 등을 첨가하여 제조할 수 있다.The pharmaceutical or functional food containing the anti-obesity or body fat reducing composition of the present invention may be a solid preparation or a liquid preparation. Solid form preparations include, but are not limited to, tablets, capsules, granules, powders, transdermals, suppositories, and the like. Solid form preparations may include excipients, binders, disintegrants, glidants, coatings and the like. Liquid formulations include, but are not limited to, aqueous solutions, suspensions, emulsions, syrups, aerosols, or sterile injectable solutions, and can be prepared by adding suitable colorants, flavors, stabilizers, and the like.
예를 들어, 정제는 약제학적으로 허용되는 적당한 부형제(말토덱스트린) 및 D-솔비톨분말, 이산화규소 등의 약제학적으로 허용되는 적당한 결합제, 스테아린산마그네슘 등의 약제학적으로 허용되는 적당한 활택제와 혼합한 후 타정기를 이용하여 제조될 수 있다.For example, tablets may be mixed with suitable pharmaceutically acceptable excipients (maltodextrin) and pharmaceutically acceptable suitable binders such as D-sorbitol powder, silicon dioxide, and pharmaceutically acceptable suitable glidants such as magnesium stearate. It can be prepared using a tablet press.
본 발명의 항비만 또는 체지방 감소용 조성물은 치료해야 할 질환 및 개체의 상태에 따라 경구제, 주사제, 흡입제 등으로 투여될 수 있으나 이에 한정되는 것은 아니다. 투여경로에 따라 통상적으로 사용되고 있는 비독성인, 약제학적으로 허용되는 운반체, 첨가제 등을 포함하는 적당한 제형으로 제제화 될 수 있다.The anti-obesity or body fat reducing composition of the present invention may be administered as an oral, injectable, inhalant, etc., depending on the condition to be treated and the condition of the individual, but is not limited thereto. It may be formulated into a suitable formulation including non-toxic, pharmaceutically acceptable carriers, additives, and the like, commonly used according to the route of administration.
경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데, 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 현탁액, 유제, 동결건조제제가 포함된다.Oral liquid preparations include suspensions, solvents, emulsions, and syrups.In addition to the commonly used simple diluents, water and liquid paraffin, various excipients may be included, such as wetting agents, sweeteners, fragrances, and preservatives. have. Formulations for parenteral administration include sterile aqueous solutions, suspensions, emulsions, and lyophilized preparations.
항비만 또는 체지방 감소라는 발명의 목적을 달성하기 위하여 상기 조성물은 동물시험 결과를 토대로 1.5g/day 이하의 유효성분을 1일 투여 용량으로 하는 것이 바람직하다. 예를 들어, 상기 조성물은 1일 투여량이 유효성분을 기준으로 0.1 ~ 300mg/kg의 양으로 투여될 수 있다. 상기 투여량은 환자의 상태(연령, 체중, 성별 등)에 따라서 변할 수 있다. 필요에 따라서는 편리성을 위하여 1일 총 투여량이 하루 동안 나뉘어 투여될 수 있다.In order to achieve the object of the invention, such as anti-obesity or body fat reduction, it is preferable that the composition has a daily dose of 1.5 g / day or less of an active ingredient based on animal test results. For example, the composition may be administered in an amount of 0.1 to 300mg / kg daily dose based on the active ingredient. The dosage may vary depending on the patient's condition (age, weight, gender, etc.). If necessary, the total daily dose may be divided into one day for convenience.
이하, 본 발명의 이해를 돕기 위하여 실시예 등을 들어 상세하게 설명하기로 한다. 그러나, 본 발명에 따른 실시예들은 여러가지 다른 형태로 변형될 수 있으며, 본 발명의 범위가 하기 실시예들에 의하여 한정되는 것으로 해석되어서는 안된다. 본 발명의 실시예들은 당업계에서 평균적인 지식을 가진 자에게 본 발명을 보다 완전하게 설명하기 위해 제공되는 것이다.Hereinafter, examples and the like will be described in detail to help understand the present invention. However, embodiments according to the present invention may be modified in many different forms, and the scope of the present invention should not be construed as being limited by the following examples. Embodiments of the present invention are provided to more fully describe the present invention to those skilled in the art.
[실시예 1]Example 1 흰강낭콩 및 아위버섯으로부터 본 발명에 따른 조성물의 제조Preparation of Compositions According to the Invention from White Kidney Beans and Agaric Mushrooms
도 1에 도시되어 있는 바와 같은 공정에 따라 흰강낭콩(Phaseolus multiflorus var. albus Bailey)과 아위버섯(Pleurotus ferulae) 추출물을 제조하였다.White kidney beans ( Phalotus multiflorus var. Albus Bailey ) and agaric mushroom ( Pleurotus ) according to the process as shown in Figure ferulae ) extract was prepared.
구체적으로 다음과 같이 추출물 함유 조성물을 얻었다.Specifically, the extract-containing composition was obtained as follows.
흰강낭콩 건조 분말 5kg에 정제수를 3~10배수 가하고 24시간 교반하면서 추출하였다. 제조된 추출액을 여과하고(No.2 whatman, Maidstone, England), 여액을 감압 상태에서 농축시켜(rotary vacuum evaporator) 추출물을 얻었다. 이 추출물을 동결 건조하여(PVTFD10R, ILSHIN, Daejeon, Korea) 최종적으로1.07kg의 흰강낭콩 추출 분말을 얻었다.Purified water was added 3 to 10 times to 5 kg of white kidney beans dry powder, and extracted with stirring for 24 hours. The extracted extract was filtered (No. 2 whatman, Maidstone, England) and the filtrate was concentrated under reduced pressure (rotary vacuum evaporator) to obtain an extract. The extract was freeze-dried (PVTFD10R, ILSHIN, Daejeon, Korea) to finally obtain 1.07 kg white kidney bean extract powder.
아위버섯 건조 분말 5kg에 정제수를 3~10배수 가하고 80℃에서10시간 교반하면서 추출하였다. 제조된 추출액을 여과하고, 여액을 감압 상태에서 농축시켜 추출물을 얻었다. 추출물에 덱스트린을 첨가하여 분무건조 하였으며, 최종적으로 1.01kg의 아위버섯 추출 분말을 얻었다.Purified water was added 3 to 10-fold to 5 kg of the above-mentioned mushroom dry powder, and extracted with stirring at 80 ° C for 10 hours. The prepared extract was filtered and the filtrate was concentrated under reduced pressure to obtain an extract. Dextrin was added to the extract, followed by spray drying. Finally, 1.01 kg of Awi mushroom extract powder was obtained.
흰강낭콩 추출 분말 및 아위버섯 추출 분말을 각각 -20℃의 냉동고에 보관하면서 하기 실험 시에 추출물을 단독으로 사용하거나 혼합하여 사용하였다.White kidney bean extract powder and awi mushroom extract powder were stored in a freezer at -20 ° C., respectively, and the extracts were used alone or in the following experiments.
[실시예 2]Example 2 α-아밀라아제(amylase) 저해 시험을 통한 항비만 효과 평가Evaluation of anti-obesity effect through α-amylase inhibition test
α-아밀라아제 저해 활성은 효소 반응에 의해 감소하는 가용성 전분의 양을 요오드 반응법으로 측정하여 평가하였다.α-amylase inhibitory activity was evaluated by measuring the amount of soluble starch decreased by the enzymatic reaction by the iodine reaction method.
인체 타액 유래의 α-아밀라아제를 PBS(인산염 완충액)에 20 unit/ml 농도로 용해시켜 사용하였고, α-아밀라아제의 기질로서 가용성 전분을 PBS(인산염 완충액)에 1% 농도로 녹여서 사용하였다.Human saliva-derived α-amylase was dissolved in PBS (phosphate buffer) at a concentration of 20 units / ml, and soluble starch was used as a substrate of α-amylase in 1% concentration in PBS (phosphate buffer).
α-아밀라아제에 대한 저해 활성을 측정하기 위하여 290μl PBS, 10μl α-아밀라아제 용액(20unit/ml) 및 50μl 추출물(1.0 mg/ml)을 혼합한 후 37℃에서 10분간 인큐베이션하였다.To measure the inhibitory activity against α-amylase, 290 μl PBS, 10 μl α-amylase solution (20 units / ml) and 50 μl extract (1.0 mg / ml) were mixed and incubated at 37 ° C. for 10 minutes.
인큐베이션한 혼합물에 기질인 1% 가용성 전분 350μl를 첨가하고, 다시 37℃에서 30분간 인큐베이션하여 반응시켰다.To the incubated mixture, 350 μl of 1% soluble starch as a substrate was added, and again incubated at 37 ° C. for 30 minutes to react.
반응 후 잔존하는 가용성 전분의 양을 측정하기 위해, 반응액(700μl)에 300μl 요오드 용액(0.1% KI + 0.01% I2/0.05N HCl)을 가하여 발색시키고, 분광광도계를 이용하여 620nm에서 흡광도를 측정하였다.To measure the amount of soluble starch remaining after the reaction, 300 μl of iodine solution (0.1% KI + 0.01% I 2 /0.05N HCl) was added to the reaction solution (700 μl), and the absorbance was measured at 620 nm using a spectrophotometer. Measured.
α-아밀라아제 저해제의 표준물질로서 아카보즈(acarbose) 물질 100μg/ml의 농도로 DMSO에 녹여서 추출물과 비교 평가하였다.As a standard of the α-amylase inhibitor, it was dissolved in DMSO at a concentration of 100 μg / ml of acarbose, and compared with the extract.
시험군은 흰강낭콩 추출분말, 아위버섯 추출분말, 흰강낭콩 및 아위버섯의 혼합 추출 분말(1:1~1:5 및 1:1~5:1) 군으로 평가하였다(혼합된 추출물의 농도도 1.0 mg/ml를 유지하도록 한다). 대조군에서는 표준물질(acarbose)을 사용하였다.The test group was evaluated with white kidney bean extract powder, awi mushroom extract powder, mixed extract powder (1: 1 ~ 1: 5 and 1: 1 ~ 5: 1) group of white kidney bean and awi mushroom (concentration of mixed extract) Maintain 1.0 mg / ml). In the control group, acarbose was used.
하기 표 1은 대조군, 시험군, black 1 및 2의 각 조성 및 시험 과정을 정리한 것이다.Table 1 below summarizes the composition and test procedure of the control group, test group, black 1 and 2.
시험 조성물의 조성Composition of the Test Composition
대조군Control 추출물 시험군Extract test group Blank 1Blank 1 Blank 2 Blank 2
α-아밀라아제 용액(20unit/ml)α-amylase solution (20 units / ml) 10 μl10 μl 10 μl10 μl
PBS 완충액PBS buffer 290 μl290 μl 290 μl290 μl 300 μl300 μl 300 μl300 μl
저해제 (흰강낭콩 및 아위버섯 추출물)Inhibitors (White Kidney Bean and Agaric Mushroom Extract) -- 50 μl50 μl -- 50 μl50 μl
표준물질 (아카보즈) DMSO 용액Standard (Akaboz) DMSO Solution 50 μl50 μl -- 50 μl50 μl --
프리 인큐베이션 (37℃, 10분간)Free incubation (37 ℃, 10 minutes)
1% 가용성 전분 용액1% Soluble Starch Solution 350 μl350 μl 350 μl350 μl 350 μl350 μl 350 μl350 μl
인큐베이션 (37℃, 10분간)Incubation (37 ℃, 10 minutes)
I2 용액 (0.1% KI + 0.01% I2/0.05N HCl)I 2 solution (0.1% KI + 0.01% I 2 /0.05N HCl) 300 μl300 μl 300 μl300 μl 300 μl300 μl 300 μl300 μl
OD 측정 (620nm)OD measurement (620nm)
측정 결과를 도 2에 나타내었다. 도 2에 나타나는 것과 같이, 본 발명에 따른 항비만 조성물은 흰강낭콩 추출 분말의 비율이 증가할수록 α-아밀라아제 저해 활성이 증가하였다.The measurement results are shown in FIG. As shown in Figure 2, the anti-obesity composition according to the present invention increased the α-amylase inhibitory activity as the ratio of white kidney beans extract powder increases.
[실시예 3] Example 3 TGL(triglyceride lipase) 활성 시험을 통한 항비만 효과 평가Evaluation of anti-obesity effect through TGL (triglyceride lipase) activity test
리파제(Lipase)는 트리글리세라이드(Triglyceride)를 분해하는 역할을 한다. 대표적인 비만치료제인 오르리스타트(orlistat)는 트리글리세라이드를 분해하는 리파제에 비가역적인 결합을 하여 이를 불활성화 시킴으로써 체내에서 트리글리세라이드의 흡수 및 콜레스테롤의 흡수를 감소시킨다. 분해되지 못한 트리글리세라이드 및 콜레스테롤은 미변환체로 대변으로 배설된다.Lipase is responsible for breaking down triglycerides. Orlistat, a typical obesity treatment, reduces the absorption of triglycerides and cholesterol in the body by irreversibly binding and inactivating lipases that degrade triglycerides. Triglycerides and cholesterol that are not degraded are excreted unchanged in feces.
트리글리세라이드 리파제(TGL) 활성 평가의 표준물질로서 오르리스타트를 100μg/ml의 농도로 DMSO에 녹여서 추출물과 비교 평가하였다.Orlistat as a standard for the evaluation of triglyceride lipase (TGL) activity was dissolved in DMSO at a concentration of 100 μg / ml and compared with the extract.
16μl 기질(substrate) 혼합물(120mM Tauricholic acid 용액 5ul + 1M Enzyme Assay buffer(1M NaH2PO4, 1M NaCl, pH 7.0) 10ul + 400mM P-NPB(p-니트로페닐 부티레이트) 1ul)을 각 웰(96well plate)에 넣는다. 각 웰에 표준물질인 오르리스타트 함유 DMSO 용액 54 ul 또는 추출물(농도 250μg/ml) 54 ul을 넣는다. 플레이트 리더(Plate reader)를 이용하여 405nm에서 흡광도를 측정한다.16 μl substrate mixture (5 μl of 120 mM Tauricholic acid solution + 1 M Enzyme Assay buffer (1 M NaH 2 PO 4 , 1 M NaCl, pH 7.0) 10 ul + 400 mM P-NPB (p-nitrophenyl butyrate) 1 ul) was added to each well (96well). plate). In each well, add 54 ul of standard orlistat-containing DMSO solution or 54 ul of extract (concentration 250 μg / ml). Absorbance is measured at 405 nm using a plate reader.
효소(2mg/ml TGL solution 10ul + 0.1% BSA 완충액 20ul)를 웰에 넣어 혼합한 후, 빛을 차단하고, 10분간 상온에서 인큐베이션 시킨다. 플레이트 리더를 이용하여 405nm에서 흡광도를 측정한다.Enzyme (2 mg / ml TGL solution 10ul + 0.1% BSA buffer 20ul) was added to the wells and mixed, the light is blocked, and incubated at room temperature for 10 minutes. Absorbance is measured at 405 nm using a plate reader.
시험군은 흰강낭콩 추출 분말, 아위버섯 추출 분말, 흰강낭콩 추출물과 아위버섯 추출물의 혼합물(1:1~1:5 및 1:1~5:1)을 사용한 군으로 평가하였다(단일의 추출물 및 혼합된 추출물 농도는 모두 250μg/ml가 되도록 한다). 음성 대조군(control group)은 추출물이나 시험물질을 넣지 않은 것이다.The test group was evaluated using a group of white kidney bean extract powder, awi mushroom extract powder, a mixture of white kidney bean extract and awi mushroom extract (1: 1 to 1: 5 and 1: 1 to 5: 1) (single extract and The mixed extract concentrations should all be 250 μg / ml). Negative control groups do not contain extracts or test substances.
그 결과를 도 3에 나타내었다. 도 3에 나타나는 것과 같이, 본 발명에 따른 항비만 조성물은 아위버섯 비율이 증가할수록 트리글리세라이드 효소의 활성이 증가하였다.The results are shown in FIG. As shown in Figure 3, the anti-obesity composition according to the present invention increased the activity of triglyceride enzymes as the ratio of agaric mushrooms increased.
[[ 실시예Example 4] 고지방 식이(45%  4] High Fat Diet (45% HFDHFD ) 비만 유발모델에서 추출물의 혼합비율별 항비만 효과 평가Evaluation of Anti-obesity Effect by Mixing Ratio in Extracts
8주령의 C57BL/6J 수컷 마우스 33마리를 일주일 간 적응시킨 후, 고지방 식이 (45% HFD(Research diet, D12451) pellet form-free diet)를 2주 동안 급여하여 비만을 유도하였다.Thirty-three C57BL / 6J male mice, 8 weeks old, were acclimated for a week, followed by feeding a high fat diet (45% HFD (Research diet, D12451) pellet form-free diet) for 2 weeks to induce obesity.
2주 후 다음과 같이 5개의 군으로 분류하여 실험을 진행하였다:Two weeks later, the experiment was divided into five groups as follows:
(i) 고지방식이만을 섭취한 음성 대조군[Con(-), n=10], 이하 'Con(-)'이라 칭함],(i) negative control group that consumed only high fat diet [Con (-), n = 10], hereinafter referred to as 'Con (-)',
(ii) 고지방식이에 오르리스타트와 아카보스(orlistat+acarbose)를 혼합하여 섭취한 양성 대조군(HFD+orlistat+acarbose, n=8, 이하 'Con(+)'이라칭함),(ii) a positive control group (HFD + orlistat + acarbose, n = 8, hereinafter referred to as 'Con (+)') mixed with orlistat and acarbose (orlistat + acarbose) in a high-fat diet;
(iii) 고지방식이에 본 발명의 항비만 조성물(흰강낭콩:아위버섯 1:1)를 투여한 실험군1(HFD+mixture, n=8, 이하 'Case1'이라 칭함),(iii) Experimental group 1 (HFD + mixture, n = 8, hereinafter referred to as 'Case1') to which the anti-obesity composition of the present invention (white kidney bean: awi mushroom 1: 1) was administered to a high fat diet,
(iv) 고지방식이에 본 발명의 항비만 조성물(흰강낭콩:아위버섯 2:1)를 투여한 실험군2(HFD+mixture, n=8, 이하 'Case2'이라 칭함),(iv) experimental group 2 (HFD + mixture, n = 8, hereinafter referred to as 'Case2') in which the anti-obesity composition of the present invention (white kidney bean: Awi mushroom 2: 1) was administered to a high fat diet,
(v) 고지방식이에 본 발명의 항비만 조성물(흰강낭콩:아위버섯 3:1)를 투여한 실험군3(HFD+mixture, n=8, 이하 'Case3'이라 칭함)(v) Experiment group 3 (HFD + mixture, n = 8, hereinafter referred to as 'Case3') in which the anti-obesity composition of the present invention (white kidney bean: Awi mushroom 3: 1) was administered to a high fat diet.
실험 기간 동안 음수와 식이는 자유롭게 급여하였으며, 체지방량 및 체중을 측정하였다. 시험 용량은 200mg/kg으로 투여 진행 하였다.Negative and diet were freely fed and body fat mass and body weight were measured during the experiment. The test dose was administered at 200 mg / kg.
항비만 조성물[Case 3] 혼합 추출물이, 고지방식이 투여군[Con(-)] 대비 8주차에서 체지방량 및 체중을 감소시키는 경향성을 도4 및 도 5에서 확인할 수 있었다.The anti-obesity composition [Case 3] mixed extract, the tendency to reduce the body fat mass and weight at 8 weeks compared to the high-fat diet group [Con (-)] was confirmed in Figures 4 and 5.
이는 고지방식이의 섭취가 체지방량 및 체중을 증가시켰고, 본 발명의 항비만 조성물[Case3]의 섭취가 이러한 체지방량 및 체중 증가를 억제시켰다는 것을 의미한다.This means that the intake of high fat diet increased body fat mass and body weight, and that the ingestion of the anti-obesity composition [Case3] of the present invention inhibited such body fat mass and weight gain.
[[ 실시예Example 5] 고지방 식이 비만 유발모델에서 추출물 농도별  5] Different concentrations of extracts in high fat diet obesity induction model 항비만Anti-obesity 효과 평가 Effect evaluation
동물시험 및 식이Animal testing and diet
8주령의 C57BL/6J 수컷 84마리를 8주간(56일간) 하기와 같은 7개 시험군 별로 구별하여 식이를 적용하였다.Eighty-eight male C57BL / 6J males were divided into seven test groups for eight weeks (56 days) and the diet was applied.
시험군은7개의 군으로 분류하였다. 즉The test group was divided into seven groups. In other words
(i) 일반식이만을 섭취한 군(n=12), 이하 'G1'이라 칭함,(i) group ingesting only a general diet (n = 12), hereinafter referred to as 'G1',
(ii) 고지방식이만을 섭취한 군(n=12), 이하 'G2'이라 칭함,(ii) group ingesting only high fat diet (n = 12), hereinafter referred to as 'G2',
(iii) 고지방식이에 제니칼(orlistat 40mg/kg/day)를 혼합하여 섭취한 군 (HFD+orlistat, n=12, 이하 'G3'이라 칭함),(iii) a group ingested with a high-fat diet mixed with zenical (orlistat 40mg / kg / day) (HFD + orlistat, n = 12, hereinafter referred to as 'G3'),
(iv) 고지방식이에 가르시니아 캄보지아(200mg/kg/day)를 혼합하여 섭취한 군 (HFD+가르시니아 캄보지아, n=12, 이하 'G4'이라 칭함),(iv) a group ingested by mixing Garcinia cambogia (200 mg / kg / day) with a high fat diet (HFD + Garcinia cambogia, n = 12, hereinafter referred to as 'G4'),
(v) 고지방식이에 본 발명의 항비만 조성물(흰강낭콩:아위버섯 3:1 100mg/kg/day)를 투여한 군(HFD+mixture, n=12, 이하 'G5'이라 칭함),(v) a group administered with the anti-obesity composition of the present invention (white kidney bean: Awi mushroom 3: 1 100 mg / kg / day) in a high fat diet (HFD + mixture, n = 12, hereinafter referred to as 'G5'),
(vi) 고지방식이에 본 발명의 항비만 조성물(흰강낭콩:아위버섯 3:1 200mg/kg/day)를 투여한 군(HFD+mixture, n=12, 이하 'G6'이라 칭함),(vi) the group to which the anti-obesity composition of the present invention (white kidney bean: Awi mushroom 3: 1 200 mg / kg / day) was administered to a high fat diet (HFD + mixture, n = 12, hereinafter referred to as 'G6'),
(vii) 고지방식이에 본 발명의 항비만 조성물(흰강낭콩:아위버섯 3:1 300mg/kg/day)를 투여한 군(HFD+mixture, n=12, 이하 'G7'이라 칭함).(vii) A group to which the anti-obesity composition of the present invention (white kidney bean: Awi mushroom 3: 1 300 mg / kg / day) was administered to a high fat diet (HFD + mixture, n = 12, hereinafter referred to as 'G7').
시험 기간 동안 음수와 식이는 자유롭게 급여하였으며, ① 체중(항비만 조성물 투여 개시일, 그 이후에는 주 2회 및 부검일에 측정), ② 체지방(항비만 조성물 투여 개시 후 8주째(부검 전)에 모든 동물의 체지방량을 마이크로-CT(Micro-CT)로 촬영하여 측정), ③ 분변 내 탄수화물의 함량(항비만 조성물 투여 후 8주차 시료에 대하여 ELISA분석으로 측정), ④ 간 조직 내 TG(트리글리세라이드)(항비만 조성물 투여 전, 항비만 조성물 투여 개시 후 4, 6, 7 주째 및 8주째(부검시)에 채혈하여 분리한 혈청으로 분석) 변화 등을 측정하였다.Negative and diet were freely fed during the trial period, including: ① body weight (measured at the start of anti-obesity composition administration, twice a week thereafter and on autopsy day), and ② body fat (eight weeks after initiation of anti-obesity composition administration) Body fat mass measured by micro-CT (micro-CT)), ③ Carbohydrate content in feces (measured by ELISA analysis on the 8th week sample after anti-obesity composition administration), ④ TG (triglyceride) in liver tissue Changes were measured (analyzed by blood samples collected at 4, 6, 7, and 8 weeks after the start of the anti-obesity composition administration and at the time of autopsy).
각 시험군의 구성 및 투여량의 설정은 하기 표 2와 같다:The composition and dose settings of each test group are shown in Table 2 below:
시험군의 구성 및 투여량 설정Test Group Configuration and Dose Setting
군group 비만유도여부Obesity Induction 동물수(마리)Animal count (mari) 투여물질Substance 투여량(mg/kg/day)Dose (mg / kg / day) 투여액량(mL/kg/day)Dosage amount (mL / kg / day) 투여횟수Number of doses
G1G1 NN 1212 D.WD.W -- 1010 2 회/일2 times / day
G2G2 YY 1212 D.WD.W -- 1010 2 회/일2 times / day
G3G3 YY 1212 오르리스타트 Orlistat 4040 1010 2 회/일2 times / day
G4G4 YY 1212 가르시니아 캄보지아 Garcinia Cambogia 200200 1010 2 회/일2 times / day
G5G5 YY 1212 저용량 항비만 조성물Low dose anti-obesity composition 100 100 1010 2 회/일2 times / day
G6G6 YY 1212 중용량 항비만 조성물Medium Dose Anti-Obesity Composition 200 200 1010 2 회/일2 times / day
G7G7 YY 1212 고용량 항비만 조성물High dose anti-obesity composition 300 300 1010 2 회/일2 times / day
일반증상 및 건강상태를 확인하고, 정상식이 대조군 대비 10% 이상의 체중증가가 유발된 동물 84마리를 시험에 사용하였다.The general symptoms and health status were confirmed, and 84 animals having a weight gain of at least 10% compared to the normal diet were used for the test.
(1)(One) 체중변화 측정Weight change measurement
항비만 조성물 투여개시일, 그 이후에는 주 2회 및 부검일에 체중을 측정하였다.Body weights were measured on the day of administration of the anti-obesity composition, afterwards twice a week and on an autopsy day.
항비만 조성물 투여개시 전, 모든 비만유도군 (G2-G7)의 체중 수준은 정상 대조군(G1)에 비하여 유의하게 높은 것으로 나타났다(p <0.001). 또한 유발대조군(G2)에서는 전 관찰기간동안 정상대조군(G1)에 비해 유의한 체중증가를 보였다(p<0.001). 결과는 도 6에 나타내었다.Before starting the anti-obesity composition, all the obesity induction groups (G2-G7) were significantly higher than the normal control group (G1) (p <0.001). In addition, the induced control group (G2) showed significant weight gain over the entire observation period compared to the normal control group (G1) (p <0.001). The results are shown in FIG.
이는 고지방식이의 섭취가 체중이 증가시켰음을 의미하며, 본 발명의 항비만 조성물 고용량군(G7)의 섭취가 이러한 체중 증가를 억제한 것을 의미한다.This means that the intake of a high-fat diet increased the weight, and that the ingestion of the anti-obesity composition high dose group (G7) of the present invention inhibited such weight gain.
(2)(2) 마이크로 CT를 이용한 지방량 분석Fat mass analysis using micro CT
항비만 조성물 투여 개시 후 8주째(부검 전)에 모든 동물의 체지방량을 측정하기 위하여 Micro-CT(vivaCT 8-, SCANCO Medical, Switzerland)로 촬영하였다. 체지방의 측정 부위는 2번째 요추 기시부로부터 5번째 요추 종지부(L2-L5)까지의 공간에 존재하는 복부 지방 및 피하 지방을 설정하여 분석하였다.Eight weeks after the start of anti-obesity composition administration (before necropsy) was taken by Micro-CT (vivaCT 8-, SCANCO Medical, Switzerland) to measure the body fat mass of all animals. The measurement site of body fat was analyzed by setting the abdominal fat and subcutaneous fat which exist in the space from the 2nd lumbar starting point to the 5th lumbar end (L2-L5).
유발대조군(G2)은 비유발대조군에 비해, 총지방량, 복부지방량 및 피하지방량 모두 유의한 증가를 보였다. 그 결과는 도 7에 나타내었다(p<0.001).The induced control group (G2) showed a significant increase in total fat, abdominal fat and subcutaneous fat compared to the non-induced control. The results are shown in FIG. 7 (p <0.001).
이는 고지방식이의 섭취가 체내 총지방량, 복부지방량 및 피하지방량 증가시켰음을 의미하며, 본 발명의 항비만 조성물 고용량군(G7)의 섭취가 이러한 체지방 증가를 억제한 것을 의미한다.This means that the intake of a high-fat diet increased the total body fat, abdominal fat and subcutaneous fat in the body, and that the intake of the anti-obesity composition high dose group (G7) of the present invention inhibited such an increase in body fat.
(3)(3) 분변Feces 내 탄수화물함량 측정 Carbohydrate Content Measurement
항비만 조성물 투여 개시 전, 그 이후에는 주 1회 각 사육상자별로 분변을 채집하였다. 채집된 분변은 분석 전까지 초저온 냉동고(약 -70℃이하)에 보관하였으며, 항비만 조성물 투여 후 2주 및 8주차 시료에 대하여 ELISA분석를 이용하여 분석하였다.Before starting the anti-obesity composition administration, feces were collected by each breeding box once a week. Collected feces were stored in a cryogenic freezer (about -70 ℃ or less) until analysis, and analyzed by ELISA analysis for the samples 2 and 8 weeks after administration of the anti-obesity composition.
분변 분석결과, 유발대조군(G2)과 비교시 고용량 항비만 조성물 투여군(G7)에서는 8주차에 탄수화물의 유의한 증가가 관찰되었다. 이를 도 8에 나타내었다(p<0.001).Fecal analysis showed a significant increase in carbohydrates at week 8 in the high dose anti-obesity composition-administered group (G7) compared to the induced control group (G2). This is shown in FIG. 8 (p <0.001).
이는 고용량 항비만 조성물(G7)의 투여가 탄수화물의 흡수를 방해하여 체내 지방의 축적 억제한 것을 의미한다.This means that administration of the high dose anti-obesity composition (G7) inhibited the absorption of carbohydrates and inhibited the accumulation of fat in the body.
(4)(4) 간장 내 트리글리세라이드(triglyceride) 함량 측정Determination of Triglyceride Content in Soy Sauce
부검일에 동물을 에테르(ether)로 흡입마취하고, 마취가 확인되면 개복하여 후대정맥에서 주사기를 이용하여 채혈한 뒤, 복대동맥 및 후대정맥을 절단하여 방혈 및 치사시켰다. 간 조직을 적출한 후, 분석 전까지 초저온 냉동고(약 -70℃이하)에 보관 후ELISA 분석를 이용하여 분석하였다.On the day of necropsy, animals were inhaled with anesthesia, and when anesthesia was confirmed, they were opened, and blood was collected using a syringe from the posterior vena cava. After removing the liver tissue, it was stored in an ultra-cold freezer (about -70 ℃ or less) until analysis, and analyzed by ELISA analysis.
간장 내 TG(triglyceride) 함량 분석 결과, 유발대조군(G2)은 비유발대조군(G1)에 비해 유의한 증가를 보였고(p<0.001), 유발대조군(G2)에 비해 고용량 항비만 조성물 투여군(G7)에서 유의한 감소를 보였다. 이를 도9에 나타내었다.(p<0.005).As a result of analysis of TG (triglyceride) content in the liver, the induced control group (G2) showed a significant increase compared to the non-induced control group (G1) (p <0.001), and the high dose anti-obesity composition group (G7) compared to the induced control group (G2). Showed a significant decrease. This is shown in FIG. 9 (p <0.005).
이는 항비만 조성물 투여가 고지방식이에 의하여 상승한 TG 함량을 유의하게 감소시킴으로써 체내의 지방 축적을 억제한 것을 의미한다.This means that administration of the anti-obesity composition inhibited fat accumulation in the body by significantly reducing the elevated TG content by high fat diet.
본 발명의 조성물은 본 발명은 부작용이 적어 인체에 안전하고, 비만의 예방 또는 체지방 감소 효과가 우수한 조성물 및 이를 함유하는 의약품 또는 기능성 식품을 제공하기 위한 것이다.The composition of the present invention is to provide a composition having a low side effect and safe for the human body, excellent in preventing obesity or reducing body fat, and a pharmaceutical or functional food containing the same.

Claims (14)

  1. 흰강낭콩 추출물 및 아위버섯 추출물을 포함하는 비만 예방, 치료 또는 개선용 조성물.A composition for preventing, treating or improving obesity comprising white kidney bean extract and agaric mushroom extract.
  2. 제1항에 있어서, 상기 흰강낭콩 추출물은 물, 알코올 또는 물과 알코올의 혼합물을 추출용매로 하여 추출한 것인 조성물.The composition of claim 1, wherein the white kidney bean extract is extracted using water, alcohol or a mixture of water and alcohol as an extraction solvent.
  3. 제1항에 있어서, 상기 아위버섯 추출물은 물, 알코올 또는 물과 알코올의 혼합물을 추출용매로 하여 추출한 것인 조성물.The composition of claim 1, wherein the extract of Awi mushroom is extracted using water, alcohol or a mixture of water and alcohol as an extraction solvent.
  4. 제1항에 있어서, 상기 흰강낭콩 추출물 및 상기 아위버섯 추출물은 물, 알코올 또는 물과 알코올의 혼합물을 추출용매로 하여 추출한 것인 조성물.The composition of claim 1, wherein the white kidney bean extract and the awi mushroom extract are extracted with water, alcohol or a mixture of water and alcohol as an extraction solvent.
  5. 제1항 내지 제4항 중 어느 한 항에 있어서, 상기 아위버섯 추출물은 추출 시 열을 가하여 추출한 것인 조성물.The composition according to any one of claims 1 to 4, wherein the awi mushroom extract is extracted by applying heat during extraction.
  6. 제2항 내지 제4항 중 어느 한 항에 있어서, 상기 흰강낭콩 추출물 또는 상기 아위버섯 추출물은 물, 알코올 또는 물과 알코올의 혼합물을 추출용매로 하여 추출한 후, 비극성 용매를 추출용매로 하여 더 추출한 것인 조성물.The extract of any one of claims 2 to 4, wherein the white kidney bean extract or the above-mentioned mushroom extract is extracted with water, alcohol or a mixture of water and alcohol as an extraction solvent, and then further extracted with a nonpolar solvent as an extraction solvent. Composition.
  7. 제1항 내지 제4항 중 어느 한 항에 있어서, 상기 흰강낭콩 추출물 및 상기 아위버섯 추출물의 함량비는 건조시킨 고형분의 중량을 기준으로 1:1 내지 5:1인 것을 특징으로 하는 조성물.The composition according to any one of claims 1 to 4, wherein the content ratio of the white kidney bean extract and the awi mushroom extract is 1: 1 to 5: 1 based on the weight of the dried solids.
  8. 제1항 내지 제4항 중 어느 한 항에 있어서, 상기 흰강낭콩 추출물 및 상기 아위버섯 추출물의 함량비는 건조시킨 고형분의 중량을 기준으로 2:1 내지 4:1인 것을 특징으로 하는 조성물.The composition according to any one of claims 1 to 4, wherein the content ratio of the white kidney beans extract and the extract of Awi mushrooms is 2: 1 to 4: 1 based on the weight of the dried solids.
  9. 흰강낭콩 및 아위버섯의 혼합물의 추출물을 포함하는 비만 예방, 치료 또는 개선용 조성물.A composition for preventing, treating or improving obesity, comprising an extract of a mixture of white kidney beans and agar mushroom.
  10. 제9항에 있어서, 상기 추출물은 물, 알코올 또는 물과 알코올의 혼합물을 추출용매로 하여 추출한 것인 조성물.The composition of claim 9, wherein the extract is extracted using water, alcohol or a mixture of water and alcohol as an extraction solvent.
  11. 제10 항에 있어서, 상기 추출물은 추출 시 열을 가하여 추출한 것인 조성물.The composition of claim 10, wherein the extract is extracted by applying heat during extraction.
  12. 제10 항에 있어서, 상기 추출물은 물, 알코올 또는 물과 알코올의 혼합물을 추출용매로 하여 추출한 후, 비극성 용매를 추출용매로 하여 더 추출한 것인 조성물.The composition of claim 10, wherein the extract is extracted with water, alcohol or a mixture of water and alcohol as an extraction solvent, and then further extracted with a nonpolar solvent as the extraction solvent.
  13. 제1항 내지 제4항 및 제9항 내지 제12항 중 어느 한 항에 따른 조성물을 포함하는 약학 조성물 또는 건강 기능성 식품.A pharmaceutical composition or health functional food comprising the composition according to any one of claims 1 to 4 and 9 to 12.
  14. 제7 항에 따른 조성물을 포함하는 약학 조성물 또는 건강 기능성 식품.A pharmaceutical composition or health functional food comprising the composition of claim 7.
PCT/KR2019/003131 2018-05-23 2019-03-18 Anti-obesity or body fat reduction composition comprising navy bean extract and pleurotus eryngii extract WO2019225847A1 (en)

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KR1020180058477A KR20190133482A (en) 2018-05-23 2018-05-23 An anti-obesity or body fat reducing composition containing extract from a white kidney bean and a mushroom

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KR101341475B1 (en) * 2013-05-16 2013-12-13 주식회사 소울네이처푸드 Healthy diet food composite without adverse effect and manufacturing method thereof
KR101389955B1 (en) * 2013-05-21 2014-04-30 주식회사 위즈코즈 리테일 Preparation method of coated tablet having body fat reducing function
KR20150048698A (en) * 2015-04-21 2015-05-07 경상북도 Composition Comprising Water Extracts from Pleurotus eryngii var. ferulea (Pf.). for Treating or Preventing hyperlipidemia
KR20160141027A (en) * 2015-05-27 2016-12-08 경상북도 Phamaceutical composition or healthy food comprising water extracts from Pleurotus eryngii var. ferulea (Pf.). for treating or preventing metabolic disorder
KR101855005B1 (en) * 2016-11-21 2018-05-04 최종철 Method for manufacturing funtional cereals containing white kidney bean

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US6953787B2 (en) 2002-04-12 2005-10-11 Arena Pharmaceuticals, Inc. 5HT2C receptor modulators

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Publication number Priority date Publication date Assignee Title
KR101341475B1 (en) * 2013-05-16 2013-12-13 주식회사 소울네이처푸드 Healthy diet food composite without adverse effect and manufacturing method thereof
KR101389955B1 (en) * 2013-05-21 2014-04-30 주식회사 위즈코즈 리테일 Preparation method of coated tablet having body fat reducing function
KR20150048698A (en) * 2015-04-21 2015-05-07 경상북도 Composition Comprising Water Extracts from Pleurotus eryngii var. ferulea (Pf.). for Treating or Preventing hyperlipidemia
KR20160141027A (en) * 2015-05-27 2016-12-08 경상북도 Phamaceutical composition or healthy food comprising water extracts from Pleurotus eryngii var. ferulea (Pf.). for treating or preventing metabolic disorder
KR101855005B1 (en) * 2016-11-21 2018-05-04 최종철 Method for manufacturing funtional cereals containing white kidney bean

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