KR20210127290A - Composition for preventing, improving or treating obesity - Google Patents
Composition for preventing, improving or treating obesity Download PDFInfo
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- KR20210127290A KR20210127290A KR1020200044729A KR20200044729A KR20210127290A KR 20210127290 A KR20210127290 A KR 20210127290A KR 1020200044729 A KR1020200044729 A KR 1020200044729A KR 20200044729 A KR20200044729 A KR 20200044729A KR 20210127290 A KR20210127290 A KR 20210127290A
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Abstract
Description
본 발명은 천연 추출물을 유효성분으로 포함하는, 비만 치료용 조성물에 관한 것이다. The present invention relates to a composition for treating obesity, comprising a natural extract as an active ingredient.
비만은 심혈관계질환, 고혈압 및 Type II 당뇨병과 같은 다양한 치사성 대사 질환의 원인으로, 비만시 지방세포는 장기형 에너지원으로 지질을 저장할 뿐만 아니라 지방세포 및 비지방세포의 대사와 염증에 관여하는 다양한 adipokine을 분비하여 만성 염증을 유발하고, 인슐린 저항성과 같은 관련 대사성 질환을 야기한다. 최근에 들어, 전세계적으로 고열량의 식이와 함께 운동 부족으로 인한 비만으로 Type II 당뇨병으로 알려진 대사 증후군의 발병 증가가 일어나고 있으며, 2025년에는 대사성 증후군 환자가 현재의 2배 즉, 대략 3억 명에 육박할 것으로 예측되고 있다. 복부 비만과 같이 비정상적인 국소 지방 축적에 의한 비만은 고혈압, 고지혈증, 혈액 응고 장애, 혈관 염증, 비정상적인 인슐린 분비증가를 동반한 인슐린 저항성과 같은 동맥 죽종상 병증을 심각하게 유발할 수 있는 다양한 원인을 제공하고, 최종적으로 치사적인 심혈관계 질환에 대한 유병율 증가의 요인이 된다. 지방산의 과다한 섭취는 다양한 조직에서 triglyceride (TG)의 축적을 유발하여, 지방분해의 증가를 수반함과 동시에 혈중 순환 지방산의 증가를 초래하고, 지방세포에서 인슐린 저항성을 유발하여, 결과적으로 근육, 췌장 및 간과 같은 비지방세포에서 지방 축적을 일으킨다. 지방세포에서 인슐린 저항성이 유발되면, 잉여의 지방산 결합 및 운반 단백질이 비지방세포의 지방산 흡수 증가를 초래하고, 특히 근육세포의 경우 인슐린 매개성 포도당 대사에 악영향을 미치며, 이와 동시에 췌장에서는, 유리 지방산에 장기간 노출되어, 소위 지방독성 (lipotoxicity) 기전에 의해 인슐린 분비 장애가 초래되는 악순환이 반복된다. 이 경우, 간에서도 고농도의 유리지방산이 축적되어, 인슐린에 대한 저항성이 초래되고, 다량의 포도당을 간에서부터 유리시키기 시작한다. 간세포 내 TG 의 축적은 또한 비알코올성 간 지방병증(non-alcoholic fatty liver disease; NAFLD)을 유발하며, 포도당 대사를 주로 담당하는 간 세포의 지방축적을 유발 하여, 지방간염(steatohepatitis)을 이차적으로 일으키고, 최종적으로 간세포의 괴사에 의한 섬유화를 유발한다. 따라서 간세포의 지방 합성과 분해의 균형은 대사 증후군 시 초래되는 인슐린 저항성과 NAFLD의 유발을 억제할 수 있는 중요한 치료 표적이 되어왔다. Obesity is the cause of various lethal metabolic diseases such as cardiovascular disease, hypertension and Type II diabetes. It secretes adipokine, causing chronic inflammation and related metabolic diseases such as insulin resistance. Recently, the incidence of metabolic syndrome, also known as Type II diabetes, is increasing worldwide due to obesity due to lack of exercise along with a high-calorie diet. is expected to approach. Obesity caused by abnormal local fat accumulation, such as abdominal obesity, provides various causes that can seriously cause arterial atheromatosis, such as high blood pressure, hyperlipidemia, blood clotting disorders, vascular inflammation, and insulin resistance with abnormal increase in insulin secretion. Ultimately, it becomes a factor in increasing the prevalence of fatal cardiovascular disease. Excessive intake of fatty acids causes the accumulation of triglyceride (TG) in various tissues, accompanied by an increase in lipolysis and at the same time an increase in circulating fatty acids in the blood, and insulin resistance in adipocytes, resulting in muscle and pancreas. and fat accumulation in non-adipocytes such as the liver. When insulin resistance is induced in adipocytes, excess fatty acid binding and carrier proteins lead to increased fatty acid uptake by non-adipocytes, particularly in the case of muscle cells, which adversely affects insulin-mediated glucose metabolism, while at the same time, in the pancreas, free fatty acids Long-term exposure to lipotoxicity repeats a vicious cycle in which insulin secretion is impaired by the so-called lipotoxicity mechanism. In this case, a high concentration of free fatty acids is also accumulated in the liver, resulting in resistance to insulin, and a large amount of glucose begins to be liberated from the liver. Accumulation of TG in hepatocytes also causes non-alcoholic fatty liver disease (NAFLD), and causes fat accumulation in hepatocytes mainly responsible for glucose metabolism, resulting in secondary steatohepatitis. , which ultimately causes fibrosis by necrosis of hepatocytes. Therefore, the balance of hepatocyte fat synthesis and decomposition has become an important therapeutic target that can inhibit the induction of insulin resistance and NAFLD caused during metabolic syndrome.
현재 다양한 대사증후군 치료제들이 개발되어 있으며, 근래에 들어 적절한 혈당 조절과 함께 당뇨 및 관련 합병증의 주요 병인으로 지목되고 있는 산화 스트레스의 적절한 제어가 당뇨 치료에 가장 핵심적인 방법으로 부각됨에 따라, 부작용이 낮고 보다 효과적인 α-glucosidase 차단제 또는 항산화제들의 개발이 시도되고 있다.Currently, various metabolic syndrome treatments have been developed, and in recent years, proper control of oxidative stress, which is pointed out as a major cause of diabetes and related complications, along with proper blood sugar control, has emerged as the most essential method for diabetes treatment, so it has low side effects and low side effects. The development of more effective α-glucosidase blockers or antioxidants is being attempted.
이들 중 metformin은 대포적인 경구용 biguanide 계열 항당뇨 치 료제로 AMPK activator로 잘 알려져 있다. Metformin은 신장 기능이 정상적인 과 체중 및 비만 type II 당뇨병 환자를 치료하기 위해 가장 먼저 사용되는 약물이며, 당뇨병에 의한 심각한 부작용 중 하나인 심혈관계 질환 발병을 낮출 수 있고, 지방의 소화 분해에 직접 관여하는 췌장의 효소원 과립의 분비 및 간 당대사 관련 효소의 활성을 조절할 수 있는 유일한 약물로 알려져 있다. Metformin 은 현재 전세계적으로 가장 많이 처방되는 당뇨치료제로 알려져 있다. Metformin 은 주로 type II 당뇨병 치료제로 사용되나, 다낭성 난소 증후군(polycystic ovary syndrome) 및 성조숙 (premature puberty)에 대한 처방 역시 증가되고 있는 추세이다. 한편, metformin 은 신장 장애에 따른 lactic acidosis 와 같은 부작용 역시 잘 알려져 있다.Among them, metformin is a well-known AMPK activator as an oral biguanide antidiabetic treatment. Metformin is the first drug used to treat overweight and obese type II diabetic patients with normal renal function. It is known as the only drug that can control the secretion of pancreatic enzyme granules and the activity of enzymes related to hepatic glucose metabolism. Metformin is currently known as the most prescribed diabetes treatment worldwide. Metformin is mainly used as a treatment for type II diabetes, but prescriptions for polycystic ovary syndrome and premature puberty are also increasing. On the other hand, the side effects of metformin such as lactic acidosis due to renal impairment are also well known.
그리하여, 부작용이 낮고 보다 효과적인 천연물 유래의 대체 건강기능식품 및 의약품의 개발이 요구되고 있는 실정이다. Therefore, there is a demand for the development of alternative health functional foods and medicines derived from natural products that have low side effects and are more effective.
본 명세서 전체에 걸쳐 다수의 문헌이 참조되고 그 인용이 표시되어 있다. 인용된 문헌의 개시 내용은 그 전체로서 본 명세서에 참조로 삽입되어 본 발명이 속하는 기술 분야의 수준 및 본 발명의 내용이 보다 명확하게 설명된다. Numerous references are referenced throughout this specification and citations thereof are indicated. The disclosures of the cited documents are incorporated herein by reference in their entirety to more clearly describe the content of the present invention and the level of the art to which the present invention pertains.
본 발명자들은 비만의 치료 및 억제의 효과를 나타내면서 부작용이 없는 천연물을 개발하고자 연구 노력한 결과, 고추냉이잎 추출물, 감국 추출물, 오미자박 추출물, 커피체리 추출물, 케롭 추출물 및 머루 추출물이 현저한 비만 예방, 개선 및 치료 효과가 있음을 밝혀냄으로써, 본 발명을 완성하게 되었다. As a result of the present inventors' research efforts to develop natural products without side effects while exhibiting the effects of treatment and suppression of obesity, the wasabi leaf extract, the chrysanthemum extract, the omijabak extract, the coffee cherry extract, the kerob extract, and the mulberry extract significantly prevent and improve obesity. And by finding that there is a therapeutic effect, the present invention was completed.
본 발명의 하나의 관점은 고추냉이잎 추출물, 감국 추출물, 오미자박 추출물, 커피체리 추출물, 케롭 추출물 및 머루 추출물로 이루어진 군으로부터 선택되는 1 이상을 유효성분으로 포함하는 비만의 예방, 개선 또는 치료를 위한 조성물을 제공하는 것이다.One aspect of the present invention is the prevention, improvement or treatment of obesity comprising as an active ingredient at least one selected from the group consisting of wasabi leaf extract, chrysanthemum extract, omijabak extract, coffee cherry extract, kerob extract, and mulberry extract. To provide a composition for
고추냉이(Wasabia / Eutrema japonica Matsum.)는 오랫동안 약용되어 온 일본 자생식물이며, allyisothiocyanate 와 같은 이소티오시아네이트(isothiocyanate) 계열 화합물질을 다량 함유하여, 독특한 자극성 맛을 나타내므로 향신료 또는 피클로 이용되어 온 식물이다. 항산화 및 항암 효과가 잘 알려 있으나, 와사비 뿌리 이외 다른 부분, 특히 잎 부분의 생리활성은 잘 알려져 있지 않다. 본 발명의 고추냉이잎 추출물은 유효성분으로서 시니그린(sinigrin)을 1.0~27.7mg/g 포함하는 것으로서, 식욕 감소를 일으키지 않으면서, 체중감소, 체지방 감소 및 복부 지방 감소로 이루어진 군으로부터 선택되는 1 이상의 효과를 갖는 것으로 확인되었다.Wasabi (Wasabia / Eutrema japonica Matsum.) is a native plant in Japan that has been used medicinally for a long time. It is a whole plant. Although antioxidant and anticancer effects are well known, the physiological activity of parts other than wasabi root, especially leaf parts, is not well known. The wasabi leaf extract of the present invention contains 1.0 to 27.7 mg/g of sinigrin as an active ingredient, and does not cause appetite reduction, and is selected from the group consisting of weight loss, body fat reduction and abdominal fat reduction. It was confirmed to have the above effect.
감국(Chrysanthemum indicum)은 우리나라에 자생적으로 광범위하게 분포하고 있는 야생 약초로, 고혈압 및 중감염성 질환 등 다양한 면역질환을 치료하기 위해 전통적으로 사용해 왔다. 현재 감국의 항산화, 진통, 항감염, 항바이러스 및 항염 효과가 비교적 잘 알려져 있다.Chrysanthemum indicum is a wild herb that is widely distributed in Korea and has been traditionally used to treat various immune diseases such as high blood pressure and severe infectious diseases. Currently, the antioxidant, analgesic, anti-infective, antiviral and anti-inflammatory effects of chrysanthemum are relatively well known.
오미자(Schisandra chinensis)는 단맛, 신맛, 떫은맛, 매운맛, 짠맛의 5가지 맛을 가진 열매로, 항산화 및 항염 효과를 나타내는 페놀성 화합물을 다량 함유 하고 있는 것으로 알려져 있다. 그러나 오미자박(Schizandrae Fructus Pomace)의 생리활성은 잘 알려져 있지 않다. 본 발명의 오미자박 추출물은 유효성분으로서 쉬잔드린(schizandrin)을 0.4~2.5mg/g 포함하는 것으로서, 식욕 감소를 일으키지 않으면서, 체중감소, 체지방 감소 및 복부 지방 감소로 이루어진 군으로부터 선택되는 1 이상의 효과를 갖는 것으로 확인되었다.Schisandra chinensis (Schisandra chinensis) is a fruit with five flavors: sweet, sour, astringent, spicy, and salty. However, the physiological activity of Schizandrae Fructus Pomace is not well known. The omijabak extract of the present invention contains 0.4 to 2.5 mg/g of schizandrin as an active ingredient, and without causing a decrease in appetite, at least one selected from the group consisting of weight loss, body fat reduction and abdominal fat reduction. was confirmed to be effective.
커피체리는 커피나무에서 열린 커피 열매 중에서 커피 생두(coffee bean)를 제거하고 남은 과육(pulp)을 의미한다. 커피 음료는 개인차가 존재하지만, 대략 하루 4-6잔의 커피 섭취에 의해 생리활성을 나타낼 수 있는 충분한 양의 활성성분이 섭취되는 것으로 알려져 있으며, 카페인, caffeoylquinic acids (CQAs)와 같은 물질이 대표적인 커피의 활성 성분으로 알려져 있다. 이와 같이 커피 음료의 항산화 효능은 비교적 잘 알려져 있지만, 커피체리의 생리활성은 잘 알려져 있지 않다. 본 발명의 유효성분으로 사용하는 커피체리 추출물은 커피 음료와는 상이한 것으로서 카페인 및 카페인 유도체 화합물을 포함하지 않으면서도 체중감소, 체지방 감소 및 복부 지방 감소로 이루어진 군으로부터 선택되는 1 이상의 효과를 나타내는 것으로 확인되었다. Coffee cherry refers to the pulp remaining after removing coffee beans among coffee berries opened from a coffee tree. Although there are individual differences in coffee drinks, it is known that a sufficient amount of active ingredients to exhibit physiological activity is ingested by consuming 4-6 cups of coffee a day, and substances such as caffeine and caffeoylquinic acids (CQAs) are representative coffees. known as an active ingredient in As such, the antioxidant effect of coffee drinks is relatively well known, but the physiological activity of coffee cherries is not well known. The coffee cherry extract used as the active ingredient of the present invention is different from the coffee beverage, and it is confirmed that it exhibits at least one effect selected from the group consisting of weight loss, body fat reduction and abdominal fat reduction without including caffeine and caffeine derivative compounds. became
케롭(Carob)은 지중해 연안에 자생하는 Ceratonia siliqua 의 콩모양 열매로, 미국 및 호주의 일부 지역에서도 자생하는 것으로 알려져 있다. 케롭은 매우 높은 tannin 을 함유하여, 특이한 자극성 (astringency)를 유발하므로, 식용이 극히 제한되는 것으로 알려져 있다. Carob (Carob) is a bean-shaped fruit of Ceratonia siliqua, native to the Mediterranean coast, and is known to be native to some parts of the United States and Australia. It is known that kerob contains very high tannins, causing a specific astringency, so its edible is extremely limited.
머루(Vitis coignetiae Pulliat)는 아시아에 자생하는 포도의 일종으로, 머루 주스 및 와인이 약용되어 왔다. 머루에는 다른 포도류 보다 더 풍부한 폴리페놀 및 안토시아닌 성분이 존재하는 것으로 알려져 있으며, 이와 관련된 항산화 활성이 현재 알려져 있다. Meru (Vitis coignetiae Pulliat) is a kind of grapes that are native to Asia, and has been medicinally used for grapefruit juice and wine. Muroo is known to contain more abundant polyphenol and anthocyanin components than other grapes, and the related antioxidant activity is currently known.
본 발명의 조성물은 유효성분으로서 상기 천연성분들의 추출물을 포함하는데, 본 명세서에서 사용되는 용어 '추출물'은 원물을 착즙, 또는 원물에 추출용매를 처리하여 얻은 추출 결과물이나 이를 제형화(예컨대, 분말화)한 가공물도 포함하는 의미를 갖는다.The composition of the present invention includes an extract of the natural ingredients as an active ingredient, and the term 'extract' as used herein refers to an extraction result obtained by squeezing the raw material or treating the raw material with an extraction solvent or formulating it (eg, powder It has a meaning that also includes a processed product.
본 발명의 조성물에서 이용되는 추출물을 원물에 추출용매를 처리하여 얻는 경우에는, 다양한 추출용매가 이용될 수 있는데 예컨대, 극성 용매 또는 비극성 용매를 이용할 수 있다. 극성 용매로는 (i) 물, (ii) 알코올(바람직하게는, 메탄올, 에탄올, 프로판올, 부탄올, 노말-프로판올, 이소-프로판올, 노말-부탄올, 1-펜탄올, 2-부톡시에탄올 또는 에틸렌글리콜), (iii) 아세트산, (iv) DMFO(dimethyl-formamide) 및 (v) DMSO(dimethyl sulfoxide) 등을 사용할 수 있고, 비극성 용매로는 아세톤, 아세토나이트릴, 에틸 아세테이트, 메틸 아세테이트, 플루오로알칸, 펜탄, 헥산, 2,2,4-트리메틸펜탄, 데칸, 사이클로헥산, 사이클로펜탄, 디이소부틸렌, 1-펜텐, 1-클로로부탄, 1-클로로펜탄, o-자일렌, 디이소프로필 에테르, 2-클로로프로판, 톨루엔, 1-클로로프로판, 클로로벤젠, 벤젠, 디에틸 에테르, 디에틸 설파이드, 클로로포름, 디클로로메탄, 1,2-디클로로에탄, 어닐린, 디에틸아민, 에테르, 사염화탄소 및 THF 등을 사용할 수도 있다.When the extract used in the composition of the present invention is obtained by treating the raw material with an extraction solvent, various extraction solvents may be used, for example, a polar solvent or a non-polar solvent may be used. Polar solvents include (i) water, (ii) alcohols (preferably methanol, ethanol, propanol, butanol, n-propanol, iso-propanol, n-butanol, 1-pentanol, 2-butoxyethanol or ethylene glycol), (iii) acetic acid, (iv) dimethyl-formamide (DMFO), and (v) dimethyl sulfoxide (DMSO) can be used, and the non-polar solvent is acetone, acetonitrile, ethyl acetate, methyl acetate, fluoro Alkanes, pentane, hexane, 2,2,4-trimethylpentane, decane, cyclohexane, cyclopentane, diisobutylene, 1-pentene, 1-chlorobutane, 1-chloropentane, o-xylene, diisopropyl ether, 2-chloropropane, toluene, 1-chloropropane, chlorobenzene, benzene, diethyl ether, diethyl sulfide, chloroform, dichloromethane, 1,2-dichloroethane, aniline, diethylamine, ether, carbon tetrachloride and THF or the like may also be used.
바람직하게는, 본 발명에서 이용되는 추출물은 원물을 착즙하거나, 또는 물, 탄소수가 1 내지 4의 저급 알코올 및 이들의 혼합물로 이루어진 군 중에서 선택된 어느 하나를 추출 용매로 사용하여 추출한 것일 수 있지만, 이것으로 제한되는 것은 아니다.Preferably, the extract used in the present invention may be extracted by squeezing the raw material or using any one selected from the group consisting of water, lower alcohols having 1 to 4 carbon atoms, and mixtures thereof as an extraction solvent, but this is not limited to
또한, 본 명세서에서 사용되는 용어 '추출물'은 상술한 바와 같이 당업계에서 조추출물(crude extract)로 통용되는 의미를 갖지만, 광의적으로는 추출물을 추가적으로 분획(fractionation)한 분획물도 포함한다. 즉, 원물을 착즙 또는 상술한 추출용매를 이용하여 얻은 추출물뿐만 아니라, 여기에 정제과정을 추가적으로 적용하여 얻은 것도 포함한다. 예컨대, 상기 추출물을 일정한 분자량 컷-오프 값을 갖는 한외 여과막을 통과시켜 얻은 분획, 다양한 크로마토그래피(크기, 전하, 소수성 또는 친화성에 따른 분리를 위해 제작된 것)에 의한 분리 등, 추가적으로 실시된 다양한 정제 방법을 통해 얻어진 분획도 본 발명의 추출물에 포함되는 것이다.In addition, the term 'extract' used in the present specification has the meaning commonly used as a crude extract in the art as described above, but in a broad sense also includes a fraction obtained by additionally fractionating the extract. That is, it includes not only extracts obtained by squeezing the raw material or using the above-mentioned extraction solvent, but also those obtained by additionally applying a purification process thereto. For example, a fraction obtained by passing the extract through an ultrafiltration membrane having a constant molecular weight cut-off value, separation by various chromatography (prepared for separation according to size, charge, hydrophobicity or affinity), etc. The fraction obtained through the purification method is also included in the extract of the present invention.
또한, 본 발명의 추출물은 이후 추가적인 과정, 예컨대 여과하거나 농축 또는 건조과정을 수행하여 용매를 제거한 것, 또는 여과, 농축 및 건조를 모두 수행한 것일 수도 있다. 여과는 예를 들어 여과지를 이용하거나 감압여과기를 이용할 수 있으며, 농축은 감압 농축기, 건조는 분무건조 하거나 동결건조법 등을 수행하여 분말 상태의 추출물을 얻을 수도 있다.In addition, the extract of the present invention may be obtained by removing the solvent by performing an additional process, such as filtration, concentration, or drying, or all of filtration, concentration and drying. For filtration, for example, filter paper or a reduced pressure filter may be used, and concentration may be performed with a reduced pressure concentrator, and drying may be performed by spray-drying or freeze-drying to obtain a powdery extract.
본 발명의 조성물에서 상기 유효성분은 고추냉이잎 추출물, 감국 추출물, 오미자박 추출물, 커피체리 추출물, 케롭 추출물 및 머루 추출물로 이루어진 군으로부터 선택되는 2 이상의 조합일 수 있으며, 바람직하게는 상기 혼합물 또는 복합물은 고추냉이잎 추출물, 감국 추출물, 오미자박 추출물 및 커피체리 추출물로부터 선택되는 2 이상의 조합일 수 있다. 상기 2 이상의 조합은 각각의 단일 추출물에 대비하여 상승효과를 갖는 것을 특징으로 한다.In the composition of the present invention, the active ingredient may be a combination of two or more selected from the group consisting of a wasabi leaf extract, chrysanthemum extract, omijabak extract, coffee cherry extract, kerob extract, and mulberry extract, preferably the mixture or complex may be a combination of two or more selected from horseradish leaf extract, chrysanthemum extract, omijabak extract, and coffee cherry extract. The combination of two or more is characterized in that it has a synergistic effect compared to each single extract.
기존 천연 추출물의 경우 식욕 감소를 통해 체중 및 체지방을 감수시키는 경우가 대부분이지만, 본 발명의 조성물은 식욕 감소를 일으키지 않으면서, 체중감소, 체지방 감소 및 복부 지방 감소로 이루어진 군으로부터 선택되는 1 이상의 효과를 나타낼 수 있다.In the case of existing natural extracts, in most cases, weight and body fat are reduced through appetite reduction, but the composition of the present invention does not cause appetite reduction, and at least one effect selected from the group consisting of weight loss, body fat reduction and abdominal fat reduction can represent
또한 본 발명은 상기 유효성분을 함유하는 조성물을 포함하고, 약학적으로 허용되는 담체, 부형제 또는 희석제 등을 추가하여 약학적 단위 투여형으로 제형화된 대사증후군의 예방 및 치료를 위한 약학 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for the prevention and treatment of metabolic syndrome formulated in a pharmaceutical unit dosage form by adding a pharmaceutically acceptable carrier, excipient or diluent, including a composition containing the active ingredient, and the like. do.
상기 "약학적으로 허용가능한"이란, 생리학적으로 허용되고 인간에게 투여될 때, 활성성분의 작용을 저해하지 않으며 통상적으로 위장 장애, 현기증과 같은 알레르기 반응 또는 이와 유사한 반응을 일으키지 않는 비독성의 조성물을 말한다.The "pharmaceutically acceptable" means a non-toxic composition that is physiologically acceptable and does not inhibit the action of the active ingredient when administered to humans and does not normally cause allergic reactions such as gastrointestinal disorders, dizziness, or similar reactions. say
상기 담체, 부형제 또는 희석제의 예로는, 락토즈, 덱스트로즈, 수크로즈, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀루로즈, 메틸 셀룰로즈, 폴리비닐피롤리돈, 물, 메틸하이드록시벤조에이트, 프로필하이드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유 등이 포함될 수 있다. 또한 상기 약학적 조성물은 충진제, 항응집제, 윤활제, 습윤제, 향료, 유화제 또는 방부제 등을 추가로 포함할 수 있다.Examples of the carrier, excipient or diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose , polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In addition, the pharmaceutical composition may further include a filler, an anti-agglomeration agent, a lubricant, a wetting agent, a fragrance, an emulsifier or a preservative.
용어 "약학적으로 유효한 양"이란, 음성 대조군에 비해 그 이상의 반응을 나타내는 양을 말하며 바람직하게는 대사증후군의 예방 및/또는 치료의 효과를 나타내기에 충분한 양을 말한다.The term "pharmaceutically effective amount" refers to an amount that exhibits a response higher than that of a negative control group, and preferably refers to an amount sufficient to exhibit the effect of preventing and/or treating metabolic syndrome.
또한, 본 발명의 약학적 조성물은 포유동물에 투여된 후 활성 성분의 신속, 지속 또는 지연된 방출을 제공할 수 있도록 당업계에 공지된 방법을 사용하여 제형화될 수 있다. 제형은 분말, 과립, 정제, 에멀젼, 시럽, 에어로졸, 연질 또는 경질 젤라틴 캡슐, 멸균 주사용액, 멸균 분말의 형태일 수 있다.In addition, the pharmaceutical compositions of the present invention may be formulated using methods known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to a mammal. Formulations may be in the form of powders, granules, tablets, emulsions, syrups, aerosols, soft or hard gelatin capsules, sterile injectable solutions, sterile powders.
본 발명의 약학적 조성물의 투여 경로로는 이에 한정되는 것은 아니지만, 경구적 또는 비경구적으로 투여될 수 있다. 비경구적 투여 경로로는 예를 들어, 경피, 비강, 복강, 근육, 피하 또는 정맥 등의 여러 가지 경로가 포함될 수 있다. 또한, 본 발명의 약학적 조성물은 대사증후군의 예방 및/또는 치료 효과를 가지는 공지의 화합물과 병행하여 투여할 수 있다.The route of administration of the pharmaceutical composition of the present invention is not limited thereto, but may be administered orally or parenterally. Parenteral routes of administration may include, for example, multiple routes such as transdermal, nasal, intraperitoneal, intramuscular, subcutaneous or intravenous. In addition, the pharmaceutical composition of the present invention may be administered in parallel with a known compound having a preventive and/or therapeutic effect on metabolic syndrome.
또 다른 양태로, 본 발명은 상기 조성물 중 어느 하나의 조성물을 포함하는 식품 조성물을 제공한다.In another aspect, the present invention provides a food composition comprising any one of the above compositions.
본 발명의 식품 조성물은 식품, 기능성 식품(functional food), 영양 보조제(nutritional supplement), 건강식품(health feed) 및 식품 첨가제(food additives) 등의 모든 천연 소재의 가공 형태를 포함한다. 상기 유형의 식품 조성물은 당업계에 공지된 통상적인 방법에 다라 다양한 형태로 제조할 수 있다.The food composition of the present invention includes processed forms of all natural materials such as foods, functional foods, nutritional supplements, health feeds and food additives. Food compositions of this type can be prepared in various forms according to conventional methods known in the art.
예를 들어, 건강식품으로는 본 발명의 추출물 자체를 차, 주스 및 드링크의 형태로 제조하여 음용하도록 하거나, 과립화, 캡슐화 또는 분말화하여 섭취할 수 있다. 또한, 본 발명의 추출물 이외에, 백작약, 산수유, 가시오가피, 영지버섯, 진피, 초두충, 당귀, 치자, 황기, 맥아, 탱자, 비타민C, 프락토올리고당, 스테비오사이드, 정제수, 말토덱스트린 등을 본 발명의 목적으로 저해하지 않는 범위 내에서 단독으로 또는 혼합하여 더 포함할 수 있으나, 본 발명의 식품 조성물이 추가로 포함할 수 있는 다른 약효 성분 및/또는 첨가제는 상기 예들에 한정되는 것은 아니다.For example, as a health food, the extract of the present invention may be prepared in the form of tea, juice, and drink to be consumed, or granulated, encapsulated or powdered. In addition, in addition to the extracts of the present invention, the present invention includes white peony, cornflower oil, spiny hornwort, reishi mushroom, dermis, choucifera, angelica, gardenia, astragalus, malt, tangja, vitamin C, fructooligosaccharide, stevioside, purified water, maltodextrin, and the like. It may be further included alone or in a mixture within the range not inhibited for the purpose of, but other medicinal ingredients and/or additives that may be additionally included in the food composition of the present invention are not limited to the above examples.
예를 들어, 본 발명에 따른 식품 조성물은 수용성 비타민으로서 티아민(비타민B1), 리보플라빈, 아스코르브산, 니아신, 및 비타민B6를 포함할 수 있고, 지방산으로서 미리스틴산, 팔미트산, 스테아린산, 올레인산, 리놀레인산 등을 포함할 수 있으며, 약산 성분으로서는 글리콜산 및 초산을 포함할 수 있고, 아미노산으로서 트레오닌, 발린, 메티오닌, 이소루신, 루신, 페닐알라닌, 트립토판, 및 리신의 필수아미노산 8종을 비롯하여, 아스파르트산, 세린, 글루탐산, 프롤린, 글리신, 알라닌, 시스테인, 티로신, 히스티딘, 알지닌 등을 포함할 수 있다.For example, the food composition according to the present invention may include thiamine (vitamin B1), riboflavin, ascorbic acid, niacin, and vitamin B6 as water-soluble vitamins, and myristic acid, palmitic acid, stearic acid, oleic acid, Linoleic acid and the like, and glycolic acid and acetic acid as the weak acid component, and 8 essential amino acids of threonine, valine, methionine, isoleucine, leucine, phenylalanine, tryptophan, and lysine as amino acids; aspartic acid, serine, glutamic acid, proline, glycine, alanine, cysteine, tyrosine, histidine, arginine, and the like.
본 발명의 조성물은 식욕 감소를 일으키지 않으면서, 체중감소, 체지방 감소 및 복부 지방 감소로 이루어진 군으로부터 선택되는 1 이상의 효과를 나타내며, 이에 의하여 비만의 예방, 개선 또는 치료 효과를 나타낸다.The composition of the present invention exhibits at least one effect selected from the group consisting of weight loss, body fat reduction and abdominal fat reduction without causing appetite reduction, thereby exhibiting an effect of preventing, improving or treating obesity.
도 1은 NFD 또는 HFD 공급 마우스에서 추출물 투여에 따른 체중 변화를 나타낸 것이다.
도 2는 NFD 또는 HFD 공급 마우스에서 추출물 투여에 따른 체중 변화를 나타낸 것이다.
도 3은 NFD 또는 HFD 공급 마우스에서 촬영한 전신 DEXA 이미지가 포함된 대표적인 총 체질량 및 복부 지방 패드 이미지이다.
A = NFD 공급과 함께 비히클(증류수) 10 ml/kg 경구 투여 마우스 (Intact control)
B = HFD 공급과 함께 비히클 10 ml/kg 경구 투여 마우스로 (HFD control)
C = HFD 공급과 함께 메트포르민 250 mg/kg 경구 투여 마우스 (Metformin)
D = HFD 공급과 함께 SFP 200 mg/kg 경구 투여 마우스 (SFP)
E = HFD 공급과 함께 WL 200 mg/kg 경구 투여 마우스 (WL)
F = HFD 공급과 함께 CF 200 mg/kg 경구 투여 마우스 (CF)
G = HFD 공급과 함께 CBP 200 mg/kg 경구 투여 마우스 (CBP)
H = HFD 공급과 함께 CR 200 mg/kg 경구 투여 마우스 (CR)
I = HFD 공급과 함께 CGR 200 mg/kg 경구 투여 마우스 (CGR)
도 4는 NFD 또는 HFD 공급 마우스에서 추출물 투여에 따른 전체 신체 및 복부 지방 밀도를 나타낸 그래프이다.
도 5는 실시예 I에서 제조한 오미자박 추출물의 HPLC 결과를 나타낸 것이다.
도 6은 실시예 I에서 제조한 고추냉이잎 추출물의 HPLC 결과를 나타낸 것이다.1 shows the change in body weight according to the administration of the extract in NFD or HFD-fed mice.
Figure 2 shows the change in body weight according to the administration of the extract in NFD or HFD-fed mice.
3 is a representative total body mass and abdominal fat pad image including whole body DEXA images taken from NFD or HFD fed mice.
A = Vehicle (distilled water) 10 ml/kg orally administered to mice (Intact control) with NFD feeding
B = with
C = Mice (Metformin) administered orally at 250 mg/kg metformin with HFD feeding
D =
E = Mice (WL) administered
F =
G =
H =
I =
Figure 4 is a graph showing the total body and abdominal fat density according to the administration of the extract in NFD or HFD fed mice.
5 shows the HPLC results of the omijabak extract prepared in Example I.
6 shows the HPLC results of the wasabi leaf extract prepared in Example I.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명 하고자 한다. 이들 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로서, 본 발명의 범위가 이들 실시예에 의해 제한되지 않는다는 것은 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자에게 있어서 자명할 것이다. Hereinafter, the present invention will be described in more detail through examples. These examples are only for illustrating the present invention in more detail, and it will be apparent to those of ordinary skill in the art to which the present invention pertains that the scope of the present invention is not limited by these examples.
실시예Example
I. 시험물질제조I. Preparation of test substances
1. 오미자박 추출물 제조1. Preparation of omijabak extract
오미자박(SFP; Schizandrae Fructus Pomace)을 분쇄한 후 10배수의 물(V/V)을 용매로 하여, 100℃에서 6시간동안 추출 한 후 5배수의 물을 용매로 하여 100℃에서 4시간동안 추출하였다. 그 후, 여과하여 60~65℃에서 20~25brix 가 되도록 농축한 다음, inlet 175℃, outlet 80℃의 조건에서 분무건조(Spray dry) 하여 연갈색 분말(light brown powders)로서 오미자박 추출물을 제조하였다. After pulverizing Schisandrae Fructus Pomace (SFP; Schizandrae Fructus Pomace), 10 times water (V/V) was used as a solvent, and extraction was performed at 100° C. for 6 hours. Then, 5 times water was used as a solvent for 4 hours at 100° C. extracted. After that, it was filtered and concentrated to 20-25 brix at 60~65℃, and then spray-dried under the conditions of inlet 175℃ and outlet 80℃ to prepare omijabak extract as light brown powders. .
2. 고추냉이잎 추출물 제조2. Preparation of wasabi leaf extract
고추냉이잎(WL; Wasabi Leaf)을 분쇄한 후 18배수의 물(V/V)을 용매로 하여, 100℃에서 8시간 추출하였다. 그 후, 여과하여 60~65℃에서 20~25brix 가 되도록 농축한 다음, inlet 175℃, outlet 75℃의 조건에서 분무건조(Spray dry) 하여 진갈색 분말(deep brown powders)로서 고추냉이잎 추출물을 제조하였다. After the wasabi leaf (WL; Wasabi Leaf) was pulverized, 18-fold water (V/V) was used as a solvent, and extraction was performed at 100° C. for 8 hours. After that, it was filtered and concentrated to 20-25 brix at 60~65℃, and then spray dried under the conditions of inlet 175℃ and outlet 75℃ to prepare wasabi leaf extract as deep brown powders did.
3. 감국 추출물 제조3. Preparation of Chrysanthemum Extract
감국(CF; Chrysanthemi Folium)을 분쇄한 후 후 18배수의 물(V/V)을 용매로 하여, 100℃에서 8시간동안 추출하였다. 그 후, 여과하여 60~65℃에서 20~25brix 가 되도록 농축한 다음, inlet 175℃, outlet 75℃의 조건에서 분무건조(Spray dry) 하여 적갈색 분말(reddish brown powders)로서 감국 추출물을 제조하였다. Chrysanthemi Folium (CF) was pulverized and then extracted with 18-fold water (V/V) as a solvent at 100° C. for 8 hours. Thereafter, the chrysanthemum extract was prepared as reddish brown powders by filtration and concentration to 20-25 brix at 60-65°C, and then spray-drying under the conditions of inlet 175°C and outlet 75°C.
4. 커피체리 추출물 제조4. Preparation of coffee cherry extract
커피체리(CBP; Coffee Berry Pulp)를 분쇄한 후 후 10배수의 물(V/V)을 용매로 하여, 60~70℃에서 3시간동안 2회 반복 추출하였다. 그 후, 여과하여 60~65℃에서 20~25brix 가 되도록 농축한 다음, 60~70℃에서 감압을 통해 건조한 후 milling 과 sizing 하여 갈색 분말(brown powders)로서 커피체리 추출물을 제조하였다. After grinding coffee cherries (CBP; Coffee Berry Pulp), 10 times water (V/V) was used as a solvent, and extraction was repeated twice for 3 hours at 60-70°C. After that, it was filtered and concentrated to 20-25 brix at 60~65℃, dried under reduced pressure at 60~70℃, milling and sizing to prepare a coffee cherry extract as brown powders.
5. 캐롭 추출물 제조5. Carob Extract Preparation
캐롭(CR; Carob)을 분쇄한 후 후 10배수의 30% 에탄올(에탄올:물=30:70, V/V)을 용매로 하여, 70℃에서 6시간동안 추출하였다. 그 후, 여과하여 60~65℃에서 20~25brix 가 되도록 농축한 다음, 60~70℃에서 감압을 통해 건조한 후 milling 과 sizing 하여 연 노랑색 분말(light yellow powders)로서 캐롭 추출물을 제조하였다. After grinding Carob (CR; Carob), 10
6. 머루덩굴 추출물 제조6. Manufacture of blackberry extract
머루덩굴(CGR; Crimson Grapevine Radix)을 분쇄한 후 10배수의 물(V/V)을 용매로 하여, 121℃에서 8시간동안 추출 한 후 5배수의 물을 용매로 하여 121℃에서 4시간동안 추출하였다. 그 후, 여과하여 60~65℃에서 20~25brix 가 되도록 농축한 다음, inlet 175℃, outlet 75℃의 조건에서 분무건조(Spray dry) 하여 적갈색 분말(reddish brown powders)로서 머루덩굴 추출물을 제조하였다. After pulverizing Crimson Grapevine Radix (CGR), extraction was performed at 121°C for 8 hours using 10-fold water (V/V) as a solvent, and then using 5-fold water as a solvent at 121°C for 4 hours. extracted. After that, it was filtered and concentrated to 20-25 brix at 60~65℃, and then spray dried under the conditions of inlet 175℃ and outlet 75℃ to prepare reddish brown powders. .
II. 물질 분석II. material analysis
1. 오미자박 추출물의 유효성분 함량 분석1. Analysis of Active Ingredient Content of Omijabak Extract
오미자박 추출물을 100mg 달아 50ml의 물을 넣어 녹인 다음 filter 후 시료로 사용 하였다. 쉬잔드린 표준품 약 10mg을 정밀하게 달아 각각 메탄올을 넣어 정확하게 20mL로 하여 표준액으로 하였다. 검액 및 표준액 10 μL씩을 가지고 다음 조건으로 액체크로마토그래프법에 따라 시험하여 검액의 피크면적 ATa, ATb 및 ATc과 표준액의 피크면적 ASa, ASb 및 ASc를 측정하였다.100 mg of omijabak extract was weighed, dissolved in 50 ml of water, and then filtered and used as a sample. About 10 mg of the shizandrin standard was precisely weighed, methanol was added to each, and the volume was made exactly 20 mL, and it was used as a standard solution. 10 μL of each of the sample solution and the standard solution was tested according to the liquid chromatography method under the following conditions, and the peak areas ATa, ATb and ATc of the sample solution and the peak areas ASa, ASb and ASc of the standard solution were measured.
쉬잔드린의 양(mg)=쉬잔드린 표준품의 양(mg) × (ATa/ASa) × 1/5 Amount of schizandrine (mg) = Amount of standard shizandrin (mg) × (ATa/ASa) × 1/5
좌외부흡광광도계로 측정파장 254nm 에서 측정하였으며, 내경 4~6mm, 길이 15~25mm의 5~10um의 액체크로마토그래프용 옥타데실실리카겔을 충전하여 사용하였으며, 이동상은 아세토니트릴:물:포름사혼합액(70:30:0.1)으로 유량은 0.6ml/분 으로 측정하였다.It was measured with a left external absorbance spectrophotometer at a measurement wavelength of 254 nm, and an octadecyl silica gel for liquid chromatography with an inner diameter of 4 to 6 mm and a length of 15 to 25 mm was filled and used, and the mobile phase was an acetonitrile: water: formsa mixture ( 70:30:0.1) and the flow rate was measured at 0.6ml/min.
측정결과 오미자박 추출물의 쉬잔드린 함량은 0.5~2.0mg/g을 갖는 것으로 확인하였다. As a result of the measurement, it was confirmed that the shizandrin content of the omijabak extract was 0.5 to 2.0 mg/g.
2. 와사비잎추출물의 유효성분 함량 분석2. Analysis of Active Ingredient Content of Wasabi Leaf Extract
와사비잎추출물을 각각 500mg을 달아 50% ACN 50ml을 넣은 후 75℃에서 1시간 중탕 한 다음 filter 후 시료로 사용하였다. 표준품은 50% CAN에 mg/ml의 농도로 제조 후 사용하였다. 228nm의 흡수파장에서 측정하였으며, CAPCELL PAK C18, 4.6×250mm, 5um 의 컬럼을 사용하여 01% TFA와 ACN 을 전개용매로 하여 0.5ml/min 의 조건에서 측정하였다. Weighed 500 mg of each wasabi leaf extract, put 50 ml of 50% ACN, and bathed at 75° C. for 1 hour, then filtered and used as a sample. The standard was prepared at a concentration of mg/ml in 50% CAN and then used. Measured at an absorption wavelength of 228 nm, using a CAPCELL PAK C18, 4.6×250 mm, 5 μm column, using 01% TFA and ACN as developing solvents, was measured at 0.5 ml/min.
와사비잎 추출물의 지표성분인 시니그린(sinigrin)의 함량은 2.2~6mg/g을 갖는 것으로 확인하였다. It was confirmed that the content of sinigrin, an indicator component of the wasabi leaf extract, was 2.2 to 6 mg/g.
III. 효능 평가III. Efficacy evaluation
1. 동물 모델 확립1. Establishment of animal models
기존에 비만 치료제의 개발을 위한 다양한 실험동물 모델이 개발되었으나, 대부분 너무 심각한 비만이 유발되어 이미 확립된 비만증에 대한 치료제의 약효 평가에 적당할 뿐, 예방 또는 기능성 식품 개발에 부적당한 것으로 평가되었다. In the past, various experimental animal models for the development of anti-obesity drugs have been developed, but most of them cause too severe obesity, so they are only suitable for evaluating the efficacy of an already established therapeutic agent for obesity, and were evaluated to be inappropriate for prevention or development of functional foods.
본 발명자들은 고지방 사료(high fat diet, HFD) 공급에 의해 설치류인 마우스에서도 비만이 발생함을 확인하였다. 즉, HFD 공급으로 ICR mice 에서 사람의 비만 발생과 유사하고, 기능성 식품의 약효 평가에 적당한 정도의 비만이 유도될 수 있음을 확인하여 HFD 를 이용한 실험동물 모델을 확립하였다.The present inventors confirmed that obesity occurs even in mice, which are rodents, by supplying a high fat diet (HFD). That is, by confirming that HFD supply can induce obesity to a degree similar to human obesity in ICR mice and to evaluate the efficacy of functional foods, an experimental animal model using HFD was established.
구체적으로 총 200마리의 6주령 암컷 ICR 마우스 [OrientBio, Seungnam, Korea]를 7일간 실험실 환경에 순응시킨 후, 1 주일간 HFD에 적응시킨 다음 일정한 체중 증가를 나타내는 실험동물만 선별하여 실험에 사용하였다. 모든 실험동물은 대구한의대학교 실험동물윤리위원회의 사전승인 하에 동물실험윤리 기준에 따라 취급하였다. 정상 대조군에서는 일반 NFD(Normal fat diet)를 동일한 방법으로 공급하였다.Specifically, a total of 200 6-week-old female ICR mice [OrientBio, Seungnam, Korea] were acclimatized to the laboratory environment for 7 days, then acclimatized to HFD for 1 week, and only experimental animals showing constant weight gain were selected and used for the experiment. All experimental animals were handled in accordance with the animal experimental ethics standards under the prior approval of the Laboratory Animal Ethics Committee of Daegu Haany University. In the normal control group, a normal NFD (Normal fat diet) was supplied in the same way.
실험물질로는 상기 제조한 6 종류의 천연물 추출물(SPF, WL, CF, CBP, CR 및 CGR)을 사용하였다. 실험물질 투여 용량은 직접적인 상호 비교를 위해 200 mg/kg으로 설정하였고, 이를 위하여 상기 제조한 6 종류의 천연물 추출물 각각을 20 mg/ml의 농도로 멸균 증류수에 용해시켜, 마우스의 일반 경구투여 volume 인 10 ml/kg으로 매일 1 회씩 84일간 강제 경구투여 하였다. The six types of natural extracts (SPF, WL, CF, CBP, CR and CGR) prepared above were used as test materials. The dose of the test substance was set at 200 mg/kg for direct mutual comparison, and for this purpose, each of the six types of natural extracts prepared above was dissolved in sterile distilled water at a concentration of 20 mg/ml, and the normal oral administration volume of the mouse was It was forcibly administered orally at 10 ml/kg once a day for 84 days.
대조약물로 사용한 metformin 의 투여 용량은 이전의 참고문헌을 바탕으로 250 mg/kg으로 설정하였다. Metformin 역시 25 mg/ml 농도로 멸균 증류수에 용해시킨 다음 10 ml/kg의 용량(250 mg/kg)으로 매일 1 회씩 84일간 경구투여 하였다. The administered dose of metformin used as a control drug was set at 250 mg/kg based on the previous references. Metformin was also dissolved in sterile distilled water at a concentration of 25 mg/ml and then orally administered at a dose of 10 ml/kg (250 mg/kg) once daily for 84 days.
정상 및 HFD 대조군에서는 동일한 투여 및 보정 스트레스를 가하기 위하여 실험물질 대신 멸균 증류수만 동일한 방법으로 동일한 기간 동안 강제 경구 투여하였다.In the normal and HFD control groups, in order to apply the same administration and corrective stress, only sterile distilled water was forcibly administered orally for the same period in the same way instead of the test substance.
2. 체중 및 평균 사료 섭취량의 변화2. Changes in body weight and average feed intake
항비만 효과를 검증하기 위하여 체중의 변화 및 평균 사료 섭취량의 변화를 평가하였고 실험결과를 하기 표 1에 나타내었다.To verify the anti-obesity effect, changes in body weight and average feed intake were evaluated, and the experimental results are shown in Table 1 below.
실험결과, HFD 대조군에서는 정상 대조군에 비해 유의성 있는(p<0.01) 체중의 증가가 고지방사료 공급 7일 후부터 인정되었으며, 1주일간의 HFD 적응기간 및 84일간의 실험 물질 투여기간 동안의 증체량 역시 각각 정상 대조군에 비해 유의성 있는(p<0.01) 증가를 나타내었다. 한편 CF 200 mg/kg 투여군에서는 투여 시작 14 일 후부터, SFP 및 WL 200 mg/kg 투여군에서는 투여 시작 21 일 후부터, metformin 250 mg/kg, CBP 및 CR 200 mg/kg 투여군에서는 투여 시작 28일 후부터, CGR 200 mg/kg 투여군에서는 투여 시작 35일 후부터 각각 HFD 대조군에 비해 유의성 있는(p<0.01 또는 p<0.05) 체중의 감소가 인정되기 시작하였으며, HFD 대조군에 비해 유의성 있는 (p<0.01) 84 일간의 실험물질 투여기간 동안의 증체량 감소 역시 metformin 250 mg/kg 을 포함한 모든 실험물질 투여에서 인정되었다. 특히, WL 및 CF 200 mg/kg 은 metformin 250 mg/kg 보다 더 우수한 HFD 유발 체중 및 증체량 증가 억제 효과를 동일한 순서로 각각 나타내었으며, SFP 및 CBP 200 mg/kg 은 metformin 250 mg/kg 과 비교할만한 체중 및 증체량 감소 효과를 HFD 마우스에서 동일한 순서로 각각 나타내었다(표 1 및 도 1 및 2 참조). 투여기간 84일 동안의 증체량은 HFD 대조군의 경우, 정상 대조군에 비해 356.50%의 변화를 나타내었으나, metformin 250 mg/kg, SPF, WL, CF, CBP, CR 및 CGR 200 mg/kg 투여군에서는 HFD 대조군에 비해 각각 -59.26, -60.08, -71.03, -65.66, -59.04, -50.49 및 -49.34%의 변화를 나타내었다.As a result of the experiment, in the HFD control group, a significant (p<0.01) increase in body weight was recognized from 7 days after the supply of the high-fat feed compared to the normal control group, and the weight gain during the HFD adaptation period of 1 week and the administration of the test substance for 84 days was also normal, respectively. It showed a significant (p<0.01) increase compared to the control group. On the other hand, from 14 days after administration in the
평균 사료 섭취량의 경우, 정상 대조군에 비해 유의성 있는(p<0.01) 평균 사료 섭취량의 감소가 HFD 대조군에서 인정되었으나, HFD 대조군에 비해 유의성 있는 평균 사료 섭취량의 변화는 SFP 200 mg/kg 투여군을 포함한 모든 실험물질 투여군에서 인정되지 않았다(표 1). 평균 사료 섭취량은 HFD 대조군의 경우, 정상 대조군에 비해 -10.69%의 변화를 나타내었으나, metformin 250 mg/kg, SPF, WL, CF, CBP, CR 및 CGR 200 mg/kg 투여군에서는 HFD 대조군에 비해 각각 -1.53, -1.87, 1.23, -1.52, 1.25, -0.78 및 0.55%의 변화를 나타내어 식욕 감소를 일으키지 않음이 확인되었다.In the case of average feed intake, a significant (p<0.01) decrease in average feed intake was recognized in the HFD control group compared to the normal control group. It was not recognized in the test substance administration group (Table 1). Mean feed intake was -10.69% in the HFD control group compared to the normal control group, but metformin 250 mg/kg, SPF, WL, CF, CBP, CR and
또한 지표성분의 함량에 따른 효과의 차이를 확인하기 위하여 희석에 의해 쉬잔드린을 0.4 mg/g 포함하는 오미자박 추출물(비교예 1) 및 시니그린을 1.0 mg/g 포함하는 와사비잎 추출물(비교예 2)를 준비하고 평균 사료 섭취량의 변화를 조사한 결과 HFD 대조군에 비해 각각 -3.25%(비교예 1) 및 -3.98%(비교예 2)의 변화를 나타내었는바, 특정 지표성분의 함량과 식욕 감소 방지 효과와의 연관성이 확인되었다.In addition, in order to confirm the difference in the effect according to the content of the indicator component, by dilution, omijabak extract containing 0.4 mg/g shizandrin (Comparative Example 1) and wasabi leaf extract containing 1.0 mg/g shinigrin (Comparative Example) As a result of preparing 2) and examining the change in the average feed intake, it showed a change of -3.25% (Comparative Example 1) and -3.98% (Comparative Example 2), respectively, compared to the HFD control, the content of specific indicator components and decreased appetite A correlation with the prevention effect was confirmed.
3. 체지방 및 복부 지방량의 변화3. Changes in body fat and abdominal fat mass
항비만 효과를 검증하기 위하여 체중의 변화 및 평균 사료 섭취량의 변화를 평가하였고 실험결과를 도 3 및 4에 나타내었다.To verify the anti-obesity effect, changes in body weight and changes in average feed intake were evaluated, and the experimental results are shown in FIGS. 3 and 4 .
HFD 대조군에서는 정상 대조군에 비해 유의성 있는 (p<0.01) 체지방 및 복부 축적 지방량의 증가가 각각 인정된 반면, WL 200 mg/kg 투여군을 포함한 모든 실험물질 투여군에서는 HFD 대조군에 비해 유의성 있는 (p<0.01) 체지방 및 복부 축적 지방량의 감소를 각각 나타내었으며, 특히, WL 및 CF 200 mg/kg 은 metformin 250 mg/kg 보다 더 우수한 HFD 유발 체지방 및 복부 지방량 증가 억제 효과를 동일한 순서로 각각 나타내었으며, SFP 및 CBP 200 mg/kg은 metformin 250 mg/kg과 비교할만한 체지방 및 복부 지방량 감소 효과를 HFD 마우스에서 동일한 순서로 각각 나타내었다(도 3 및 4). 체지방량은 HFD 대조군의 경우, 정상 대조군에 비해 141.34%의 변화를 나타내었으나, metformin 250 mg/kg, SPF, WL, CF, CBP, CR 및 CGR 200 mg/kg 투여군에서는 HFD 대조군에 비해 각각 -31.52, -32.18, -46.44, -40.14, -30.41, 24.55 및 -23.52%의 변화를 나타내었다. 복부 지방량은 HFD 대조군의 경우, 정상 대조군에 비해 157.47%의 변화를 나타내었으나, metformin 250 mg/kg, SPF, WL, CF, CBP, CR 및 CGR 200 mg/kg 투여군에서는 HFD 대조군에 비해 각각 -35.12, -35.88, -51.02, -44.52, 34.23, -24.26 및 -23.65%의 변화를 나타내었다.In the HFD control group, a significant (p<0.01) increase in body fat and abdominal fat accumulation was recognized, respectively, compared to the normal control group, whereas in all the test substance administration groups including the
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