WO2009134010A2 - Pharmaceutical composition using herbal extract for prevention and treatment of obesity and metabolic disorders - Google Patents

Pharmaceutical composition using herbal extract for prevention and treatment of obesity and metabolic disorders Download PDF

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WO2009134010A2
WO2009134010A2 PCT/KR2009/001542 KR2009001542W WO2009134010A2 WO 2009134010 A2 WO2009134010 A2 WO 2009134010A2 KR 2009001542 W KR2009001542 W KR 2009001542W WO 2009134010 A2 WO2009134010 A2 WO 2009134010A2
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obesity
extract
weight
treatment
composition
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PCT/KR2009/001542
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French (fr)
Korean (ko)
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WO2009134010A3 (en
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이경희
이용오
김유선
조영석
홍준기
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주식회사 유유
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Priority to CN2009801153374A priority Critical patent/CN102014944B/en
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Publication of WO2009134010A3 publication Critical patent/WO2009134010A3/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/75Rutaceae (Rue family)
    • A61K36/754Evodia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/75Rutaceae (Rue family)
    • A61K36/752Citrus, e.g. lime, orange or lemon
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/88Liliopsida (monocotyledons)
    • A61K36/899Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/04Anorexiants; Antiobesity agents

Definitions

  • the present invention relates to a composition for preventing or treating obesity and metabolic syndrome using a composite herbal medicine.
  • Obesity was already prescribed as a disease in 1996 by the World Health Organization. About 150 million people worldwide have experienced obesity, a health risk factor, and since obesity is directly related to various adult diseases, there is an urgent need for treatment for obesity. In addition, the market size of obesity drugs is on the rise due to the improvement of economic level and increased interest in appearance.
  • Obesity is a problem that obesity itself causes constipation, indigestion, gastrointestinal disorders due to the abdominal pressure by the fat tissue, as well as the risk factors of many adult diseases. Obesity is known to cause all kinds of complications such as cancer, arteriosclerosis, heart disease, high blood pressure, diabetes and other complications, and in 1996, the World Health Organization (WHO) warned that obesity is a disease that needs treatment.
  • WHO World Health Organization
  • Metabolic syndrome is characterized by insulin resistance, abdominal obesity, hyperlipidemia, hypertension, hyperglycemia, and is a particularly frequent symptom in obese people.
  • the WHO warned the American Medical Association (JAMA) that anyone with a metabolic syndrome is more likely to become a diabetic, stroke or heart disease patient.
  • JAMA American Medical Association
  • Metabolic syndrome patients are those who overlap three or more of the following five symptoms.
  • Obesity is a condition where excess fat is accumulated in the body, and fat is accumulated in the body due to excessive intake of sugar (carbohydrate) or excessive intake of fat.
  • sugar carbohydrate
  • the mechanism of reaching obesity is that by over-ingesting the sugar, the sugar in the food is digested and becomes monosaccharide and absorbed into the body through the small intestine.Increased blood sugar increases insulin secreted by the stimulus and acts on fat cells to release the monosaccharide in the blood. Fat cells are taken in and converted into fat.
  • fat which is the highest calorie among food ingredients, is broken down by pancreatic lipase and absorbed through the small intestine, resulting in an increase in stored calories due to excess calories. That is, obesity is caused by excess fat intake.
  • Glycolytic digestion which inhibits the path to obesity due to excessive intake of glucose, suppressed the rise in blood sugar, or suppressed the adsorption of cholic acid, which inhibits the path to obesity, by inhibiting the absorption of monosaccharides or by excessive intake of fat, cholesterol lowering It is thought that obesity can be prevented and improved by the action, the blood triglyceride lowering action, or the lipase inhibitory action, and the research on the pharmaceutical component which has these actions is continuing.
  • Glycolytic digestive enzyme inhibitors currently being used as drugs include acarbose (Acarbose, Bayer Pharmaceutical Co., Ltd.) and Bogriboose (AO-128, Daeda Pharmaceutical Co., Ltd.), a post-prandial hyperglycemic improver. These animals have been shown to have an inhibitory effect on post-prandial blood sugar levels in animal and clinical trials. Exp. Med.vol. 175, 87 (1979), Japanese Society for Agricultural Chemistry vol. 63, 217 (1989), New Current vol. 6, 2 (1995).
  • methods of inhibiting the path leading to obesity by ingesting fat include cholic acid adsorption excretion, cholesterol lowering, blood triglyceride lowering, lipase inhibition, and the like.
  • Drugs with cholic acid excretion include cholstyramine, a hypercholesterolemic drug, which is an anion exchange resin.
  • the anion exchange resin is circulated in the gut [Makino Isaora, Taisha, vol. 24, No.
  • adsorption and fixation of the intestinal cholic acid prevents resorption of the cholic acid, promotes the conversion of cholesterol into the cholic acid in the liver, and consequently lowers the blood cholesterol concentration.
  • the usage of cholestyramine is that 9 g is taken in 100 mL of water, so the dose is very high, and when taken, the rough unpleasant texture of the resin remains in the mouth, making it very difficult for the patient to take it. There was a problem.
  • Some anti-obesity drugs have been developed, which consist of extracts of several herbal drugs or mixtures.
  • Korean Patent Publication No. 2007-0042755 discloses a composition for inhibiting or treating obesity using a ginseng component, and in KR0733336, a composition for preventing or treating obesity or hyperlipidemia using a root is registered.
  • the applicant of the patent has registered a patent for the treatment of obesity using the herbal medicines such as white hair roots and the inhibitory composition (or extract) through the registration publications KR0573590, KR0573591 and KR0573592, but further research has been found to be superior in abdominal fat reduction. It is a new invention of the composition of the present invention to effect.
  • the present inventors confirmed that the complex extracts of the herbal medicines, Osuyu, Baek-geun-geun and Cheongpi, were effective in inhibiting weight gain, abdominal fat reduction, and triglyceride and blood glucose levels through animal experiments.
  • in vitro tests confirmed the effect of increasing the activity of AMPK enzyme, a biomarker associated with obesity and diabetes, and also confirmed the effect of increasing glucose uptake in myocytes and adipocytes.
  • an object of the present invention is to provide a composition for the prevention and treatment of obesity and metabolic syndrome, which contains a complex extract of Evodiamine Fructus , Cerrus Unshiu Markovich and White Hair Root (Imperatae Rhizoma) as an active ingredient.
  • the present invention has another object to provide a health food containing the complex extract.
  • An object of the present invention is to provide a composition for the prevention and treatment of obesity and metabolic syndrome, which contains a complex extract of Evodiamine Fructus , Cerrus Unshiu Markovich and White Root Muscle (Imperatae Rhizoma) as an active ingredient.
  • the complex extract includes a health food containing the complex extract.
  • the complex extract according to the present invention promotes the expression of genes related to the prevention and treatment of obesity and metabolic syndrome in cells, and has a very good weight gain inhibitory effect and high levels of triglycerides and blood glucose in blood in mice fed high fat diet. Improves glucose uptake in myocytes and adipocytes.
  • Figure 1 shows the combined effect of the present invention AMPK enzyme activity using the obese animal model.
  • Figure 3 is a measure of the increase in glucose uptake capacity in the muscle cells of the complex extract according to the present invention.
  • Figure 4 measures the increase in glucose uptake capacity in mast cells of the complex extract according to the present invention.
  • the present invention for achieving the above object, in the composition for the prevention and treatment of obesity and metabolic syndrome containing a complex extract of sorghum ( Evodiamine Fructus ), cheongpi (Citrus Unshiu Markovich) and white hair root (Imperatae Rhizoma) as an active ingredient It is about.
  • sorghum Evodiamine Fructus
  • cheongpi Citrus Unshiu Markovich
  • white hair root Imperatae Rhizoma
  • the complex extract according to the present invention may be prepared by first obtaining a method such as cold water extraction, hot water extraction or solvent extraction according to a conventional method, drying, and then mixing in the above ratio.
  • each herbal may be extracted in different ways. For example, it can be manufactured by the following method.
  • each of the sewage, skin and white hair roots that have been screened and cut to the appropriate size are prepared.
  • 0.1 to 10 parts by weight of cheongpi, 0.1 to 30 parts by weight of white hair root are used based on 1 part by weight of sewage oil.
  • 10 to 100 times the amount of each aqueous solution of alcohol is added, extraction is performed for 4 to 8 hours at 70 to 100 ° C., followed by rapid freezing for 10 to 20 hours at -50 to -30 ° C., and 30 to 30 at a pressure of 0.1 to 0.5 Torr.
  • the dry powder of each herbal medicine is mixed by the said ratio, and the composite extract powder which concerns on this invention is obtained.
  • the solid content of each herbal extract before drying may be investigated in advance, and then the extract may be mixed so as to have the above ratio, and then dried in a batch to obtain a composite extract powder according to the present invention.
  • the composite extract according to the present invention may be obtained by first mixing each herbal dry matter of a calculated ratio so as to finally be the above ratio, and then extracting them in a batch.
  • a mixture of 1.0 parts by weight of dried sewage extract, 0.1 to 10 parts by weight of dried skin extract and 0.1 to 30 parts by weight of dried white hair root extract is prepared by a method such as cold water extraction, hot water extraction or solvent extraction according to a conventional method.
  • the mixture may be used as it is by filtration, concentrated to use, or lyophilized to be used as powder.
  • it can be manufactured by the following method. First, the sewage, skin and white hair roots, which have been selected and trimmed to an appropriate size, are mixed in accordance with the mixing ratio.
  • the complex extract according to the present invention can be seen in the preparation examples and examples below, by increasing the cellular uptake of AMPK at the same time to increase the intracellular AMPK activity, a conventional conventional herbal medicine or commercial drugs for the treatment and inhibition of obesity It is much better and safer than that.
  • the complex extract of the present invention can be prepared as a pharmaceutical.
  • the complex extract of the present invention can be administered to mammals such as mice, livestock, humans, etc. by various routes. All modes of administration can be expected, for example by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or cerebrovascular injections.
  • the present invention provides a health functional food comprising the composition and a food acceptable food supplement additive exhibiting a prophylactic and therapeutic effect of obesity and metabolic syndrome.
  • a food acceptable food supplement additive exhibiting a prophylactic and therapeutic effect of obesity and metabolic syndrome.
  • the food to which the complex extract can be added include various foods, beverages, gums, teas, vitamin complexes, and health functional foods.
  • the present invention includes a health food for improving obesity and metabolic syndrome containing a complex extract as an active ingredient.
  • the health food may contain various supplemental herbal medicines, vitamins, minerals, dietary fiber, and other medicinal-food supplements (eg, excipients, enhancers, coatings, etc.).
  • the amount of the complex extract in the food or beverage in the case of the health food of the present invention can generally be added to 0.0001 to 100% by weight, preferably 80% by weight or less of the total food weight, 100 ml to the health beverage composition It can be added in a ratio of 0.0001 to 10 g, preferably 5.0 g or less as a reference.
  • a 10-fold weight of 70% aqueous ethanol solution was mixed with 1 Kg of dried sewage, white hair root and skin skin, which were previously screened and cut into appropriate sizes, and then heated and subjected to primary extraction at 85 ° C. for 6 hours. Thereafter, the primary filtrate was collected separately by filtration, and the filtered crude drug was further mixed with an aqueous 10% weight 70% ethanol aqueous solution, followed by heating to carry out secondary extraction at 85 ° C. for 6 hours. Subsequently, the resultant was filtered to obtain a secondary filtrate, followed by rapid freezing with the primary filtrate at 70 ° C. for 12 hours, vacuum drying for at least 36 hours under a pressure of 0.23 Torr or less, and then grinding to obtain respective dry powders.
  • the obtained sewage oil, white hair root and dermis extract powder was mixed with 1 part by weight of white hair root extract and 3 parts by weight of dermis extract based on 1 part by weight of sewage extract to obtain a composite extract powder (composite extract) of the present invention.
  • each dry herbal medicine was mixed in the final extract. That is, dry sewage oil, white hair root and green skin, which were previously screened and cut to an appropriate size, were mixed, a 10-fold weight of 70% ethanol aqueous solution was poured, and heated to carry out primary extraction at 85 ° C. for 6 hours. Thereafter, the primary filtrate was collected separately by filtration, and the filtered crude drug was further mixed with an aqueous 10% weight 70% ethanol aqueous solution, followed by heating to carry out secondary extraction at 85 ° C. for 6 hours. Subsequently, the resultant was filtered to obtain a secondary filtrate, followed by rapid freezing with the primary filtrate at 70 ° C. for 12 hours, vacuum drying for at least 36 hours under a pressure of 0.23 Torr or less, and then grinding to obtain respective dry powders.
  • the cells were treated with the composite extract of the preparation, and then AMPK activity was examined over time. Activation of the AMPK enzyme increases glucose uptake, inhibits fatty acid synthesis, and induces fatty acid oxidation, and thus this experiment can confirm the prophylaxis or treatment of obesity and metabolic syndrome of the complex extract of the present invention.
  • mice purchased 20 to 25 g of 6-week-old C57BL / 6 mice from the central laboratory animals, and allowed them to freely feed and water in the animal room, and after one week, divided them into four groups as follows.
  • HFD High Fat Diet
  • mice were separated by weight, and 5 mice were placed in cages so that an average of 36 to 37 g of HFD was put into two cages (10 mice).
  • the average diet weight was 27 g.
  • High-fat diet mice were orally administered with the complex extract of the present invention for 10 weeks every day to observe the weight change and intake of the mice.
  • HFD normal diet control diet fed a normal diet
  • HFD high fat diet control group fed 45% high fat diet
  • HFD + complex extract high fat diet + complex extract (500 mg / kg)
  • HFD + sibutramine high fat diet Used as a positive control with this + sibutramine (2 mg / kg).
  • blood was collected from the orbital vein, and each tissue was extracted and weighed for analysis.
  • blood index analysis blood collection was performed using plasma after centrifugation of whole blood obtained from the orbital vein for 30 minutes at 1,500 rpm after fasting on the previous day (8-10 hours), and astaxet triglycerides, glucose and cholesterol. (cholesterol) kits were purchased and measured with an ELISA reader.
  • Figure 2 is the result of comparing the weight change pattern between each group for 10 weeks.
  • the body weight of the mice was temporarily decreased until 2 weeks. This may be due to the stress of the mouse by oral administration.
  • Body weight gained again from 3 weeks, and significantly increased weight suppression effect in group administered 500 mg / kg of complex extract at 5 weeks compared with control group. This effect lasted up to 10 weeks.
  • the body weight of the high-fat diet group HFD
  • the complex extract group was 41.3 at the 500 mg / kg dose, respectively. ⁇ 1.7.
  • the weight of the sibutramine-treated group which was a positive control group, was 43.3 ⁇ 1.7, which was lower than that of the high-fat diet.
  • the complex extract of the present invention was found to have better activity in weight inhibition than the positive control group.
  • the high fat diet significantly increased abdominal fat, significantly increased liver and kidney weights, and the weight of other organs was not significantly changed.
  • the high-fat diet group was 4.5 ⁇ 0.5, whereas the combined extracts showed 3.2 ⁇ 0.4 of abdominal fat reduction on average by 30%.
  • Table 2 shows the plasma-derived plasma of the mice obtained from orbital vein after fasting overnight (8 hours) after oral administration of the complex extract to diet-induced obesity for 10 weeks. Blood glucose and cholesterol were analyzed.
  • the high-fat diet control group HFD
  • the complex extract group was 123.4 ⁇ 12.2 at 500 mg / kg dose compared to the high-fat diet control group. Neutral lipid reduction effect was shown.
  • the high-fat diet control group increased 255.6 ⁇ 30.1 mg / dL compared to the general diet group (RD), whereas the complex extract group showed 204.1 ⁇ 14.5 mg / dL at 500 mg / kg dose.
  • the blood glucose reduction effect was shown.
  • the high fat diet was more effective than the control group, but the cholesterol was less correlated with the body weight.
  • the composite extract according to the present invention was found to be useful for the reduction of neutral lipid and blood glucose levels as well as the weight loss effect.
  • the complex extract of the present invention was dissolved in water and treated with different concentrations of cells for 24 hours, followed by MTT analysis to select the highest cytotoxicity (cytotoxic) concentration and glucose absorption ability in C2C12 myocytes (Fig. 3).
  • the complex extract of the present invention was observed to increase glucose uptake better than insulin at a 100 ⁇ g / mL dose, which is considered to be effective for glucose uptake.
  • the composite extract of the present invention was dissolved in water to investigate the effect on glucose uptake using 3T3L1 adipocytes at low concentrations of cytotoxicity (FIG. 4).
  • the complex extract of the present invention was observed to increase glucose uptake to a similar extent to 100 nM insulin, indicating a good glucose uptake effect.
  • the composite extract according to the present invention confirmed the effect of inhibiting weight gain and improving neutral lipid and blood glucose levels through animal experiments and enhancing the activity of AMPK enzyme, a biomarker related to the prevention or treatment of obesity and metabolic syndrome, through in vitro tests. It was confirmed that the effect of increasing the glucose uptake capacity in myocytes and adipocytes.
  • the composite extract according to the present invention was confirmed that it can be usefully applied to the treatment and prevention of diseases associated with obesity and metabolic syndrome.
  • the above ingredients were mixed and prepared in a conventional manner, and then injected into a 2 ml ampoule and sterilized to prepare an injection.
  • the tablets were prepared by mixing the above components and tableting according to a conventional method for producing tablets.
  • the capsules were prepared by mixing the above components and filling the capsules according to a conventional method for preparing capsules.
  • Purified water was added to adjust the total volume to 1000 ml. According to the conventional method for preparing a liquid, the above components were mixed to prepare a liquid.
  • Vitamin A (0.275 mg as Retinyl Palmitate) &........ 500 IU
  • Vitamin C ... ..50 mg
  • Glycerin ginseng calcium (4.76 mg as calcium) ... 25 mg
  • Iron sulphate (5.0 mg as iron) ... 15.45 mg
  • composition ratio of the complex extract of the present invention, vitamins and minerals, etc. are mixed with the components suitable for the health functional food in a preferred embodiment, the composition ratio may be arbitrarily modified, and according to the conventional health functional food manufacturing method After mixing the above components to prepare a granule, it can be used for preparing a nutraceutical composition according to a conventional method.
  • Purified water was added to adjust the total volume to 900 ml. It is prepared according to a conventional healthy beverage manufacturing method.
  • composition ratio is a composition that is relatively suitable for a preferred beverage in a preferred embodiment
  • the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.

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Abstract

The present invention relates to a composition using composite herbal extracts for prevention and treatment of obesity and metabolic disorder. More specifically, the invention provides a composition containing Evodiae Fructus, Imperatae Rhizoma, and Citrus unshiu Markovich for prevention and treatment of obesity and metabolic syndromes or syndrome X.

Description

[규칙 제26조에 의한 보정 06.10.2009] 복합 생약재를 이용한 비만 및 대사증후군의 예방 또는 치료용 조성물[Revision according to Rule 26.06.10.2009] Composition for the prevention or treatment of obesity and metabolic syndrome using complex herbal medicine
본 발명은 복합 생약재를 이용한 비만 및 대사증후군의 예방 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for preventing or treating obesity and metabolic syndrome using a composite herbal medicine.
비만은 세계보건기구(WHO)에 의해서 1996년에 이미 질병으로 규정된 바 있다. 전 세계적으로 약 1억 5천만 명이 건강위험 요인인 비만을 경험한 바 있으며, 이러한 비만은 여러 가지 성인병과 직접적인 관련이 있으므로 비만치료제의 필요성이 절실하게 대두되었다. 또한, 경제 수준의 향상과 외모에 대한 관심 증가로 비만치료제의 시장규모는 증가일로에 있다. Obesity was already prescribed as a disease in 1996 by the World Health Organization. About 150 million people worldwide have experienced obesity, a health risk factor, and since obesity is directly related to various adult diseases, there is an urgent need for treatment for obesity. In addition, the market size of obesity drugs is on the rise due to the improvement of economic level and increased interest in appearance.
비만치료제 시장은 2000년 약 13억 달러 규모이었고 연평균 20%에 가까운 고성장을 하고 있어 2010년이면 80억 달러에 이를 전망이다. 현재 최종단계의 임상시험 중이거나 FDA의 승인을 기다리고 있는 비만치료제 들이 10여종에 이르며 이미 제니칼, 리덕틸 등은 미국 FDA에 의해서 승인을 받았을 뿐 아니라 국내에도 소개되어 급속히 확산되고 있다[보건산업기술동향, 2001 겨울].The market for obesity drugs was about $ 1.3 billion in 2000 and is growing at an annual average of nearly 20%. There are more than 10 kinds of obesity treatments currently in final stage of clinical trials or waiting for FDA's approval.Jenical and Reductil have already been approved by the US FDA as well as introduced in Korea and are rapidly spreading. [Health Industry Technology Trend, 2001 winter].
비만의 유해성은 비만 그 자체로 지방조직에 의한 복부의 압박으로 인하여 변비와 소화 불량, 위장 장해 등을 일으키는 경우가 많을 뿐만 아니라, 이로 인해 많은 성인병들의 위험요소가 된다는데 문제가 있다. 비만은 암을 비롯한 동맥경화, 심장병, 고혈압, 당뇨병 등과 같은 성인병과 합병증을 일으키는 등 만병의 근원이라고 알려져 있으며 1996년 세계보건기구(WHO)도 비만은 치료가 필요한 병이라고 경고한 바 있다. 75만 명을 대상으로 한 연구에 의하면 평균 체중보다 40% 이상인 남성과 여성에서 정상 체중인 사람들 보다 사망률이 1.9배 증가된 것으로 조사되었다. 특히, 최근에 들어서 이러한 비만은 당뇨병 및 고혈압 등의 발생 전단계로 판단되는 소위 대사증후군(X-증후군)의 발병 원인이 되는 것으로 밝혀지고 있으며 이의 유병률은 전 세계 인구의 1/4에 이르는 것으로 나타나고 있어 그 심각성은 커져가고 있다.Obesity is a problem that obesity itself causes constipation, indigestion, gastrointestinal disorders due to the abdominal pressure by the fat tissue, as well as the risk factors of many adult diseases. Obesity is known to cause all kinds of complications such as cancer, arteriosclerosis, heart disease, high blood pressure, diabetes and other complications, and in 1996, the World Health Organization (WHO) warned that obesity is a disease that needs treatment. A study of 750,000 people reported a 1.9-fold increase in mortality in men and women over 40% above average body weight compared to those of normal weight. In particular, in recent years, such obesity has been found to be the cause of the development of the so-called metabolic syndrome (X-syndrome), which is considered to be a pre-development stage of diabetes and hypertension, and its prevalence is found to be one quarter of the world's population. Its seriousness is growing.
대사증후군은 인슐린 저항성, 복부 비만, 고지혈증, 고혈압, 고혈당의 특징을 가지고 있는 것으로, 특히 비만자에 있어서 자주 발생되는 증상이다. 그 내용은 세계 보건기구가 미국의사협회지(JAMA)에 경고한 내용으로 이와 같은 대사증후군 환자는 누구나 당뇨병이나 뇌졸중 또는 심장병 환자가 될 확률이 크다.Metabolic syndrome is characterized by insulin resistance, abdominal obesity, hyperlipidemia, hypertension, hyperglycemia, and is a particularly frequent symptom in obese people. The WHO warned the American Medical Association (JAMA) that anyone with a metabolic syndrome is more likely to become a diabetic, stroke or heart disease patient.
다음과 같은 다섯 가지 증세 중 3가지 이상이 겹쳐있는 자를 대사증후군 환자라 한다.Metabolic syndrome patients are those who overlap three or more of the following five symptoms.
(1) 허리둘레 ------- (남) 100 cm 이상 (여) 88 cm 이상(1) Waist circumference ------- (Male) More than 100 cm (Female) More than 88 cm
(2) 혈압 ----------- 135 / 80 mmHg 이상(2) Blood pressure ----------- 135/80 mmHg or more
(3) 혈당 ----------- 110 (공복시) mg/이 이상(3) blood sugar ----------- 110 (fasting) mg / or more
(4) 중성지질 ------- 150 mg/dl 이상(4) Neutral lipid ------- 150 mg / dl or more
(5) HDL levels ----- (남) 40 mg/dl 이하 (여) 50 mg/dl 이하(5) HDL levels ----- (male) 40 mg / dl or less (female) 50 mg / dl or less
이러한 대사증후군 환자는 궁극적으로 비만에서 유래하고 있다는 사실이 자명한 이때 비만의 관리는 향후 대부분의 성인병으로의 발생 전단계인 대사증후군 환자의 발생과 관련하여 더욱 중요하게 인식되고 있다.It is clear that the metabolic syndrome patients are ultimately derived from obesity. At this time, the management of obesity is more important in relation to the occurrence of metabolic syndrome patients, which is a pre-development stage of most adult diseases.
비만은 신체에 지방이 과잉되게 축적된 상태이며, 지방이 체내에 축적되는 원인은 당질(탄수화물)의 과잉 섭취 또는 지방을 과잉섭취 하는 데 있다. 비만에 달하는 메카니즘은 당질을 과잉 섭취함으로써 음식물 중에 함유되어 있는 당질이 소화되어 단당이 되고 소장을 통해 체내로 흡수되며, 혈당이 상승하여 그 자극으로 분비되는 인슐린이 지방세포에 작용해서 혈액 중의 단당을 지방세포가 받아들이게 되어 지방으로 전환되는 것이다. 또한, 식품성분 중 가장 고칼로리인 지방은 췌장 리파아제에 의해 분해되어 소장을 통해 흡수되며, 섭취 칼로리의 과잉으로 저장 칼로리가 증가되는 결과가 된다. 즉, 과잉 지방섭취에 의해 비만이 되는 것이다.Obesity is a condition where excess fat is accumulated in the body, and fat is accumulated in the body due to excessive intake of sugar (carbohydrate) or excessive intake of fat. The mechanism of reaching obesity is that by over-ingesting the sugar, the sugar in the food is digested and becomes monosaccharide and absorbed into the body through the small intestine.Increased blood sugar increases insulin secreted by the stimulus and acts on fat cells to release the monosaccharide in the blood. Fat cells are taken in and converted into fat. In addition, fat, which is the highest calorie among food ingredients, is broken down by pancreatic lipase and absorbed through the small intestine, resulting in an increase in stored calories due to excess calories. That is, obesity is caused by excess fat intake.
따라서, 비만에 달하는 이들의 어떤 경로의 일부분을 저해함으로써 항비만 작용을 발생시키려는 생각을 바탕으로 현재 각종 항비만제에 관한 연구가 진행되고 있다. Therefore, research on various anti-obesity agents is currently being conducted based on the idea of generating anti-obesity effects by inhibiting a part of certain pathways leading to obesity.
당질 과잉 섭취로 비만이 되는 경로를 저해하는 당질분해 소화효소저해작용, 혈당상승 억제작용, 또는 단당 흡수 억제작용에 의해 또는 지방 과잉 섭취에 의해 비만에 달하는 경로를 저해하는 콜산 흡착 배설작용, 콜레스테롤 저하작용, 혈중 트리글리세리드 저하작용, 또는 리파아제 저해작용에 의해 비만을 예방 및 개선할 수 있다고 생각되어, 이들 작용을 가지는 의약성분에 대한 연구가 계속하여 진행되고 있다.Glycolytic digestion, which inhibits the path to obesity due to excessive intake of glucose, suppressed the rise in blood sugar, or suppressed the adsorption of cholic acid, which inhibits the path to obesity, by inhibiting the absorption of monosaccharides or by excessive intake of fat, cholesterol lowering It is thought that obesity can be prevented and improved by the action, the blood triglyceride lowering action, or the lipase inhibitory action, and the research on the pharmaceutical component which has these actions is continuing.
탄수화물(당질)의 과잉 섭취로 인한 급격한 식후 혈당 상승과 과다한 인슐린 분비는, 비만 외에도 당뇨병 혹은 고지혈증을 야기하며[약리와 치료 Vol. 19, No. 10 Oct. 274, 1991], 당질 분해 소화효소를 저해함으로써 당뇨병 혹은 고지혈증도 예방 및 개선할 수 있다고 알려져 있다. 따라서, 당질분해 소화효소 저해제, 단당흡수 억제제, 또는 혈당상승 억제제는 항당뇨병제, 항고지혈증제, 또는 항동맥경화증제로 유용하다고 생각된다. 현재 의약품으로 사용되고 있는 당질 분해 소화효소 저해제로는 α-글루코시다아제 저해제인 아카보스(Acarbose, 바이엘약품 주식회사)나 식후 과혈당 개선제인 보그리보오즈(AO-128, 다께다약품 주식회사)가 있다. 이들은 동물시험이나 임상시험에서 식후 혈당치의 상승 억제효과가 확인되었고, 항비만, 항당뇨병에 대한 유효성도 보고되었다[Res. Exp. Med.vol. 175, 87(1979), 일본 농예화학회지 vol. 63, 217(1989), New Current vol. 6, 2(1995)]. 또한, 지방(트리글리세리드) 섭취로 비만에 달하는 경로를 저해하는 방법으로는 콜산 흡착 배설, 콜레스테롤 저하, 혈중 트리글리세리드 저하, 리파아제 저해 등이 있다. 콜산 배설작용을 가지는 의약으로는 고콜레스테롤 혈증치료제인 콜레스티라민(colestyramine)이 있고, 이것은 음이온교환수지이다. 음이온 교환수지를 경구 투여하는 것에 의해 음이온 교환수지는 장간순환(腸肝循環)[마끼노 이사오라, 다이샤, vol. 24, No. 8, 685-692, 1987]하고 있는 장내의 콜산을 흡착 고정하여 콜산의 재흡수를 방해하고, 간장에서 콜레스테롤의 콜산으로의 변환을 촉진시켜, 그 결과 혈중 콜레스테롤 농도를 저하시키는 작용을 가진다. 그러나, 콜레스티라민의 용법이 9 g을 100 mL의 물에 현탁해서 복용하게 되어 있어서, 1 회 투여량이 매우 많고, 복용 시에는 수지의 거칠거칠한 불쾌한 감촉이 입안에 남아서 환자가 무척 복용하기 어렵다는 문제점이 있었다.Sudden postprandial blood sugar rise and excessive insulin secretion due to excessive intake of carbohydrates (sugars) can lead to diabetes or hyperlipidemia in addition to obesity [pharmacology and treatment Vol. 19, No. 10 Oct. 274, 1991] is known to inhibit and improve diabetes or hyperlipidemia by inhibiting glycolysis digestive enzymes. Therefore, glycosylated digestive enzyme inhibitors, monosaccharide absorption inhibitors, or blood glucose elevation inhibitors are considered to be useful as antidiabetic agents, antihyperlipidemic agents, or antiarteriosclerosis agents. Glycolytic digestive enzyme inhibitors currently being used as drugs include acarbose (Acarbose, Bayer Pharmaceutical Co., Ltd.) and Bogriboose (AO-128, Daeda Pharmaceutical Co., Ltd.), a post-prandial hyperglycemic improver. These animals have been shown to have an inhibitory effect on post-prandial blood sugar levels in animal and clinical trials. Exp. Med.vol. 175, 87 (1979), Japanese Society for Agricultural Chemistry vol. 63, 217 (1989), New Current vol. 6, 2 (1995). In addition, methods of inhibiting the path leading to obesity by ingesting fat (triglyceride) include cholic acid adsorption excretion, cholesterol lowering, blood triglyceride lowering, lipase inhibition, and the like. Drugs with cholic acid excretion include cholstyramine, a hypercholesterolemic drug, which is an anion exchange resin. By oral administration of the anion exchange resin, the anion exchange resin is circulated in the gut [Makino Isaora, Taisha, vol. 24, No. 8, 685-692, 1987] adsorption and fixation of the intestinal cholic acid prevents resorption of the cholic acid, promotes the conversion of cholesterol into the cholic acid in the liver, and consequently lowers the blood cholesterol concentration. However, the usage of cholestyramine is that 9 g is taken in 100 mL of water, so the dose is very high, and when taken, the rough unpleasant texture of the resin remains in the mouth, making it very difficult for the patient to take it. There was a problem.
상기와 같이 각각의 작용을 가지는 수많은 화학 합성 화합물이 보고되고, 의약품으로 사용되고 있지만, 이들은 복용량이 많다거나 복용 시에 불쾌감이 있다는 문제점이 있으며, 또한 화학 합성 화합물이기 때문에 투여 시에 피험자가 인체에 대한 안전성에 불안을 느끼는 경우가 있었다. As described above, a number of chemical synthetic compounds having respective actions have been reported and used as medicines, but they have a problem in that they have a high dose or are unpleasant at the time of taking them, and because they are chemical synthetic compounds, the subjects may not In some cases, safety was anxiety.
따라서, 이와 같은 안전성 문제로 인해 국내외적으로 천연물을 이용한 제품 개발이 증가하고 있다.Therefore, due to such safety issues, product development using natural products at home and abroad is increasing.
특히, 의이인(Cocis semen), 산약(Dioscoreae rhizoma), 길경(Platycodi radix, 도라지), 오미자(Schizandrae fructus), 귤피(Citus unshiu Markovich), 알로에(Aloe vera), 산더덕(Adenophorae radix; 사삼) 등 몇 가지 생약 단독 또는 혼합물의 추출물로 이루어진 비만억제용 약제 등이 개발되어 있다. 또한, 공개공보 KR2007-0042755에서는 인삼성분을 이용한 비만 억제 또는 치료용 조성물이 공개되어 있으며 등록공보 KR0733336에서는 갈근을 이용한 비만 또는 고지혈증의 예방 또는 치료용 조성물이 등록되어 있다.In particular, Cois semen, Dioscoreae rhizoma, Gilkyung (Platycodi radix, bellflower), Schizandrae fructus, Citrus unshiu Markovich, Aloe vera, Adenophorae radix (Sasam), etc. Some anti-obesity drugs have been developed, which consist of extracts of several herbal drugs or mixtures. In addition, Korean Patent Publication No. 2007-0042755 discloses a composition for inhibiting or treating obesity using a ginseng component, and in KR0733336, a composition for preventing or treating obesity or hyperlipidemia using a root is registered.
그러나, 이제까지 알려진 이러한 천연물 유래의 제품의 경우, 그 소재가 귀하여 매우 고가이거나, 적절한 효과를 얻기 위해 많은 양을 섭취해야 하거나, 실제 비만억제 및 고지혈증 방지를 위한 효과가 미미한 경우가 많았다.However, in the case of such natural-derived products so far known, the material is very expensive, many times to consume a large amount to obtain a proper effect, or the effect to prevent obesity and prevent hyperlipidemia in many cases.
따라서, 천연소재이면서도 입수가 용이하고, 보다 복합적인 효과를 나타낼 수 있는 새로운 생약 조성물을 연구 개발할 필요성이 있다.Therefore, there is a need to research and develop a new herbal composition that can be easily obtained even though it is a natural material and can have a more complex effect.
또한, 본 특허의 출원인은 등록공보 KR0573590, KR0573591 및 KR0573592를 통해 백모근 등의 생약제제를 이용한 비만 치료, 억제용 조성물(또는 추출물)에 관한 특허를 등록한 바 있으나 추가연구를 통해 복부지방 감소 등에서 보다 우수한 효과를 나타내는 본 발명의 조성물을 새로이 발명하게 되었다.In addition, the applicant of the patent has registered a patent for the treatment of obesity using the herbal medicines such as white hair roots and the inhibitory composition (or extract) through the registration publications KR0573590, KR0573591 and KR0573592, but further research has been found to be superior in abdominal fat reduction. It is a new invention of the composition of the present invention to effect.
이에, 본 발명자들은 생약제제인 오수유, 백모근 및 청피의 복합 추출물이 동물실험을 통해 체중 증가 억제 활성 및 복부지방 감소 효과와 중성지질과 혈당의 수치 개선에 효과가 있음을 확인하였다. 또한, In vitro 시험에서 비만 및 당뇨 질환 관련 바이오마커인 AMPK 효소의 활성을 증가시키는 효과를 확인하였으며, 또한 근세포 및 지방 세포에서 포도당의 흡수능을 증가 시키는 효과를 확인함으로써 본 발명을 완성하게 되었다.Therefore, the present inventors confirmed that the complex extracts of the herbal medicines, Osuyu, Baek-geun-geun and Cheongpi, were effective in inhibiting weight gain, abdominal fat reduction, and triglyceride and blood glucose levels through animal experiments. In addition, in vitro tests confirmed the effect of increasing the activity of AMPK enzyme, a biomarker associated with obesity and diabetes, and also confirmed the effect of increasing glucose uptake in myocytes and adipocytes.
따라서, 본 발명은 오수유(Evodiamine Fructus), 청피(Citrus Unshiu Markovich) 및 백모근(Imperatae Rhizoma)의 복합 추출물을 유효성분으로 함유하는 비만과 대사증후군의 예방 및 치료용 조성물을 제공하는데 그 목적이 있다.Accordingly, an object of the present invention is to provide a composition for the prevention and treatment of obesity and metabolic syndrome, which contains a complex extract of Evodiamine Fructus , Cerrus Unshiu Markovich and White Hair Root (Imperatae Rhizoma) as an active ingredient.
또한, 본 발명은 상기 복합 추출물을 함유하는 건강식품을 제공하는데 또 다른 목적이 있다.In addition, the present invention has another object to provide a health food containing the complex extract.
본 발명은 오수유(Evodiamine Fructus), 청피(Citrus Unshiu Markovich) 및 백모근(Imperatae Rhizoma)의 복합 추출물을 유효성분으로 함유하는 비만과 대사증후군의 예방 및 치료용 조성물을 제공하는데 그 목적이 있다.An object of the present invention is to provide a composition for the prevention and treatment of obesity and metabolic syndrome, which contains a complex extract of Evodiamine Fructus , Cerrus Unshiu Markovich and White Root Muscle (Imperatae Rhizoma) as an active ingredient.
또한, 상기 복합 추출물을 함유하는 건강식품을 포함한다.In addition, it includes a health food containing the complex extract.
본 발명에 의한 복합 추출물은 세포에서 비만과 대사증후군 예방 및 비만 치료에 관련된 유전자의 발현을 촉진시키며, 고지방 식이를 투여한 마우스의 경우 매우 우수한 체중 증가 억제 효과 및 혈액 중 중성지질 및 혈당의 수치를 개선시키며 근세포 및 지방세포에서 포도당 흡수가 뛰어난 효과를 나타낸다.The complex extract according to the present invention promotes the expression of genes related to the prevention and treatment of obesity and metabolic syndrome in cells, and has a very good weight gain inhibitory effect and high levels of triglycerides and blood glucose in blood in mice fed high fat diet. Improves glucose uptake in myocytes and adipocytes.
도 1은 본 발명에 의한 복합 추출물이 비만 동물모델을 이용한 AMPK 효소 활성 효과를 나타낸 것이다. Figure 1 shows the combined effect of the present invention AMPK enzyme activity using the obese animal model.
도 2는 10주간의 실험 마우스들의 체중 변화를 나타낸 것이다.2 shows body weight changes of experimental mice for 10 weeks.
도 3은 본 발명에 따른 복합 추출물의 근세포에서의 포도당 흡수능 증가를 측정한 것이다.Figure 3 is a measure of the increase in glucose uptake capacity in the muscle cells of the complex extract according to the present invention.
도 4는 본 발명에 따른 복합 추출물의 비만 세포에서의 포도당 흡수능 증가를 측정한 것이다.Figure 4 measures the increase in glucose uptake capacity in mast cells of the complex extract according to the present invention.
이하, 본 발명을 더욱 상세히 설명하면 다음과 같다.Hereinafter, the present invention will be described in more detail.
상기와 같은 목적을 달성하기 위한 본 발명은, 오수유(Evodiamine Fructus), 청피(Citrus Unshiu Markovich) 및 백모근(Imperatae Rhizoma)의 복합 추출물을 유효성분으로 함유하는 비만과 대사증후군의 예방 및 치료용 조성물에 관한 것이다.The present invention for achieving the above object, in the composition for the prevention and treatment of obesity and metabolic syndrome containing a complex extract of sorghum ( Evodiamine Fructus ), cheongpi (Citrus Unshiu Markovich) and white hair root (Imperatae Rhizoma) as an active ingredient It is about.
본 발명에서 오수유 추출물 1.0 중량부에 대하여 청피 추출물 0.1 ~ 10 중량부 및 백모근 추출물 0.1 ~ 30 중량부를 혼합하여 복합 추출물을 유효성분으로 사용하는 것이 바람직하다.In the present invention, it is preferable to mix 0.1 ~ 10 parts by weight and 0.1 ~ 30 parts by weight of the white hair root extract with respect to 1.0 parts by weight of sewage extract to use the composite extract as an active ingredient.
본 발명에 의한 복합 추출물은, 먼저 통상의 방법에 따라 냉수 추출, 열수 추출 또는 용매 추출 등의 방법으로 수득하고 건조한 다음, 상기 비율로 혼합하여 제조될 수 있다. 이 경우, 상기 각 생약은 서로 다른 방법으로 추출될 수도 있을 것이다. 예를 들면, 다음과 같은 방법으로 제조될 수 있다. The complex extract according to the present invention may be prepared by first obtaining a method such as cold water extraction, hot water extraction or solvent extraction according to a conventional method, drying, and then mixing in the above ratio. In this case, each herbal may be extracted in different ways. For example, it can be manufactured by the following method.
먼저, 선별되고 적절한 크기로 절단한 오수유, 청피 및 백모근 각각을 준비한다. 이때, 오수유 1 중량부에 대하여 청피 0.1 ~ 10 중량부, 백모근 0.1 ~ 30 중량부를 사용한다. 각각의 생약의 10 ~ 100 배량의 알콜 수용액을 가하고 70 ~ 100 ℃에서 4 ~ 8 시간 추출을 행한 다음 -50 ~ -30 ℃에서 10 ~ 20시간 급속 동결하고, 0.1 ~ 0.5 토르의 압력에서 30 ~ 40시간 진공 건조한 다음 분쇄하여 건조 분말을 준비한다. 이어서 각 생약의 건조분말을 상기 비율에 따라 혼합하여 본 발명에 의한 복합 추출 분말을 수득한다. 물론, 건조되기 전의 각 생약 추출물의 고형물 함량을 사전에 조사한 다음 상기 비율이 되도록 추출물을 혼합한 다음 일괄적으로 건조하여 본 발명에 의한 복합 추출 분말을 얻을 수도 있다.First, each of the sewage, skin and white hair roots that have been screened and cut to the appropriate size are prepared. At this time, 0.1 to 10 parts by weight of cheongpi, 0.1 to 30 parts by weight of white hair root are used based on 1 part by weight of sewage oil. 10 to 100 times the amount of each aqueous solution of alcohol is added, extraction is performed for 4 to 8 hours at 70 to 100 ° C., followed by rapid freezing for 10 to 20 hours at -50 to -30 ° C., and 30 to 30 at a pressure of 0.1 to 0.5 Torr. Vacuum dried for 40 hours and then ground to prepare dry powder. Subsequently, the dry powder of each herbal medicine is mixed by the said ratio, and the composite extract powder which concerns on this invention is obtained. Of course, the solid content of each herbal extract before drying may be investigated in advance, and then the extract may be mixed so as to have the above ratio, and then dried in a batch to obtain a composite extract powder according to the present invention.
한편, 본 발명에 의한 복합 추출물은, 최종적으로 상기 비율이 될 수 있도록 계산된 비율의 각 생약 건조물을 먼저 혼합한 다음 일괄적으로 추출하여 수득되는 것도 가능하다. 이를 위하여, 건조 오수유 추출물 1.0 중량부, 건조 청피 추출물 0.1 ~ 10 중량부 및 건조 백모근 추출물 0.1 ~ 30 중량부의 혼합물을 통상의 방법에 따라 냉수 추출, 열수 추출 또는 용매 추출 등의 방법으로 각 성분의 혼합물을 추출한 다음, 여과하여 그대로 사용하거나, 농축하여 사용하거나, 동결 건조하여 분말상으로 사용할 수 있다. 예를 들면, 다음과 같은 방법으로 제조될 수 있다. 먼저, 선별되고 적절한 크기로 다듬어진 오수유, 청피 및 백모근을 상기 혼합비율에 맞추어 혼합한다. 상기 혼합물에 10 ~ 100 배량의 알콜 수용액을 가하고 70 ~ 100 ℃에서 4 ~ 8 시간 추출을 행한 다음 -50 ~ -30 ℃에서 10 ~ 20시간 급속 동결하고, 0.1 ~ 0.5 토르의 압력에서 30 ~ 40시간 진공 건조한 다음 분쇄하여 본 발명에 의한 복합 추출물 분말을 수득한다.Meanwhile, the composite extract according to the present invention may be obtained by first mixing each herbal dry matter of a calculated ratio so as to finally be the above ratio, and then extracting them in a batch. To this end, a mixture of 1.0 parts by weight of dried sewage extract, 0.1 to 10 parts by weight of dried skin extract and 0.1 to 30 parts by weight of dried white hair root extract is prepared by a method such as cold water extraction, hot water extraction or solvent extraction according to a conventional method. After extraction, the mixture may be used as it is by filtration, concentrated to use, or lyophilized to be used as powder. For example, it can be manufactured by the following method. First, the sewage, skin and white hair roots, which have been selected and trimmed to an appropriate size, are mixed in accordance with the mixing ratio. 10-100 times the amount of aqueous alcohol solution was added to the mixture, extraction was performed at 70-100 ° C. for 4-8 hours, and then rapidly frozen at -50 ° -30 ° C. for 10-20 hours, and 30-40 at a pressure of 0.1-0.5 Torr. Drying in vacuo for time and then pulverizing yields the composite extract powder according to the present invention.
본 발명자들은 많은 실험과 검토 결과, 상기와 같은 함량비가 되어야 가장 우수한 생약 조성물이 얻어짐을 확인하였다.As a result of many experiments and studies, the inventors have confirmed that the best herbal composition is obtained only when the content ratio is as described above.
또한, 본 발명에 의한 복합 추출물은 아래 제조예 및 실시예에서 볼 수 있듯이, 세포 내 AMPK 활성을 증가시킴과 동시에 세포 내 포도당 흡수를 증가시켜 종래의 기존 생약 또는 시판 중인 비만 치료 및 억제용 합성 의약품에 비해 월등히 우수하고 안전한 효과를 나타낸다.In addition, the complex extract according to the present invention can be seen in the preparation examples and examples below, by increasing the cellular uptake of AMPK at the same time to increase the intracellular AMPK activity, a conventional conventional herbal medicine or commercial drugs for the treatment and inhibition of obesity It is much better and safer than that.
따라서, 본 발명의 복합 추출물은 의약품으로 제조 가능하다.Therefore, the complex extract of the present invention can be prepared as a pharmaceutical.
본 발명의 복합 추출물은 쥐, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직강 또는 정맥, 근육, 피하, 자궁내 경막 또는 뇌혈관내 주사에 의해 투여될 수 있다.The complex extract of the present invention can be administered to mammals such as mice, livestock, humans, etc. by various routes. All modes of administration can be expected, for example by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or cerebrovascular injections.
또한, 본 발명은 비만 및 대사증후군의 예방 및 치료효과를 나타내는 상기 조성물 및 식품학적으로 허용 가능한 식품보조 첨가제를 포함하는 건강기능식품을 제공한다. 복합 추출물을 첨가할 수 있는 식품으로는 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합제, 건강기능식품류 등이 있다.In addition, the present invention provides a health functional food comprising the composition and a food acceptable food supplement additive exhibiting a prophylactic and therapeutic effect of obesity and metabolic syndrome. Examples of the food to which the complex extract can be added include various foods, beverages, gums, teas, vitamin complexes, and health functional foods.
또한, 본 발명은 복합 추출물을 유효성분으로 함유하는 비만 및 대사증후군 개선용 건강식품을 포함한다. 상기 건강식품에는, 상기 복합 추출물 이외에 필요에 따라 다양한 보조 생약제, 비타민, 미네랄, 식이섬유 및 기타 의약용-식품용 보조제(예컨대, 부형제, 증강제, 코팅제 등) 등이 함유될 수 있을 것이다In addition, the present invention includes a health food for improving obesity and metabolic syndrome containing a complex extract as an active ingredient. In addition to the complex extract, the health food may contain various supplemental herbal medicines, vitamins, minerals, dietary fiber, and other medicinal-food supplements (eg, excipients, enhancers, coatings, etc.).
또한, 비만 및 대사증후군의 예방 및 치료를 목적으로 식품 또는 음료에 첨가될 수 있다. 이때, 식품 또는 음료 중의 상기 복합 추출물의 양은, 일반적으로 본 발명의 건강식품의 경우 전체 식품 중량의 0.0001 ~ 100 중량%, 바람직하게는 80 중량% 이하로 가할 수 있으며, 건강 음료 조성물에는 100 ml를 기준으로 0.0001 ~ 10 g, 바람직하게는 5.0 g 이하의 비율로 가할 수 있다.It may also be added to foods or beverages for the purpose of preventing and treating obesity and metabolic syndrome. At this time, the amount of the complex extract in the food or beverage, in the case of the health food of the present invention can generally be added to 0.0001 to 100% by weight, preferably 80% by weight or less of the total food weight, 100 ml to the health beverage composition It can be added in a ratio of 0.0001 to 10 g, preferably 5.0 g or less as a reference.
이하, 본 발명을 실시예 및 적용예에서 보다 상세하게 설명한다. 하기 실시예는 본 발명을 보다 상세히 설명하고자하는 예시적인 것일 뿐 이에 의해 본 발명의 기술적 사상의 본질이 변하거나 범위가 축소되는 것은 아니다. 하기 실시예에서 제시되지 않은 여러 가지 실시예 및 적용예들이 가능함은 당업자에게 있어 당연할 것이다.Hereinafter, the present invention will be described in more detail in Examples and Application Examples. The following examples are merely illustrative of the present invention in detail, and thus, the nature of the technical idea of the present invention is not changed or reduced in scope. It will be apparent to those skilled in the art that various embodiments and applications not shown in the following examples are possible.
제조예 : 복합 추출물의 제조Preparation Example: Preparation of Complex Extract
(1) 미리 선별하여 적절한 크기로 절단한 각각 1 Kg의 건조 오수유, 백모근 및 청피에 10배 중량의 70% 에탄올 수용액을 혼합한 다음 가열하여 85 ℃에서 6시간 동안 1차 추출을 실시하였다. 이후 여과하여 1차 여과액은 따로 모으고 여과된 생약에 추가로 10배 중량의 70% 에탄올 수용액을 혼합한 다음 가열하여 85 ℃에서 6시간 동안 2차 추출을 실시하였다. 이후 여과하여 2차 여과액을 수득한 후 1차 여과액과 함께 영하 70 ℃에서 12시간 급속 동결하고, 0.23토르 이하의 압력 하에서 36시간 이상 진공 건조한 다음 분쇄하여 각각의 건조분말을 수득하였다.(1) A 10-fold weight of 70% aqueous ethanol solution was mixed with 1 Kg of dried sewage, white hair root and skin skin, which were previously screened and cut into appropriate sizes, and then heated and subjected to primary extraction at 85 ° C. for 6 hours. Thereafter, the primary filtrate was collected separately by filtration, and the filtered crude drug was further mixed with an aqueous 10% weight 70% ethanol aqueous solution, followed by heating to carry out secondary extraction at 85 ° C. for 6 hours. Subsequently, the resultant was filtered to obtain a secondary filtrate, followed by rapid freezing with the primary filtrate at 70 ° C. for 12 hours, vacuum drying for at least 36 hours under a pressure of 0.23 Torr or less, and then grinding to obtain respective dry powders.
수득된 오수유, 백모근 및 청피 추출 건조분말을 오수유 추출물 1 중량부에 대하여 백모근 추출물 1 중량부, 청피 추출물 3 중량부로 혼합하여 본 발명의 복합 추출 분말(복합 추출물)을 수득하였다.The obtained sewage oil, white hair root and dermis extract powder was mixed with 1 part by weight of white hair root extract and 3 parts by weight of dermis extract based on 1 part by weight of sewage extract to obtain a composite extract powder (composite extract) of the present invention.
(2) 미리 상기 각 생약의 추출효율을 분석한 다음 최종 추출물에서 각 건조 생약을 혼합하였다. 즉, 미리 선별하여 적절한 크기로 절단되어 있는 건조 오수유, 백모근 및 청피를 혼합하고 10배 중량의 70% 에탄올 수용액을 부은 다음 가열하여 85 ℃에서 6시간 동안 1차 추출을 실시하였다. 이후 여과하여 1차 여과액은 따로 모으고 여과된 생약에 추가로 10배 중량의 70% 에탄올 수용액을 혼합한 다음 가열하여 85 ℃에서 6시간 동안 2차 추출을 실시하였다. 이후 여과하여 2차 여과액을 수득한 후 1차 여과액과 함께 영하 70 ℃에서 12시간 급속 동결하고, 0.23토르 이하의 압력 하에서 36시간 이상 진공 건조한 다음 분쇄하여 각각의 건조분말을 수득하였다.(2) The extraction efficiency of each herbal medicine was analyzed beforehand, and then each dry herbal medicine was mixed in the final extract. That is, dry sewage oil, white hair root and green skin, which were previously screened and cut to an appropriate size, were mixed, a 10-fold weight of 70% ethanol aqueous solution was poured, and heated to carry out primary extraction at 85 ° C. for 6 hours. Thereafter, the primary filtrate was collected separately by filtration, and the filtered crude drug was further mixed with an aqueous 10% weight 70% ethanol aqueous solution, followed by heating to carry out secondary extraction at 85 ° C. for 6 hours. Subsequently, the resultant was filtered to obtain a secondary filtrate, followed by rapid freezing with the primary filtrate at 70 ° C. for 12 hours, vacuum drying for at least 36 hours under a pressure of 0.23 Torr or less, and then grinding to obtain respective dry powders.
(3) 여러 지표 성분의 분석 결과 및 in vitro, in vivo 실험 결과, 상기 2가지 방법으로 제조된 본 발명에 의한 생약 조성물은 동일물로 확인되었다. 따라서, 이하 실험에서는 2가지 방법에 의한 것을 구별하지 않고 실시예에 이용하였다.(3) As a result of analysis of various indicator components and in vitro and in vivo experiments, the herbal compositions according to the present invention prepared by the two methods were identified as the same. Therefore, in the following experiment, the thing by two methods was used for an Example without distinguishing.
실시예 1 : 복합 추출물의 AMPK 효소 활성 측정Example 1 Determination of AMPK Enzyme Activity of Complex Extracts
세포에 상기 제조예의 복합 추출물을 처리한 후에 시간에 따른 AMPK 활성을 조사하였다. AMPK 효소의 활성화는 포도당 흡수를 증가시키고, 지방산 합성을 억제하며 지방산 산화 촉진을 유도하므로 본 실험은 본 발명의 복합 추출물의 비만 및 대사증후군의 예방 또는 치료 가능성을 확인해 볼 수 있다. The cells were treated with the composite extract of the preparation, and then AMPK activity was examined over time. Activation of the AMPK enzyme increases glucose uptake, inhibits fatty acid synthesis, and induces fatty acid oxidation, and thus this experiment can confirm the prophylaxis or treatment of obesity and metabolic syndrome of the complex extract of the present invention.
도 1에서 확인할 수 있듯이, 본 발명의 복합 추출물에서 양성대조군인 AICAR와 비교해 볼 때 AMPK 효소 발현을 크게 증가시킴을 확인할 수 있다.As can be seen in Figure 1, in the composite extract of the present invention can be seen to significantly increase the AMPK enzyme expression compared to the positive control AICAR.
실시예 2 : 복합 추출물의 동물모델에서 체중 증가에 미치는 효과 검색 및 지방축적과 혈장 내 지방과 당에 미치는 효능 조사Example 2 Screening of the Effects of Complex Extracts on Weight Gain in Animal Models and Their Effects on Fat Accumulation and Plasma Fat and Sugar
(1) 실험동물은 20 ~ 25 g의 6주령 C57BL/6 마우스를 중앙실험동물에서 구입하여 동물실에서 자유로이 먹이와 물을 섭취하게 하고 일주일 후에 다음과 같이 4군으로 나누어 6주 동안 정상식이(Regular Diet, RD)와 45% 고지방식이(High Fat Diet, HFD)를 투여하였다. 6주후 마우스를 무게에 따라 다시 분리하여 HFD의 경우 평균 36 ~ 37 g이 되도록 케이지에 5마리씩 넣고 한 그룹에 케이지 2개 (10마리씩)로 나누어 본 실험을 착수하였다. 정상식이의 무게는 평균 27 g이었다. 고지방식이 마우스에 본 발명의 복합 추출물을 매일 10 주간 경구 투여하며 마우스의 체중변화와 섭취량을 관찰하였다.(1) Experimental animals purchased 20 to 25 g of 6-week-old C57BL / 6 mice from the central laboratory animals, and allowed them to freely feed and water in the animal room, and after one week, divided them into four groups as follows. Regular Diet (RD) and 45% High Fat Diet (HFD). Six weeks later, the mice were separated by weight, and 5 mice were placed in cages so that an average of 36 to 37 g of HFD was put into two cages (10 mice). The average diet weight was 27 g. High-fat diet mice were orally administered with the complex extract of the present invention for 10 weeks every day to observe the weight change and intake of the mice.
RD: 정상식이를 공급한 정상식이 대조군, HFD: 45% 고지방식이를 공급한 고지방식이 대조군, HFD + 복합 추출물: 고지방식이+복합 추출물(500 mg/kg), HFD + 시부트라민: 고지방식이 + 시부트라민(2 mg/kg)으로 양성대조군으로 사용.RD: normal diet control diet fed a normal diet, HFD: high fat diet control group fed 45% high fat diet, HFD + complex extract: high fat diet + complex extract (500 mg / kg), HFD + sibutramine: high fat diet Used as a positive control with this + sibutramine (2 mg / kg).
(2) 대사증후군(metabolic syndrome)의 치료 효과를 알아보기 위해 고지방식이를 6주간 하여 비만이 유도된 마우스(diet induced obesity)에 본 발명의 복합 추출물을 500 mg/kg의 용량으로 매일 일정한 시간에 경구로 고지방식이와 함께 10주간 투여하였다. 1주에 두 번 체중을 측정하고 이틀에 한번 먹이 섭취량을 측정하였다. 10주 후에 마우스의 안구에서 혈액을 채취하는 방법으로 죽인 후 혈액을 모으고 마우스의 각 조직을 적출하여 무게를 측정하고 분석실험에 사용하였다. (2) To determine the therapeutic effect of metabolic syndrome (medibolic syndrome) for 6 weeks in a high fat diet mouse fat (diet induced obesity) in the mouse (diet induced obesity) of the compound extract of the present invention at a constant time of 500 mg / kg daily Was administered orally with high fat diet for 10 weeks. Body weights were measured twice a week and food intake was measured once every two days. Ten weeks later, blood was collected from the eyeballs of the mice, and the blood was collected, each tissue of the mouse was extracted, weighed, and used in the assay.
(3) 시료 채취 및 혈액지표 분석(3) Sampling and Blood Indicator Analysis
마지막 희생 시에 안와정맥에서 혈액을 채취하고 각 조직을 적출하여 무게를 재고 분석실험에 사용하였다. 혈액 지표 분석을 위하여 혈액채취는 전일(8-10 시간) 절식 후에 안와 정맥에서 얻은 전혈을 1,500 rpm에서 30분간 원심분리한 후에 혈장을 사용하였고 아산셋트 중성지방(triglycerides), 포도당(glucose), 콜레스테롤(cholesterol) 킷트를 구입하여 ELISA 리더로 측정하였다.At the last sacrifice, blood was collected from the orbital vein, and each tissue was extracted and weighed for analysis. For blood index analysis, blood collection was performed using plasma after centrifugation of whole blood obtained from the orbital vein for 30 minutes at 1,500 rpm after fasting on the previous day (8-10 hours), and astaxet triglycerides, glucose and cholesterol. (cholesterol) kits were purchased and measured with an ELISA reader.
(4) 실험 결과(4) experimental results
① 체중 변화① weight change
도 2는 10주 동안 각 그룹간 체중 변화양상을 비교한 결과이다. 도 2에서 보듯이 고지방 식이로 6주간 비만증을 유도한 후에 시료를 투여하면 마우스의 체중이 2주까지 일시적으로 감소하는 현상을 보였다. 이는 경구 투여에 의한 마우스의 스트레스 때문인 것으로 사료되었다. 3주째부터 체중이 다시 증가하고 5주째부터 유의하게 복합 추출물을 500 mg/kg으로 투여한 군에서 대조군과 비교시 유의한 체중 억제 효과가 보이기 시작하며 이러한 효과는 10주까지 지속되었다. 10주째 체중을 그룹 간 비교해보면, 일반식이 투여군(RD, 29.5± 1.2)에 비해 고지방식이 투여군(HFD)의 체중은 46.5± 1.5로 증가한 반면, 복합 추출물 투여군은 각각 500 mg/kg 용량에서 41.3± 1.7을 나타내었다. 한편, 양성대조군 대조 약물인 시부트라민 투여군의 체중은 43.3± 1.7로 고지방식이에 비해 감소하였다. 본 실험 결과 본 발명의 복합 추출물은 양성대조군보다 체중 억제에 우수한 활성을 가진 것으로 나타났다. Figure 2 is the result of comparing the weight change pattern between each group for 10 weeks. As shown in FIG. 2, when the sample was administered after inducing obesity for 6 weeks with a high fat diet, the body weight of the mice was temporarily decreased until 2 weeks. This may be due to the stress of the mouse by oral administration. Body weight gained again from 3 weeks, and significantly increased weight suppression effect in group administered 500 mg / kg of complex extract at 5 weeks compared with control group. This effect lasted up to 10 weeks. Compared with the groups at 10 weeks, the body weight of the high-fat diet group (HFD) increased to 46.5 ± 1.5 compared to the normal diet group (RD, 29.5 ± 1.2), whereas the complex extract group was 41.3 at the 500 mg / kg dose, respectively. ± 1.7. Meanwhile, the weight of the sibutramine-treated group, which was a positive control group, was 43.3 ± 1.7, which was lower than that of the high-fat diet. As a result of the present experiment, the complex extract of the present invention was found to have better activity in weight inhibition than the positive control group.
② 조직무게 분석② Organization weight analysis
다음 표 1은 10주 후 마우스의 복부지방(Adipose tissue), 간(liver), 신장(kidney), 비장(spleen), 뇌(brain), 뒷다리 근육(muscle) 등 조직을 적출하여 이중 지방, 간, 신장, 비장 무게를 측정한 결과이다. In Table 1, 10 weeks after the abdominal fat (liver), liver (liver), kidney (kidney), spleen (spleen), brain (brain), muscles (hind muscles), etc. tissues were extracted to double fat, liver This is a result of measuring the weight of the kidney, height and spleen.
정상식이(RD)에 비해 고지방식이 대조군(HFD)의 경우 복부지방이 크게 증가하였고 간과 신장 무게도 유의하게 증가하였으며, 그 외의 장기들의 무게는 큰 변화가 없었다. 지방조직의 경우 고지방식이 그룹이 4.5± 0.5인데 반해 복합 추출물을 투여한 경우 각각 3.2± 0.4로 평균 30% 가량 복부지방 감소 효과를 나타내었다.Compared to the normal diet (RD), the high fat diet (HFD) significantly increased abdominal fat, significantly increased liver and kidney weights, and the weight of other organs was not significantly changed. In the case of adipose tissue, the high-fat diet group was 4.5 ± 0.5, whereas the combined extracts showed 3.2 ± 0.4 of abdominal fat reduction on average by 30%.
표 1
Figure PCTKR2009001542-appb-I000001
Table 1
Figure PCTKR2009001542-appb-I000001
③ 혈액 분석③ blood analysis
다음 표 2는 식이로 유도된 비만 쥐(Diet-induced obesity)에 10주 동안 복합 추출물을 경구 투여 후 밤새(8시간) 절식 후 안와정맥에서 얻은 마우스의 혈액을 원심분리하여 혈장을 모으고 중성지질, 혈당 및 콜레스테롤을 분석한 것이다. 중성지질의 경우 고지방식이 대조군(HFD)은 142.8± 11.4 mg/㎗로 일반식이 투여군 (RD)에 비해 크게 증가한 반면, 복합 추출물 투여군은 500 mg/kg 용량에서 123.4± 12.2 로 고지방식이 대조군과 비교 시 중성지질 감소효과를 나타내었다. 혈당의 경우, 고지방식이 대조군(HFD)은 255.6± 30.1 mg/㎗로 일반식이 투여군(RD)에 비해 크게 증가한 반면 복합 추출물 투여군은 500 mg/kg 용량에서 204.1± 14.5 mg/㎗을 나타내어 고지방식이 대조군과 비교하여 혈당 감소효과를 나타내었다. 중성지질과 혈당의 경우는 체중과 비슷하게 고지방식이 대조군에 비해 효능이 있음을 보였으나 콜레스테롤의 경우는 전체적으로 체중과 상관관계가 적어 시료들이 콜레스테롤에 미치는 효과는 상대적으로 중요하지 않은 것으로 사료된다.The following Table 2 shows the plasma-derived plasma of the mice obtained from orbital vein after fasting overnight (8 hours) after oral administration of the complex extract to diet-induced obesity for 10 weeks. Blood glucose and cholesterol were analyzed. In the case of triglycerides, the high-fat diet control group (HFD) increased to 142.8 ± 11.4 mg / dL compared to the general diet group (RD), whereas the complex extract group was 123.4 ± 12.2 at 500 mg / kg dose compared to the high-fat diet control group. Neutral lipid reduction effect was shown. In the case of blood glucose, the high-fat diet control group (HFD) increased 255.6 ± 30.1 mg / dL compared to the general diet group (RD), whereas the complex extract group showed 204.1 ± 14.5 mg / dL at 500 mg / kg dose. Compared with this control group, the blood glucose reduction effect was shown. In the case of triglyceride and blood glucose, the high fat diet was more effective than the control group, but the cholesterol was less correlated with the body weight.
표 2
Figure PCTKR2009001542-appb-I000002
TABLE 2
Figure PCTKR2009001542-appb-I000002
이에 의해, 본 발명에 의한 복합 추출물은 체중 감소 효과뿐만 아니라 중성지질과 혈당 수치의 감소에도 유용하게 사용될 수 있음을 확인할 수 있었다.As a result, the composite extract according to the present invention was found to be useful for the reduction of neutral lipid and blood glucose levels as well as the weight loss effect.
실시예 3 : 복합 추출물의 근세포 및 지방세포에서 포도당 흡수능 조사Example 3 Investigation of Glucose Absorption Capacity in Myofas and Adipocytes of the Complex Extract
(1) 본 발명에 의한 복합 추출물을 C2C12 근세포와 3T3 L1 지방세포에서 포도당 흡수 효능을 조사하여 비만 및 당뇨 치료제로서 개발 가능성을 조사함.(1) Investigation of the glucose uptake effect of C2C12 myocytes and 3T3 L1 adipocytes in the complex extract according to the present invention to investigate the possibility of development as a therapeutic agent for obesity and diabetes.
(2) C2C12 근세포에서 조성물의 포도당 흡수능 증가 효과(2) Effect of Increasing Glucose Uptake of Composition on C2C12 Myocytes
본 발명의 복합 추출물을 물에 녹여 세포에 다른 농도로 24시간 처리 후 MTT 분석을 수행하여 세포독성(cytotoxic) 하지 않은 최고 농도를 선택하고 C2C12 근세포에서 포도당 흡수능을 조사하였다(도 3). 본 발명의 복합 추출물은 100 ㎍/mL 용량에서 인슐린 보다 우수하게 포도당 흡수를 증가시키는 것으로 관찰되어 포도당 흡수에 효과가 좋은 것으로 사료된다. The complex extract of the present invention was dissolved in water and treated with different concentrations of cells for 24 hours, followed by MTT analysis to select the highest cytotoxicity (cytotoxic) concentration and glucose absorption ability in C2C12 myocytes (Fig. 3). The complex extract of the present invention was observed to increase glucose uptake better than insulin at a 100 μg / mL dose, which is considered to be effective for glucose uptake.
(3) 3T3 L1 지방세포에서 조성물의 포도당 흡수 효과(3) Glucose uptake effect of composition in 3T3 L1 adipocytes
본 발명의 복합 추출물을 물에 녹여 세포독성(cytotoxicity)이 적은 농도에서 3T3L1 지방세포(adipocytes)를 사용하여 포도당 흡수에 대한 효과를 조사하였다(도 4). 본 발명의 복합 추출물이 100 nM 인슐린과 유사한 정도로 포도당 흡수를 증가시키는 것으로 관찰되어 포도당 흡수 효능이 우수한 것으로 나타났다.The composite extract of the present invention was dissolved in water to investigate the effect on glucose uptake using 3T3L1 adipocytes at low concentrations of cytotoxicity (FIG. 4). The complex extract of the present invention was observed to increase glucose uptake to a similar extent to 100 nM insulin, indicating a good glucose uptake effect.
결론적으로, 본 발명에 의한 복합 추출물은 동물실험을 통해 체중 증가 억제 및 중성지질과 혈당 수치의 개선 효과를 확인하였으며 in vitro 시험을 통해 비만 및 대사증후군 예방 또는 치료 관련 바이오마커인 AMPK 효소 활성을 증진시키는 효과를 입증하였으며 근세포 및 지방세포에서의 포도당 흡수능을 증가시킴을 확인하였다. In conclusion, the composite extract according to the present invention confirmed the effect of inhibiting weight gain and improving neutral lipid and blood glucose levels through animal experiments and enhancing the activity of AMPK enzyme, a biomarker related to the prevention or treatment of obesity and metabolic syndrome, through in vitro tests. It was confirmed that the effect of increasing the glucose uptake capacity in myocytes and adipocytes.
이에 의해, 본 발명에 의한 복합 추출물은 비만 및 대사증후군과 연관된 질병의 치료 및 예방에 유용하게 적용될 수 있음을 확인할 수 있었다.Thereby, the composite extract according to the present invention was confirmed that it can be usefully applied to the treatment and prevention of diseases associated with obesity and metabolic syndrome.
제제예 1: 주사제의 제조Formulation Example 1 Preparation of Injection
제조예의 (1) 복합 추출물..................100 ㎎(1) Complex extract of Preparation Example .................. 100 mg
pH 조절제...................................적량pH adjuster ...
상기의 성분을 혼합하고 통상의 방법으로 제조한 후, 2 ㎖ 용량의 앰플에 충전하고 멸균하여 주사제를 제조하였다.The above ingredients were mixed and prepared in a conventional manner, and then injected into a 2 ml ampoule and sterilized to prepare an injection.
제제예 2: 정제의 제조Formulation Example 2: Preparation of Tablet
제조예의 (1) 복합 추출물................... 50 ㎎(1) Complex Extract of Preparation Example ......................................... 50 mg
유당........................................125 ㎎Lactose ............... 125 mg
미결정 셀룰로오즈............................75 ㎎Microcrystalline cellulose ... 75 mg
스테아린산 마그네슘.........................적량Magnesium Stearate ...............
상기의 성분을 혼합하고 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조하였다.The tablets were prepared by mixing the above components and tableting according to a conventional method for producing tablets.
제제예 3: 캡슐제의 제조Formulation Example 3 Preparation of Capsule
제조예의 (1) 복합 추출물..................100 ㎎(1) Complex extract of Preparation Example .................. 100 mg
유당.......................................125 ㎎Lactose ............... 125 mg
전분.......................................125 ㎎Starch ............... 125 mg
탈크........................................적량Talc ..............................
스테아린산 마그네슘.........................적량Magnesium Stearate ...............
상기의 성분을 혼합하고 통상의 캡슐제의 제조방법에 따라서 캡슐에 충전하여 캡슐제를 제조하였다.The capsules were prepared by mixing the above components and filling the capsules according to a conventional method for preparing capsules.
제제예 4: 액제의 제조Formulation Example 4 Preparation of Liquid
제조예의 (1) 복합 추출물....................1000 ㎎(1) Complex extract of preparation example ..... 1000 mg
분당.........................................20 gMin .......................................... 20 g
이성화당.....................................20 gIsomerized sugar ......................................... 20 g
레몬향......................................적량Lemon Flavor ......................
정제수를 가하여 전체 1000 ㎖로 맞추었다. 통상의 액제의 제조방법에 따라 상기의 성분을 혼합하여 액제를 제조하였다.Purified water was added to adjust the total volume to 1000 ml. According to the conventional method for preparing a liquid, the above components were mixed to prepare a liquid.
제제예 5: 건강기능식품의 제조Formulation Example 5 Preparation of Health Functional Food
제조예의 (1) 복합 추출물 ................................100 ㎎(1) Complex extract of preparation example ......................... 100 mg
비타민 A (레티닐 팔미틴산염으로서 0.275 mg) ............. 500 IUVitamin A (0.275 mg as Retinyl Palmitate) ............. 500 IU
DL-알파-토코페롤..........................................20 ㎎DL-alpha-tocopherol ......................................... 20 mg
비타민 B1 질산염.........................................1.5 ㎎Vitamin B1 Nitrate ......................................... 1.5 mg
비타민 B2................................................1.8 ㎎Vitamin B2 ..................... 1.8 mg
피리독신염산염.............................................2 ㎎Pyridoxine Hydrochloride ............................................... 2 mg
비타민 B12.................................................2 ㎍Vitamin B12 ... .2 μg
비오틴...................................................0.1 ㎎Biotin ... ..0.1 mg
니코틴산아미드.............................................5 ㎎Nicotinic acid amide ......................................... 5 mg
엽산.....................................................0.1 ㎎Folic Acid ... .... 0.1 mg
판토텐산칼슘...............................................5 ㎎Calcium Pantothenate ......................................................... 5 Mg
비타민 C..................................................50 ㎎Vitamin C ... ..50 mg
글리세로인삼칼슘(칼슘으로서 4.76 mg).......................25 ㎎Glycerin ginseng calcium (4.76 mg as calcium) ... 25 mg
황산철(철로서 5.0 mg)...................................15.45 ㎎Iron sulphate (5.0 mg as iron) ... 15.45 mg
황산아연(아연으로서 1.0 mg)..............................2.74 ㎎Zinc sulfate (1.0 mg as zinc) ........................ 2.74 mg
황산동(동으로서 0.5 mg).................................1.256 ㎎Copper sulfate (0.5 mg as copper) ..
황산망간(망간으로서 0.5 mg)..............................1.54 ㎎Manganese sulfate (0.5 mg as manganese) ........................ 1.54 mg
상기 본 발명의 복합 추출물과 비타민 및 무기질 등의 조성비는 비교적 건강기능식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강기능식품 제조방법에 따라 상기의 성분을 혼합한 다음 과립을 제조하고, 통상의 방법에 따라 건강기능식품 조성물 제조에 사용할 수 있다.Although the composition ratio of the complex extract of the present invention, vitamins and minerals, etc. are mixed with the components suitable for the health functional food in a preferred embodiment, the composition ratio may be arbitrarily modified, and according to the conventional health functional food manufacturing method After mixing the above components to prepare a granule, it can be used for preparing a nutraceutical composition according to a conventional method.
제제예 6: 건강 음료의 제조Formulation Example 6 Preparation of Healthy Drinks
제조예의 (1) 복합 추출물.................500 ㎎(1) Complex extract of the preparation example ....... 500 mg
구연산....................................1000 ㎎Citric Acid ......................................... 1000 mg
올리고당....................................20 ㎎Oligosaccharide ... 20 mg
타우린.....................................100 ㎎Taurine ........................... 100 mg
정제수를 가하여 전체 900 ㎖로 맞추었다. 통상의 건강음료 제조방법에 따라 제조한다.Purified water was added to adjust the total volume to 900 ml. It is prepared according to a conventional healthy beverage manufacturing method.
상기 조성비는 비교적 기호 음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 수요계층, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.Although the composition ratio is a composition that is relatively suitable for a preferred beverage in a preferred embodiment, the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.

Claims (5)

  1. 오수유(Evodiamine Fructus), 청피(Citrus Unshiu Markovich) 및 백모근(Imperatae Rhizoma)의 복합 추출물을 유효성분으로 함유하는 것을 특징으로 하는 비만과 대사증후군의 예방 및 치료용 조성물.A composition for the prevention and treatment of obesity and metabolic syndrome, comprising a complex extract of Evodiamine Fructus , Citrus Unshiu Markovich and White Root (Imperatae Rhizoma) as an active ingredient.
  2. 제 1 항에 있어서, 상기 복합 추출물은 오수유 추출물 1.0 중량부를 기준으로, 청피 추출물 0.1 ~ 10 중량부 및 백모근 추출물 0.1 ~ 30 중량부를 혼합한 것임을 특징으로 하는 비만과 대사증후군의 예방 및 치료용 조성물.According to claim 1, wherein the complex extract is based on 1.0 parts by weight of sewage oil extract, 0.1 ~ 10 parts by weight of the extract and 0.1 ~ 30 parts by weight of white hair root extract, characterized in that the composition for the prevention and treatment of obesity and metabolic syndrome.
  3. 제 1 항에 있어서, 세포 내 AMPK 활성 증진 및 포도당 흡수능 증가에 따른 비만과 대사증후군의 예방 및 치료 효과를 갖는 것을 특징으로 하는 조성물.The composition according to claim 1, wherein the composition has a prophylactic and therapeutic effect on obesity and metabolic syndrome according to the enhancement of intracellular AMPK activity and glucose uptake.
  4. 오수유(Evodiamine Fructus), 청피(Citrus Unshiu Markovich) 및 백모근(Imperatae Rhizoma)의 복합 추출물을 유효성분으로 함유하는 것을 특징으로 하는 비만과 대사증후군 개선용 건강식품.Health food for improving obesity and metabolic syndrome, characterized in that it contains a complex extract of Evodiamine Fructus , Citrus Unshiu Markovich, and White Root (Imperatae Rhizoma) as an active ingredient.
  5. 제 4 항에 있어서, 상기 복합 추출물은 오수유 추출물 1.0 중량부를 기준으로, 청피 추출물 0.1 ~ 10 중량부 및 백모근 추출물 0.1 ~ 30 중량부를 혼합한 것임을 특징으로 하는 건강식품.According to claim 4, wherein the complex extract is based on 1.0 parts by weight of sewage oil extract, health food, characterized in that the mixture 0.1 ~ 10 parts by weight and 0.1 ~ 30 parts by weight of white hair root extract.
PCT/KR2009/001542 2008-04-29 2009-03-26 Pharmaceutical composition using herbal extract for prevention and treatment of obesity and metabolic disorders WO2009134010A2 (en)

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WO2014208799A1 (en) * 2013-06-28 2014-12-31 재단법인 아산사회복지재단 Composition for preventing or treating fatty liver comprising evodiae fructus extract and alkaloid compound isolated therefrom as active ingredients
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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997047209A1 (en) * 1996-06-12 1997-12-18 Kyowa Hakko Kogyo Co., Ltd. Lipid metabolism ameliorants
KR19990011833A (en) * 1997-07-25 1999-02-18 김이현 Pharmaceutical composition for the treatment of gynecological diseases and women's obesity and preparation method of the same
KR20050078601A (en) * 2004-02-02 2005-08-05 주식회사 유유 New herbal composition for treatment and prevention of obesity
WO2005072757A1 (en) * 2004-02-02 2005-08-11 Yuyu Inc. Imperatae rhizoma extract for treatment and prevention of obesity

Family Cites Families (1)

* Cited by examiner, † Cited by third party
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US20070224299A1 (en) * 2006-03-23 2007-09-27 Talbot Shawn M Weight loss with citrus flavonoids

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997047209A1 (en) * 1996-06-12 1997-12-18 Kyowa Hakko Kogyo Co., Ltd. Lipid metabolism ameliorants
KR19990011833A (en) * 1997-07-25 1999-02-18 김이현 Pharmaceutical composition for the treatment of gynecological diseases and women's obesity and preparation method of the same
KR20050078601A (en) * 2004-02-02 2005-08-05 주식회사 유유 New herbal composition for treatment and prevention of obesity
WO2005072757A1 (en) * 2004-02-02 2005-08-11 Yuyu Inc. Imperatae rhizoma extract for treatment and prevention of obesity

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