WO2012036344A1 - Appetite suppressant food composition comprising a specific compound as an active ingredient - Google Patents

Appetite suppressant food composition comprising a specific compound as an active ingredient Download PDF

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Publication number
WO2012036344A1
WO2012036344A1 PCT/KR2010/008111 KR2010008111W WO2012036344A1 WO 2012036344 A1 WO2012036344 A1 WO 2012036344A1 KR 2010008111 W KR2010008111 W KR 2010008111W WO 2012036344 A1 WO2012036344 A1 WO 2012036344A1
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Prior art keywords
appetite
ghrelin
ginsenoside
composition
food
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PCT/KR2010/008111
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French (fr)
Korean (ko)
Inventor
김인호
한대석
이창호
조승목
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한국식품연구원
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Priority claimed from KR1020100091517A external-priority patent/KR101155426B1/en
Priority claimed from KR1020100108541A external-priority patent/KR101250198B1/en
Application filed by 한국식품연구원 filed Critical 한국식품연구원
Publication of WO2012036344A1 publication Critical patent/WO2012036344A1/en

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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
    • 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
    • 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

Definitions

  • the present invention relates to an appetite suppressant food ingredient composition
  • an appetite suppressant food ingredient composition comprising a specific compound as an active ingredient, more specifically hesperetin (hesperetin), ginsenoside-Rb1 (ginsenoside-Rb1), 3-hydroxyflavone (3- hydroxyflavone, hesperidin, ginsenoside-Rg1, beta-D-glucan, ⁇ -D-glucan, rutin, flavonone, naringin, melatonin ( It relates to an appetite suppressing composition and at least one functional food for suppressing appetite containing at least one component selected from the group consisting of melatonin, quercetin and ascorbic acid.
  • Obesity is the highest in the United States (32% of the population), with a body mass index (BMI) of 30 or higher, and Mexico, 30%, the UK, 23%, Greece, Australia, and New Zealand, 21%. have. In Korea, 1.5% to 2 million people, 3.5% of the total population, are obese, but the population of obesity is increasing very rapidly due to westernization and diversification of dietary life.
  • BMI body mass index
  • Obesity has led to adult disease, including diabetes, hypertension, cardiovascular disease, cancer and mental distress, to some of the causes of death, and also affects national productivity, activity and competitiveness.
  • obesity of children and adolescents in Korea which has undergone many changes in their diet and educational environment, is increasing rapidly, and the recovery of treatment after the onset of pediatric diabetes is not easy, causing serious severity.
  • Obesity-related treatments have been tried in various ways such as drug administration, exercise, diet, psychotherapy, and surgery, but it is difficult to improve by specific methods, and complex treatments and patient will are important.
  • drug administration the drug was developed on the basis of lipolysis or digestive enzyme inhibition, but it has side effects.
  • appetite control appetite control to fundamentally regulate the intake of food
  • appetite suppression by the food ingredient composition as a first attempt is meaningful as an invention with novelty, originality and progressiveness
  • reductil has been released as a drug to control obesity due to appetite control, but it is required to access food or natural products with side effects such as loss of appetite, insomnia, depression, and blood pressure. Therefore, there is a need for a composition for appetite suppression that can contribute to suppression of obesity by creating a new value as an appetite suppressing food material while minimizing side effects.
  • the present invention first developed an appetite suppression method by a food ingredient composition as a means of preventing obesity, and in the method of demonstrating the appetite suppression effect, a test system for suppressing ghrelin that promotes appetite is first discovered in a cell differentiation degree. Therefore, food ingredients were applied and appetite suppression effects were scientifically verified.
  • Korean Patent Publication No. 2004-0097813 discloses an anti-obesity functional composition having three functions such as appetite suppression, body fat reduction, and bowel activation.
  • Korean Patent Publication No. 2004-0036111 discloses ginseng and polyphenol-based substances or bioflavonoids. Foods for improving lipid metabolism and anti-obesity including a powder or extract of a plant comprising a systemic substance have been disclosed, but differ from the appetite suppressing food ingredient composition of the present invention.
  • the present invention is derived from the above requirements, the present invention is desired to develop a functional material that can suppress the appetite, but many limitations due to safety problems such as limitations and side effects of body fat decomposition, digestion inhibition method nowadays, hesperetin, ginsenoside-Rb1, 3-hydroxyflavone, hesperidin, hesperidin and ginsenoside Ginsenoside-Rg1, beta-D-glucan, ⁇ -D-glucan, rutin, flavonone, naringin, melatonin, quercetin and ascorbic acid
  • the present invention was completed by developing an appetite suppressing composition containing at least one component selected from the group consisting of acid) as an active ingredient.
  • the present invention first developed an appetite suppression method by a food ingredient composition as a solution to obesity suppression, and also in the method of proving appetite suppression effect, by first discovering a test system that suppresses Ghrelin to promote appetite according to the degree of cell differentiation Food ingredients were applied and appetite suppression effects were scientifically verified.
  • the present invention is an active ingredient hesperetin (hesperetin), ginsenoside-Rb1 (ginsenoside-Rb1), 3-hydroxyflavone (3-hydroxyflavone), hesperidin (hesperidin), ginsenoside Ginsenoside-Rg1, beta-D-glucan, beta-D-glucan, rutin, flavonone, naringin, melatonin, quercetin and ascorbic acid It provides a composition for suppressing appetite containing at least one component selected from the group consisting of ascorbic acid).
  • hesperetin hesperetin
  • ginsenoside-Rb1 ginsenoside-Rb1
  • 3-hydroxyflavone 3-hydroxyflavone
  • hesperidin hesperidin
  • ginsenoside-Rg1 ginsenoside-Rg1
  • Beta-D-glucan rutin, flavonone, flanone, naringin, melatonin, quercetin and ascorbic acid
  • the appetite suppressant composition of the present invention is effective for suppressing appetite, and because it uses food ingredients, no side effects appear even after taking for a long time, and it is possible to secure safety, very useful in functional food industry for appetite suppression It will be an invention.
  • the method to prove the appetite suppression effect was the first to discover the ghrelin test system that promotes appetite, and to provide the first model to scientifically verify the appetite suppression effect by applying food ingredients according to the degree of cell differentiation.
  • FIG. 1 shows the concentration of ghrelin as a multinucleate differentiation inhibitory activity when 0.1 ⁇ g / ml of each food ingredient is added to human umbilical vein endothelial cell (HUVEC) cells.
  • HUVEC human umbilical vein endothelial cell
  • FIG. 2 shows the concentration of ghrelin as a multinucleate differentiation inhibitory activity when 1 or 10 ⁇ g / ml of each food ingredient is added to human umbilical vein endothelial cells (HUVEC) cells. .
  • HUVEC human umbilical vein endothelial cells
  • ginsenoside-Rb1 sibutramine (positive control)
  • 2 ascorbic acid
  • 3 beta-D-glucan
  • 4 hesperetin
  • 5 alpha-lipoic acid ( ⁇ ) -lipoic acid)
  • 6 serotonin
  • 7 melatonin
  • 8 alpha-tocopherol
  • 9 ginsenoside-Rb1
  • 10 ginsenoside-Rg1 (ginsenoside-Rg1)
  • 11 naringenin
  • FIG. 3 shows that each food ingredient is treated at 60 ° C., 80 ° C. and 100 ° C. for 5 minutes, and then food ingredients are added to human umbilical vein endothelial cells (HUVEC) cells, respectively, and the amount of ghrelin is measured. .
  • HUVEC human umbilical vein endothelial cells
  • Figure 4 is treated with each food ingredient at 60 °C, 80 °C and 100 °C for 5 minutes, and then added food ingredients to human umbilical vein endothelial cells (HUVEC) cells, respectively, the cell proliferation capacity and the amount of ghrelin (ghrelin) It is measured.
  • HUVEC human umbilical vein endothelial cells
  • ginsenoside-Rb1 sibutramine (positive control)
  • 2 ascorbic acid
  • 3 beta-D-glucan
  • 4 hesperetin
  • 5 alpha-lipoic acid ( ⁇ ) -lipoic acid)
  • 6 serotonin
  • 7 melatonin
  • 8 alpha-tocopherol
  • 9 ginsenoside-Rb1
  • 10 ginsenoside-Rg1 (ginsenoside-Rg1)
  • 11 naringenin
  • FIG. 5 shows that the food ingredients are added to human umbilical vein endothelial cells (HUVEC) cells after treatment of each food ingredient at pH 2, 5 and 7 within 5 minutes, respectively, and the amount of ghrelin is measured.
  • HUVEC human umbilical vein endothelial cells
  • FIG. 6 shows that each food ingredient is treated within 5 minutes at pH 2, 5, and 7, and then the food ingredient is added to human umbilical vein endothelial cells (HUVEC) cells to measure cell proliferation and ghrelin levels. It is.
  • HUVEC human umbilical vein endothelial cells
  • ginsenoside-Rb1 sibutramine (positive control)
  • 2 ascorbic acid
  • 3 beta-D-glucan
  • 4 hesperetin
  • 5 alpha-lipoic acid ( ⁇ ) -lipoic acid)
  • 6 serotonin
  • 7 melatonin
  • 8 alpha-tocopherol
  • 9 ginsenoside-Rb1
  • 10 ginsenoside-Rg1 (ginsenoside-Rg1)
  • 11 naringenin
  • Figure 7 shows the weight change and dietary intake of the rats in the normal diet (control), high fat diet (control), high fat diet + 3-hydroxyflavone (3-hydroxyflavone) administration group (A) respectively .
  • Figure 8 shows the rats in the normal diet group (normal), high fat diet (control), high fat diet + 3-hydroxyflavone (3-hydroxyflavone) administration group (A) and the activity of the rats, respectively.
  • the present invention is an active ingredient hesperetin (hesperetin), ginsenoside-Rb1 (ginsenoside-Rb1), 3-hydroxyflavone (3-hydroxyflavone), hesperidin (hesperidin), gin Ginsenoside-Rg1, beta-D-glucan, ⁇ -D-glucan, rutin, flavonone, naringin, melatonin, quercetin and ascorbate It provides a composition for suppressing appetite containing at least one component selected from the group consisting of acid (ascorbic acid).
  • the appetite suppression may be an effect of inhibiting the activity of ghrelin (ghrelin), an appetite-stimulating hormone.
  • the active ingredient included in the composition of the present invention may maintain ghrelin inhibitory activity even after 5 minutes treatment at a temperature of 60 ⁇ 100 °C. From this, the ghrelin inhibitory activity is maintained even when the food ingredient is heated, thereby indirectly confirming the possibility of maintaining appetite suppressing activity of the food ingredient during processing.
  • the active ingredient included in the composition of the present invention can maintain the ghrelin inhibitory activity even after 5 minutes treatment at pH 2 ⁇ 10. From this, it was indirectly determined that the appetite suppression effect was maintained overall by suppressing ghrelin activity even when ingesting food components in the body.
  • Appetite suppressing compositions of the present invention may include suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.
  • compositions of the present invention may be used in the form of their pharmaceutically acceptable salts, and may be used alone or in combination with other pharmaceutically active compounds, as well as in a suitable collection.
  • the appetite suppressing composition according to the present invention is formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, external preparations, suppositories, and sterile injectable solutions, respectively, according to a conventional method. Can be used.
  • Carriers, excipients and diluents that may be included in the appetite suppressant composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Various compounds or mixtures, including cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil and the like.
  • diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules and the like, and such solid preparations include at least one excipient such as starch, calcium carbonate and sucrose in the ingredients. ) Or lactose, gelatin and the like are mixed.
  • lubricants such as magnesium stearate and talc are also used.
  • Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin.
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories.
  • the non-aqueous solvent and suspending agent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used.
  • As the base of the suppository witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
  • Preferred dosages of the appetite suppressant composition of the present invention vary depending on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art.
  • the appetite suppressing composition of the present invention is preferably administered at 0.0001 to 100 mg / kg, preferably 0.001 to 100 mg / kg per day. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect.
  • the appetite suppressant composition of the present invention can be administered to various mammals such as mice, mice, livestock, humans. All modes of administration can be expected, for example by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.
  • the invention also relates to hesperetin, hesperetin, ginsenoside-Rb1, 3-hydroxyflavone, 3-hydroxyflavone, hesperidin, ginsenoside-Rg1, ginsenoside-Rg1, Beta-D-glucan, rutin, flavonone, flanone, naringin, melatonin, quercetin and ascorbic acid It provides a functional food for suppressing appetite containing at least one ingredient as an active ingredient.
  • the appetite suppressing composition of the present invention When used as a food additive, the appetite suppressing composition may be added as it is or used with other foods or food ingredients, and may be appropriately used according to a conventional method.
  • the blending amount of the active ingredient can be suitably determined according to the purpose of its use (prevention, health or therapeutic treatment). Generally, in the manufacture of food or beverages the components of the invention are added in an amount of up to 15 parts by weight, preferably up to 10 parts by weight relative to the raw materials. However, in the case of long-term intake for health and hygiene or health control, the amount may be below the above range, and the active ingredient may be used in an amount above the above range because there is no problem in terms of safety. .
  • Examples of the food to which the substance can be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, drinks, Alcoholic beverages and vitamin complexes, and the like and include all foods in a conventional sense.
  • the functional beverage composition containing the meat suppressing composition of the present invention may contain various flavors, natural carbohydrates, and the like as additional components, as in general beverages.
  • the above-mentioned natural carbohydrates are glucose, monosaccharides such as fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, sugar alcohols such as xylitol, sorbitol and erythritol.
  • sweetening agent natural sweetening agents such as tautin and stevia extract, synthetic sweetening agents such as saccharin and aspartame, and the like can be used.
  • the ratio of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 ml of the composition of the present invention.
  • the appetite suppressing composition of the present invention includes various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, Alcohols, carbonating agents used in carbonated drinks, and the like.
  • the appetite suppressing composition of the present invention may contain a flesh for preparing natural fruit juice, fruit juice beverage and vegetable beverage. These components can be used independently or in combination. The proportion of such additives is not critical but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.
  • the food ingredient for appetite suppression test system is to make it possible to obtain a single ingredient, and it is 3-hydroxyflavone, rutin, quercetin, flavonone, flavonone, Naringin, hesperidin, catechin, capsaicin, caffeine, theobromine, ascorbic acid, beta-D-glucan, ⁇ -D-glucan, Hesperetin, lipoic acid, serotonin, serotonin, melatonin, tocopherol, ginsenoside-Rb1, ginsenoside-Rg1, ginsenoside-Rg1, Naringenin and sibutramine (sibutramin, positive control) were obtained.
  • the target food ingredients were dissolved in DMSO, diluted and used for each concentration.
  • the final concentration of DMSO was 0.1% or less to prepare a cell test sample solution.
  • HUVEC human umbilical vein endothelial cells
  • EGM-2 medium FBS, Hydrocortisone, hFGF, VEGF.R3-IGF-1, Ascorbic acid, hEGF, GA-1000, Heparin
  • FBS Hydrocortisone
  • hFGF vascular endothelial growth factor
  • VEGF.R3-IGF-1 Ascorbic acid
  • hEGF GA-1000
  • Heparin Heparin
  • Samples for ghrelin analysis were separated into supernatant and cell lysate. After completion of the experiment, the recovered culture was centrifuged (3,000 rpm, 20 minutes, 4 °C) to recover only the supernatant, cell lysate was centrifuged for 10 minutes at 10000 rpm after separating the cells with Trypsin-EDTA. After removing the supernatant and preparing a cell lysate using a solution containing 1% of Triton X-100 in the obtained cells, the content of ghrelin was measured using a HUMAN unacylated ghrelin kit (SPI-Bio).
  • the method of measuring ghrelin was placed in a well of standard diluent buffer and 100 ul of sample, and 100 ul of anti-unacylated ghrelin-AChE tracer was added. After 3 hours of incubation at room temperature, the culture solution was completely removed and washed 5 times with diluted wash solution. After drying the plate, absorbance was measured at 405 nm after adding 200 ul of Ellman's reagent.
  • the inhibitory activity of ghrelin an appetite-stimulating hormone according to heating temperature, was investigated for food ingredient concentrations that had high inhibitory activity against ghrelin. After a certain amount of food ingredients were treated at 60 ° C., 80 ° C. and 100 ° C. for 5 minutes, and prepared at concentrations having high inhibitory activity against ghrelin, the cell proliferation ability and the amount of ghrelin were measured.
  • the ghrelin inhibitory activity was investigated according to the pH change of food ingredients under acidic, neutral and basic conditions. Each food solution was dipped in each pH solution at a concentration of 10% within 5 minutes, and then lyophilized to prepare a concentration having high inhibitory activity against ghrelin, and then the cell proliferation ability and the amount of ghrelin were measured.
  • mice were 4 weeks old C57BL / 6J male mice, and the day and night cycle (12 hours light / 12 hours night) was controlled and the indoor temperature was raised in the animal breeding room of 22 ⁇ 25 °C.
  • One week of adaptation mice were fed high fat diets supplemented with 40% bee tallow to normal diet for 8 weeks to induce the high fat diet group.
  • the experimental animals were divided into the normal group and the high-fat diet group, and the dietary intake and body weight were measured periodically.
  • 3-hydroxyflavone a food ingredient expected to have anti-obesity effect
  • S-mart program Pan Lab, Spain
  • a program that measures all movements of a given place using a computer sensor for 1 hour in a white matt acrylic box of 40 ⁇ 40 ⁇ 40 cm in width, length, and height.
  • the behavior of was measured after 3 weeks of food ingredient treatment.
  • the image obtained from the digital camera installed about 2.5m above the box is transferred to the computer and tracked according to the movement of the subject by recognizing the center point of the white subject image using the principle of contrasting the white subject against the black background. It was. Then, the trajectory of the movement of the test animal was quantified to quantify the distance moved.
  • Human umbilical vein endothelial cell (HUVEC) cells contain food ingredients (3-hydroxyflavone, rutin, quercetin, flavonone, naringin, hesperidin, When catechin, capsaicin, caffeine, and theobromine were added at 0.1 ⁇ g / ml, the concentration of ghrelin was measured by multinucleate differentiation inhibitory activity compared to the control. (FIG. 1). As a result, the concentration of ghrelin (ghrelin) was 79% compared to the control, and the content of ghrelin was lower than 20%, and quercetin was 90% compared to the control. Showed relatively high ghrelin (ghrelin) content. Compared with the control in all treatments, the content of ghrelin was reduced, and it was confirmed that the effect of suppressing appetite.
  • UAVEC Human umbilical vein endothelial cell
  • sibutramine a positive control, had a content of 75% (25% inhibition) at a concentration of 1 ug / ml, and high ghrelin at 68% (32% inhibition) at 10 ug / ml.
  • Inhibitory activity was ascorbic acid (ascorbic acid) showed a secretion rate of 93% and 94% at concentrations of 1 ug / ml and 10 ug / ml, respectively.
  • the concentration of ghrelin decreased as the concentration of sample increased in concentration-dependent manner, showing the lowest content of 85% at the concentration of 10 ug / ml, and 1 ug / for hesperetin.
  • the highest inhibitory activity was shown to be 79%, and low value of 85% even at 10 ug / ml.
  • Melatonin had a low ghrelin content of 87% at 10 ug / ml, and ginsenoside-Rb1 gradually decreased with increasing concentrations to 76% at 10 ug / ml.
  • Ginsenoside-Rg1 (ginsenoside-Rg1) also showed a tendency to decrease the content of ghrelin in a concentration-dependent manner, showing a low content of 84% at 10 ug / ml.
  • 3 and 4 show the content of ghrelin according to the heating temperature of the food ingredient.
  • the cell proliferation ability according to the temperature was found to maintain the overall cell proliferation ability even when the temperature is increased to 60 ⁇ 100 °C.
  • the content of ghrelin according to the temperature change is maintained stably.
  • Ghrelin (ghrelin) is mostly 80 ⁇ 90% in the temperature range of 60 ⁇ 100 °C it was judged that the inhibitory effect is maintained about 20 to 10%. From this, even when the food ingredients are heated, cell proliferation and ghrelin inhibitory activity is maintained, thereby indirectly confirming the possibility of maintaining appetite suppressing activity of the food ingredients during processing.
  • the content of ghrelin was investigated according to the pH change of food ingredients under acidic, neutral, and basic conditions (FIGS. 5 and 6).
  • the residual amount of ghrelin was similar to that of the temperature treatment because the residual amount of ghrelin was lower than that of the control in all treatments even when pH 2, 7 and 10 were changed in the food ingredients. From this, it was indirectly determined that the appetite suppression effect was maintained overall by suppressing ghrelin activity even when ingesting food components in the body.

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Abstract

The present invention relates to an appetite suppressant food composition comprising a specific compound as an active ingredient. More particularly, the present invention relates to a composition and food having the function of suppressing appetite, comprising at least one ingredient selected from the group consisting of hesperetin, ginsenoside-Rb1, 3-hydroxyflavone, hesperidin, ginsenoside-Rg1, β-D-glucan, rutin, flavanone, naringin, melatonin, quercetin and ascorbic acid, which has an appetite suppressing effect by suppressing the activity of ghrelin, which is an appetite-stimulating hormone.

Description

특정 화합물을 유효성분으로 포함하는 식욕억제 식품성분 조성물Appetite suppressant food ingredient composition comprising a specific compound as an active ingredient
본 발명은 특정 화합물을 유효성분으로 포함하는 식욕억제 식품성분 조성물에 관한 것으로, 더욱 상세하게는 헤스페레틴(hesperetin), 진세노사이드-Rb1(ginsenoside-Rb1), 3-히드록시플라본(3-hydroxyflavone), 헤스페리딘(hesperidin), 진세노사이드-Rg1(ginsenoside-Rg1), 베타-D-글루칸(β-D-glucan), 루틴(rutin), 플라보논(flavanone), 나린진(naringin), 멜라토닌(melatonin), 케르세틴(quercetin) 및 아스코르브산(ascorbic acid)으로 이루어진 군으로부터 선택되는 하나 이상의 성분을 함유하는 식욕억제용 조성물 및 식욕억제용 기능성 식품에 관한 것이다.The present invention relates to an appetite suppressant food ingredient composition comprising a specific compound as an active ingredient, more specifically hesperetin (hesperetin), ginsenoside-Rb1 (ginsenoside-Rb1), 3-hydroxyflavone (3- hydroxyflavone, hesperidin, ginsenoside-Rg1, beta-D-glucan, β-D-glucan, rutin, flavonone, naringin, melatonin ( It relates to an appetite suppressing composition and at least one functional food for suppressing appetite containing at least one component selected from the group consisting of melatonin, quercetin and ascorbic acid.
비만인구는 BMI(body mass index) 30 이상인 경우를 기준으로 미국이 전 인구의 32%로 가장 높으며, 멕시코가 30%, 영국 23%, 그리스, 호주, 뉴질랜드가 21%로 비만인구가 높은 국가들이 있다. 우리나라는 전 인구의 3.5%인 150~200만 명이 비만 인구이나, 식생활의 서구화, 다원화 등의 이유로 비만 인구가 매우 빠른 속도로 증가하고 있다.Obesity is the highest in the United States (32% of the population), with a body mass index (BMI) of 30 or higher, and Mexico, 30%, the UK, 23%, Greece, Australia, and New Zealand, 21%. have. In Korea, 1.5% to 2 million people, 3.5% of the total population, are obese, but the population of obesity is increasing very rapidly due to westernization and diversification of dietary life.
비만은 당뇨, 고혈압, 심혈관이상, 암, 정신적 고통 등 성인병 유발에서 사망원인의 일부에까지 이르게 되었으며 국가 생산성, 활동성 및 경쟁력에도 영향을 미친다. 특히 식생활과 교육환경의 변화를 많이 겪게 된 우리나라 소아, 청소년의 비만은 급격히 증가하고 있으며, 소아당뇨 등 발병된 후 치료회복이 쉽지않은 심각성을 야기하고 있다.Obesity has led to adult disease, including diabetes, hypertension, cardiovascular disease, cancer and mental distress, to some of the causes of death, and also affects national productivity, activity and competitiveness. In particular, the obesity of children and adolescents in Korea, which has undergone many changes in their diet and educational environment, is increasing rapidly, and the recovery of treatment after the onset of pediatric diabetes is not easy, causing serious severity.
비만억제 관련 치료는 약물투여, 운동, 식이요법, 정신치료, 수술요법 등 다양한 시도가 있어왔으나 특정한 방법에 의하여 개선되기는 어려우며 복합적인 치료와 환자의 의지가 중요하다. 약물투여의 경우 지방분해나 소화효소저해에 의한 방법을 원리로 약제가 개발되었으나 부작용을 동반하고 있다.Obesity-related treatments have been tried in various ways such as drug administration, exercise, diet, psychotherapy, and surgery, but it is difficult to improve by specific methods, and complex treatments and patient will are important. In the case of drug administration, the drug was developed on the basis of lipolysis or digestive enzyme inhibition, but it has side effects.
비만의 해결방법으로 생성 및 축적된 비만세포를 분해하거나 소화효소를 저해하는 방법이 보편적으로 시도되었으나, 섭취하는 식품의 소화저해나 생성된 지방을 분해한다고 하더라도 비만환자의 폭식에 의하여 지속적으로 다량의 식품이 체내에 공급된다면 소화저해나 지방분해는 섭취하는 속도와 양에 비하여 역할이 제한적일 수밖에 없다.As a solution to obesity, a method of degrading and accumulating mast cells or inhibiting digestive enzymes has been generally attempted. If food is supplied to the body, digestion or lipolysis has a limited role compared to the rate and amount of ingestion.
따라서, 식품의 섭취를 근본적으로 조절하는 식욕조절(appetite control)은 근본적인 해결에 대한 접근방법이 될 수 있으며, 식품성분 조성물에 의한 식욕억제는 최초 시도로서 신규성, 독창성 및 진보성을 갖는 발명으로서 의의를 갖는다.Thus, appetite control (appetite control) to fundamentally regulate the intake of food can be an approach to the fundamental solution, the appetite suppression by the food ingredient composition as a first attempt is meaningful as an invention with novelty, originality and progressiveness Have
현재 식욕조절에 의한 비만억제는 약물로서 Reductil이 출시된 적이 있으나 식욕부진, 불면, 우울, 혈압 상승 등의 부작용을 동반하여 식품이나 천연물에 의한 접근이 요구된다. 따라서, 부작용을 최소화하면서 식욕억제 식품소재로서 새로운 가치를 창출하여 비만억제에 기여할 수 있는 식욕억제를 위한 조성물이 필요한 실정이다.Currently, reductil has been released as a drug to control obesity due to appetite control, but it is required to access food or natural products with side effects such as loss of appetite, insomnia, depression, and blood pressure. Therefore, there is a need for a composition for appetite suppression that can contribute to suppression of obesity by creating a new value as an appetite suppressing food material while minimizing side effects.
본 발명은 비만억제의 해결수단으로서 식품성분 조성물에 의한 식욕억제 방법을 최초로 개발하였으며, 식욕억제 효과를 증명하는 방법에 있어서도 식욕을 촉진하는 그렐린(Ghrelin)을 억제하는 시험계를 최초로 발굴하여 세포분화도에 따라 식품성분을 적용하고 식욕억제 효과를 과학적으로 검증하였다.The present invention first developed an appetite suppression method by a food ingredient composition as a means of preventing obesity, and in the method of demonstrating the appetite suppression effect, a test system for suppressing ghrelin that promotes appetite is first discovered in a cell differentiation degree. Therefore, food ingredients were applied and appetite suppression effects were scientifically verified.
한국공개특허 제2004-0097813호에는 식욕억제, 체지방 감소 및 배변 활성화 등 3가지 기능을 갖는 항비만 기능성 조성물이 개시되어 있으며, 한국공개특허 제2004-0036111호에는 인삼 및 폴리페놀계 물질 또는 바이오플라보노이드계 물질을 포함하는 식물의 분말 또는 추출물을 포함하는 지질대사 개선 및 항비만용 식품이 개시되어 있으나, 본 발명의 식욕억제 식품성분 조성물과는 상이하다.Korean Patent Publication No. 2004-0097813 discloses an anti-obesity functional composition having three functions such as appetite suppression, body fat reduction, and bowel activation. Korean Patent Publication No. 2004-0036111 discloses ginseng and polyphenol-based substances or bioflavonoids. Foods for improving lipid metabolism and anti-obesity including a powder or extract of a plant comprising a systemic substance have been disclosed, but differ from the appetite suppressing food ingredient composition of the present invention.
본 발명은 상기와 같은 요구에 의해 도출된 것으로서, 본 발명은 식욕을 억제시킬 수 있는 기능성 소재의 개발이 요망되고 있으나, 체지방분해, 소화저해 방법의 한계성 및 부작용 등 안전성의 문제 때문에 많은 제약을 받고 있는 요즘, 식품성분이면서 식욕을 억제할 수 있는 헤스페레틴(hesperetin), 진세노사이드-Rb1(ginsenoside-Rb1), 3-히드록시플라본(3-hydroxyflavone), 헤스페리딘(hesperidin), 진세노사이드-Rg1(ginsenoside-Rg1), 베타-D-글루칸(β-D-glucan), 루틴(rutin), 플라보논(flavanone), 나린진(naringin), 멜라토닌(melatonin), 케르세틴(quercetin) 및 아스코르브산(ascorbic acid)으로 이루어진 군으로부터 선택되는 하나 이상의 성분을 유효성분으로 함유하는 식욕억제용 조성물을 개발함으로써 본 발명을 완성하였다.The present invention is derived from the above requirements, the present invention is desired to develop a functional material that can suppress the appetite, but many limitations due to safety problems such as limitations and side effects of body fat decomposition, digestion inhibition method Nowadays, hesperetin, ginsenoside-Rb1, 3-hydroxyflavone, hesperidin, hesperidin and ginsenoside Ginsenoside-Rg1, beta-D-glucan, β-D-glucan, rutin, flavonone, naringin, melatonin, quercetin and ascorbic acid The present invention was completed by developing an appetite suppressing composition containing at least one component selected from the group consisting of acid) as an active ingredient.
또한, 본 발명은 비만억제의 해결수단으로서 식품성분 조성물에 의한 식욕억제 방법을 최초로 개발하였으며, 식욕억제 효과를 증명하는 방법에 있어서도 식욕을 촉진하는 Ghrelin을 억제하는 시험계를 최초로 발굴하여 세포분화도에 따라 식품성분을 적용하고 식욕억제효과를 과학적으로 검증하였다.In addition, the present invention first developed an appetite suppression method by a food ingredient composition as a solution to obesity suppression, and also in the method of proving appetite suppression effect, by first discovering a test system that suppresses Ghrelin to promote appetite according to the degree of cell differentiation Food ingredients were applied and appetite suppression effects were scientifically verified.
상기 과제를 해결하기 위해, 본 발명은 유효성분으로 헤스페레틴(hesperetin), 진세노사이드-Rb1(ginsenoside-Rb1), 3-히드록시플라본(3-hydroxyflavone), 헤스페리딘(hesperidin), 진세노사이드-Rg1(ginsenoside-Rg1), 베타-D-글루칸(β-D-glucan), 루틴(rutin), 플라보논(flavanone), 나린진(naringin), 멜라토닌(melatonin), 케르세틴(quercetin) 및 아스코르브산(ascorbic acid)으로 이루어진 군으로부터 선택되는 하나 이상의 성분을 함유하는 식욕억제용 조성물을 제공한다. In order to solve the above problems, the present invention is an active ingredient hesperetin (hesperetin), ginsenoside-Rb1 (ginsenoside-Rb1), 3-hydroxyflavone (3-hydroxyflavone), hesperidin (hesperidin), ginsenoside Ginsenoside-Rg1, beta-D-glucan, beta-D-glucan, rutin, flavonone, naringin, melatonin, quercetin and ascorbic acid It provides a composition for suppressing appetite containing at least one component selected from the group consisting of ascorbic acid).
또한, 본 발명은 헤스페레틴(hesperetin), 진세노사이드-Rb1(ginsenoside-Rb1), 3-히드록시플라본(3-hydroxyflavone), 헤스페리딘(hesperidin), 진세노사이드-Rg1(ginsenoside-Rg1), 베타-D-글루칸(β-D-glucan), 루틴(rutin), 플라보논(flavanone), 나린진(naringin), 멜라토닌(melatonin), 케르세틴(quercetin) 및 아스코르브산(ascorbic acid)으로 이루어진 군으로부터 선택되는 하나 이상의 성분을 유효성분으로 함유하는 식욕억제용 기능성 식품을 제공한다. 식욕억제 효과를 증명하는 방법에서도 식욕을 촉진하는 그렐린(ghrelin)을 억제하는 시험계를 최초로 발굴하여 세포분화도에 따라 식품성분을 적용하고 식품성분의 식욕억제효과를 과학적으로 검증하였다.In addition, the present invention, hesperetin (hesperetin), ginsenoside-Rb1 (ginsenoside-Rb1), 3-hydroxyflavone (3-hydroxyflavone), hesperidin (hesperidin), ginsenoside-Rg1 (ginsenoside-Rg1), Beta-D-glucan, rutin, flavonone, flanone, naringin, melatonin, quercetin and ascorbic acid It provides a functional food for suppressing appetite containing at least one ingredient as an active ingredient. In the method of proving appetite suppression effect, a test system that suppresses ghrelin that promotes appetite was first discovered, and food ingredients were applied according to the degree of cell differentiation, and the appetite suppression effect of food ingredients was scientifically verified.
본 발명에 따르면, 본 발명의 식욕억제 조성물은 식욕억제에 효과적이며, 식품성분을 이용하기 때문에 장기간 복용하여도 부작용이 나타나지 않고, 안전성을 확보할 수 있어, 식욕억제를 위한 기능성 식품산업상 매우 유용한 발명이 될 것이다.According to the present invention, the appetite suppressant composition of the present invention is effective for suppressing appetite, and because it uses food ingredients, no side effects appear even after taking for a long time, and it is possible to secure safety, very useful in functional food industry for appetite suppression It will be an invention.
또한 식욕억제 효과를 증명하는 방법에서도 식욕을 촉진하는 그렐린(ghrelin) 시험계를 최초로 발굴하여 세포분화도에 따라 식품성분을 적용함으로써 식욕억제효과를 과학적으로 검증하는 모델을 최초로 제공하였다.In addition, the method to prove the appetite suppression effect was the first to discover the ghrelin test system that promotes appetite, and to provide the first model to scientifically verify the appetite suppression effect by applying food ingredients according to the degree of cell differentiation.
도 1은 HUVEC(human umbilical vein endothelial cell) 세포에 각각의 식품성분을 0.1 ㎍/㎖씩 첨가하였을 때 대조구와 비교하여 그렐린(ghrelin)의 농도를 다핵(multinucleate) 분화 억제 활성으로 측정한 것이다.FIG. 1 shows the concentration of ghrelin as a multinucleate differentiation inhibitory activity when 0.1 μg / ml of each food ingredient is added to human umbilical vein endothelial cell (HUVEC) cells.
1: 3-히드록시플라본(3-hydroxyflavone), 2: 루틴(rutin), 3: 케르세틴(quercetin), 4: 플라보논(flavanone), 5: 나린진(naringin), 6: 헤스페리딘(hesperidin), 7: 카테킨(catechin), 8: 카페인(caffeine), 9: 테오브로민(theobromine), 10: 캡사이신(capsaicin)1: 3-hydroxyflavone, 2: rutin, 3: quercetin, 4: flavonone, 5: naringin, 6: hesperidin, 7 : Catechin, 8: caffeine, 9: theobromine, 10: capsaicin
도 2는 HUVEC(human umbilical vein endothelial cell) 세포에 각각의 식품성분을 1 또는 10 ㎍/㎖씩 첨가하였을 때 대조구와 비교하여 그렐린(ghrelin)의 농도를 다핵(multinucleate) 분화 억제 활성으로 측정한 것이다.FIG. 2 shows the concentration of ghrelin as a multinucleate differentiation inhibitory activity when 1 or 10 ㎍ / ml of each food ingredient is added to human umbilical vein endothelial cells (HUVEC) cells. .
1: 시부트라민(sibutramine, positive control), 2: 아스코르브산(ascorbic acid), 3: 베타-D-글루칸(β-D-glucan), 4: 헤스페레틴(hesperetin), 5: 알파-리포산(α-lipoic acid), 6: 세로토닌(serotonin), 7: 멜라토닌(melatonin), 8: 알파-토코페롤(α-tocopherol), 9: 진세노사이드-Rb1(ginsenoside-Rb1), 10: 진세노사이드-Rg1(ginsenoside-Rg1), 11: 나린제닌(naringenin)1: sibutramine (positive control), 2: ascorbic acid, 3: beta-D-glucan, 4: hesperetin, 5: alpha-lipoic acid (α) -lipoic acid), 6: serotonin, 7: melatonin, 8: alpha-tocopherol, 9: ginsenoside-Rb1, 10: ginsenoside-Rg1 (ginsenoside-Rg1), 11: naringenin
도 3은 각각의 식품성분을 60℃, 80℃ 및 100℃에서 5분간 처리한 후, HUVEC(human umbilical vein endothelial cell) 세포에 식품성분을 각각 첨가하고, 그렐린(ghrelin)의 양을 측정한 것이다.FIG. 3 shows that each food ingredient is treated at 60 ° C., 80 ° C. and 100 ° C. for 5 minutes, and then food ingredients are added to human umbilical vein endothelial cells (HUVEC) cells, respectively, and the amount of ghrelin is measured. .
1: 3-히드록시플라본(3-hydroxyflavone), 2: 루틴(rutin), 3: 케르세틴(quercetin), 4: 플라보논(flavanone), 5: 나린진(naringin), 6: 헤스페리딘(hesperidin), 7: 카테킨(catechin), 8: 카페인(caffeine), 9: 테오브로민(theobromine), 10: 캡사이신(capsaicin)1: 3-hydroxyflavone, 2: rutin, 3: quercetin, 4: flavonone, 5: naringin, 6: hesperidin, 7 : Catechin, 8: caffeine, 9: theobromine, 10: capsaicin
도 4는 각각의 식품성분을 60℃, 80℃ 및 100℃에서 5분간 처리한 후, HUVEC(human umbilical vein endothelial cell) 세포에 식품성분을 각각 첨가하여, 세포증식능과 그렐린(ghrelin)의 양을 측정한 것이다.Figure 4 is treated with each food ingredient at 60 ℃, 80 ℃ and 100 ℃ for 5 minutes, and then added food ingredients to human umbilical vein endothelial cells (HUVEC) cells, respectively, the cell proliferation capacity and the amount of ghrelin (ghrelin) It is measured.
1: 시부트라민(sibutramine, positive control), 2: 아스코르브산(ascorbic acid), 3: 베타-D-글루칸(β-D-glucan), 4: 헤스페레틴(hesperetin), 5: 알파-리포산(α-lipoic acid), 6: 세로토닌(serotonin), 7: 멜라토닌(melatonin), 8: 알파-토코페롤(α-tocopherol), 9: 진세노사이드-Rb1(ginsenoside-Rb1), 10: 진세노사이드-Rg1(ginsenoside-Rg1), 11: 나린제닌(naringenin)1: sibutramine (positive control), 2: ascorbic acid, 3: beta-D-glucan, 4: hesperetin, 5: alpha-lipoic acid (α) -lipoic acid), 6: serotonin, 7: melatonin, 8: alpha-tocopherol, 9: ginsenoside-Rb1, 10: ginsenoside-Rg1 (ginsenoside-Rg1), 11: naringenin
도 5는 각각의 식품성분을 pH 2, 5 및 7에서 5분 이내로 처리한 후, HUVEC(human umbilical vein endothelial cell) 세포에 식품성분을 각각 첨가하고, 그렐린(ghrelin)의 양을 측정한 것이다.FIG. 5 shows that the food ingredients are added to human umbilical vein endothelial cells (HUVEC) cells after treatment of each food ingredient at pH 2, 5 and 7 within 5 minutes, respectively, and the amount of ghrelin is measured.
1: 3-히드록시플라본(3-hydroxyflavone), 2: 루틴(rutin), 3: 케르세틴(quercetin), 4: 플라보논(flavanone), 5: 나린진(naringin), 6: 헤스페리딘(hesperidin), 7: 카테킨(catechin), 8: 카페인(caffeine), 9: 테오브로민(theobromine), 10: 캡사이신(capsaicin)1: 3-hydroxyflavone, 2: rutin, 3: quercetin, 4: flavonone, 5: naringin, 6: hesperidin, 7 : Catechin, 8: caffeine, 9: theobromine, 10: capsaicin
도 6은 각각의 식품성분을 pH 2, 5 및 7에서 5분 이내로 처리한 후, HUVEC(human umbilical vein endothelial cell) 세포에 식품성분을 각각 첨가하여, 세포증식능과 그렐린(ghrelin)의 양을 측정한 것이다.FIG. 6 shows that each food ingredient is treated within 5 minutes at pH 2, 5, and 7, and then the food ingredient is added to human umbilical vein endothelial cells (HUVEC) cells to measure cell proliferation and ghrelin levels. It is.
1: 시부트라민(sibutramine, positive control), 2: 아스코르브산(ascorbic acid), 3: 베타-D-글루칸(β-D-glucan), 4: 헤스페레틴(hesperetin), 5: 알파-리포산(α-lipoic acid), 6: 세로토닌(serotonin), 7: 멜라토닌(melatonin), 8: 알파-토코페롤(α-tocopherol), 9: 진세노사이드-Rb1(ginsenoside-Rb1), 10: 진세노사이드-Rg1(ginsenoside-Rg1), 11: 나린제닌(naringenin)1: sibutramine (positive control), 2: ascorbic acid, 3: beta-D-glucan, 4: hesperetin, 5: alpha-lipoic acid (α) -lipoic acid), 6: serotonin, 7: melatonin, 8: alpha-tocopherol, 9: ginsenoside-Rb1, 10: ginsenoside-Rg1 (ginsenoside-Rg1), 11: naringenin
도 7은 쥐를 각각 정상식이군(normal), 고지방식이군(control), 고지방식이+3주간 3-히드록시플라본(3-hydroxyflavone) 투여군(A)으로 사육하면서 체중변화와 식이 섭취량을 나타낸 것이다.Figure 7 shows the weight change and dietary intake of the rats in the normal diet (control), high fat diet (control), high fat diet + 3-hydroxyflavone (3-hydroxyflavone) administration group (A) respectively .
도 8은 쥐를 각각 정상식이군(normal), 고지방식이군(control), 고지방식이+3주간 3-히드록시플라본(3-hydroxyflavone) 투여군(A)으로 사육하고 쥐의 활동량을 나타낸 것이다.Figure 8 shows the rats in the normal diet group (normal), high fat diet (control), high fat diet + 3-hydroxyflavone (3-hydroxyflavone) administration group (A) and the activity of the rats, respectively.
본 발명의 목적을 달성하기 위해, 본 발명은 유효성분으로 헤스페레틴(hesperetin), 진세노사이드-Rb1(ginsenoside-Rb1), 3-히드록시플라본(3-hydroxyflavone), 헤스페리딘(hesperidin), 진세노사이드-Rg1(ginsenoside-Rg1), 베타-D-글루칸(β-D-glucan), 루틴(rutin), 플라보논(flavanone), 나린진(naringin), 멜라토닌(melatonin), 케르세틴(quercetin) 및 아스코르브산(ascorbic acid)으로 이루어진 군으로부터 선택되는 하나 이상의 성분을 함유하는 식욕억제용 조성물을 제공한다.In order to achieve the object of the present invention, the present invention is an active ingredient hesperetin (hesperetin), ginsenoside-Rb1 (ginsenoside-Rb1), 3-hydroxyflavone (3-hydroxyflavone), hesperidin (hesperidin), gin Ginsenoside-Rg1, beta-D-glucan, β-D-glucan, rutin, flavonone, naringin, melatonin, quercetin and ascorbate It provides a composition for suppressing appetite containing at least one component selected from the group consisting of acid (ascorbic acid).
본 발명의 조성물에서, 상기 식욕억제는 식욕촉진 호르몬인 그렐린(ghrelin)의 활성을 억제하는 효과일 수 있다.In the composition of the present invention, the appetite suppression may be an effect of inhibiting the activity of ghrelin (ghrelin), an appetite-stimulating hormone.
본 발명의 조성물에 포함된 유효성분은 60~100℃의 온도에서 5분간 처리 후에도 그렐린 억제 활성이 유지될 수 있다. 이로부터 식품성분을 가열하는 경우에도 그렐린(ghrelin) 억제 활성이 유지되므로 가공 중 식품성분의 식욕억제 활성유지 가능성을 간접적으로 확인할 수 있었다.The active ingredient included in the composition of the present invention may maintain ghrelin inhibitory activity even after 5 minutes treatment at a temperature of 60 ~ 100 ℃. From this, the ghrelin inhibitory activity is maintained even when the food ingredient is heated, thereby indirectly confirming the possibility of maintaining appetite suppressing activity of the food ingredient during processing.
또한, 본 발명의 조성물에 포함된 유효성분은 pH 2~10에서 5분간 처리 후에도 그렐린 억제 활성이 유지될 수 있다. 이로부터 식품성분의 체내섭취시에도 그렐린(ghrelin) 활성 억제로 식욕 억제 효과는 전반적으로 유지됨을 간접적으로 판단할 수 있었다.In addition, the active ingredient included in the composition of the present invention can maintain the ghrelin inhibitory activity even after 5 minutes treatment at pH 2 ~ 10. From this, it was indirectly determined that the appetite suppression effect was maintained overall by suppressing ghrelin activity even when ingesting food components in the body.
본 발명의 식욕억제용 조성물은 약학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 포함할 수 있다.Appetite suppressing compositions of the present invention may include suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.
본 발명의 식욕억제용 조성물의 약학적 투여 형태는 이들의 약학적 허용 가능한 염의 형태로도 사용될 수 있고, 또한 단독으로 또는 타 약학적 활성 화합물과 결합뿐만 아니라 적당한 집합으로 사용될 수 있다.Pharmaceutical dosage forms of the appetite suppressant composition of the present invention may be used in the form of their pharmaceutically acceptable salts, and may be used alone or in combination with other pharmaceutically active compounds, as well as in a suitable collection.
본 발명에 따른 식욕억제용 조성물은, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다. 식욕억제용 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유 등을 포함한 다양한 화합물 혹은 혼합물을 들 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 성분에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(calcium carbonate), 수크로스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용된다. 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, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈 (tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.The appetite suppressing composition according to the present invention is formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, external preparations, suppositories, and sterile injectable solutions, respectively, according to a conventional method. Can be used. Carriers, excipients and diluents that may be included in the appetite suppressant composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Various compounds or mixtures, including cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil and the like. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules and the like, and such solid preparations include at least one excipient such as starch, calcium carbonate and sucrose in the ingredients. ) Or lactose, gelatin and the like are mixed. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
본 발명의 식욕억제용 조성물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 그러나, 바람직한 효과를 위해서, 본 발명의 식욕억제용 조성물은 1일 0.0001 내지 100 mg/kg으로, 바람직하게는 0.001 내지 100 mg/kg으로 투여하는 것이 좋다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.Preferred dosages of the appetite suppressant composition of the present invention vary depending on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. However, for the desired effect, the appetite suppressing composition of the present invention is preferably administered at 0.0001 to 100 mg / kg, preferably 0.001 to 100 mg / kg per day. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect.
본 발명의 식욕억제용 조성물은 쥐, 생쥐, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁 내 경막 또는 뇌혈관내 (intracerebroventricular) 주사에 의해 투여될 수 있다.The appetite suppressant composition of the present invention can be administered to various mammals such as mice, mice, livestock, humans. All modes of administration can be expected, for example by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.
본 발명은 또한, 헤스페레틴(hesperetin), 진세노사이드-Rb1(ginsenoside-Rb1), 3-히드록시플라본(3-hydroxyflavone), 헤스페리딘(hesperidin), 진세노사이드-Rg1(ginsenoside-Rg1), 베타-D-글루칸(β-D-glucan), 루틴(rutin), 플라보논(flavanone), 나린진(naringin), 멜라토닌(melatonin), 케르세틴(quercetin) 및 아스코르브산(ascorbic acid)으로 이루어진 군으로부터 선택되는 하나 이상의 성분을 유효성분으로 함유하는 식욕억제용 기능성 식품을 제공한다.The invention also relates to hesperetin, hesperetin, ginsenoside-Rb1, 3-hydroxyflavone, 3-hydroxyflavone, hesperidin, ginsenoside-Rg1, ginsenoside-Rg1, Beta-D-glucan, rutin, flavonone, flanone, naringin, melatonin, quercetin and ascorbic acid It provides a functional food for suppressing appetite containing at least one ingredient as an active ingredient.
본 발명의 상기 식욕억제용 조성물을 식품첨가물로 사용하는 경우, 상기 식욕억제용 조성물을 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효 성분의 혼합양은 그의 사용 목적(예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다. 일반적으로, 식품 또는 음료의 제조시에 본 발명의 성분은 원료에 대하여 15 중량부 이하, 바람직하게는 10 중량부 이하의 양으로 첨가된다. 그러나, 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하일 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로도 사용될 수 있다.When the appetite suppressing composition of the present invention is used as a food additive, the appetite suppressing composition may be added as it is or used with other foods or food ingredients, and may be appropriately used according to a conventional method. The blending amount of the active ingredient can be suitably determined according to the purpose of its use (prevention, health or therapeutic treatment). Generally, in the manufacture of food or beverages the components of the invention are added in an amount of up to 15 parts by weight, preferably up to 10 parts by weight relative to the raw materials. However, in the case of long-term intake for health and hygiene or health control, the amount may be below the above range, and the active ingredient may be used in an amount above the above range because there is no problem in terms of safety. .
상기 식품의 종류에는 특별한 제한은 없다. 상기 물질을 첨가할 수 있는 식품의 예로는 육류, 소세지, 빵, 쵸코렛, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알콜 음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 식품을 모두 포함한다.There is no particular limitation on the kind of food. Examples of the food to which the substance can be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, drinks, Alcoholic beverages and vitamin complexes, and the like and include all foods in a conventional sense.
본 발명의 식육억제용 조성물이 함유된 기능성 음료 조성물은 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드, 말토스, 슈크로스와 같은 디사카라이드, 및 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드, 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 감미제로서는 타우마틴, 스테비아 추출물과 같은 천연 감미제나, 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 ㎖당 일반적으로 약 0.01~0.04 g, 바람직하게는 약 0.02~0.03 g 이다.The functional beverage composition containing the meat suppressing composition of the present invention may contain various flavors, natural carbohydrates, and the like as additional components, as in general beverages. The above-mentioned natural carbohydrates are glucose, monosaccharides such as fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, sugar alcohols such as xylitol, sorbitol and erythritol. As the sweetening agent, natural sweetening agents such as tautin and stevia extract, synthetic sweetening agents such as saccharin and aspartame, and the like can be used. The ratio of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 ml of the composition of the present invention.
상기 외에 본 발명의 식욕억제용 조성물은 여러가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 식욕억제용 조성물은 천연 과일쥬스, 과일쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 혼합하여 사용할 수 있다. 이러한 첨가제의 비율은 크게 중요하진 않지만 본 발명의 조성물 100 중량부당 0.01 ~ 0.1 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the appetite suppressing composition of the present invention includes various nutrients, vitamins, electrolytes, flavoring agents, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, Alcohols, carbonating agents used in carbonated drinks, and the like. In addition, the appetite suppressing composition of the present invention may contain a flesh for preparing natural fruit juice, fruit juice beverage and vegetable beverage. These components can be used independently or in combination. The proportion of such additives is not critical but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.
이하 본 발명을 실시예를 통하여 보다 상세하게 설명한다. 그러나, 이들 실시예는 본 발명을 예시적으로 설명하기 위한 것으로 본 발명의 범위가 이들 실시예에 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail with reference to Examples. However, these examples are for illustrative purposes only and the scope of the present invention is not limited to these examples.
1. 시료의 확보1. Securing Sample
(1) 식욕 억제 소재의 선발(1) Selection of appetite suppression material
식욕억제 시험계 적용을 위한 식품성분은 단일성분의 확보가 가능한 성분으로 하였으며 항비만 가능성이 있는 3-히드록시플라본(3-hydroxyflavone), 루틴(rutin), 케르세틴(quercetin), 플라보논(flavanone), 나린진(naringin), 헤스페리딘(hesperidin), 카테킨(catechin), 캡사이신(capsaicin), 카페인(caffeine), 테오브로민(theobromine), 아스코르브산(ascorbic acid), 베타-D-글루칸(β-D-glucan), 헤스페레틴(hesperetin), 리포산(lipoic acid), 세로토닌(serotonin), 멜라토닌(melatonin), 토코페롤(tocopherol), 진세노사이드-Rb1(ginsenoside-Rb1), 진세노사이드-Rg1(ginsenoside-Rg1), 나린제닌(naringenin) 및 시부트라민(sibutramin, positive control)을 확보하였다.The food ingredient for appetite suppression test system is to make it possible to obtain a single ingredient, and it is 3-hydroxyflavone, rutin, quercetin, flavonone, flavonone, Naringin, hesperidin, catechin, capsaicin, caffeine, theobromine, ascorbic acid, beta-D-glucan, β-D-glucan, Hesperetin, lipoic acid, serotonin, serotonin, melatonin, tocopherol, ginsenoside-Rb1, ginsenoside-Rg1, ginsenoside-Rg1, Naringenin and sibutramine (sibutramin, positive control) were obtained.
(2) 세포시험용 검액 제조(2) Preparation of Cell Test Sample Solution
대상 식품성분은 DMSO에 용해한 후 희석하여 농도별로 사용하였고, DMSO의 최종농도는 0.1% 이하로 하여 세포시험용 검액을 제조하였다.The target food ingredients were dissolved in DMSO, diluted and used for each concentration. The final concentration of DMSO was 0.1% or less to prepare a cell test sample solution.
2. 식욕 촉진 호르몬 그렐린(ghrelin)의 활성 시험2. Test of appetite-stimulating hormone ghrelin
(1) HUVEC 세포 배양(1) HUVEC cell culture
HUVEC(human umbilical vein endothelial cell)은 영사이언스에서 분양받아 사용하였다. 2% 젤라틴(gelatin) 코팅한 100 mm 디쉬(dish)에 EGM-2 배지(FBS, Hydrocortisone, hFGF, VEGF. R3-IGF-1, Ascorbic acid, hEGF, GA-1000, Heparin)를 이용하여 37℃, 5% CO2가 유지되는 배양기에서 배양하였다. 세포가 컨플루언트(confluent)되면 trypsin-EDTA로 처리하여 계대 배양하였으며 배지는 2~3일에 한 번씩 교환하였다. HUVEC (human umbilical vein endothelial cells) was used by Young Science. 37 ° C using EGM-2 medium (FBS, Hydrocortisone, hFGF, VEGF.R3-IGF-1, Ascorbic acid, hEGF, GA-1000, Heparin) in a 100 mm dish coated with 2% gelatin , And incubated in an incubator maintained at 5% CO 2 . When the cells were confluent, the cells were passaged with trypsin-EDTA and the medium was exchanged every 2 to 3 days.
(2) 그렐린 분석(ghrelin assay)(2) ghrelin assay
그렐린(ghrelin) 분석을 위한 시료는 상등액과 cell lysate로 분리하여 사용하였다. 실험 종료 후 회수한 배양액은 원심분리(3,000 rpm, 20 분, 4℃)하여 상층액만을 회수하였고, cell lysate는 Trypsin-EDTA로 세포를 분리한 후 10000 rpm에서 10분간 원심분리하였다. 상등액을 제거하고 얻어진 세포에 1%의 Triton X-100을 함유하는 용액을 이용하여 cell lysate를 제조한 후 HUMAN unacylated ghrelin kit(SPI-Bio)를 이용하여 그렐린(ghrelin) 함량을 측정하였다. 즉, 그렐린(ghrelin)의 측정법은 standard diluent buffer와 샘플 100 ul를 웰에 넣고, Anti-unacylated ghrelin-AChE tracer 100 ul를 첨가하였다. 실온에서 3시간 배양 후 배양액을 완전히 제거하고 diluted wash solution으로 5회 이상 세척하였다. 그리고 플레이트를 건조한 후, Ellman's reagent 200 ul 첨가 후 405 nm에서 흡광도를 측정하였다. Samples for ghrelin analysis were separated into supernatant and cell lysate. After completion of the experiment, the recovered culture was centrifuged (3,000 rpm, 20 minutes, 4 ℃) to recover only the supernatant, cell lysate was centrifuged for 10 minutes at 10000 rpm after separating the cells with Trypsin-EDTA. After removing the supernatant and preparing a cell lysate using a solution containing 1% of Triton X-100 in the obtained cells, the content of ghrelin was measured using a HUMAN unacylated ghrelin kit (SPI-Bio). In other words, the method of measuring ghrelin was placed in a well of standard diluent buffer and 100 ul of sample, and 100 ul of anti-unacylated ghrelin-AChE tracer was added. After 3 hours of incubation at room temperature, the culture solution was completely removed and washed 5 times with diluted wash solution. After drying the plate, absorbance was measured at 405 nm after adding 200 ul of Ellman's reagent.
3. 온도와 pH에 따른 식품성분의 세포증식능과 그렐린(ghrelin) 억제 활성3. Cell Proliferation and Ghrelin Inhibitory Activity of Food Ingredients According to Temperature and pH
(1) 온도에 따른 식품성분의 세포증식능과 그렐린(ghrelin) 억제 활성화 변화(1) Changes in Cell Proliferation and Ghrelin Inhibition Activation of Food Ingredients with Temperature
식품성분의 가공 중 안정성을 조사하기 위하여 그렐린(ghrelin)에 대한 억제 활성이 높았던 식품성분 농도를 대상으로 가열온도에 따른 식욕촉진 호르몬인 그렐린(ghrelin)의 억제 활성도를 조사하였다. 일정량의 식품성분을 60℃, 80℃ 및 100℃에서 각각 5분간 처리하고 그렐린(ghrelin)에 대한 억제 활성이 높았던 농도로 제조한 후 세포증식능과 그렐린(ghrelin)의 양을 측정하였다.In order to investigate the stability during processing of food ingredients, the inhibitory activity of ghrelin, an appetite-stimulating hormone according to heating temperature, was investigated for food ingredient concentrations that had high inhibitory activity against ghrelin. After a certain amount of food ingredients were treated at 60 ° C., 80 ° C. and 100 ° C. for 5 minutes, and prepared at concentrations having high inhibitory activity against ghrelin, the cell proliferation ability and the amount of ghrelin were measured.
(2) pH에 따른 식품성분의 세포증식능과 그렐린(ghrelin) 억제 활성화 변화(2) Changes in Cell Proliferation and Ghrelin Inhibition Activation of Food Ingredients According to pH
식품성분의 식욕 억제의 체내 활성을 간접 시험하고자 산성, 중성, 염기성의 조건에서 식품성분의 pH 변화에 따른 그렐린(ghrelin) 억제 활성을 조사하였다. 각 pH 용액에 10%의 농도로 각각의 식품성분을 5분 이내로 담근 다음 동결 건조하여 그렐린(ghrelin)에 대한 억제 활성이 높았던 농도로 제조한 후 세포증식능과 그렐린(ghrelin)의 양을 측정하였다. To indirectly test the body's activity of appetite suppression of food ingredients, the ghrelin inhibitory activity was investigated according to the pH change of food ingredients under acidic, neutral and basic conditions. Each food solution was dipped in each pH solution at a concentration of 10% within 5 minutes, and then lyophilized to prepare a concentration having high inhibitory activity against ghrelin, and then the cell proliferation ability and the amount of ghrelin were measured.
4. 동물실험4. Animal Experiment
(1) 실험동물사육(1) Experimental animal breeding
실험동물은 4주령의 C57BL/6J 수컷 마우스를 사용하였고, 밤낮주기(12시간 light/12 시간 night)가 조절되며 실내온도는 22~25℃인 동물사육실에서 사육하였다. 1주일의 적응기를 거친 마우스를 정상 식이에 40% 우지(beef tallow)가 첨가된 고지방 조제사료를 8주간 급여하여 고지방식이 섭취군을 유도하였다(표 1). 실험 중 실험동물은 정상군, 고지방식이 섭취군으로 나누어 관리하며 주기적으로 섭취 식이량과 체중을 측정하였다.The experimental animals were 4 weeks old C57BL / 6J male mice, and the day and night cycle (12 hours light / 12 hours night) was controlled and the indoor temperature was raised in the animal breeding room of 22 ~ 25 ℃. One week of adaptation mice were fed high fat diets supplemented with 40% bee tallow to normal diet for 8 weeks to induce the high fat diet group. During the experiment, the experimental animals were divided into the normal group and the high-fat diet group, and the dietary intake and body weight were measured periodically.
표 1 실험적 식이의 조성물(g/Kg diet)
성분 정상식이1) 고지방식이2)
카세인(Casein) 200 200
DL-메티오닌(DL-Methionine) 3 3
옥수수전분(Corn starch) 150 150
설탕(Sucrose) 500 345
셀룰로오스(Cellulose) 50 50
옥수수기름(Corn oil) 50 -
우지(Beer tallow) - 205
소금 혼합물(Salt mixture) 35 35
비타민 혼합물(Vitamin mixture) 10 10
콜린 비타르트레이트(Choline bitartrate) 2 2
지방(Fat) % (Calories) 11.7 40.0
Table 1 Experimental dietary composition (g / Kg diet)
ingredient Normal diet 1) High-fat diet 2)
Casein 200 200
DL-Methionine 3 3
Corn starch 150 150
Sucrose 500 345
Cellulose 50 50
Corn oil 50 -
Beer tallow - 205
Salt mixture 35 35
Vitamin mixture 10 10
Choline bitartrate 2 2
Fat% (Calories) 11.7 40.0
1) 정상식이: AIN-76A diet #100000(Dyets Inc., Bethlehem, PA, USA) 1) Normal diet: AIN-76A diet # 100000 (Dyets Inc., Bethlehem, PA, USA)
2) 고지방식이: AIN-76 diet #100496(Dyets Inc., Bethlehem, PA, USA) 2) High-fat diet: AIN-76 diet # 100496 (Dyets Inc., Bethlehem, PA, USA)
(2) 동물 예비실험 후보소재의 선정(2) Selection of candidate material for preliminary animal experiment
본 실험실에서 항-비만 효과가 예상되는 식품성분인 3-히드록시플라본(3-hydroxyflavone)을 고지방식이한 마우스에 3주간 10 mg/kg의 농도로 복강 내 투여하여 처치하였다.In the laboratory, 3-hydroxyflavone, a food ingredient expected to have anti-obesity effect, was treated by intraperitoneal administration to high-fat diet mice at a concentration of 10 mg / kg for 3 weeks.
(3) 보행성 활동량(locomotor activity) 측정(3) measuring locomotor activity
컴퓨터 센서를 이용하여 지정된 장소의 모든 움직임을 측정하는 프로그램인 S-mart program(Pan Lab, Spain)을 이용하여 가로, 세로, 높이가 각각 40×40×40 ㎝인 하얀색 무광택 아크릴 상자에서 1시간 동안의 행동을 3주간의 식품성분 처리 후에 측정하였다. 상자 약 2.5 m 위에 설치된 디지털 카메라에서 얻어진 화상을 컴퓨터에 전달하여, 검은 배경에 흰색 피사체의 대조의 원리를 이용하여 흰색 피험동물 상(image)의 중심점을 인식하는 방식으로 피험동물의 움직임을 따라 추적하였다. 그 다음, 피험동물의 움직임의 궤적을 테이터화하여 움직인 거리를 정량화하였다.Use the S-mart program (Pan Lab, Spain), a program that measures all movements of a given place using a computer sensor, for 1 hour in a white matt acrylic box of 40 × 40 × 40 cm in width, length, and height. The behavior of was measured after 3 weeks of food ingredient treatment. The image obtained from the digital camera installed about 2.5m above the box is transferred to the computer and tracked according to the movement of the subject by recognizing the center point of the white subject image using the principle of contrasting the white subject against the black background. It was. Then, the trajectory of the movement of the test animal was quantified to quantify the distance moved.
실시예 1: 식품성분 첨가 시 그렐린(ghrelin)의 농도변화Example 1 Changes in Ghrelin Concentration upon Addition of Food Ingredients
HUVEC(human umbilical vein endothelial cell) 세포에 식품성분(3-히드록시플라본(3-hydroxyflavone), 루틴(rutin), 케르세틴(quercetin), 플라보논(flavanone), 나린진(naringin), 헤스페리딘(hesperidin), 카테킨(catechin), 캡사이신(capsaicin), 카페인(caffeine), 테오브로민(theobromine))을 0.1 ㎍/㎖로 각각 첨가하였을 때 대조구와 비교하여 그렐린(ghrelin)의 농도를 다핵(multinucleate) 분화 억제 활성으로 측정하였다(도 1). 그 결과, 그렐린(ghrelin)의 농도는 3-히드록시플라본(3-hydroxyflavone)이 대조구 대비 79%로 20% 이상 그렐린(ghrelin)의 함량이 낮았고, 케르세틴(quercetin)이 대조구 대비 90%로 식품성분 중 비교적 높은 그렐린(ghrelin) 함량을 보였다. 모든 처리구에서 대조구와 비교했을 때 그렐린(ghrelin)의 함량이 감소하여 식욕 억제의 효과가 있음을 확인할 수 있었다.Human umbilical vein endothelial cell (HUVEC) cells contain food ingredients (3-hydroxyflavone, rutin, quercetin, flavonone, naringin, hesperidin, When catechin, capsaicin, caffeine, and theobromine were added at 0.1 ㎍ / ml, the concentration of ghrelin was measured by multinucleate differentiation inhibitory activity compared to the control. (FIG. 1). As a result, the concentration of ghrelin (ghrelin) was 79% compared to the control, and the content of ghrelin was lower than 20%, and quercetin was 90% compared to the control. Showed relatively high ghrelin (ghrelin) content. Compared with the control in all treatments, the content of ghrelin was reduced, and it was confirmed that the effect of suppressing appetite.
또한, HUVEC(human umbilical vein endothelial cell) 세포에 식품성분(아스코르브산(ascorbic acid), 베타-D-글루칸(β-D-glucan), 헤스페레틴(hesperetin), 리포산(lipoic acid), 세로토닌(serotonin), 멜라토닌(melatonin), 토코페롤(tocopherol), 진세노사이드-Rb1(ginsenoside-Rb1), 진세노사이드-Rg1(ginsenoside-Rg1), 나린제닌(naringenin) 및 시부트라민(sibutramin, positive control))을 1 또는 10 ㎍/㎖로 각각 첨가하였을 때 대조구와 비교하여 그렐린(ghrelin)의 농도를 다핵(multinucleate) 분화 억제 활성으로 측정하였다(도 2). 다핵(multinucleate) 상태는 증식률의 급격히 상승하는 시점을 계대 배양 30시간으로 정하여 시료를 처리하였다. 그 결과, 양성대조구인 시부트라민(sibutramine)의 경우 1 ug/ml의 농도에서 75%(억제율 25%)의 함량을 나타냈고, 10 ug/ml에서는 68%(억제율 32%)로 높은 그렐린(ghrelin) 억제활성을 나타냈고, 아스코르브산(ascorbic acid)은 1 ug/ml과 10 ug/ml의 농도에서 각각 93%와 94%의 분비율을 나타냈다. 글루칸(glucan)의 경우 농도 의존적으로 시료농도가 증가하면서 그렐린(ghrelin)의 함량이 감소하여 10 ug/ml의 농도에서 85%로 가장 낮은 함량을 보였고, 헤스페레틴(hesperetin)의 경우 1 ug/ml의 농도에서는 79%의 함량으로 가장 높은 억제활성을 보였으며, 10 ug/ml에서도 85%의 낮은 값을 나타냈다. 멜라토닌(melatonin)의 경우 10 ug/ml에서 87%로 낮은 그렐린(ghrelin) 함량을 보였으며, 진세노사이드-Rb1(ginsenoside-Rb1)은 농도가 증가하면서 점차적으로 감소하여 10 ug/ml에서 76%의 낮은 함량을 보였으며, 진세노사이드-Rg1 (ginsenoside-Rg1) 역시 농도 의존적으로 그렐린(ghrelin)의 함량이 감소하는 경향을 보이며 10 ug/ml에서 84%의 낮은 함량을 나타내었다. 따라서, 아스코르브산(ascorbic acid), 베타-D-글루칸(β-D-glucan), 헤스페레틴(hesperetin), 멜라토닌(melatonin), 진세노사이드-Rb1(ginsenoside-Rb1) 및 진세노사이드-Rg1(ginsenoside-Rg1) 처리구에서 대조구와 비교했을 때 그렐린(ghrelin)의 함량이 감소하여 식욕 억제의 효과가 있음을 확인할 수 있었다.In addition, food ingredients (ascorbic acid, beta-D-glucan, hesperetin, lipoic acid, serotonin (HUVEC) cells in human umbilical vein endothelial cells (HUVEC) serotonin, melatonin, tocopherol, ginsenoside-Rb1, ginsenoside-Rg1, naringenin, and sibutramine (sibutramin, positive control) The concentration of ghrelin was measured as multinucleate differentiation inhibitory activity compared to the control when added at 1 or 10 μg / ml, respectively (FIG. 2). In the multinucleate state, the samples were treated by setting the time of rapid increase in the proliferation rate to 30 hours of passage culture. As a result, sibutramine, a positive control, had a content of 75% (25% inhibition) at a concentration of 1 ug / ml, and high ghrelin at 68% (32% inhibition) at 10 ug / ml. Inhibitory activity was ascorbic acid (ascorbic acid) showed a secretion rate of 93% and 94% at concentrations of 1 ug / ml and 10 ug / ml, respectively. In the case of glucan, the concentration of ghrelin decreased as the concentration of sample increased in concentration-dependent manner, showing the lowest content of 85% at the concentration of 10 ug / ml, and 1 ug / for hesperetin. At the concentration of ml, the highest inhibitory activity was shown to be 79%, and low value of 85% even at 10 ug / ml. Melatonin had a low ghrelin content of 87% at 10 ug / ml, and ginsenoside-Rb1 gradually decreased with increasing concentrations to 76% at 10 ug / ml. Ginsenoside-Rg1 (ginsenoside-Rg1) also showed a tendency to decrease the content of ghrelin in a concentration-dependent manner, showing a low content of 84% at 10 ug / ml. Thus, ascorbic acid, beta-D-glucan, β-D-glucan, hesperetin, melatonin, ginsenoside-Rb1 and ginsenoside-Rg1 Compared to the control in the (ginsenoside-Rg1) treatment, the content of ghrelin was decreased, and it was confirmed that the appetite suppression effect was observed.
실시예 2: 온도에 따른 그렐린(ghrelin)의 함량Example 2 Content of Ghrelin with Temperature
식품성분의 가열 온도에 따른 그렐린(ghrelin)의 함량을 도 3 및 4에 나타내었다. 그 결과, 온도에 따른 세포의 증식능은 온도를 60~100℃로 증가시킨 경우에도 세포 증식능은 전반적으로 유지됨을 알 수 있었다. 또한, 온도 변화에 따른 그렐린(ghrelin)의 함량은 안정적으로 유지됨을 알 수 있었다. 그렐린(ghrelin)은 60~100℃ 온도 대에서 대부분 80~90% 함량으로 억제효과가 20~10% 정도 유지되는 것으로 판단되었다. 이로부터 식품성분을 가열하는 경우에도 세포 증식과 그렐린(ghrelin) 억제활성이 유지되므로 가공 중 식품성분의 식욕억제 활성유지 가능성을 간접적으로 확인할 수 있었다. 3 and 4 show the content of ghrelin according to the heating temperature of the food ingredient. As a result, the cell proliferation ability according to the temperature was found to maintain the overall cell proliferation ability even when the temperature is increased to 60 ~ 100 ℃. In addition, it was found that the content of ghrelin according to the temperature change is maintained stably. Ghrelin (ghrelin) is mostly 80 ~ 90% in the temperature range of 60 ~ 100 ℃ it was judged that the inhibitory effect is maintained about 20 to 10%. From this, even when the food ingredients are heated, cell proliferation and ghrelin inhibitory activity is maintained, thereby indirectly confirming the possibility of maintaining appetite suppressing activity of the food ingredients during processing.
실시예 3: pH에 따른 그렐린(ghrelin)의 함량Example 3 Content of Ghrelin with pH
식품성분의 체내 활성을 간접 판단하고자 산성, 중성, 염기성 조건에서 식품성분의 pH 변화에 따른 그렐린(ghrelin)의 함량을 조사하였다(도 5 및 6). 그 결과, 그렐린(ghrelin) 잔존량은 식품성분에 pH 2, 7 및 10 변화처리시에도 대체적으로 모든 처리구에서 그렐린(ghrelin) 잔존량이 대조구보다 낮아 억제 효과를 나타내어 온도처리의 경우와 유사하였다. 이로부터 식품성분의 체내섭취시에도 그렐린(ghrelin) 활성 억제로 식욕 억제 효과는 전반적으로 유지됨을 간접적으로 판단할 수 있었다.In order to indirectly determine the body activity of food ingredients, the content of ghrelin was investigated according to the pH change of food ingredients under acidic, neutral, and basic conditions (FIGS. 5 and 6). As a result, the residual amount of ghrelin was similar to that of the temperature treatment because the residual amount of ghrelin was lower than that of the control in all treatments even when pH 2, 7 and 10 were changed in the food ingredients. From this, it was indirectly determined that the appetite suppression effect was maintained overall by suppressing ghrelin activity even when ingesting food components in the body.
실시예 4: 실험동물의 식이 섭취량과 체중 변화Example 4 Dietary Intake and Weight Change of Experimental Animals
조제사료로 사육하면서 정상식이군, 고지방식이군, 고지방식이+3주간 3-히드록시플라본(3-hydroxyflavone) 투여군에 따른 체중변화를 비교해 본 결과, 8주간의 고지방 식이로 체중의 증가가 정상식이군에 유의하게 증가하며, 3-히드록시플라본(3-hydroxyflavone) 투여 시, 식이 섭취의 감소가 나타나고 그에 따른 체중증가의 감소 현상을 보였다(도 7).As a result of comparing the weight change according to the normal diet group, the high fat diet group, and the high fat diet + 3-hydroxyflavone administration group, the weight gain was increased by 8-week high fat diet. Significantly increased, and when administered to 3-hydroxyflavone (3-hydroxyflavone), a decrease in dietary intake was shown, resulting in a decrease in weight gain (Fig. 7).
실시예 5: 보행성 활동량(locomotor activity) 측정Example 5 Locomotor Activity Measurement
3-히드록시플라본(3-hydroxyflavone) 투여에 따른 체중 증가의 억제가 행동량 증가에 의한 에너지 소비 증가 때문인지 확인하기 위해 3주간의 고지방식이군에 3-히드록시플라본(3-hydroxyflavone) 투여 후, 보행성 활동량을 측정하였다. 1시간 동안의 공간 적응 후, 2시간 동안의 움직임 측정에서 어떤 그룹도 유의한 차이를 보이지 않았다. 따라서, 3-히드록시플라본(3-hydroxyflavone) 투여에 의한 체증 증가 억제 효과는 식이 섭취량 감소에 의한 것임을 확인할 수 있었다(도 8).After 3 weeks of 3-hydroxyflavone administration to the high-fat diet group to determine whether the inhibition of weight gain following 3-hydroxyflavone administration was due to increased energy consumption In addition, the amount of walking activity was measured. After 1 hour of spatial adaptation, there was no significant difference in any group in the measurement of movement for 2 hours. Therefore, it was confirmed that the effect of inhibiting weight gain by administration of 3-hydroxyflavone was due to a decrease in dietary intake (FIG. 8).

Claims (5)

  1. 유효성분으로 헤스페레틴(hesperetin), 진세노사이드-Rb1(ginsenoside-Rb1), 3-히드록시플라본(3-hydroxyflavone), 헤스페리딘(hesperidin), 진세노사이드-Rg1(ginsenoside-Rg1), 베타-D-글루칸(β-D-glucan), 루틴(rutin), 플라보논(flavanone), 나린진(naringin), 멜라토닌(melatonin), 케르세틴(quercetin) 및 아스코르브산(ascorbic acid)으로 이루어진 군으로부터 선택되는 하나 이상의 성분을 함유하는 식욕억제용 조성물.Hesperetin, Ginsenoside-Rb1, 3-hydroxyflavone, Hesperidin, Ginsenoside-Rg1, Ginsenoside-Rg1, Beta- One selected from the group consisting of D-glucan, rutin, flavonone, flanone, naringin, melatonin, quercetin and ascorbic acid Appetite suppression composition containing the above component.
  2. 제1항에 있어서, 상기 식욕억제는 식욕촉진 호르몬인 그렐린(ghrelin)의 활성을 억제하는 효과인 것을 특징으로 하는 식욕억제용 조성물.The appetite suppressing composition of claim 1, wherein the appetite suppressant is an effect of inhibiting the activity of ghrelin, which is an appetite-stimulating hormone.
  3. 제2항에 있어서, 상기 조성물은 60~100℃의 온도에서 그렐린 억제 활성이 유지되는 것을 특징으로 하는 식욕억제용 조성물.According to claim 2, wherein the appetite suppressing composition, characterized in that the ghrelin inhibitory activity is maintained at a temperature of 60 ~ 100 ℃.
  4. 제2항에 있어서, 상기 조성물은 pH 2~10에서 그렐린 억제 활성이 유지되는 것을 특징으로 하는 식욕억제용 조성물.The composition for suppressing appetite according to claim 2, wherein the composition maintains ghrelin inhibitory activity at pH 2 to 10.
  5. 헤스페레틴(hesperetin), 진세노사이드-Rb1(ginsenoside-Rb1), 3-히드록시플라본(3-hydroxyflavone), 헤스페리딘(hesperidin), 진세노사이드-Rg1(ginsenoside-Rg1), 베타-D-글루칸(β-D-glucan), 루틴(rutin), 플라보논(flavanone), 나린진(naringin), 멜라토닌(melatonin), 케르세틴(quercetin) 및 아스코르브산(ascorbic acid)으로 이루어진 군으로부터 선택되는 하나 이상의 성분을 유효성분으로 함유하는 식욕억제용 기능성 식품.Hesperetin, ginsenoside-Rb1, 3-hydroxyflavone, hesperidin, ginsenoside-Rg1, beta-D-glucan (β-D-glucan), rutin, flavonone (flavanone), naringin (naringin), melatonin (melatonin), quercetin (quercetin) and ascorbic acid (ascorbic acid) Functional food for appetite suppression containing as an active ingredient.
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EP2990036A1 (en) * 2014-07-30 2016-03-02 Symrise AG Hydroxyflavones for stimulating appetite
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