KR102232163B1 - The composition for anti-diabets andanti-obesity, comprising the extract of oreopanax costaricensis - Google Patents
The composition for anti-diabets andanti-obesity, comprising the extract of oreopanax costaricensis Download PDFInfo
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- KR102232163B1 KR102232163B1 KR1020180136429A KR20180136429A KR102232163B1 KR 102232163 B1 KR102232163 B1 KR 102232163B1 KR 1020180136429 A KR1020180136429 A KR 1020180136429A KR 20180136429 A KR20180136429 A KR 20180136429A KR 102232163 B1 KR102232163 B1 KR 102232163B1
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- fraction
- extract
- obesity
- oreopanax
- preventing
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
본 발명은 오레오파낙스 코스타리센시스(OREOPANAX COSTARICENSIS, OC) 추출물 또는 이의 분획물을 유효성분으로 포함하는 항비만 및 항당뇨 조성물에 관한 것이다. 상기 OC 추출물 및 분획물은 in vitro에서 지방세포로의 분화와 당 흡수(glucose uptake)를 저해하였고, in vivo에서 OGTT(Oral glucose tolerance test) 평가결과 항당뇨 효능이 있음을 확인하였다. 따라서, 본 발명의 OC 추출물 또는 이의 분획물을 유효성분으로 포함하는 조성물은 항비만 및 항당뇨 효과를 나타내므로, 비만 또는 당뇨의 예방 또는 치료에 유용하게 사용될 수 있다.The present invention relates to an anti-obesity and anti-diabetic composition comprising an Oreopanax COSTARICENSIS (OC) extract or a fraction thereof as an active ingredient. The OC extracts and fractions inhibited differentiation into adipocytes and glucose uptake in vitro, and as a result of the OGTT (Oral glucose tolerance test) evaluation in vivo, it was confirmed that they have antidiabetic efficacy. Accordingly, the composition comprising the OC extract or a fraction thereof of the present invention as an active ingredient exhibits anti-obesity and anti-diabetic effects, and thus can be usefully used in the prevention or treatment of obesity or diabetes.
Description
본 발명은 OREOPANAX COSTARICENSIS 추출물 또는 분획물을 유효성분으로 포함하는 항당뇨 및 항비만 효능이 있는 약학 조성물 또는 건강기능식품 조성물에 관한 것이다.The present invention relates to a pharmaceutical composition or health functional food composition having anti-diabetic and anti-obesity efficacy comprising an OREOPANAX COSTARICENSIS extract or fraction as an active ingredient.
생활방식과 경제성장의 변화에 따라 식습관에도 많은 변화가 있었다. 특히, 바쁜 현대인들은 패스트푸드와 같이 고열량 식품을 많이 섭취함에도 불구하고, 적은 운동량으로 인하여 체중 과다 및 비만이 증가하고 있다. 체중 과다는 체질량 지수(BMI, 체중을 키의 제곱으로 나눈 비만 척도)가 25 이상 30 미만을 의미하며, 비만은 체질량 지수가 30 이상 일 때를 의미한다.There have also been many changes in eating habits with changes in lifestyle and economic growth. Particularly, busy modern people consume a lot of high-calorie foods such as fast food, but excessive weight and obesity are increasing due to a small amount of exercise. Excessive weight means that the body mass index (BMI, weight divided by the square of height) is 25 or more and less than 30, and obesity means when the body mass index is 30 or more.
체중 과다는 혈압과 콜레스테롤 수치를 높여 심장 질환 등의 각종 성인병의 발병률을 증가시킨다. 특히, 비만이 여러 가지 질병에 미치는 영향은 매우 심각하여 전 세계 당뇨병 환자의 80%, 심장질환의 21%가 비만이 원인인 것으로 보고된 바 있다. 이 외에도 자궁암, 신장암, 유방암 등 각종 암 또한, 비만과 직·간접적으로 연관되어 있으며, 비만이나 과체중의 경우 수면무호흡증, 골관절염, 담석증 등의 발병률도 정상인보다 높다(Stein CJ, The epidemic of obesity. J Clin Endocrinol Metab 2004; 89: 2522-2525).Excessive weight increases blood pressure and cholesterol levels, increasing the incidence of various adult diseases such as heart disease. In particular, the effect of obesity on various diseases is very serious, and it has been reported that 80% of diabetic patients and 21% of heart diseases around the world are the cause of obesity. In addition, various cancers such as uterine cancer, kidney cancer, and breast cancer are also directly or indirectly related to obesity, and in the case of obesity or overweight, the incidence of sleep apnea, osteoarthritis, and cholelithiasis is also higher than that of normal people (Stein CJ, The epidemic of obesity. J Clin Endocrinol Metab 2004; 89: 2522-2525).
특히, 경제 성장과 더불어 식습관의 변화와 비만 등의 질환이 증가함에 따라 당뇨병의 유병율이 높아지고 있는 추세이다. 현재 당뇨병은 전 세계적으로 중요한 성인병 중의 하나이다. 당뇨병을 그대로 방치하게 되면 합병증으로 진전되는 것을 피할 수 없다. 통상 당뇨병에 걸린 후 10 ~ 20년이 지나면 체내 거의 모든 기관이 손상을 받아 당뇨성 망막병증(diabetic retinopathy), 당뇨성 백내장(diabetic cataract), 당뇨성 신증(diabetic nephropathy), 당뇨성 신경병증(diabetic neuropathy), 심장병, 암, 골다공증 등으로 나타난다. 따라서, 당뇨병을 치료하기 위하여 여러가지 약물이 개발되고 있는 실정이다.In particular, the prevalence of diabetes is on the rise as the economy grows and changes in dietary habits and diseases such as obesity increase. Currently, diabetes is one of the most important adult diseases around the world. If diabetes is left unattended, it cannot be avoided from developing into complications. Usually, 10 to 20 years after diabetes, almost all organs in the body are damaged, resulting in diabetic retinopathy, diabetic cataract, diabetic nephropathy, and diabetic neuropathy. neuropathy), heart disease, cancer, osteoporosis, etc. Therefore, various drugs are being developed to treat diabetes.
본 발명의 목적은 당뇨병 및 비만에 효과적인 식물 추출물을 제공하는 것으로, 구체적으로 OREOPANAX COSTARICENSIS(OC) 추출물 또는 이의 분획물이 항당뇨 및 항비만 효과가 있음을 확인함으로써 본 발명을 완성하였다.It is an object of the present invention to provide a plant extract effective against diabetes and obesity, and in particular, the present invention was completed by confirming that the OREOPANAX COSTARICENSIS (OC) extract or a fraction thereof has anti-diabetic and anti-obesity effects.
상기 목적을 달성하기 위해, To achieve the above object,
본 발명의 일 측면으로 OREOPANAX COSTARICENSIS(OC) 추출물 또는 이의 분획물을 유효성분으로 포함하는 당뇨병 예방 또는 치료용 약학 조성물을 제공한다.In one aspect of the present invention, there is provided a pharmaceutical composition for preventing or treating diabetes, comprising an OREOPANAX COSTARICENSIS (OC) extract or a fraction thereof as an active ingredient.
본 발명의 다른 측면으로 OC 추출물 또는 이의 분획물을 유효성분으로 포함하는 비만 예방 또는 치료용 약학 조성물을 제공한다.Another aspect of the present invention provides a pharmaceutical composition for preventing or treating obesity comprising an OC extract or a fraction thereof as an active ingredient.
본 발명의 다른 측면으로 OC 추출물 또는 이의 분획물을 유효성분으로 포함하는 당뇨병 예방 또는 개선용 건강기능식품 조성물을 제공한다.Another aspect of the present invention provides a health functional food composition for preventing or improving diabetes, comprising an OC extract or a fraction thereof as an active ingredient.
본 발명의 다른 측면으로 OC 추출물 또는 이의 분획물을 유효성분으로 포함하는 비만 예방 또는 개선용 건강기능식품 조성물을 제공한다.Another aspect of the present invention provides a health functional food composition for preventing or improving obesity, comprising an OC extract or a fraction thereof as an active ingredient.
OC 추출물 또는 이의 분획물이 항당뇨 효과가 있는지 확인하기 위해, OC 추출물 또는 분획물이 In vitro에서 당 흡수(glucose uptake)에 미치는 영향을 측정하였다. 또한, In vivo에서 혈액 속 당 흡수를 혈당강하제로 알려진 메트포민(Metformin)과 비교하였다. 그 결과, OC 추출물 또는 이의 분획물을 처리한 그룹은 우수한 항당뇨 및 항비만 효과가 있음을 확인하였다.In order to confirm whether the OC extract or a fraction thereof has an antidiabetic effect, the effect of the OC extract or fraction on glucose uptake in vitro was measured. In addition, the absorption of glucose in the blood in vivo was compared with metformin, which is known as a hypoglycemic agent. As a result, it was confirmed that the group treated with the OC extract or its fractions had excellent anti-diabetic and anti-obesity effects.
도 1은 OREOPANAX COSTARICENSIS 추출물의 MPLC 크로마토그램을 나타낸 것이다.
도 2 내지 도 4는 254 nm, 280 nm 및 360 nm의 파장에서 UPLC의 PDA 분석 결과를 나타낸 것이다.
도 5는 OC 용매 분획물의 수득 방법을 도식화한 것이다.
도 6은 칼럼분획물 및 용매분획물의 동등성 및 지표 성분 확인
도 7는 OC 메탄올 추출물 및 칼럼분획물의 세포독성을 L6 근육세포에서 확인한 것이다.
도 8은 OC 메탄올 추출물 및 칼럼분획물이 포도당 흡수에 미치는 정도를 L6 근육세포에서 확인한 것이다.
도 9는 OC 메탄올 추출물 및 용매 분획물의 세포독성을 L6 근육세포에서 확인한 것이다.
도 10은 OC 용매 메탄올 추출물 및 용매분획물이 포도당 흡수에 미치는 정도를 L6 근육세포에서 확인한 것이다.
도 11 내지 도 13은 OC 메탄올 추출물 및 용매분획물이 혈중 당 흡수에 미치는 영향을 확인한 것이다.
도 14는 OC 메탄올 추출물 및 용매분획물의 세포독성을 3T3-L1 세포에서 확인한 것이다.
도 15는 OC 메탄올 추출물 및 용매분획물이 지질 축적에 미치는 영향을 분화된 3T3-L1 세포에서 확인한 결과를 그래프로 나타낸 것이다.1 shows an MPLC chromatogram of an OREOPANAX COSTARICENSIS extract.
2 to 4 show PDA analysis results of UPLC at wavelengths of 254 nm, 280 nm and 360 nm.
5 is a schematic diagram of a method of obtaining an OC solvent fraction.
Figure 6 is the equivalence of the column fraction and the solvent fraction and confirmation of index components
Figure 7 shows the cytotoxicity of the OC methanol extract and the column fraction was confirmed in L6 muscle cells.
8 shows the extent to which the OC methanol extract and the column fraction affect glucose absorption in L6 muscle cells.
9 shows the cytotoxicity of the OC methanol extract and the solvent fraction confirmed in L6 muscle cells.
10 shows the extent of the OC solvent methanol extract and the solvent fraction on glucose absorption in L6 muscle cells.
11 to 13 confirm the effect of the OC methanol extract and the solvent fraction on blood glucose absorption.
14 shows cytotoxicity of OC methanol extracts and solvent fractions confirmed in 3T3-L1 cells.
15 is a graph showing the results of confirming the effect of OC methanol extract and solvent fraction on lipid accumulation in differentiated 3T3-L1 cells.
이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
본 발명의 일 측면은 오레오파낙스 코스타리센시스(OREOPANAX COSTARICENSIS, 이하 OC라 한다) 추출물 또는 이의 분획물을 유효성분으로 포함하는 당뇨병 예방 또는 치료용 약학 조성물에 대한 것이다.One aspect of the present invention relates to a pharmaceutical composition for preventing or treating diabetes comprising an extract or a fraction thereof, oreopanax costaricensis (OREOPANAX COSTARICENSIS, hereinafter referred to as OC) as an active ingredient.
상기 오레오파낙스 코스타리센시스는 두릅나무과(Araliaceae)과의 속씨식물이다. 상기 오레오파낙스 속에는 85가지의 종이 포함될 수 있다.The Oreopanax costarisensis is a genus plant of the Araliaceae family. 85 species may be included in the Oreopanax.
본원 명세서에서 사용되는 용어, "추출물"은 오레오파낙스 코스타리센시스를 용매를 이용하여 오레오파낙스 코스타리센시스에 포함된 성분을 수득한 것을 의미한다. 상기 오레오파낙스 코스타리센시스 추출물을 수득할 때, 오레오파낙스 코스타리센시스는 재배한 것 또는 시판되는 것 등 제한 없이 사용할 수 있으며, 오레오파낙스 코스타리센시스는 잎, 줄기 또는 뿌리가 모두 이용가능하고, 구체적으로 잎일 수 있으나, 이에 한정되지 않는다.As used herein, the term "extract" refers to obtaining a component contained in Oreopanax costarisencis using a solvent of Oreopanax costarisencis. When obtaining the Oreopanax costarisencis extract, Oreopanax costaricensis can be used without limitation, such as cultivated or commercially available ones, and Oreopanax costarisensis can be used with leaves, stems, or roots. And, specifically, it may be a leaf, but is not limited thereto.
수득 단계에서 추출 용매는 물, 알코올 또는 이들의 혼합물을 사용할 수 있으며, 상기 알코올로는 C1 내지 C3의 저급 알코올을 이용할 수 있다. 저급 알코올로는 메탄올, 에탄올 또는 프로판올을 이용할 수 있다. 상기 추출 방법은 열수 추출, 침지 추출, 환류 냉각 추출 또는 초음파 추출 등의 추출 방법을 사용할 수 있으나 이에 한정되지 않는다.In the obtaining step, water, alcohol, or a mixture thereof may be used as the extraction solvent, and a lower alcohol of C 1 to C 3 may be used as the alcohol. Methanol, ethanol or propanol can be used as the lower alcohol. The extraction method may be an extraction method such as hot water extraction, immersion extraction, reflux cooling extraction, or ultrasonic extraction, but is not limited thereto.
상기 추출은 건조된 오레오파낙스 코스타리센시스의 건조중량에 1배 내지 20배의 용매를 첨가하여 추출할 수 있으며, 구체적으로 용매를 2배 내지 5배 첨가하여 추출할 수 있다. 추출 온도는 20℃ 내지 100℃ 일 수 있으며, 구체적으로 20℃ 내지 40℃일 수 있으며, 더 구체적으로 실온일 수 있으나, 이에 한정되지 않는다. 또한, 추출 시간은 10시간 내지 48시간일 수 있으며, 구체적으로 15시간 내지 30시간일 수 있고, 더 구체적으로 24시간일 수 있으나, 이에 한정되지 않는다. 아울러, 추출 횟수는 1회 내지 5회일 수 있으며, 3회 내지 4회 반복 추출할 수 있고, 구체적으로 3회일 수 있으나, 이에 한정되는 것은 아니다.The extraction may be extracted by adding 1 to 20 times the solvent to the dry weight of the dried Oreopanax costarisensys, and specifically, it may be extracted by adding 2 to 5 times the solvent. The extraction temperature may be 20°C to 100°C, specifically 20°C to 40°C, and more specifically room temperature, but is not limited thereto. In addition, the extraction time may be 10 to 48 hours, specifically 15 to 30 hours, more specifically 24 hours, but is not limited thereto. In addition, the number of extractions may be 1 to 5 times, may be repeatedly extracted 3 to 4 times, and specifically 3 times, but is not limited thereto.
추출 방법의 일 실시예로는 중합액체크로마토그래피(MPLC)를 이용할 수 있다. 일 실시예로는 오레오파낙스 코스타리센시스를 정제수를 이용하여 추출한 후 메탄올을 이용하여 MPLC 분획물을 수득할 수 있다.As an example of the extraction method, polymerization liquid chromatography (MPLC) may be used. As an example, after extracting Oreopanax costarisensis using purified water, an MPLC fraction may be obtained using methanol.
상기 수득 단계에서는 추출물을 감압 농축하는 과정이 추가로 포함될 수 있으며, 상기 감압 농축은 진공감압농축기 또는 진공회전증발기를 이용할 수 있으나, 이에 한정되지 않는다. 또한, 상기 제조 단계는 상기 감압 농축 과정을 거친 추출물을 건조하는 단계를 추가로 포함할 수 있다. 상기 건조는 감압건조, 진공건조, 비등건조, 분무건조 또는 동결건조일 수 있으나, 이에 한정되지 않는다.In the obtaining step, a process of concentrating the extract under reduced pressure may be additionally included, and the concentration under reduced pressure may be performed using a vacuum vacuum concentrator or a vacuum rotary evaporator, but is not limited thereto. In addition, the manufacturing step may further include drying the extract that has undergone the vacuum concentration process. The drying may be vacuum drying, vacuum drying, boiling drying, spray drying, or freeze drying, but is not limited thereto.
또한, 상기 추출물은 추출액, 추출액의 희석액 또는 농축액, 추출액을 건조하여 얻어지는 건조물, 또는 이들 조정제물 또는 정제물을 모두 포함한다.In addition, the extract includes an extract, a dilution or concentrate of the extract, a dried product obtained by drying the extract, or all of these preparations or purified products.
본원 명세서에서 사용되는 용어, "분획물"은 다양한 구성성분을 포함하는 혼합물로부터 특정 성분 또는 특정 그룹을 분리하는 분획방법에 의하여 얻어진 결과물을 의미한다. 구체적으로, 헥산, 클로로포름, 에틸아세테이트, 부탄올 또는 이들의 혼합용매 분획물일 수 있다. 본원 명세서의 분획법은 당뇨병의 예방 또는 치료에 사용되는 물질을 수득하기 위한 방법이라면 그 방법에 제한되지 않는다.As used herein, the term "fraction" refers to a product obtained by a fractionation method for separating a specific component or a specific group from a mixture containing various constituents. Specifically, it may be hexane, chloroform, ethyl acetate, butanol, or a mixed solvent fraction thereof. The fractionation method in the present specification is not limited to the method as long as it is a method for obtaining a substance used in the prevention or treatment of diabetes.
오레오파낙스 코스타리센시스 분획물은 전술한 오레오파낙스 코스타리센시스 추출물을 물, 메탄올, 에탄올 및 부탄올 등과 같은 C1 내지 C3의 저급 알콜의 극성 용매에 현탁하고, 이를 헥산, 디클로로메탄 또는 부탄올 등의 유기용매로 분획하는 과정을 수회 반복 분배하여 얻을 수 있다. 일 실시예로, 오레오파낙스 코스타리센시스의 메탄올 추출물을 헥산으로 3회 분획하여 헥산 분획물을 얻었고, 남은 물층 분획을 클로로포름 용매로 3회 반복 분획하여 클로로포름 분획물을 얻었다. 상기에서 남은 물층 분획을 부탄올로 3회 반복 분배하여 부탄올 분획물을 얻을 수 있다.Oreopanax costarisencis fraction is suspended in a polar solvent of a lower alcohol of C 1 to C 3 such as water, methanol, ethanol and butanol, the above-described Oreopanax costarisencis extract, and it is hexane, dichloromethane or butanol. The process of fractionation with an organic solvent of can be obtained by repeating distribution several times. As an example, the methanol extract of Oreopanax costarisencis was fractionated three times with hexane to obtain a hexane fraction, and the remaining water layer fraction was repeatedly fractionated three times with a chloroform solvent to obtain a chloroform fraction. The water layer fraction remaining above may be repeatedly distributed with butanol three times to obtain a butanol fraction.
본원 명세서에서 사용된 용어 "당뇨병"이란 인슐린의 분비량이 부족하거나 인슐린의 작용 및 기능이 충분히 이루어지지 않을 때 나타나는 질병을 의미한다. 이 병에 걸릴 경우 글리코겐, 단백질 및 지방질의 과도한 분해로 간 또는 혈액 중 글루코스 농도의 비정상적인 증가를 일으켜 당뇨 및 케톤뇨를 초래하고, 수분 및 전해질 대사의 이상으로 전해질 상실에 의한 혈액 농축 상태와 함께 순환장애, 신장장애 등의 병적 상태를 가져오게 된다. 당뇨병은 인슐린 의존형 당뇨병(I형)과 인슐린 비의존성 당뇨병(II형)으로 구분된다. 당뇨병 진단은 일반적으로 혈중 글루코스 농도 측정을 통해서 가능한데, 기준에 따라서 차이를 나타낸다. 인간에게서는 일반적으로 혈중에서 글루코스가 평소 200 mg/dl 이상, 공복시 140 mg/dl 이상일 때 당뇨병으로 진단한다.The term "diabetes" as used herein refers to a disease that occurs when the secretion of insulin is insufficient or the action and function of insulin are not sufficiently performed. In the case of this disease, excessive decomposition of glycogen, protein and fat causes abnormal increase in glucose concentration in the liver or blood, causing diabetes and ketonuria, and circulation disorder with blood concentration due to electrolyte loss due to abnormal water and electrolyte metabolism. , Kidney disorders, and other pathological conditions. Diabetes is divided into insulin-dependent diabetes (type I) and insulin-independent diabetes (type II). Diabetes can be diagnosed generally by measuring blood glucose levels, but there are differences according to the criteria. In humans, diabetes is generally diagnosed when glucose in the blood is usually 200 mg/dl or more and 140 mg/dl or more when fasting.
본 발명의 또 다른 측면은 오레오파낙스 코스타리센시스(OREOPANAX COSTARICENSIS, OC) 추출물 또는 이의 분획물을 유효성분으로 포함하는 비만 예방 또는 치료용 약학 조성물에 대한 것이다.Another aspect of the present invention relates to a pharmaceutical composition for preventing or treating obesity, comprising an Oreopanax COSTARICENSIS (OC) extract or a fraction thereof as an active ingredient.
이때, 상기 추출물은 물, C1 내지 C3의 저급 알코올 또는 이의 혼합물로 추출될 수 있으며, 구체적인 사항은 상술한 바와 같다. 또한, 상기 분획물은 메탄올 추출물을 중합액체크로마토그래피를 통해 수득된 것일 수 있다. 또한, 상기 분획물은 상술한 용매 분획법을 통해 수득한 헥산 분획물, 클로로포름 분획물, 부탄올 분획물 일 수 있다. 구체적인 사항은 상술한 바와 같다.In this case, the extract may be extracted with water, a lower alcohol of C 1 to C 3 or a mixture thereof, and specific details are as described above. In addition, the fraction may be obtained through polymerization liquid chromatography of the methanol extract. In addition, the fraction may be a hexane fraction, a chloroform fraction, and a butanol fraction obtained through the above-described solvent fractionation method. Details are as described above.
본원 명세서에서 사용된 용어, "비만"이란 체내 지방이 과도하게 축적된 상태를 말한다. 비만의 기준은 상기 체내 지방이 체중의 25% 이상, 여자는 30~35% 이상이면 비만이라고 할 수 있는데, 일반적 측정방법으로는 체중(kg)/신장(m)2으로 나타내는 체질량지수(BMI; Body Mass Index)가 널리 쓰이고 있다. 서양인 체질량지수가 30 kg/m2이 초과되면 비만, 25 ~ 30 kg/m2인 경우에는 과체중으로 정의하며, 동양인의 경우에는 이보다 2 정도 낮은 28 kg/m2이 초과되면 비만, 23~28 kg/m2은 과체중이라고 할 수 있다. 이외에도 허리대비 엉덩이 둘레비(WHR; Waist to Hip Ratio) 또는 복부지방량을 기준으로 비만을 정의할 수 있으며, 본 발명에서는 상기한 기준을 포함하여 이외의 통상적인 기준으로 정의된 비만의 모든 경우를 포함한다.As used herein, the term "obesity" refers to an excessive accumulation of body fat. Criteria for obesity may be described as obesity if the body fat is 25% or more of body weight, women more than 30-35%, body mass general measurement methods as is shown by the weight (kg) / height (m) 2 index (BMI; Body Mass Index) is widely used. When Western
본 발명의 약학 조성물은 약제학적으로 허용 가능한 첨가제를 더 포함할 수 있으며, 이때 약제학적으로 허용 가능한 첨가제로는 전분, 젤라틴화 전분, 미결정셀룰로오스, 유당, 포비돈, 콜로이달실리콘디옥사이드, 인산수소칼슘, 락토스, 만니톨, 엿, 아라비아고무, 전호화전분, 옥수수전분, 분말셀룰로오스, 히드록시프로필셀룰로오스, 오파드라이, 전분글리콜산나트륨, 카르나우바 납, 합성규산알루미늄, 스테아린산, 스테아린산마그네슘, 스테아린산알루미늄, 스테아린산칼슘, 백당, 덱스트로스, 소르비톨 및 탈크 등이 사용될 수 있다. 본 발명에 따른 약제학적으로 허용 가능한 첨가제는 상기 조성물에 대해 0.1 ~ 90 중량부 포함될 수 있으나, 이에 한정되는 것은 아니다.The pharmaceutical composition of the present invention may further include a pharmaceutically acceptable additive, wherein the pharmaceutically acceptable additives include starch, gelatinized starch, microcrystalline cellulose, lactose, povidone, colloidal silicon dioxide, calcium hydrogen phosphate, Lactose, mannitol, syrup, gum arabic, pregelatinized starch, corn starch, powdered cellulose, hydroxypropyl cellulose, opadry, sodium starch glycolate, lead carnauba, synthetic aluminum silicate, stearic acid, magnesium stearate, aluminum stearate, stearic acid Calcium, sucrose, dextrose, sorbitol, talc, and the like can be used. The pharmaceutically acceptable additive according to the present invention may be included in an amount of 0.1 to 90 parts by weight with respect to the composition, but is not limited thereto.
본 발명의 약학 조성물은 실제 임상 투여 시에 경구 및 비경구의 여러 가지 제형으로 투여될 수 있는데, 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제될 수 있다.The pharmaceutical composition of the present invention can be administered in various oral and parenteral dosage forms at the time of actual clinical administration. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants, etc. are used. Can be prepared using.
경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 본 발명의 혼합 추출물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(Calcium carbonate), 수크로스(Sucrose), 락토오스(Lactose) 또는 젤라틴 등을 섞어 조제될 수 있다. 또한, 단순한 부형제 이외에 마그네슘 스티레이트, 탈크 같은 윤활제들도 사용될 수 있다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제 및 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다.Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and these solid preparations include at least one excipient, such as starch, calcium carbonate, and water in the mixed extract of the present invention. It can be prepared by mixing sucrose, lactose, or gelatin. In addition, in addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid preparations for oral use include suspensions, liquid solutions, emulsions and syrups, but may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to water and liquid paraffin, which are commonly used simple diluents. .
비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 포함될 수 있다. 비수성용제, 현탁용제로 는 프로필렌글리콜(Propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.Formulations for parenteral administration may include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized formulations, and suppositories. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerogelatin, and the like may be used.
본 발명의 조성물은 목적하는 방법에 따라 경구 투여하거나 비경구 투여할 수 있으며, 비경구 투여시 피부 외용 또는 복강 내 주사, 직장 내 주사, 피하주사, 정맥주사, 근육 내 주사 또는 흉부 내 주사 주입방식을 선택할 수 있다. 투여량은 환자의 체중, 연령, 성별, 건강상태, 식이, 투여시간, 투여방법, 배설율 및 질환의 중증도 등에 따라 그 범위가 다양할 수 있다.The composition of the present invention can be administered orally or parenterally according to a desired method, and when administered parenterally, external use of the skin or intraperitoneal injection, rectal injection, subcutaneous injection, intravenous injection, intramuscular injection or intrathoracic injection injection method You can choose. The dosage range may vary depending on the patient's weight, age, sex, health status, diet, administration time, administration method, excretion rate, and severity of disease.
본 발명의 조성물의 투여량은 환자의 체중, 연령, 성별, 건강상태, 식이, 투여시간, 투여방법, 배설율 및 질환의 중증도에 따라 그 범위가 다양하며, 일일 투여량은 본 발명의 추출물의 양을 기준으로 0.0001 mg/kg 내지 100 mg/kg일 수 있으며, 구체적으로 0.001 mg/kg 내지 10 mg/kg일 수 있으며, 하루 1회 내지 6회 투여될 수 있으나, 이에 제한되지 않는다.The dosage of the composition of the present invention varies according to the patient's weight, age, sex, health status, diet, administration time, administration method, excretion rate, and severity of disease, and the daily dosage is the extract of the present invention. Based on the amount, it may be 0.0001 mg/kg to 100 mg/kg, specifically 0.001 mg/kg to 10 mg/kg, and may be administered once to 6 times a day, but is not limited thereto.
본 발명의 또 다른 측면은 오레오파낙스 코스타리센시스(OREOPANAX COSTARICENSIS, OC) 추출물 또는 이의 분획물을 유효성분으로 포함하는 당뇨병 예방 또는 개선용 건강기능식품 조성물에 대한 것이다.Another aspect of the present invention relates to a health functional food composition for preventing or improving diabetes comprising an Oreopanax COSTARICENSIS (OC) extract or a fraction thereof as an active ingredient.
본 발명의 또 다른 측면은 오레오파낙스 코스타리센시스(OREOPANAX COSTARICENSIS, OC) 추출물 또는 이의 분획물을 유효성분으로 포함하는 비만 예방 또는 개선용 건강기능식품 조성물에 대한 것이다.Another aspect of the present invention relates to a health functional food composition for preventing or improving obesity comprising an Oreopanax COSTARICENSIS (OC) extract or a fraction thereof as an active ingredient.
본원 명세서에서 사용된 용어, "예방"은 상기 약학 조성물의 투여로 대상 질환의 발생, 확산 및 재발을 억제시키거나 지연시키는 모든 행위를 의미하고, "개선"은 상기 조성물의 투여로 대상 질환 또는 대상 증세가 호전되거나 이롭게 변경되는 모든 행위를 의미한다.As used herein, the term "prevention" refers to any action that inhibits or delays the occurrence, spread, and recurrence of a target disease by administration of the pharmaceutical composition, and "improvement" refers to a target disease or target by administration of the composition. It refers to any action in which symptoms improve or are beneficially changed.
본 발명의 조성물을 유효성분으로 함유하는 건강기능식품 조성물은, 상기 본 발명의 추출물에 포함되는 각각의 성분이 인체에 안전한 물질이고, 이를 섭취한 경우에도 당뇨병 예방 또는 개선에 효과가 있을 뿐만 아니라, 비만 예방이나 개선에 효과가 있으므로 식품로 사용될 수 있다.In the health functional food composition containing the composition of the present invention as an active ingredient, each component contained in the extract of the present invention is a material that is safe for the human body, and even when ingested, it is effective in preventing or improving diabetes, It can be used as food because it is effective in preventing or improving obesity.
식품으로는, 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합제, 건강 기능성 식품류 등으로 사용될 수 있다. 상기 식품은 공지의 제조방법에 따라 정제, 과립, 분말, 캅셀, 액상의 용액 및 환 등의 제형으로 제조할 수 있으며, 본 발명에 따른 추출물의 함량은 제형에 따라 식품 조성물 총 중량을 기준으로 0.0001 내지 100중량%로 조절할 수 있다. 본 발명에 의한 추출물을 유효성분으로 함유하는 외에는 다른 성분에는 특별한 제한이 없으며, 통상의 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다.As food, it can be used, for example, in various foods, beverages, gum, tea, vitamin complexes, health functional foods, and the like. The food can be prepared in formulations such as tablets, granules, powders, capsules, liquid solutions, and pills according to a known manufacturing method, and the content of the extract according to the present invention is 0.0001 based on the total weight of the food composition depending on the formulation. It can be adjusted to 100% by weight. Except for containing the extract according to the present invention as an active ingredient, there is no particular limitation on other ingredients, and various conventional flavoring agents or natural carbohydrates may be contained as additional ingredients.
상기 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진 등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 ㎖당 일반적으로 약 1 내지 20 g, 바람직하게는 약 5 내지 12 g이다.Examples of the natural carbohydrates include monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, and the like; And polysaccharides, for example, common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those described above, natural flavoring agents (taumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.)) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.
상기 외에 본 발명의 조성물은, 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다.In addition to the above, the composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavors and natural flavoring agents, coloring agents and heavy weight agents (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid and It may contain salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonates used in carbonated beverages, and the like.
그 밖에 본 발명에 의한 식품 조성물은 천연 과일 쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0 내지 약 20 중량부의 범위에서 선택될 수 있다.In addition, the food composition according to the present invention may contain flesh for the manufacture of natural fruit juice and fruit juice beverages and vegetable beverages. These components may be used independently or in combination. The proportion of these additives is not so critical, but may be selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.
상기 건강기능식품(functional food)이란, 특정보건용 식품(food for special health use, FoSHU)과 동일한 용어로, 영양 공급 외에도 생체조절기능이 효율적으로 나타나도록 가공된 의학, 의료효과가 높은 식품을 의미한다. 여기서 "기능(성)"이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건용도에 유용한 효과를 얻는 것을 의미한다. 본 발명의 식품은 당 업계에서 통상적으로 사용되는 방법에 의하여 제조 가능하며, 상기 제조시에는 당 업계에서 통상적으로 첨가하는 원료 및 성분을 첨가하여 제조할 수 있다. 또한 상기 식품의 제형 또한 식품으로 인정되는 제형이면 제한 없이 제조될 수 있다. 본 발명의 식품 조성물은 다양한 형태의 제형으로 제조될 수 있으며, 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용 시 발생할 수 있는 부작용 등이 없는 장점이 있고, 휴대성이 뛰어나다.The term "functional food" is the same term as food for special health use (FOSHU), and refers to foods with high medical and medical effects that have been processed to efficiently display bioregulatory functions in addition to nutritional supply. do. Here, the term "function (sex)" means obtaining useful effects for health purposes such as controlling nutrients or physiological effects on the structure and function of the human body. The food of the present invention can be prepared by a method commonly used in the art, and during the production, raw materials and ingredients commonly added in the art can be added to prepare it. In addition, the formulation of the food may be prepared without limitation as long as it is a formulation recognized as a food. The food composition of the present invention may be prepared in various forms of formulation, and unlike general drugs, it has the advantage of not having side effects that may occur when taking a drug for a long time using food as a raw material, and is excellent in portability.
이하, 본 발명을 하기 실시예에 의하여 더욱 상세하게 설명한다. 단, 하기 실시예는 본 발명을 예시하기 위한 것일 뿐, 본 발명의 범위가 이들만으로 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail by the following examples. However, the following examples are for illustrative purposes only, and the scope of the present invention is not limited thereto.
실시예Example 1. One. OREOPANAXOREOPANAX COSTARICENSISCOSTARICENSIS (( OCOC ) 추출물의 제조) Preparation of extract
실시예Example 1.1. 1.1. 중압액체크로마토그래피(MPLC)를Medium pressure liquid chromatography (MPLC) 이용한 Used OC의OC's 메탄올 Methanol 분획물Fraction 제조 Produce
OREOPANAX COSTARICENSIS의 메탄올 추출물에서 분획물을 수득하기 위하여, Armen spot prepII를 이용하여 중압액체크로마토그래피(MPLC)를 수행하였다. 구체적인 방법은 하기와 같다:In order to obtain a fraction from the methanol extract of OREOPANAX COSTARICENSIS, medium pressure liquid chromatography (MPLC) was performed using Armen spot prepII. The specific method is as follows:
실시예 1.2. UPLC를 통한 MPLC 분획물의 지표 성분 확인Example 1.2. Identification of indicator components of MPLC fractions through UPLC
상기 분획물을 분석하기 위하여, ACQUITYTM Ultra Performance LC 및 검출기로 UV 200 내지 400 nm의 파장, CAD(charged aerosol detection), MS(Mass spectrometry)를 이용하여 UPLC(Ultra Performance Liquid Chromatography) 및 분획물의 성분 분석을 수행하였다. 이때, 용매 A는 0.1% FA D.W를 사용하였으며, 용매 B는 0.1 FA ACN(acetonitrile) 용매를 이용하였다. Gradient는 하기 <표 3>과 같이 하여 분석을 수행하였다.In order to analyze the fraction, using an ACQUITY TM Ultra Performance LC and a detector with a wavelength of
이때, 컬럼은 ACQUITY UPLC® BEH C18 1.7 ㎛, 2.1 X 100 ㎜를 사용하였으며, 흡광도를 측정하기 위하여 280 nm, 254 nm, 230 nm, 360 nm 파장으로 UV를 조사하여 분석을 수행하였다. 투여 부피는 1 mg/ml으로 5 ㎕을 투여하였다.At this time, ACQUITY UPLC® BEH C18 1.7 μm, 2.1 X 100 mm was used as the column, and analysis was performed by irradiating UV with wavelengths of 280 nm, 254 nm, 230 nm, and 360 nm to measure absorbance. The dosage volume was 1 mg/ml, and 5 μl was administered.
실시예Example 2. 용매 분획법을 통한 2. Through the solvent fractionation method OCOC 분획물의Fraction 제조 Produce
실시예Example 2.1. 용매 분획법을 통한 2.1. Through solvent fractionation OCOC 분획물의Fraction 제조 Produce
도 9의 방법으로 용매 분획물을 수득하였다. 구체적으로, OC 메탄올 추출물 23.1 g을 1.5 L의 헥산에 혼합한 후 헥산 분획물을 분리하는 과정을 3회 수행한 후, 이를 감압건조시켜 OC 헥산 분획물 991.7 mg을 수득하였다. 또한, OC 헥산 분획물 제거한 물층을 클로로포름 1.5 L와 혼합하여 클로로포름 분획물을 분리하는 과정을 3회 수행한 후, 이를 감압건조시켜, OC 클로로포름 분획물 3.87 g을 수득하였다. 또한, OC 클로로포름 분획을 제거한 물층을 부탄올 1.5 L와 혼합하여 부탄올 분획물을 분리하는 과정을 3회 수행한 후, 이를 감압건조시켜, OC 부탄올 분획물을 6.49 g을 수득하였다. 이후, 물층을 12.63 g 수득하였다.A solvent fraction was obtained by the method of FIG. 9. Specifically, after 23.1 g of OC methanol extract was mixed with 1.5 L of hexane, the process of separating the hexane fraction was performed three times, and then dried under reduced pressure to obtain 991.7 mg of the OC hexane fraction. In addition, the water layer from which the OC hexane fraction was removed was mixed with 1.5 L of chloroform to separate the chloroform fraction three times, and then dried under reduced pressure to obtain 3.87 g of the OC chloroform fraction. In addition, the aqueous layer from which the OC chloroform fraction was removed was mixed with 1.5 L of butanol to separate the butanol fraction three times, and then dried under reduced pressure to obtain 6.49 g of the OC butanol fraction. Thereafter, 12.63 g of an aqueous layer was obtained.
실시예Example 2.2. 2.2. UPLCUPLC -MS를 통한 -Through MS 칼럼분획물Column fraction 및 And 용매분획물의Of the solvent fraction 지표 성분 확인 Identification of indicator components
상기 칼럼 및 용매 분획물을 분석하기 위하여, 상술한 실시예 1.2.의 방법과 동일한 방법으로 활성이 확인된 분획물의 동등성 비교 및 지표성분 분석을 수행하였다 (도 6 및 표 4).In order to analyze the column and solvent fractions, the equivalence comparison and index component analysis of the fractions whose activity was confirmed in the same manner as in Example 1.2. described above were performed (FIG. 6 and Table 4).
469,
367765,603,
469,
367
-α-D-arabinopyranosyl)-hederagenin-28-O-(β-D-glucopyranosyl
-(1->4)-β-D-glucopyranosyl) ester3β-O-(β-D-glucopyranosyl-(1->3)-α-L-rhamnopyranosyl-(1->2)
-α-D-arabinopyranosyl)-hederagenin-28-O-(β-D-glucopyranosyl
-(1->4)-β-D-glucopyranosyl) ester
469765,603,
469
28-O-[α-L-rhamnopyranosyl-(1->4)
-β-D-glucopyranosyl-(1->6)-β-D-glucopyranosyl] ester3-O-α-L-arabinopyranosyl echinocystic acid
28-O-[α-L-rhamnopyranosyl-(1->4)
-β-D-glucopyranosyl-(1->6)-β-D-glucopyranosyl] ester
469765,603,
469
469749,603,
469
485955,749,
485
4691115,749,
469
3β,23-dihydroxy olean-18-en-28-oic acid 28-O-[α-L- rhamnopyranosyl-(1->4)-β-D-6-O-acetyl glucopyranosyl-(
1->6)-β-D-glucopyranosyl] ester3-O-[αz-l-rhamnopyranosyl-(1->2)-α-larabinopyranosyl]
3β,23-dihydroxy olean-18-en-28-oic acid 28-O-[α-L- rhamnopyranosyl-(1->4)-β-D-6-O-acetyl glucopyranosyl-(
1->6)-β-D-glucopyranosyl] ester
587,
469953,791,
587,
469
실험예Experimental example 1. One. 항당뇨Antidiabetic 효과 확인 Check the effect
실험예Experimental example 1.1. 세포 독성 확인: In vitro 실험 1.1. Confirmation of cytotoxicity: in vitro experiment
L6-GLUT4myc 세포 분화 완료 후 serum-free 배지로 교환하고 6 시간 배양하였다. OC 메탄올 추출물(OC-To) 또는 1부터 6번 분획(OC_Fr.1 내지 6)을 20 μM 또는 40 μM의 농도로 24 시간 동안 처리한 후, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide(MTT) 시약을 최종농도 50 μM로 처리하고 1시간 추가 배양했다. 이후, 배지를 모두 버리고 세포 내 생성된 비수용성 포마잔은 DMSO에 녹여 540 nm에서 흡광도를 측정하였다.After completion of the L6-GLUT4myc cell differentiation, it was exchanged with a serum-free medium and cultured for 6 hours. After treating the OC methanol extract (OC-To) or
도 7에서 OC 메탄올 추출물과 6번 분획(OC_Fr.6)의 최종농도 20 μM과 40 μM의 24시간 처리군에서 세포의 생장이 대조군 대비 20%로 감소된 것으로 보아 세포 독성을 확인할 수 있었다. 나머지 분획에서는 세포 독성이 확인되지 않았다.In FIG. 7, cytotoxicity was confirmed as the cell growth was reduced to 20% compared to the control group in the 24-hour treatment group with a final concentration of 20 μM and 40 μM of OC methanol extract and fraction 6 (OC_Fr.6). No cytotoxicity was observed in the remaining fractions.
도 9는 OC 메탄올 추출물(OC_Total)을 용매별로 분획하여 세포 생장률을 확인한 결과를 보여준다. 핵산층(OC_Hex)과 물층(OC_DW)을 제외한 OC 메탄올 추출물과 클로로포름층(OC_CHCL3), 부탄올층(OC_BuOH)에서는 24 시간 약물처리로 세포독성이 나타나는 것을 확인할 수 있다.9 shows the result of confirming the cell growth rate by fractionating the OC methanol extract (OC_Total) by solvent. In the OC methanol extract, chloroform layer (OC_CHCL3), and butanol layer (OC_BuOH) except for the nucleic acid layer (OC_Hex) and water layer (OC_DW), cytotoxicity was observed after 24 hours of drug treatment.
실험예Experimental example 1.2. 1.2. 항당뇨Antidiabetic 효과 확인: In vitro 실험 Checking the effect: in vitro experiment
L6-GLUT4myc 근육아세포를 24-well plate에 2 X 105 cells/ml의 농도로 심은 후, 2일에 한번씩 배지를 교체해 주면서 8일 동안 분화를 유도했다. 분화 완료 후 serum-free 배지로 교환하고 6 시간 추가 배양하였다. 이후 OC 메탄올 추출물 또는 1부터 6번 분획을 20 μM 또는 40 μM의 농도로 30분간 처리하고, 이와 동시에 100 nM 돼지유래 인슐린(양성대조군)과 20 μM cytochalasin B(액틴 저해제)를 각각 30분간 처리했다. 반응 후, 0.2 μCi/ml [14C]-2-deoxy-D-glucose를 5분간 처리하였고, 세포내로 흡수되지 않은 기질은 모두 KRB 버퍼로 3회 세척하였다. 1 M의 수산화나트륨 500 μl로 세포를 용해시켜 이 중 200 μl lysate와 1 ml의 LSC Cocktail을 섞어 측정용 vial에 넣어 섬광계수측정기(Liquid Scintillation Analyzer, PerkinElmer, Tri-Carb 2910 TR)로 DPM값을 산출하였다. 또한, 모든 수치에서 cytochalasin B를 처리한 군의 값을 배제하여 GLUT4 비의존적인 포도당 흡수량을 배재하였다. L6-GLUT4myc myoblasts were planted in a 24-well plate at a concentration of 2 X 10 5 cells/ml, and differentiation was induced for 8 days by changing the medium once every 2 days. After completion of differentiation, it was exchanged with a serum-free medium and cultured for an additional 6 hours. Afterwards, the OC methanol extract or
도 8에서 100 nM 돼지유래 인슐린(양성대조군)의 처리는 대조군 대비 2배 가량 L6-GLUT4myc 근육아세포에서의 포도당 흡수를 증가시키는 것으로 보였다. 이에 시료를 처리한 군에서는 OC_To, OC_Fr.1, OC_Fr.4, OC_Fr.5, OC_Fr.6에서 농도의존적인 세포 내 포도당 흡수 증가가 관찰되었지만, 이 중 세포독성이 확인되었던 OC 메탄올 추출물과 OC_Fr.6을 제외시키면 OC_Fr.1, OC_Fr.4, OC_Fr.5가 근육세포에서의 포도당 흡수능 증가에 유효한 효능을 갖는다고 판단된다. In FIG. 8, treatment with 100 nM pig-derived insulin (positive control group) appeared to increase glucose uptake in L6-GLUT4myc myoblasts by about twice as much as that of the control group. Accordingly, in the group treated with the sample, concentration-dependent increase in intracellular glucose uptake was observed in OC_To, OC_Fr.1, OC_Fr.4, OC_Fr.5, and OC_Fr.6, but among these, OC methanol extract and OC_Fr. Excluding 6, it is judged that OC_Fr.1, OC_Fr.4, and OC_Fr.5 have effective efficacy in increasing glucose absorption capacity in muscle cells.
도 10은 OC 메탄올 추출물(OC_Total)을 용매별로 분획하여 포도당 흡수능을 확인한 결과를 보여준다. OC의 물층에서만 L6-GLUT4myc 근육세포에서의 포도당 흡수가 증가되는 것을 확인할 수 있었다.10 shows the result of confirming the glucose absorption ability by fractionating the OC methanol extract (OC_Total) by solvent. It was confirmed that glucose uptake in L6-GLUT4myc muscle cells was increased only in the water layer of OC.
실험예Experimental example 1.3. 1.3. 항당뇨Antidiabetic 효과 effect 확인:InCheck:In vivovivo 실험 Experiment
특정병원체 부재 ICR 암컷 마우스(5 주령)를 1 주일간 순화시키고 실험을 진행하였다. 시료는 10% DMSO/ 10% Tween-20에 녹이고, 양성대조물질인 Metformin은 PBS에 녹였다. 투여 액량은 10 ml/kg가 되게 하였다. 순화된 마우스는 시험 전 16시간 절식하였다. 실험 당일 마우스에 시료를 경구 투여하고 90분 후, D-(+)-glucose를 2 g/kg 용량으로 마리 당 0.2 ml씩 경구 투여하였다. D-(+)-glucose 처리 시점을 0분으로하고 이후 15, 30, 60, 120 분에 꼬리 채혈을 통해 혈당을 측정하였다.ICR female mice (5 weeks old) without a specific pathogen were acclimatized for 1 week and the experiment was carried out. The sample was dissolved in 10% DMSO/10% Tween-20, and the positive control, Metformin, was dissolved in PBS. The amount of liquid to be administered was 10 ml/kg. The acclimated mice were fasted for 16 hours before the test. On the day of the experiment, a sample was orally administered to mice and 90 minutes later, D-(+)-glucose was orally administered at a dose of 2 g/kg at 0.2 ml per head. The time point of D-(+)-glucose treatment was set to 0 minutes, and blood glucose was measured through tail blood sampling at 15, 30, 60, and 120 minutes thereafter.
도 11에서 D-(+)-glucose 처리군의 혈당변화를 살펴보면 D-(+)-glucose 처리 후 30분에 혈당이 320 mg/dL로 빠르게 높아졌다가 120 분까지 서서히 감소하는 추이를 나타낸다. 이에 OC 메탄올 추출물 250 mg/kg 또는 500 mg/kg의 전처리는 D-(+)-glucose 투여 후 혈당상승을 감쇄시켜주는 것을 확인할 수 있다. 이때 양성대조물질인 Metformin 500 mg/kg의 처리는 혈당의 상승을 약 50% 가량 낮춰주는 것으로 보였다.In FIG. 11, a change in blood sugar in the D-(+)-glucose treatment group shows a trend in which blood sugar rapidly increases to 320 mg/
도 12에서는 OC 메탄올 추출물과 용매분획물들을 500 mg/kg 농도로 전처리 했을 때 D-(+)-glucose 투여에 따른 혈당변화추이를 살펴보았다. D-(+)-glucose 투여 후 30분 혈당치를 기준으로 부탄올층, 물층, 클로로포름층, 메탄올 추출물, 헥산층 순으로 혈당강하 효능이 우수한 것으로 보였다. 도 13은 도 12의 결과를 바탕으로 30분 혈당치에서 0분의 혈당치를 빼서 혈당상승률을 그래프로 나타낸 것이다.In FIG. 12, when the OC methanol extract and the solvent fraction were pretreated at a concentration of 500 mg/kg, the change in blood glucose according to the administration of D-(+)-glucose was examined. Based on the
실험예Experimental example 2. 2. 항비만Anti-obesity 효과 확인: In vitro 실험 Checking the effect: in vitro experiment
쥐의 지방전구세포인 3T3-L1 세포를 이용하여 분화유도(DM, differentiation medium) 배지로 교환하여 6일 동안 분화를 유도하였다. 지방 분화 유도 과정은 10% (v/v) FBS와 1% (v/v) penicillin-streptomycin을 첨가한 DMEM에 500 μM IBMX, 5.2 μM DEX, 167 nM insulin을 포함한 differentiation media (DM)을 이용하여 day 0부터 day 2까지 48h 동안 처리하였고, 분화유도 후 post-differentiation media (Post-DM)은 10% (v/v) FBS와 1% (v/v) penicillin-streptomycin이 첨가된 DMEM에 167 nM insulin만을 첨가하여 day 2부터 day 4까지 처리하였다. Day 4부터 day 6까지는 10% (v/v) FBS와 1% (v/v) penicillin-streptomycin이 첨가된 DMEM으로만 48h 동안 처리하였고, day 6에 지방세포 분화를 종료하였다. 지방분화과정 중 약물의 효과를 확인하기 위하여 배지를 교환할 때마다 추출물 및 용매분획물 (10-80 μg/mL)을 함께 처리하였다.Differentiation medium (DM, differentiation medium) was used to induce differentiation for 6 days using 3T3-L1 cells, which are rat adipocytes. Adipose differentiation induction process was performed using differentiation media (DM) containing 500 μM IBMX, 5.2 μM DEX, and 167 nM insulin in DMEM supplemented with 10% (v/v) FBS and 1% (v/v) penicillin-streptomycin. Treatment was performed for 48h from
OC 추출물 및 용매분획물에 대한 항비만 활성을 평가하기 전, 쥐의 지방전구세포인 3T3-L1 세포에 미치는 OC 추출물 및 용매분획물의 세포독성을 알아보고자 CCK-8(Dojindo) 키트를 사용하여 측정한 결과, 추출물을 제외하고는 40 μg/mL 이하 농도에서는 세포 생존력에 영향을 없음을 확인하였다(도 14). 이러한 결과를 토대로, OC 추출물 및 용매분획물은 10-40 μg/mL까지 농도 의존적으로 비만세포 내 중성지방의 함량이 감소되는지의 여부를 중성지방염색시약인 Oil Red O 염색한 다음 탈염색을 통해 정량적으로 측정한 결과, 추출물 및 CHCl3 분획물 층에서 비만세포 내 지질축적이 저해되고 있음을 확인하였다(도 15).Before evaluating the anti-obesity activity against the OC extract and the solvent fraction, the cytotoxicity of the OC extract and the solvent fraction on 3T3-L1 cells, which is the adipocyte of the rat, was measured using the CCK-8 (Dojindo) kit. As a result, it was confirmed that, except for the extract, there was no effect on the cell viability at a concentration of 40 μg/mL or less (FIG. 14). Based on these results, the OC extract and solvent fraction were quantitatively determined by staining with Oil Red O, a triglyceride dyeing reagent, and then destaining to determine whether or not the content of triglycerides in mast cells decreases in a concentration-dependent manner up to 10-40 μg/mL. As a result of measurement, it was confirmed that lipid accumulation in mast cells was inhibited in the extract and the CHCl 3 fraction layer (FIG. 15).
Claims (11)
상기 추출물은 물, C1 내지 C3의 저급 알코올 또는 이의 혼합물로 추출되는 것인, 당뇨병 예방 또는 치료용 약학 조성물.The method of claim 1,
The extract will be extracted with water, C 1 to C 3 lower alcohol or a mixture thereof, a pharmaceutical composition for preventing or treating diabetes.
상기 저급 알코올은 메탄올, 에탄올, 또는 프로판올인 것인, 당뇨병 예방 또는 치료용 약학 조성물.The method of claim 2,
The lower alcohol is methanol, ethanol, or propanol, which is a pharmaceutical composition for preventing or treating diabetes.
상기 분획물은 메탄올 추출물을 중합액체크로마토그래피를 통해 수득된 것인, 당뇨병 예방 또는 치료용 약학 조성물.The method of claim 1,
The fraction is obtained through a methanol extract polymerized liquid chromatography, a pharmaceutical composition for preventing or treating diabetes.
상기 분획물은 헥산 분획물, 클로로포름 분획물, 또는 부탄올 분획물인 것인, 당뇨병 예방 또는 치료용 약학 조성물.The method of claim 1,
The fraction is a hexane fraction, a chloroform fraction, or a butanol fraction, a pharmaceutical composition for preventing or treating diabetes.
상기 추출물은 물, C1 내지 C3의 저급 알코올 또는 이의 혼합물로 추출되는 것인, 비만 예방 또는 치료용 약학 조성물.The method of claim 6,
The extract is extracted with water, C 1 to C 3 of lower alcohol or a mixture thereof, a pharmaceutical composition for preventing or treating obesity.
상기 분획물이 메탄올 추출물을 중합액체크로마토그래피를 통해 수득된 것인, 비만 예방 또는 치료용 약학 조성물.The method of claim 6,
A pharmaceutical composition for preventing or treating obesity, wherein the fraction is obtained through polymerization liquid chromatography of a methanol extract.
상기 분획물은 헥산 분획물, 클로로포름 분획물, 또는 부탄올 분획물인 것인, 비만 예방 또는 치료용 약학 조성물.The method of claim 6,
The fraction is a hexane fraction, a chloroform fraction, or a butanol fraction, wherein the pharmaceutical composition for preventing or treating obesity.
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