KR102064651B1 - Composition for preventing or improving diabetes mellitus comprising momrdica charantia (l.) extract, chrysanthemum zawadskii var. latilobum and paeonia lactiflora extract as an effective ingredient - Google Patents

Composition for preventing or improving diabetes mellitus comprising momrdica charantia (l.) extract, chrysanthemum zawadskii var. latilobum and paeonia lactiflora extract as an effective ingredient Download PDF

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KR102064651B1
KR102064651B1 KR1020170160760A KR20170160760A KR102064651B1 KR 102064651 B1 KR102064651 B1 KR 102064651B1 KR 1020170160760 A KR1020170160760 A KR 1020170160760A KR 20170160760 A KR20170160760 A KR 20170160760A KR 102064651 B1 KR102064651 B1 KR 102064651B1
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김현규
이학성
이진규
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    • A23V2200/328Foods, ingredients or supplements having a functional effect on health having effect on glycaemic control and diabetes
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Abstract

본 명세서에는 여주 추출물, 구절초 추출물 및 작약 추출물을 유효성분으로 포함하는 당뇨 예방 또는 개선용 조성물, 및 혈당 조절용 조성물이 개시된다. 본 발명에 따른 조성물은 당뇨와 관련된 다양한 인자들의 활성을 다각적으로 조절하여, 우수한 당뇨 예방 또는 개선 효과가 있다. 구체적으로, 알파-아밀라아제의 활성을 저해하고, 소장세포의 포도당 흡수를 저해하며, 근육세포에서 포도당의 흡수를 증진시켜 당뇨의 예방 또는 개선에 효과적이다.Disclosed herein is a composition for preventing or improving diabetes, and a composition for controlling blood sugar, including an extract of Yeoju, Gujeolcho, and Peony extract as active ingredients. The composition according to the present invention is to control the activity of various factors related to diabetes in a variety of ways, there is excellent diabetes prevention or improvement effect. Specifically, it is effective in preventing or improving diabetes by inhibiting the activity of alpha-amylase, inhibiting glucose absorption of small intestine cells, and promoting glucose absorption in muscle cells.

Description

여주 추출물, 구절초 추출물 및 작약 추출물을 유효 성분으로 포함하는, 당뇨 예방 또는 개선용 조성물{COMPOSITION FOR PREVENTING OR IMPROVING DIABETES MELLITUS COMPRISING MOMRDICA CHARANTIA (L.) EXTRACT, CHRYSANTHEMUM ZAWADSKII VAR. LATILOBUM AND PAEONIA LACTIFLORA EXTRACT AS AN EFFECTIVE INGREDIENT}COMPOSITION FOR PREVENTING OR IMPROVING DIABETES MELLITUS COMPRISING MOMRDICA CHARANTIA (L.) EXTRACT, CHRYSANTHEMUM ZAWADSKII VAR. LATILOBUM AND PAEONIA LACTIFLORA EXTRACT AS AN EFFECTIVE INGREDIENT}

본 발명은 여주 추출물, 구절초 추출물 및 작약 추출물을 유효성분으로 포함하는 당뇨 예방 또는 개선용 조성물에 관한 것이다.The present invention relates to a composition for preventing or improving diabetes comprising an extract of Yeoju, Gujeolcho and Peony extract as active ingredients.

당뇨는 혈액 내에 존재하는 포도당이 소변을 통해 배출되는 질환으로, 근본적인 치유가 되지 않는 만성 성인병 중의 하나이다. 급속한 경제발전에 따른 식생활의 변화로 평균수명은 연장되는 현상에 반하여 당뇨병 등의 만성질환은 증가하는 현상을 보이고 있다. 국내에서 당뇨의 유병율은 약 5~10%에 달하는 것으로 조사되어 있으며, 2007년 당뇨 환자는 400만명을 넘어서 인구 100명 중 8.3명이 당뇨 질환자이지만 2025년에는 당뇨 환자가 약 680만명으로 늘어날 것으로 예측되고 있다. 당뇨는 다양한 합병증으로 인해 환자의 수명이 5~10년 정도 단축되며, 합병증을 포함하여 현재 우리나라의 경우 사망원인 중 5순위에 있다.Diabetes is a disease in which glucose present in the blood is released through urine and is one of chronic adult diseases that are not fundamentally cured. As life expectancy changes due to rapid economic development, life expectancy increases, whereas chronic diseases such as diabetes increase. The prevalence of diabetes in Korea is estimated to be about 5 to 10%. In 2007, the number of diabetics exceeded 4 million, 8.3 out of every 100 people with diabetes, but the number of diabetics is expected to increase to about 6.8 million by 2025. have. Diabetes shortens the lifespan of patients by 5 to 10 years due to various complications, and is currently ranked 5th among the causes of death in Korea, including complications.

따라서, 당뇨병의 치료를 위한 다양한 시도들이 계속되고 있고, 특히 아카보즈(Acarbose), 보글리보스(voglibose)와 같은 약물들이 일반적으로 사용되고 있는데, 이들 약물들은 복부팽만감, 구토, 설사 등의 부작용이 발생한다. 따라서, 약물 부작용을 최소화하기 위하여 천연물을 이용한 당뇨 치료제의 개발이 계속 중인데, 단독 천연물질의 연구에만 그치는 경우가 대부분이고, 그 이유는 상승효과를 보이는 천연물질의 조합을 찾는 것이 쉽지 않기 때문이다. 천연물질은 인공 화합물질에 비해 부작용은 적지만 치료 효과가 약하므로, 서로 상승효과를 보이는 조합을 찾는 것이 매우 중요하다.Therefore, various attempts for the treatment of diabetes continue, and in particular, drugs such as Acarbose and Voglibose are generally used, and these drugs cause side effects such as bloating, vomiting and diarrhea. . Therefore, in order to minimize drug side effects, the development of a diabetes treatment using natural products is being continued. Most often, only studies of natural materials are used, because it is not easy to find a combination of natural substances showing a synergistic effect. Natural substances have fewer side effects than artificial compounds, but the therapeutic effect is weak, so it is very important to find a combination that has synergistic effects.

2015년 사망원인통계결과, 통계청, 2016.9. Cause of death statistics in 2015, Statistics Korea, 2016.9.

일 측면에서, 본 발명의 목적은, 혈당을 조절하고, 당뇨를 예방 또는 개선하는 것이다.In one aspect, the object of the present invention is to control blood sugar and prevent or improve diabetes.

일 측면에서, 본 발명의 목적은, 당뇨와 관련된 다양한 인자들을 조절할 수 있는 조성물을 제공하는 것이다.In one aspect, it is an object of the present invention to provide a composition that can control various factors associated with diabetes.

일 측면에서, 본 발명의 목적은, 알파-아밀라아제의 활성을 저해하고, 소장세포의 포도당 흡수를 저해하며, 근육세포에서 포도당의 흡수를 증진시키는 것이다.In one aspect, an object of the present invention is to inhibit the activity of alpha-amylase, inhibit glucose uptake of small intestine cells, and enhance glucose uptake in muscle cells.

일 측면에서, 본 발명의 목적은, 여주 추출물, 구절초 추출물 및 작약 추출물의 조합이 최적의 효과를 낼 수 있는 함량비를 제공하는 것이다.In one aspect, it is an object of the present invention, to provide a content ratio that the combination of bitter gourd extract, gujeolcho extract and peony extract can achieve the optimum effect.

상기 목적을 달성하기 위하여, 본 발명은 일 측면에서, 여주 추출물, 구절초 추출물 및 작약 추출물을 유효성분으로 포함하는 당뇨 예방 또는 개선, 또는 혈당 조절용 조성물을 제공한다.In order to achieve the above object, in one aspect, the present invention provides a composition for preventing or improving diabetes, or blood sugar control, comprising an extract of Yeoju, Gujeolcho, and Peony extract as active ingredients.

본 발명의 일 측면에 따른 여주 추출물, 구절초 추출물 및 작약 추출물을 유효성분으로 포함하는 조성물은, 당뇨와 관련된 다양한 인자들의 활성을 다각적으로 조절하여, 우수한 당뇨 예방 또는 개선 효과가 있다. 구체적으로, 알파-아밀라아제의 활성을 저해하고, 소장세포의 포도당 흡수를 저해하며, 근육세포에서 포도당의 흡수를 증진시켜 당뇨의 예방 또는 개선에 효과적이다.The composition comprising the extract of Yeoju, Gujeolcho and Peony extract according to an aspect of the present invention as an active ingredient, by controlling the activity of various factors related to diabetes in a variety of ways, there is an excellent diabetes prevention or improvement effect. Specifically, it is effective in preventing or improving diabetes by inhibiting the activity of alpha-amylase, inhibiting glucose absorption of small intestine cells, and promoting glucose absorption in muscle cells.

도 1은 여주, 구절초 및 작약 추출물을 처리한 후 알파-글로코시데이즈 저해활성을 확인한 결과를 보이는 것이다.
도 2는 여주, 구절초 및 작약 추출물을 처리한 후 알파-아밀라아제 활성 저해 효과를 확인한 결과를 보이는 것이다.
도 3은 여주, 구절초 및 작약 추출물을 처리한 후 소장 세포에서의 당 흡수 저해활성을 확인한 결과를 보이는 도이다.
도 4는 여주, 구절초 및 작약 추출물을 처리한 후 근육에서의 포도당 흡수 활성을 확인한 결과를 보이는 도이다.
도 5 내지 도 7은 동물실험 결과를 보이는 것으로서, 도 5는, 여주, 구절초 및 작약 추출물의 혈당 조절 효능을 확인한 동물실험 결과를 보이는 도이고, 도 6은 여주, 구절초 및 작약 추출물의 경구 내당능을 확인한 결과를 보이는 도이며, 도 7은 혈중 글루코오즈 농도(도 7a)와 당화혈색소 농도(도 7b)를 측정한 결과를 보이는 도이다.
도 1a, 2a, 3a 및 4a는 여주, 구절초 및 작약 추출물을 각각 처리한 경우, 도 1b, 2b, 3b, 4b는 여주 추출물이 과량 포함되어 있는 여주, 구절초 및 작약 추출물의 혼합물을 처리한 경우, 도 1c, 2c, 3c 및 4c는 작약 추출물이 과량 포함되어 있는 경우, 도 1d, 2d, 3d 및 4d는 구절초 추출물이 과량 포함되어 있는 경우이다.
Figure 1 shows the results of confirming the alpha-glucosidase inhibitory activity after the treatment of Yeoju, Gujeolcho and Peony extract.
Figure 2 shows the results of confirming the effect of inhibiting alpha-amylase activity after treating the extract of Yeoju, gujeolcho and peony.
Figure 3 is a diagram showing the results of confirming the glucose uptake inhibitory activity in the small intestine cells after treatment with Yeoju, gujeolcho and peony extract.
Figure 4 is a diagram showing the result of confirming the glucose absorption activity in the muscle after treating the extract of Yeoju, gujeolcho and peony.
5 to 7 shows the results of animal experiments, FIG. 5 is a diagram showing the results of animal experiments confirming the glycemic control effect of Yeoju, Gujeolcho and Peony extract, and FIG. 6 shows the oral glucose tolerance of Yeoju, Gujeolcho and Peony extract. 7 is a diagram showing the results obtained by measuring blood glucose concentration (FIG. 7A) and glycated hemoglobin concentration (FIG. 7B).
Figures 1a, 2a, 3a and 4a is treated with the bitter gourd, gujeolcho and peony extract, respectively, Figures 1b, 2b, 3b, 4b is treated with a mixture of the extract of the bitter gourd, gujeolcho and peony extract containing excess, Figures 1c, 2c, 3c and 4c is the case where the excessive amount of the peony extract, Figures 1d, 2d, 3d and 4d is the case that contains excessive Gujeolcho extract.

이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.

일 측면에서, 본 발명은, 여주(Momordica charantia L.) 추출물, 구절초(Chrysanthemum zawadskii var. latilobum) 추출물 및 작약(Paeonia lactiflora) 추출물을 유효성분으로 포함하는, 당뇨 예방 또는 개선용 조성물이다.In one aspect, the present invention, Momordica charantia L. extract, Chrysanthemum zawadskii var.latilobum extract and Peony ( Paeonia lactiflora ) extract as an active ingredient, a composition for preventing or improving diabetes.

일 측면에서, 본 발명은, 여주(Momordica charantia L.) 추출물, 구절초(Chrysanthemum zawadskii var. latilobum) 추출물 및 작약(Paeonia lactiflora) 추출물을 유효성분으로 포함하는, 혈당 조절용 조성물이다.In one aspect, the present invention, Momordica charantia L. extract, Chrysanthemum zawadskii var. Latilobum extract and Paeonia lactiflora extract as an active ingredient, a composition for blood sugar control.

여주(Momordica charantia L.)는 아시아에서 널리 재배되는 박과의 다년생 덩굴식물이다. 여주는 항산화 효능을 가지고 있는 비타민 C를 포함하여 케란틴, 카로틴, 칼슘, 철, 엽산, 판토텐산, 식물섬유, 모모르데신 등이 함유되어 있으며 항암효과와 말라리아 치료, 체중 감소, 소화 촉진 기능을 가지고 있어 한방의 재료로 널리 사용되고 있다. Lime ( Momordica charantia L.) is a perennial vine plant of edible fruit widely grown in Asia. Yeoju contains keratin, carotene, calcium, iron, folic acid, pantothenic acid, plant fiber, and Momordine, including vitamin C, which has antioxidant effects, and has anti-cancer effects, anti-malarial treatment, weight loss, and digestive function. It is widely used as a herbal material.

구절초(Chrysanthemum zawadskii var. latilobum)는 국화과에 속하는 다년생 쌍떡잎 식물로, 구절초는 전국 각처의 산지와 고원지에서 자생하고 중국, 러시아, 몽골, 일본 등지에서 자란다. 구절초는 무월경, 폐렴, 기관지염, 감기, 인두염 등에 민간요법으로 사용되고 있다. Guryolcho ( Chrysanthemum zawadskii var.latilobum ) is a perennial dicotyledonous plant belonging to the Asteraceae family. Gujeolcho is native to mountainous and highland regions around the country and grows in China, Russia, Mongolia, and Japan. Gujeolcho is used as a folk remedy for amenorrhea, pneumonia, bronchitis, cold, pharyngitis.

작약(Paeonia lactiflora)은 미나리아재비과의 여러해살이 풀인 함박꽃의 뿌리로 주로 약재로 사용된다. 작약에는 패오니플로린(Paeoniflorin), 패오놀(Paeonel), 패오닌(Paeonin), 탄닌(Tannin), 베타-시토스테롤(β-sitosterol), 트리테르페노이드(triterpenoid), 정유, 지방유, 수지 등의 성분이 다량 함유되어 있어 항산화, 함염증, 진통효과, 혈액보강, 면역 강화 등의 작용을 함에 따라 질병의 예방 및 치료에 사용되고 있다. Peony ( Paeonia lactiflora ) is the root of the perennial herbaceous perennial herbaceous flower, mainly used as a medicinal herb. Peony includes Paeoniflorin, Paeonel, Paeonin, Tannin, Beta-Sitosterol, Triterpenoid, Essential Oil, Fat Oil, Resin, etc. As it contains a large amount of antioxidants, it is used for the prevention and treatment of diseases as it acts as an antioxidant, inflammation, analgesic effect, blood reinforcement, strengthening immunity.

본 명세서에서 “당뇨”란, 인슐린의 분비량이 부족하거나 정상적인 기능이 이루어지지 않는 등의 대사질환의 일종으로, 혈중 포도당의 농도가 높아지는 고혈당을 특징으로 하며, 고혈당으로 인하여 여러 증상 및 징후를 일으키고 소변에서 포도당을 배출하게 되는 질환을 의미할 수 있다.In the present specification, "diabetes" is a kind of metabolic disease such as insufficient insulin secretion or normal function, and is characterized by high blood sugar, which increases the concentration of glucose in the blood, and causes various symptoms and signs due to high blood sugar and urine. May mean a disease that causes glucose to be released.

제1형 당뇨는, '소아 당뇨병'이라고 불리며, 유전적으로, 인슐린을 전혀 생산하지 못하는 당뇨를 의미할 수 있다. 제2형 당뇨는 후천적 원인에 의한 당뇨로서, 인슐린 저항성(insulin resistance; 혈당을 낮추는 인슐린 기능이 떨어져 세포가 포도당을 효과적으로 연소하지 못하는 것)을 특징으로 하는 당뇨를 의미할 수 있다. 상기와 같은 측면에서, 상기 당뇨는, 제1형 당뇨 또는 제2형 당뇨를 포함할 수 있다. Type 1 diabetes, referred to as 'pediatric diabetes', may genetically mean diabetes that produces no insulin at all. Type 2 diabetes may be diabetes due to an acquired cause, and may include diabetes, which is characterized by insulin resistance (insufficiency of insulin lowering blood sugar and inability of cells to burn glucose effectively). In the above aspect, the diabetes may include type 1 diabetes or type 2 diabetes.

본 명세서에서 “혈당 조절”이란, 혈중 포도당의 농도를 당뇨가 없는 사람의 수준으로 낮추는 것을 의미한다.As used herein, "blood glucose control" means lowering the concentration of glucose in the blood to the level of a person without diabetes.

일 측면에서, 상기 여주 추출물, 구절초 추출물 및 작약 추출물은, 각각 1~100: 1~100: 1~100의 중량비로 포함될 수 있다.In one aspect, the bitter gourd extract, gujeolcho extract and peony extract may be included in a weight ratio of 1 to 100: 1 to 100: 1 to 100, respectively.

상기와 같은 측면에서, 상기 여주 추출물, 구절초 추출물 및 작약 추출물은, 각각5~15: 0.5~2: 0.5~2의 중량비, 0.5~2: 5~15: 0.5~2의 중량비 또는 0.5~2: 0.5~2: 5~15의 중량비로 포함될 수 있고, 바람직하게는, 8~12: 0.8~1.2: 0.8~1.2, 0.8~1.2: 8~12:0.8~1.2, 또는 0.8~1.2: 0.8~1.2: 8~12로 포함될 수 있다. 여주 추출물, 구절초 추출물 및 작약 추출물이 상기 중량비로 포함될 때, 각 추출물의 조합에 따른 상승효과로 인하여, 여주 추출물, 구절초 추출물 및 작약 추출물 각각보다 현저히 우수한 당뇨 개선 효과를 얻을 수 있다. 또한, 상기 비율에서, 여주 추출물, 구절초 추출물 및 작약 추출물 중 어느 한가지 추출물의 함량비만 높게 설정하면, 나머지 두가지 종류의 추출물의 함량은 낮게 설정하여도, 높은 함량의 추출물을 동일 함량으로 단독 처리했을 때보다 월등히 우수한 당뇨 개선 효과를 얻을 수 있다.In the above aspect, the bitter gourd extract, gujeolcho extract and peony extract, respectively, the weight ratio of 5-15: 0.5-2: 0.5-2, 0.5-2: 5-15: 0.5-2 weight ratio or 0.5-2: It may be included in a weight ratio of 0.5 to 2: 5 to 15, preferably, 8 to 12: 0.8 to 1.2: 0.8 to 1.2, 0.8 to 1.2: 8 to 12: 0.8 to 1.2, or 0.8 to 1.2: 0.8 to 1.2 It can be included as 8 ~ 12. When Yeoju extract, Gujeolcho extract and Peony extract are included in the weight ratio, due to the synergistic effect of the combination of each extract, it is possible to obtain a significantly improved diabetes improvement effect than Yeoju extract, Gujeolcho extract and peony extract. In addition, in the above ratio, if only the content ratio of any one of the extract of Yeoju extract, Gujeolcho and Peony extract is set high, even if the content of the other two kinds of extract is set low, the high content of the extract is treated with the same content alone. Excellent diabetes improvement can be obtained.

일 구현예에서, 상기 조성물은, 알파-글루코시데이즈 활성 억제; 소장세포의 당 흡수 억제; 혈중 포도당 농도 감소; 포도당 대사 활성 증진; 및 근육세포의 당 흡수 증진 중 하나 이상의 특징을 포함할 수 있다.In one embodiment, the composition further comprises: inhibiting alpha-glucosidase activity; Inhibiting glucose uptake of small intestine cells; Decrease in blood glucose levels; Enhancing glucose metabolism activity; And enhancing glucose uptake of muscle cells.

또한, 상기와 같은 측면에서, 상기 조성물은, 상기 여주 추출물, 구절초 추출물 및 작약 추출물을, 조성물 총 중량을 기준으로 0.1~99.9%(w/w)로 포함할 수 있고, 바람직하게는 0.5~55%(w/w), 더욱 바람직하게는 3~55%(w/w)로 포함할 수 있다. In addition, in the above aspect, the composition, the extract of Yeoju, Gujeolcho and peony extract may include 0.1 to 99.9% (w / w) based on the total weight of the composition, preferably 0.5 to 55 % (w / w), more preferably 3 to 55% (w / w).

일 측면에서, 상기 추출물들의 추출용매는, 물, 유기용매 또는 이들의 혼합물일 수 있다. 상기 유기용매는, 제한되지 않고, 알코올, 아세트산, DMSO(dimethyl sulfoxide), 아세톤, 아세토나이트릴, 에틸아세테이트, 펜탄, 헥산, 클로로포름, 디에틸에테르, 사염화탄소를 포함할 수 있다. 또한, 상기 알코올은, C1-4 알코올일 수 있고, 예컨대, 메탄올, 에탄올, 프로판올, n-부탄올, 이소-부탄올일 수 있다. 상기 유기용매는 바람직하게 에탄올일 수 있다. 상기 식물 추출물들을 에탄올로 추출한 경우, 추출효율을 극대화하고, 추출물의 효과를 극대화시킬 수 있다.In one aspect, the extraction solvent of the extract may be water, an organic solvent or a mixture thereof. The organic solvent is not limited, and may include alcohol, acetic acid, dimethyl sulfoxide (DMSO), acetone, acetonitrile, ethyl acetate, pentane, hexane, chloroform, diethyl ether, and carbon tetrachloride. In addition, the alcohol may be a C 1-4 alcohol, for example, methanol, ethanol, propanol, n-butanol, iso-butanol. The organic solvent may be preferably ethanol. When the plant extracts are extracted with ethanol, it is possible to maximize the extraction efficiency, to maximize the effect of the extract.

본 명세서에서, “추출물”은 조추출물(crude extract)뿐만 아니라, 상기 조추출물을 분획(fraction)한 분획물도 포함할 수 있다. 즉, 추출물은 상술한 추출용매를 이용하여 얻은 것뿐만 아니라, 정제과정을 추가적으로 적용하여 얻은 것도 포함한다. 이와 같이 제조된 본 실시예의 추출물은 고체, 액체 등 다양한 형태로 구현될 수 있다. In the present specification, the "extract" may include not only crude extract, but also fractions obtained by fractionating the crude extract. That is, the extract includes not only those obtained by using the above-described extraction solvent, but also those obtained by additionally applying a purification process. The extract of the present embodiment prepared as described above may be implemented in various forms such as solid and liquid.

상기 여주 추출물, 구절초 추출물 및 작약 추출물은 각각 식물의 줄기, 꽃, 뿌리, 잎, 열매, 또는 전초 추출물일 수 있다. 상기 여주 추출물, 구절초 추추물 및 작약 추출물은 바람직하게, 각각 전초의 추출물일 수 있다.The bitter gourd extract, gujeolcho extract and peony extract may be the stem, flower, root, leaf, fruit, or starch extract of the plant, respectively. The bitter gourd extract, gujeolcho extract and peony extract may be preferably extracts of the outpost, respectively.

일 구현예에서, 상기 조성물은, 약학적 조성물 또는 식품 조성물일 수 있다.In one embodiment, the composition may be a pharmaceutical composition or a food composition.

본 발명의 약학적 조성물은 경구 또는 비경구의 여러 가지 제형일 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다.The pharmaceutical composition of the present invention may be in various oral or parenteral formulations. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used.

경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 하나 이상의 화합물에 적어도 하나 이상의 부형제 예를 들면, 전분, 탄산칼슘, 수크로오스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 스테아린산 마그네슘, 탈크 등과 같은 윤활제들도 사용된다.Solid form preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, which form at least one excipient such as starch, calcium carbonate, sucrose or lactose (at least one compound). lactose) and gelatin. In addition to simple excipients, lubricants such as magnesium stearate, talc and the like are also used.

경구투여를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. Liquid preparations for oral administration include suspensions, liquid solutions, emulsions, and syrups, and various excipients such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin, may be included. have.

비경구투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 포함된다. 비수성용제 및 현탁용제로는 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, 글리세로젤라틴 등이 사용될 수 있다.Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and the suspension solvent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

본 발명에 따른 약학적 조성물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 그러나, 바람직한 효과를 위해서 본 발명의 조성물은 0.001~100 mg/kg/day 로 투여될 수 있다.The preferred dosage of the pharmaceutical composition according to the present invention depends on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. However, for the desired effect, the composition of the present invention may be administered at 0.001-100 mg / kg / day.

본 발명에 따른 약학적 조성물의 투여 형태는 이들의 약학적으로 허용가능한 염의 형태로도 사용될 수 있고, 또한, 단독으로 또는 기타 약학적 활성 화합물과 결합뿐만 아니라 적당한 집합으로 사용될 수 있다.Dosage forms of the pharmaceutical compositions according to the invention may be used in the form of their pharmaceutically acceptable salts, and may also be used alone or in combination with other pharmaceutically active compounds as well as in a suitable collection.

본 발명의 약학적 조성물은 랫트, 마우스, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 복강내, 직장 또는 정맥, 근육, 피하, 자궁내 경막 또는 뇌혈관내 주사에 의해 투여될 수 있다.The pharmaceutical composition of the present invention can be administered to mammals such as rats, mice, livestock, humans, and the like by various routes. All modes of administration can be expected, for example, by oral, intraperitoneal, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or cerebrovascular injections.

본 발명의 실시예에 따른 식품 조성물은 추출혼합물 또는 혼합추출물을 단독으로 또는 다른 식품 또는 다른 식품 성분과 함께 사용할 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 본 실시예에 따른 식품조성물은 식품 제조 시에 통상적으로 첨가되는 성분을 포함하며, 예를 들어, 단백질, 탄수화물, 지방, 영양소 및 조미제를 포함한다. 또한, 식품의 종류에는 특별한 제한이 없으나, 육류, 소시지, 빵, 초콜릿, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알코올음료, 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강식품을 모두 포함한다.The food composition according to the embodiment of the present invention may be used alone or in combination with other foods or other food ingredients, extracts or mixed extracts may be suitably used according to conventional methods. The food composition according to the present embodiment includes ingredients that are commonly added during food production, and include, for example, proteins, carbohydrates, fats, nutrients and seasonings. In addition, there are no particular restrictions on the type of food, but meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products, including ice cream, various soups, drinks, tea, drinks, Alcohol drinks, vitamin complexes, and the like, and include all of the health food in the usual sense.

본 실시예에 따른 식품 조성물은 통상의 음료와 같이 여러가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드, 말토스, 수크로스와 같은 디사카라이드, 및 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드, 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 감미제로서는 타우마틴, 스테비아 추출물과 같은 천연 감미제나, 사카린, 아스파탐과 같은 합성 감미제 등을 사용할 수 있다.The food composition according to the present embodiment may contain various flavors or natural carbohydrates, etc. as additional ingredients, as in general beverages. The above-mentioned natural carbohydrates are glucose, monosaccharides such as fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, sugar alcohols such as xylitol, sorbitol and erythritol. As the sweetening agent, natural sweetening agents such as tautin and stevia extract, and synthetic sweetening agents such as saccharin and aspartame can be used.

나아가, 본 실시예의 식품 조성물은 여러가지 영양제, 비타민, 전해질, 풍미제, 착색제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 본 실시예의 식품조성물은 천연 과일주스, 과일주스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 혼합하여 사용할 수 있다.Furthermore, the food composition of the present embodiment may be formulated with various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, And carbonating agents used in carbonated drinks. In addition, the food composition of the present embodiment may contain a flesh for preparing natural fruit juice, fruit juice drink and vegetable drink. These components can be used independently or in combination.

이하 실시예를 통하여 본 발명에 대해 구체적으로 설명하기로 한다. 이들 실시예는 단지 본 발명을 예시하기 위한 것이므로, 본 발명의 범위가 이들 실시예에 의해 제한되는 것은 아니다.Hereinafter, the present invention will be described in detail with reference to Examples. These examples are only intended to illustrate the invention, so the scope of the invention is not limited by these examples.

[실시예 1] 여주, 구절초 및 작약 추출물의 제조Example 1 Preparation of Yeoju, Gujeolcho and Peony Extracts

[실시예 1-1] 여주, 구절초 및 작약 각각의 추출물 제조Example 1-1 Preparation of Extracts of Yeoju, Gujeolcho and Peony

여주, 구절초, 및 작약 각각의 생약재를 음건하고 세절하여 동일한 각각의 생약재 총 무게의 10배의 용매를 가한 뒤 4시간을 끓여 추출하여 추출물을 얻었다. 이러한 추출물을 여과하고 감압농축기로 농축하여 동결건조함으로써 추출물을 제조하였다. 또한, 실험을 위해 추출물을 10% DMSO에 10 ~ 100 mg/ml의 농도로 녹여 무균여과지(Millipore membrane, 0.45μm)로 여과한 뒤 무균상태를 유지하였다.Yeoju, Gujeolcho, and Peony were dried and shredded, and added with 10 times the solvent of the total weight of the same herbal medicine, and then boiled and extracted for 4 hours to obtain an extract. The extract was filtered, concentrated in a vacuum condenser, and lyophilized to prepare an extract. In addition, the extract was dissolved in 10% DMSO at a concentration of 10 ~ 100 mg / ml for filtration on a sterile filter paper (Millipore membrane, 0.45μm) and maintained aseptic state.

[실시예 1-2] 여주, 구절초 및 작약 추출 혼합물의 제조Example 1-2 Preparation of Yeoju, Gujeolcho and Peony Extract Mixtures

여주, 구절초, 및 작약 각각의 생약재를 음건하고 세절하여 각각 다른 무게 비율로 혼합하고, 혼합된 생약재 총 무게의 10배의 용매를 가한 뒤 4시간을 끓여 추출하여 추출물을 얻었다. 이러한 추출물을 여과하고 감압농축기로 농축하여 동결건조함으로써 추출물을 제조하였다. 또한, 실험을 위해 추출물을 10% DMSO에 10 ~ 100 mg/ml의 농도로 녹여 무균여과지(Millipore membrane, 0.45㎛)로 여과한 뒤 무균상태를 유지하였다.Yeoju, Gujeolcho, and Peony each herbal medicine was dried and shredded and mixed at different weight ratios. After adding 10 times the solvent of the total weight of the mixed herbal medicines, the mixture was boiled for 4 hours to obtain an extract. The extract was filtered, concentrated in a vacuum condenser, and lyophilized to prepare an extract. In addition, for the experiment, the extract was dissolved in 10% DMSO at a concentration of 10 to 100 mg / ml, filtered through a sterile filter paper (Millipore membrane, 0.45 ㎛) and maintained aseptic state.

[실험예 1] 알파-글루코시데이즈 저해 활성Experimental Example 1 Alpha-glucosidase Inhibitory Activity

알파-글루코시데이즈 저해활성 측정용 실험방법은 기질인 PNP-글루코사이드(glycoside)와 1 유니트 알파-글루코시데이즈(α-glucosidase, Sacchromyces cerevisiae 기원)를 이용하여 수행하였다. 각 추출물에 대한 실험을 위해, 0.1 M KPB (pH 6.9) 50 ㎕, 알파-글루코시데이즈 10 ㎕, 여주, 구절초, 및 작약 추출물 20 ㎕로 구성된 반응액을 37℃ 에서 20분간 반응시켰다. 여주, 구절초, 및 작약 추출물 은 0.05, 0.1, 0.25, 0.5 mg/ml의 농도로 처리하였다. 이 반응액에 PNP- 글루코사이드 20 ㎕를 첨가하여 20분 후의 흡광도를 분광광도계 (spectrophotometer, 405nm)로 측정하였다. 그 결과는 표 1과 같다. 실시예 1에서 알파-글루코시데이즈 저해능은, 하기 수학식 1에 의하여 구하였다:Experimental method for the measurement of alpha-glucosidase inhibitory activity was carried out using the substrate PNP-glucoside (glycoside) and 1 unit alpha-glucosidase (α-glucosidase, Sacchromyces cerevisiae origin). For the experiments on each extract, the reaction solution consisting of 50 µl of 0.1 M KPB (pH 6.9), 10 µl of alpha-glucosidase, Yeoju, Gujeolcho, and 20 µl of Peony extract were reacted at 37 ° C for 20 minutes. Yeoju, Gujeolcho, and Peony extracts were treated at concentrations of 0.05, 0.1, 0.25, 0.5 mg / ml. 20 µl of PNP-glucoside was added to the reaction solution, and the absorbance after 20 minutes was measured with a spectrophotometer (405 nm). The results are shown in Table 1. In Example 1, alpha-glucosidase inhibitory activity was calculated by the following Equation 1:

[수학식 1] 알파-글루코시데이즈 저해능Equation 1 alpha-glucosidase inhibitory ability

저해능 (Inhibition effect, %) = [(C-(S-SB))/(C-CB)] × 100Inhibition effect (%) = [(C- (S-SB)) / (C-CB)] × 100

C : 시료를 처리하지 않은 실험구의 흡광도C: Absorbance of the experimental zone without sample treatment

CB : 시료를 처리하지 않은 대조구의 흡광도CB: absorbance of the control without the sample

S : 시료를 처리한 실험구의 흡광도S: absorbance of the experimental zone treated with the sample

SB : 시료를 처리한 대조구의 흡광도SB: absorbance of the control treated with the sample

Inhibition activity (%)Inhibition activity (%) SampleSample Concentration (mg/ml)Concentration (mg / ml) 0.020.02 0.040.04 0.080.08 0.160.16 0.50.5 AcarboseAcarbose -- -- 93.86±0.2793.86 ± 0.27 -- 구절초Gujeolcho 4.97±1.714.97 ± 1.71 8.28±2.818.28 ± 2.81 15.74±1.6315.74 ± 1.63 24.8±0.3424.8 ± 0.34 37.25±4.1937.25 ± 4.19 여주Yeoju 2.84±0.772.84 ± 0.77 5.47±1.175.47 ± 1.17 15.14±0.9215.14 ± 0.92 25.46±1.4725.46 ± 1.47 28.49±2.2428.49 ± 2.24 작약Peony 8.82±0.548.82 ± 0.54 26.43±1.5526.43 ± 1.55 34.36±3.7334.36 ± 3.73 52.2±3.3152.2 ± 3.31 85.38±0.4285.38 ± 0.42

또한, 여주 추출물, 구절초 추출물의 함량비를 조절하여, 알파-글루코시데이즈 저해 활성을 측정하였다. 그 결과, 구절초, 작약 추출물의 비율을 고정한 후, 여주 추출물을 비율별로 혼합하여 처리한 실험에서는 여주의 비율이 많아짐에 따라 효소에 대한 저해 활성이 높아짐을 확인하였다. 예컨대, 여주 단일 0.16mg/ml 처리군에 비해 10:1:1 비율의 추출혼합물에서 약 40% 활성 증가를 보였다(표 2).In addition, by adjusting the content ratio of Yeoju extract, Gujeolcho extract, alpha-glucosidase inhibitory activity was measured. As a result, after fixing the ratio of gujeolcho, peony extract, it was confirmed that the inhibitory activity against the enzyme is increased as the ratio of the bitter gourd increases in the experiment in which the bitter gourd extract is mixed for each ratio. For example, compared to Yeoju single 0.16 mg / ml treatment group showed a 40% activity increase in the 10: 1: 1 ratio of the mixture (Table 2).

Inhibition activity (%)Inhibition activity (%) 여주:구절초:작약
(Ratio)
Yeoju: Gujeolcho: Peony
(Ratio)
Concentration (mg/ml)Concentration (mg / ml)
0.050.05 0.10.1 0.250.25 0.50.5 AcarboseAcarbose   90.95±0.9790.95 ± 0.97     1:1:11: 1: 1 15.22±5.5815.22 ± 5.58 22.9±2.9122.9 ± 2.91 38.9±4.2238.9 ± 4.22 52.07±5.4952.07 ± 5.49 2:1:12: 1: 1 18.06±7.2218.06 ± 7.22 24.89±6.4924.89 ± 6.49 47.81±3.647.81 ± 3.6 61.35±3.2761.35 ± 3.27 5:1:15: 1: 1 17.91±3.6817.91 ± 3.68 23.12±2.5723.12 ± 2.57 49.77±3.249.77 ± 3.2 63.64±3.9663.64 ± 3.96 10:1:110: 1: 1 18.31±1.1918.31 ± 1.19 27.48±4.9627.48 ± 4.96 52.47±2.8552.47 ± 2.85 65.8±5.0665.8 ± 5.06

또한, 여주, 작약 추출물의 비율을 고정한 후, 구절초 추출물을 비율별로 혼합하여 처리한 실험에서는 구절초의 비율이 많아짐에 따라 효소 저해 활성이 높아짐을 확인하였다. 예컨대, 구절초 단일 0.16 mg/ml처리군에 비해 1:10:1 비율의 추출혼합물에서 약 34% 활성 증가를 보였다(표 3).In addition, after fixing the ratio of Yeoju, Peony extract, in the experiments treated by mixing the Gujeolcho extract by ratio, it was confirmed that the enzyme inhibitory activity increases as the proportion of Gujeolcho increases. For example, Gujeolcho showed a 34% increase in activity in the 1: 10: 1 ratio of the extract mixture compared to the single 0.16 mg / ml treatment group (Table 3).

Inhibition activity (%)Inhibition activity (%) 여주:구절초:작약
(Ratio)
Yeoju: Gujeolcho: Peony
(Ratio)
Concentration (mg/ml)Concentration (mg / ml)
0.050.05 0.10.1 0.250.25 0.50.5 AcarboseAcarbose 103.32±0.2103.32 ± 0.2 1:1:11: 1: 1 15.22±5.5815.22 ± 5.58 22.9±2.9122.9 ± 2.91 38.9±4.2238.9 ± 4.22 52.07±5.4952.07 ± 5.49 1:2:11: 2: 1 16.28±5.0916.28 ± 5.09 21.03±2.2421.03 ± 2.24 32.71±0.7432.71 ± 0.74 49.78±2.7749.78 ± 2.77 1:5:11: 5: 1 7.16±2.787.16 ± 2.78 21.98±1.3121.98 ± 1.31 34.25±3.2734.25 ± 3.27 55.21±1.7755.21 ± 1.77 1:10:11: 10: 1 10.11±0.9710.11 ± 0.97 22.75±3.4222.75 ± 3.42 32.11±3.432.11 ± 3.4 58.29±1.5558.29 ± 1.55

또한, 여주, 구절초 추출물의 비율을 고정한 후, 작약 추출물을 비율별로 혼합하여 처리한 실험에서는 작약의 비율이 많아짐에 따라 효소 저해 활성이 높아짐을 확인하였다. 예컨대, 작약 단일 0.16mg/ml처리군에 비해 1:1:10 비율의 추출혼합물에서 약 29% 활성 증가를 보였다(표 4).In addition, after fixing the ratio of Yeoju, Gujeolcho extract, in the experiments in which the peony extract was mixed and treated in the experiment, it was confirmed that the enzyme inhibitory activity increased as the ratio of peony increased. For example, compared to the Peony single 0.16 mg / ml treatment group showed a 29% activity increase in the 1: 1: 10 ratio of the mixture (Table 4).

Inhibition activity (%)Inhibition activity (%) 여주:구절초:작약
(Ratio)
Yeoju: Gujeolcho: Peony
(Ratio)
Concentration (mg/ml)Concentration (mg / ml)
0.050.05 0.10.1 0.250.25 0.50.5 AcarboseAcarbose 103.32±0.2103.32 ± 0.2 1:1:11: 1: 1 15.22±5.5815.22 ± 5.58 22.9±2.9122.9 ± 2.91 38.9±4.2238.9 ± 4.22 52.07±5.4952.07 ± 5.49 1:1:21: 1: 2 16.58±2.6316.58 ± 2.63 20.56±5.4620.56 ± 5.46 40.9±2.6240.9 ± 2.62 63.11±12.4663.11 ± 12.46 1:1:51: 1: 5 16.87±1.6616.87 ± 1.66 24.07±2.8224.07 ± 2.82 41.17±3.7741.17 ± 3.77 77.57±4.7777.57 ± 4.77 1:1:101: 1: 10 15.74±2.0315.74 ± 2.03 24.01±1.7624.01 ± 1.76 42.26±3.1642.26 ± 3.16 81.27±3.1781.27 ± 3.17

[실험예 2] 알파-아밀라아제 활성 저해Experimental Example 2 Inhibition of Alpha-amylase Activity

알파-아밀라아제 저해활성 측정용 실험방법은 기질인 0.5% 전분용액과 1mg/10ml 농도의 알파-아밀라아제(α-amylase)를 이용하여 수행하였다. 각 추출물에 대한 실험을 위해, 20 mM Sodium Phoisphate Buffer (pH 6.9) 100 ㎕, 알파-아밀라아제 100 ㎕, 여주, 구절초, 및 작약 추출물 시료 100 ㎕, 그리고 0.5% 전분용액 200 ㎕를 첨가하여 20분 동안 37℃ 에서 반응시켰다. 여주, 구절초, 및 작약 추출물 시료는 농도별로 처리하였다(0.05, 0.1, 0.25, 0.5 mg/ml). 이 반응액에 DNS (3,5-dinitrosalicylic acid) 발색용액을 200 ㎕ 첨가한 후 15분간 95℃ 이상에서 발색시켜 흡광도를 분광광도계 (spectrophotometer, 540nm)로 측정하였다. 그 결과는 표 5와 같다.Experimental method for the measurement of alpha-amylase inhibitory activity was carried out using a 0.5% starch solution as a substrate and alpha-amylase (α-amylase) at a concentration of 1mg / 10ml. For experiments with each extract, add 20 μl of 20 mM Sodium Phoisphate Buffer (pH 6.9), 100 μl of alpha-amylase, 100 μl of bitter gourd, gujeolcho, and peony extract, and 200 μl of 0.5% starch solution for 20 minutes. It reacted at 37 degreeC. Yeoju, gujeolcho, and peony extract samples were treated by concentration (0.05, 0.1, 0.25, 0.5 mg / ml). 200 μl of a DNS (3,5-dinitrosalicylic acid) color developing solution was added to the reaction solution, followed by color development at 95 ° C. or higher for 15 minutes. The results are shown in Table 5.

알파-아밀라아제 활성 저해는 하기 수학식 2에 의하여 구하였다:Inhibition of alpha-amylase activity was obtained by the following equation (2):

[수학식 2][Equation 2]

저해능 (Inhibition effect, %) = [(C-(S-SB))/(C-CB)] × 100Inhibition effect (%) = [(C- (S-SB)) / (C-CB)] × 100

C : 시료를 처리하지 않은 실험구의 흡광도C: Absorbance of the experimental zone without sample treatment

CB : 시료를 처리하지 않은 대조구의 흡광도CB: absorbance of the control without the sample

S : 시료를 처리한 실험구의 흡광도S: absorbance of the experimental zone treated with the sample

SB : 시료를 처리한 대조구의 흡광도SB: absorbance of the control treated with the sample

여주, 구절초, 작약 추출물을 각각 처리하였을 때, 농도 의존적으로 효소의 활성을 저해함을 확인하였다. 예컨대, 0.16 mg/ml의 농도에서 여주 처리군은 약 28%, 절초 처리군은 약 32%, 그리고 작약 처리군에서는 약 30%의 저해활성을 보였다(표 5).Yeoju, gujeolcho, peony extract was treated, respectively, was confirmed to inhibit the activity of the enzyme in a concentration-dependent manner. For example, at a concentration of 0.16 mg / ml, about 28% of the Yeoju treated group, about 32% of the cutweed treated group, and about 30% of the peony treated group showed inhibitory activity (Table 5).

Inhibition activity (%)Inhibition activity (%) SampleSample Concentration (mg/ml)Concentration (mg / ml) 0.020.02 0.040.04 0.080.08 0.160.16 0.50.5 AcarboseAcarbose 58.09±1.2658.09 ± 1.26 구절초Gujeolcho 14.81±2.414.81 ± 2.4 19.62±1.919.62 ± 1.9 23.46±3.1923.46 ± 3.19 32.86±2.6432.86 ± 2.64 35.12±3.4035.12 ± 3.40 여주Yeoju 4.6±0.574.6 ± 0.57 6.45±0.496.45 ± 0.49 21.59±0.521.59 ± 0.5 28.32±0.7928.32 ± 0.79 34.97±0.8934.97 ± 0.89 작약Peony 8.91±0.248.91 ± 0.24 11.45±0.2311.45 ± 0.23 16.52±1.216.52 ± 1.2 30.42±0.9630.42 ± 0.96 39.32±0.5939.32 ± 0.59

또한, 구절초, 작약 추출물의 비율을 고정한 후, 여주 추출물을 비율별로 혼합하여 처리한 실험에서는 여주의 비율이 많아짐에 따라 효소에 대한 저해 활성이 높아짐을 확인하였다. 예컨대, 여주 단일 0.16mg/ml 처리군에 비해 10:1:1 비율의 추출혼합물에서 약 17%의 활성 증가를 보였다(표 6). In addition, after fixing the ratio of gujeolcho, peony extract, in the experiment mixed and treated with the yeast extract ratio was confirmed that the inhibitory activity against the enzyme increases as the ratio of the yeast increases. For example, compared to Yeoju single 0.16mg / ml treatment group, the activity ratio of about 17% was shown in the 10: 1: 1 ratio of the extract mixture (Table 6).

Inhibition activity (%)Inhibition activity (%) 여주:구절초:작약
(Ratio)
Yeoju: Gujeolcho: Peony
(Ratio)
Concentration (mg/ml)Concentration (mg / ml)
0.050.05 0.10.1 0.250.25 0.50.5 AcarboseAcarbose   57.89±1.8457.89 ± 1.84     1:1:11: 1: 1 26.72±0.8726.72 ± 0.87 29.71±4.0229.71 ± 4.02 32.59±0.2232.59 ± 0.22 37.19±3.3237.19 ± 3.32 2:1:12: 1: 1 28.53±0.4928.53 ± 0.49 30.59±0.8530.59 ± 0.85 32.84±0.1832.84 ± 0.18 39.9±1.3639.9 ± 1.36 5:1:15: 1: 1 29.13±2.4129.13 ± 2.41 30.2±1.7530.2 ± 1.75 34.93±0.1834.93 ± 0.18 41.33±1.0741.33 ± 1.07 10:1:110: 1: 1 38.47±2.9138.47 ± 2.91 40.82±1.2940.82 ± 1.29 42.27±2.0742.27 ± 2.07 45.47±0.9645.47 ± 0.96

또한, 여주, 작약 추출물의 비율을 고정한 후, 구절초 추출물을 비율별로 혼합하여 처리한 실험에서는 구절초의 비율이 많아짐에 따라 효소 저해 활성이 높아짐을 확인하였다. 예컨대, 구절초 단일 0.16 mg/ml 처리군에 비해 1:10:1 비율의 추출혼합물에서 약 17%의 활성 증가를 보였다(표 7).In addition, after fixing the ratio of Yeoju, Peony extract, in the experiments treated by mixing the Gujeolcho extract by ratio, it was confirmed that the enzyme inhibitory activity increases as the proportion of Gujeolcho increases. For example, compared to gujeolcho single 0.16 mg / ml treatment group showed an increase in activity of about 17% in the 1: 10: 1 ratio of the mixture (Table 7).

Inhibition activity (%)Inhibition activity (%) 여주:구절초:작약
(Ratio)
Yeoju: Gujeolcho: Peony
(Ratio)
Concentration (mg/ml)Concentration (mg / ml)
0.050.05 0.10.1 0.250.25 0.50.5 AcarboseAcarbose 59.67±5.4659.67 ± 5.46 1:1:11: 1: 1 26.72±0.8726.72 ± 0.87 29.71±4.0229.71 ± 4.02 32.59±0.2232.59 ± 0.22 37.19±3.3237.19 ± 3.32 1:2:11: 2: 1 26.39±1.5626.39 ± 1.56 32.4±0.5632.4 ± 0.56 37.85±2.0837.85 ± 2.08 40.36±1.2240.36 ± 1.22 1:5:11: 5: 1 30.68±2.5330.68 ± 2.53 33.62±2.533.62 ± 2.5 37.39±1.737.39 ± 1.7 43.26±0.4343.26 ± 0.43 1:10:11: 10: 1 35.05±1.2335.05 ± 1.23 40.02±3.3240.02 ± 3.32 43±2.3743 ± 2.37 49.43±0.9249.43 ± 0.92

또한, 여주, 구절초 추출물의 비율을 고정한 후, 작약 추출물을 비율별로 혼합하여 처리한 실험에서는 작약의 비율이 많아짐에 따라 효소 저해 활성이 높아짐을 확인하였다. 예컨대, 작약 단일 0.16mg/ml처리군에 비해 1:1:10 비율의 추출혼합물에서 약 29%의 활성 증가를 보였다(표 8).In addition, after fixing the ratio of Yeoju, Gujeolcho extract, in the experiments in which the peony extract was mixed and treated in the experiment, it was confirmed that the enzyme inhibitory activity increased as the ratio of peony increased. For example, compared to the Peony single 0.16 mg / ml treatment group showed an activity increase of about 29% in the 1: 1: 10 ratio of the mixture (Table 8).

Inhibition activity (%)Inhibition activity (%) 여주:구절초:작약
(Ratio)
Yeoju: Gujeolcho: Peony
(Ratio)
Concentration (mg/ml)Concentration (mg / ml)
0.050.05 0.10.1 0.250.25 0.50.5 AcarboseAcarbose 57.89±1.8457.89 ± 1.84 1:1:11: 1: 1 26.72±0.8726.72 ± 0.87 29.71±4.0229.71 ± 4.02 32.59±0.2232.59 ± 0.22 37.19±3.3237.19 ± 3.32 1:1:21: 1: 2 32.36±1.432.36 ± 1.4 33.67±1.7133.67 ± 1.71 35.85±1.5935.85 ± 1.59 44.55±0.5444.55 ± 0.54 1:1:51: 1: 5 33.56±0.3733.56 ± 0.37 37.38±2.3337.38 ± 2.33 45.92±1.5245.92 ± 1.52 53.03±1.5653.03 ± 1.56 1:1:101: 1: 10 39.99±0.7839.99 ± 0.78 46.25±0.2946.25 ± 0.29 49.81±0.7549.81 ± 0.75 59.6±0.0859.6 ± 0.08

[실험예 3] 소장세포에서의 포도당 흡수 저해능 확인Experimental Example 3 Confirmation of Inhibition of Glucose Uptake in Small Intestine Cells

소장에서 혈액으로 포도당 흡수의 저해활성 측정용 실험방법은 Caco-2 세포주와 2-NBDG (2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino-2-deoxygluocose)를 이용하여 측정하였다. 즉, 각 추출물에 대한 포도당 흡수저해 실험을 위해 Caco-2를 1×104cells/well 농도로 96 well plate를 사용하여 37℃, CO2 인큐베이터에서 14일 동안 배양한 후 PBS로 2회 세척한 다음 glucose 무첨가 배지 400 ㎕, 100 μM 2-NBDG 500 ㎕, 시료 (0.05, 0.1, 0.25, 0.5 mg/ml) 100 ㎕를 첨가하고 37℃에서 2시간 반응시켰다. 이 반응액을 제거하고 세포를 아이스-콜드 PBS로 3회 세척한 후 2-NBDG의 형광세기를 형광분광광도계(spectrophotofluorometer, 여기: 485nm, 발광 : 535nm)로 측정하였다. 포도당 흡수 저해활성 측정에 미치는 세포농도의 영향을 보정해 주기 위해 MTT assay를 다음과 같이 실시하였다. 형광세기 측정이 끝난 well plate에 5 mg/ml 농도의 MTT 용액 50 ㎕를 가하여 37에서 2시간 반응시킨 후 540 nm에서 흡광도를 측정하였다. *양성표준물질로는 phlorizin을 사용하였다. Experimental methods for measuring the inhibitory activity of glucose uptake into the blood in the small intestine were measured using Caco-2 cell line and 2-NBDG (2- (N- (7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino-2 -deoxygluocose), that is, for 14 days in a CO 2 incubator at 37 ° C using a 96 well plate at a concentration of 1 × 10 4 cells / well for glucose uptake experiments for each extract. After incubation, washed twice with PBS, 400 μl of glucose-free medium, 500 μl of 100 μM 2-NBDG, and 100 μl of sample (0.05, 0.1, 0.25, 0.5 mg / ml) were added and reacted at 37 ° C. for 2 hours. After removing the reaction solution and washing the cells three times with ice-cold PBS, the fluorescence intensity of 2-NBDG was measured by a spectrophotofluorometer (excitation: 485 nm, emission: 535 nm). To correct the effect of cell concentration, MTT assay was performed as follows: 5 mg / ml in well plate after fluorescence intensity measurement. MTT solution was added to separate the 50 ㎕ was measured at 540 nm after 2 hours of reaction at 37 * was used as a positive standard phlorizin.

시료에 의한 포도당 흡수 저해 활성은 아래 식에 따라 환산한 후 대조군에 표 9에 도시하였다. Glucose uptake inhibition activity by the sample is shown in Table 9 in the control group in accordance with the following equation.

포도당 흡수 저해 활성은 하기 수학식 3에 의하여 구하였다:Glucose uptake inhibitory activity was determined by the following equation (3):

[수학식 3][Equation 3]

저해능 (Inhibition effect, %) = [(Fc - Fs) / Fc] × 100Inhibition effect (%) = [(Fc-Fs) / Fc] × 100

Fs : 시료를 처리한 실험구의 형광세기Fs: Fluorescence intensity of the experimental group treated with the sample

Fc : 시료를 처리하지 않은 실험구의 형광세기Fc: Fluorescence intensity of the experimental group without sample treatment

여주, 구절초, 작약 추출물을 처리하였을 때, 농도 의존적으로 소장세포에서의 당 흡수 저해활성이 증가함을 확인하였다. 예컨대, 0.16 mg/ml의 농도에서 여주 처리군은 약 13% 구절초 처리군은 약 13% 그리고 작약 처리군에서는 약 30%의 저해 활성을 보였다.When the yeast, gujeolcho and peony extracts were treated, it was confirmed that the concentration of glucose uptake inhibitory activity was increased in small intestine cells. For example, at a concentration of 0.16 mg / ml, Yeoju treated group showed about 13% gujeolcho treated group about 13% and peony treated group showed about 30% inhibitory activity.

Uptake activityUptake activity SampleSample Concentration (mg/ml)Concentration (mg / ml) 0.020.02 0.040.04 0.080.08 0.160.16 Phlorizin (0.1 mg/ml)Phlorizin (0.1 mg / ml) 0.76±0.070.76 ± 0.07 구절초Gujeolcho 0.96±0.120.96 ± 0.12 0.92±0.130.92 ± 0.13 0.88±0.040.88 ± 0.04 0.87±0.070.87 ± 0.07 여주Yeoju 1.01±0.081.01 ± 0.08 0.94±0.140.94 ± 0.14 0.89±0.010.89 ± 0.01 0.87±0.050.87 ± 0.05 작약Peony 0.96±0.030.96 ± 0.03 0.89±0.030.89 ± 0.03 0.78±0.010.78 ± 0.01 0.7±0.050.7 ± 0.05 * Glucose uptake ratio compared with Control(1.0)* Glucose uptake ratio compared with Control (1.0)

또한, 구절초, 작약 추출물의 비율을 고정한 후, 여주 추출물을 비율별로 혼합하여 처리한 실험에서는 여주의 비율이 많아짐에 따라 소장세포에서의 당 흡수 저해활성이 높아짐을 확인하였다. 예컨대, 여주 단일 0.16mg/ml 처리군에 비해 10:1:1 비율의 추출혼합물에서 약 26%의 저해활성 증가를 보였다.In addition, after fixing the ratio of gujeolcho, peony extract, in the experiments in which the mixture of yeast extracts were mixed for each ratio, it was confirmed that as the ratio of yeast increased, glucose uptake inhibitory activity in the small intestine cells increased. For example, compared to Yeoju single 0.16mg / ml treatment group, the inhibitory activity was increased by about 26% in the 10: 1: 1 ratio of the extract mixture.

Uptake activityUptake activity 여주:구절초:작약
(Ratio)
Yeoju: Gujeolcho: Peony
(Ratio)
Concentration (mg/ml)Concentration (mg / ml)
0.050.05 0.10.1 0.250.25 0.50.5 PhlorizinPhlorizin   0.76±0.070.76 ± 0.07     1:1:11: 1: 1 0.97±0.060.97 ± 0.06 0.87±0.030.87 ± 0.03 0.73±0.110.73 ± 0.11 0.65±0.050.65 ± 0.05 2:1:12: 1: 1 0.95±0.060.95 ± 0.06 0.87±0.050.87 ± 0.05 0.74±0.040.74 ± 0.04 0.64±00.64 ± 0 5:1:15: 1: 1 0.87±0.140.87 ± 0.14 0.81±0.060.81 ± 0.06 0.71±0.070.71 ± 0.07 0.62±0.010.62 ± 0.01 10:1:110: 1: 1 0.85±0.080.85 ± 0.08 0.8±0.050.8 ± 0.05 0.71±0.070.71 ± 0.07 0.61±0.070.61 ± 0.07 * Glucose uptake ratio compared with Control(1.0)* Glucose uptake ratio compared with Control (1.0)

또한, 여주, 작약 추출물의 비율을 고정한 후, 구절초 추출물을 비율별로 혼합하여 처리한 실험에서는 구절초의 비율이 많아짐에 따라 소장세포에서의 당 흡수 저해활성이 높아짐을 확인하였다. 예컨대, 구절초 단일 (0.16 mg/ml)처리군에 비해 1:10:1 비율의 추출혼합물에서 약 27%의 저해활성 증가를 보였다.In addition, after fixing the ratio of Yeoju and Peony extract, in the experiments in which the Gujeolcho extract was mixed by ratio, it was confirmed that as the ratio of Gujeolcho increased, the glucose uptake inhibitory activity in the small intestine cells increased. For example, compared to gujeolcho single (0.16 mg / ml) treatment group showed an increase in inhibitory activity of about 27% in the 1: 10: 1 ratio of the mixture.

Uptake activityUptake activity 여주:구절초:작약
(Ratio)
Yeoju: Gujeolcho: Peony
(Ratio)
Concentration (mg/ml)Concentration (mg / ml)
0.050.05 0.10.1 0.250.25 0.50.5 PhlorizinPhlorizin   0.76±0.070.76 ± 0.07     1:1:11: 1: 1 0.97±0.060.97 ± 0.06 0.87±0.030.87 ± 0.03 0.73±0.110.73 ± 0.11 0.65±0.050.65 ± 0.05 1:2:11: 2: 1 0.92±0.080.92 ± 0.08 0.88±0.080.88 ± 0.08 0.73±0.060.73 ± 0.06 0.63±0.030.63 ± 0.03 1:5:11: 5: 1 0.92±0.050.92 ± 0.05 0.83±0.060.83 ± 0.06 0.72±0.10.72 ± 0.1 0.62±0.030.62 ± 0.03 1:10:11: 10: 1 0.91±0.030.91 ± 0.03 0.81±0.040.81 ± 0.04 0.74±0.10.74 ± 0.1 0.6±0.010.6 ± 0.01 * Glucose uptake ratio compared with Control(1.0)* Glucose uptake ratio compared with Control (1.0)

또한, 여주, 구절초 추출물의 비율을 고정한 후, 작약 추출물을 비율별로 혼합하여 처리한 실험에서는 작약의 비율이 많아짐에 따라 소장세포에서의 당 흡수 저해활성이 높아짐을 확인하였다. 예컨대, 작약 단일 (0.16mg/ml)처리군에 비해 1:1:10 비율의 추출혼합물에서 약 14%의 저해활성 증가를 보였다.In addition, after fixing the ratio of Yeoju, Gujeolcho extract, in the experiments in which the peony extract was mixed and treated in the experiment, it was confirmed that as the ratio of peony increased, glucose uptake inhibitory activity in the small intestine cells increased. For example, compared to Peony single (0.16 mg / ml) treatment group showed an increase in inhibitory activity of about 14% in the 1: 1: 10 ratio of the mixture.

Uptake activityUptake activity 여주:구절초:작약
(Ratio)
Yeoju: Gujeolcho: Peony
(Ratio)
Concentration (mg/ml)Concentration (mg / ml)
0.050.05 0.10.1 0.250.25 0.50.5 PhlorizinPhlorizin   0.76±0.070.76 ± 0.07     1:1:11: 1: 1 0.97±0.060.97 ± 0.06 0.87±0.030.87 ± 0.03 0.73±0.110.73 ± 0.11 0.65±0.050.65 ± 0.05 1:1:21: 1: 2 0.82±0.060.82 ± 0.06 0.76±0.010.76 ± 0.01 0.7±0.060.7 ± 0.06 0.63±0.10.63 ± 0.1 1:1:51: 1: 5 0.81±0.070.81 ± 0.07 0.7±0.070.7 ± 0.07 0.62±0.010.62 ± 0.01 0.57±0.030.57 ± 0.03 1:1:101: 1: 10 0.76±0.090.76 ± 0.09 0.68±0.040.68 ± 0.04 0.62±0.040.62 ± 0.04 0.56±0.10.56 ± 0.1 * Glucose uptake ratio compared with Control(1.0)* Glucose uptake ratio compared with Control (1.0)

[실험예 4] 근육세포에서의 포도당 흡수 증진 효과 확인Experimental Example 4 Confirmation of Glucose Absorption Enhancement Effect in Muscle Cells

혈액에서 근육세포로 포도당 흡수의 증가활성 측정용 실험방법은 L6 세포주와 2-NBDG (2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino-2-deoxygluocose)를 이용하여 측정하였다. 즉, 각 추출물에 대한 포도당 흡수증가 실험을 위해 L6를 1×104cells/well 농도로 96 well plate를 사용하여 37℃, CO2 인큐베이터에서 4일 동안 배양한 후 Horse serum이 들어있는 배지로 바꾸어준다. 2일 동안 배양한 후 PBS로 2회 세척한 다음 glucose 무첨가 배지 400 ㎕, 100 μM 2-NBDG 500 ㎕, 시료 (0.05, 0.1, 0.25, 0.5 mg/ml) 100 ㎕를 첨가하고 37℃에서 2시간 반응시켰다. 이 반응액을 제거하고 세포를 아이스-콜드 PBS로 3회 세척한 후 2-NBDG의 형광세기를 형광분광광도계(spectrophotofluorometer, 여기: 485nm, 발광 : 535nm)로 측정하였다. 포도당 흡수 저해활성 측정에 미치는 세포농도의 영향을 보정해 주기 위해 MTT assay를 다음과 같이 실시하였다. 형광세기 측정이 끝난 well plate에 MTT 용액 (5 mg/ml) 50 ㎕를 가하여 37℃에서 2시간 반응시킨 후 540 nm에서 흡광도를 측정하였다. 양성표준물질로는 insulin을 사용하였다. 시료에 의한 포도당 흡수 증가 활성은 아래 수학식 4에 따라 환산한 후 표 13에 나타내었다.Experimental methods for measuring the increased activity of glucose uptake into the muscle cells in the blood were measured using L6 cell line and 2-NBDG (2- (N- (7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino-2- deoxygluocose), ie L6 was incubated for 4 days in a CO 2 incubator at 37 ° C using a 96 well plate at a concentration of 1 × 10 4 cells / well for each glucose uptake experiment. Change to medium containing horse serum, incubate for 2 days, wash twice with PBS, 400 μl glucose-free medium, 500 μl 100 μM 2-NBDG, sample (0.05, 0.1, 0.25, 0.5 mg / ml) 100 μl was added and reacted for 2 hours at 37 ° C. The reaction solution was removed and the cells were washed three times with ice-cold PBS, and then the fluorescence intensity of 2-NBDG was measured using a spectrophotofluorometer (excitation: 485 nm, emission: 535 nm) The MTT assay was performed to correct the effect of cell concentration on glucose uptake inhibitory activity. 50 μl of MTT solution (5 mg / ml) was added to the well plate after the fluorescence intensity measurement, and the reaction was measured for 2 hours at 37 ° C., and then the absorbance was measured at 540 nm. The glucose uptake increasing activity by the sample is shown in Table 13 after conversion according to Equation 4 below.

[수학식 4] 근육에서의 포도당 흡수활성 계산Calculation of glucose absorption activity in muscle

증가능 (Activation effect, %) = [(Fc - Fs) / Fc] × 100Activation effect (%) = [(Fc-Fs) / Fc] × 100

Fs : 시료를 처리한 실험구의 형광세기Fs: Fluorescence intensity of the experimental group treated with the sample

Fc : 시료를 처리하지 않은 실험구의 형광세기Fc: Fluorescence intensity of the experimental group without sample treatment

Uptake activityUptake activity SampleSample Concentration (mg/ml)Concentration (mg / ml) 0.020.02 0.040.04 0.080.08 0.160.16 Insulin (500nM)Insulin (500 nM) 1.4±0.021.4 ± 0.02 구절초Gujeolcho 0.91±0.060.91 ± 0.06 0.95±0.230.95 ± 0.23 1.09±0.121.09 ± 0.12 1.11±0.081.11 ± 0.08 여주Yeoju 0.94±0.10.94 ± 0.1 1.02±0.131.02 ± 0.13 1.07±0.071.07 ± 0.07 1.1±0.141.1 ± 0.14 작약Peony 0.98±0.090.98 ± 0.09 1.07±0.111.07 ± 0.11 1.15±0.151.15 ± 0.15 1.2±0.071.2 ± 0.07 * Glucose uptake ratio compared with Control(1.0)* Glucose uptake ratio compared with Control (1.0)

표 13에서 보면 근육세포 당 흡수 증가활성 시험방법에서 여주, 구절초, 작약 추출물을 처리하였을 때, 농도 의존적으로 활성이 증가함을 확인하였다. 예컨대, 0.16 mg/ml의 농도에서 여주 처리군은 약 10% 구절초 처리군은 약 11% 그리고 작약 처리군에서는 약 20%의 활성 증가를 보였다.In Table 13, it was confirmed that activity was increased in a concentration-dependent manner when treated with Yeoju, Gujeolcho, and Peony extract in the test for increasing the activity of muscle cells. For example, at a concentration of 0.16 mg / ml, the Yeoju treated group showed about 10% increased activity in gujeolcho treated group about 11% and peony treated group about 20%.

또한, 구절초, 작약 추출물의 비율을 고정한 후, 여주 추출물을 비율별로 혼합하여 처리한 실험에서는 여주의 비율이 많아짐에 따라 근육세포의 당 흡수 활성이 높아짐을 확인하였다. 예컨데, 여주 단일 0.16mg/ml 처리군에 비해 10:1:1 비율의 추출혼합물에서 약 31%의 활성 증가를 보였다(표 14).In addition, after fixing the ratio of gujeolcho, peony extract, in the experiment mixed and treated with the extract of the Yeoju extract was confirmed that the glucose uptake activity of muscle cells increases as the ratio of the yeast increases. For example, compared to Yeoju single 0.16mg / ml treatment group, the activity ratio of about 31% was increased in the 10: 1: 1 ratio of the mixture (Table 14).

Uptake activityUptake activity 여주:구절초:작약
(Ratio)
Yeoju: Gujeolcho: Peony
(Ratio)
Concentration (mg/ml)Concentration (mg / ml)
0.050.05 0.10.1 0.250.25 0.50.5 Insulin (500nM)Insulin (500 nM)   1.4±0.021.4 ± 0.02     1:1:11: 1: 1 1.05±0.061.05 ± 0.06 1.07±0.061.07 ± 0.06 1.16±0.11.16 ± 0.1 1.29±0.081.29 ± 0.08 2:1:12: 1: 1 0.99±0.060.99 ± 0.06 1.15±0.051.15 ± 0.05 1.2±0.161.2 ± 0.16 1.3±0.211.3 ± 0.21 5:1:15: 1: 1 1.06±0.141.06 ± 0.14 1.12±0.061.12 ± 0.06 1.15±0.031.15 ± 0.03 1.34±0.11.34 ± 0.1 10:1:110: 1: 1 0.99±0.090.99 ± 0.09 1.09±0.111.09 ± 0.11 1.28±0.151.28 ± 0.15 1.41±0.211.41 ± 0.21 * Glucose uptake ratio compared with Control(1.0)* Glucose uptake ratio compared with Control (1.0)

또한, 여주, 작약 추출물의 비율을 고정한 후, 구절초 추출물을 비율별로 혼합하여 처리한 실험에서는 구절초의 비율이 많아짐에 따라 근육세포의 당 흡수 활성이 높아짐을 확인하였다. 예컨대, 구절초 단일 0.16 mg/ml 처리군에 비해 1:10:1 비율의 추출혼합물에서 약 32%의 활성 증가를 보였다.In addition, after fixing the ratio of Yeoju and Peony extract, the experiment was performed by mixing the Gujeolcho extract by ratio, and as the ratio of Gujeolcho increased, it was confirmed that the glucose uptake activity of muscle cells increased. For example, compared to gujeolcho single 0.16 mg / ml treatment group showed an increase in activity of about 32% in the 1: 10: 1 ratio of the extract mixture.

Uptake activityUptake activity 여주:구절초:작약
(Ratio)
Yeoju: Gujeolcho: Peony
(Ratio)
Concentration (mg/ml)Concentration (mg / ml)
0.050.05 0.10.1 0.250.25 0.50.5 Insulin (500nM)Insulin (500 nM)   1.4±0.021.4 ± 0.02     1:1:11: 1: 1 1.05±0.061.05 ± 0.06 1.07±0.061.07 ± 0.06 1.16±0.11.16 ± 0.1 1.29±0.081.29 ± 0.08 1:2:11: 2: 1 1±0.081 ± 0.08 1.02±0.181.02 ± 0.18 1.17±0.11.17 ± 0.1 1.34±0.11.34 ± 0.1 1:5:11: 5: 1 0.99±0.070.99 ± 0.07 1.14±0.331.14 ± 0.33 1.29±0.011.29 ± 0.01 1.42±0.241.42 ± 0.24 1:10:11: 10: 1 1.02±0.021.02 ± 0.02 1.15±0.221.15 ± 0.22 1.33±0.011.33 ± 0.01 1.43±0.31.43 ± 0.3 * Glucose uptake ratio compared with Control(1.0)* Glucose uptake ratio compared with Control (1.0)

또한, 여주, 구절초 추출물의 비율을 고정한 후, 작약 추출물을 비율별로 혼합하여 처리한 실험에서는 작약의 비율이 많아짐에 따라 근육세포의 당 흡수 활성이 높아짐을 확인하였다. 예컨대, 작약 단일 0.16mg/ml 처리군에 비해 1:1:10 비율의 추출혼합물에서 약 31%의 활성 증가를 보였다.In addition, after fixing the ratio of Yeoju, Gujeolcho extract, in the experiments in which the peony extracts were mixed by ratio, the experiment showed that the peculiar ratio of peony increased the glucose absorption activity of muscle cells. For example, compared to Peony single 0.16 mg / ml treatment group showed an increase in activity of about 31% in the 1: 1: 10 ratio of the mixture.

Uptake activityUptake activity 여주:구절초:작약
(Ratio)
Yeoju: Gujeolcho: Peony
(Ratio)
Concentration (mg/ml)Concentration (mg / ml)
0.050.05 0.10.1 0.250.25 0.50.5 Insulin (500nM)Insulin (500 nM)   1.4±0.021.4 ± 0.02     1:1:11: 1: 1 1.05±0.061.05 ± 0.06 1.07±0.061.07 ± 0.06 1.16±0.11.16 ± 0.1 1.29±0.081.29 ± 0.08 1:1:21: 1: 2 1.08±0.151.08 ± 0.15 1.14±0.131.14 ± 0.13 1.21±0.071.21 ± 0.07 1.37±0.171.37 ± 0.17 1:1:51: 1: 5 1.01±0.181.01 ± 0.18 1.11±0.111.11 ± 0.11 1.28±0.261.28 ± 0.26 1.45±0.121.45 ± 0.12 1:1:101: 1: 10 1.14±0.051.14 ± 0.05 1.22±0.11.22 ± 0.1 1.39±0.471.39 ± 0.47 1.51±0.231.51 ± 0.23 * Glucose uptake ratio compared with Control(1.0)* Glucose uptake ratio compared with Control (1.0)

[실험예 5] 혈당조절효능 확인Experimental Example 5 Checking Glucose Control Efficacy

본 실험에서는 고지방식이와 Streptozotocin(STZ) 투여로 유발된 제 2형 당뇨 마우스 모델을 이용하였다. 1주일의 순화기간을 둔 후, 2주간 고지방식이를 공급한 후 STZ를 1일 1회 3일간 복강 투여한 후 군분리를 실시하였다.In this study, we used a type 2 diabetes mouse model induced by high-fat diet and Streptozotocin (STZ) administration. After one week of purifying period, high-fat diet was fed for two weeks, and then STZ was administered once a day for three days, followed by group separation.

본 실험은 정상군(NC), 당뇨군(HFD+STZ), 양성대조군(Metformin), 저용량군(구절초,여주 및 작약을 15:10:75의 비율로 혼합(이하, 여주 외 복합물이라고 함) 100mg/kg), 고용량군(여주 외 복합물 300, 300mg/kg) 등의 총 5군으로 군당 7마리씩 구성하여 진행하였다.In this experiment, the normal group (NC), diabetic group (HFD + STZ), positive control group (Metformin), and low dose group (Gujeolcho, Yeoju, and Peony) were mixed at a ratio of 15:10:75 (hereinafter referred to as the Yeoju complex). 100mg / kg), high dose group (Yoju complex 300, 300mg / kg), including a total of five groups composed of seven dogs per group.

양성대조군의 Metformin과 시험물질은 STZ 투여 후 2주 후부터 매일 6주간 경구투여 하였고, 정상군, 당뇨군은 정제수를 시험물질 투여 일정과 동일하게 경구투여 하였다.Metformin and the test substance in the positive control group were orally administered for 6 weeks every day from 2 weeks after STZ administration. In the normal and diabetic groups, purified water was orally administered in the same manner as the test substance administration schedule.

시험물질 투여 후 주 1회(1,2,3,4,5,6 주차) 실험동물의 미정맥을 천자한 자연스럽게 흘러나오는 전혈을 이용, 공복혈당을 측정하였다.Fasting blood glucose was measured once a week (1, 2, 3, 4, 5, 6 parking) after the administration of the test substance using naturally flowing whole blood that punctures the vein of the experimental animal.

그룹group 0 day0 day 7 day7 day 14 day14 day 21 day21 day 28 day28 day 35 day35 day 42 day42 day NCNC 146.00±13.77146.00 ± 13.77 143.75±10.65143.75 ± 10.65 142.75±10.40142.75 ± 10.40 125.75±6.88125.75 ± 6.88 120.88±8.34120.88 ± 8.34 141.50±8.30141.50 ± 8.30 142.38±7.80142.38 ± 7.80 HFD+STZHFD + STZ 352.14±89.90352.14 ± 89.90 373.71±58.75373.71 ± 58.75 379.29±77.54379.29 ± 77.54 383.29±89.11383.29 ± 89.11 373.29±58.59373.29 ± 58.59 378.43±45.89378.43 ± 45.89 388.71±90.08388.71 ± 90.08 HFD+STZ+
Metformin(200)
HFD + STZ +
Metformin (200)
348.57±85.26348.57 ± 85.26 366.57±90.83366.57 ± 90.83 352.71±132.57352.71 ± 132.57 316.57±97.49316.57 ± 97.49 261.71±97.01261.71 ± 97.01 234.14±58.10234.14 ± 58.10 221.43±49.73221.43 ± 49.73
HFD+STZ+
여주 외 복합물 (100)
HFD + STZ +
Yeoju et complex (100)
346.43±79.06346.43 ± 79.06 370.29±80.66370.29 ± 80.66 368.71±74.51368.71 ± 74.51 358.29±61.55358.29 ± 61.55 319.71±92.67319.71 ± 92.67 301.14±102.46301.14 ± 102.46 287.14±80.23287.14 ± 80.23
HFD+STZ+
여주 외 복합물 (300)
HFD + STZ +
Yeoju Complex (300)
346.71±78.43346.71 ± 78.43 371.00±101.35371.00 ± 101.35 360.86±91.90360.86 ± 91.90 349.43±97.93349.43 ± 97.93 303.43±87.49303.43 ± 87.49 275.00±71.37275.00 ± 71.37 270.71±75.70270.71 ± 75.70

공복혈당 측정 결과, 시험물질 투여 군에서 당뇨군보다 혈당이 낮아짐을 확인할 수 있었다. 또한 시험물질의 용량에 따라 혈당이 감소함을 알 수 있었다.As a result of fasting blood glucose measurement, it was confirmed that blood glucose was lower in the test substance-administered group than in the diabetic group. It was also found that blood glucose decreased with the dose of test substance.

[실험예 6] 경구내당능 검사Experimental Example 6 Oral glucose tolerance test

본 실험예는 포도당 대사가 원활하게 이루어지는지 확인하기 위해 경구내당능을 측정하였다.In this experimental example, oral glucose tolerance was measured to determine whether glucose metabolism was performed smoothly.

경구내당능 검사(Oral glucose tolerance test, OGTT)는 마지막 주에 실험동물을 12시간 절식시킨 후 glucose를 2g/kg의 용량으로 경구투여하였다. Glucose 투여 직전 및 투여 후 15, 30, 45, 60, 90, 120분에 혈당을 측정하였다.In the Oral glucose tolerance test (OGTT), the animals were fasted 12 hours in the last week and then orally administered glucose at a dose of 2 g / kg. Blood glucose levels were measured immediately before and 15, 30, 45, 60, 90 and 120 minutes after administration of Glucose.

ru0 minru0 min 15 min15 min 30 min30 min 45 min45 min 60 min60 min 90 min90 min 120 min120 min 153.71±9.69153.71 ± 9.69 420.43±33.78420.43 ± 33.78 295.00±42.86295.00 ± 42.86 233.43±17.73233.43 ± 17.73 187.4±17.38187.4 ± 17.38 172.00±9.63172.00 ± 9.63 159.29±5.79159.29 ± 5.79 F+T384.14±53.22F + T384.14 ± 53.22 668.14±50.76668.14 ± 50.76 619.29±41.95619.29 ± 41.95 556.57±27.28556.57 ± 27.28 522.29±25.97522.29 ± 25.97 459.71±2239459.71 ± 2239 427.86±22.95427.86 ± 22.95 ++
fi0265.00±48.49
++
fi0265.00 ± 48.49
575.86±38.41575.86 ± 38.41 499.86±56.03499.86 ± 56.03 452.86±40.01452.86 ± 40.01 429.86±65.16429.86 ± 65.16 370.49±47.67370.49 ± 47.67 313.14±54.68313.14 ± 54.68
+
외물0341.43±87.04
+
Outer 041.43 ± 87.04
678.29±70.19678.29 ± 70.19 605.00±24.93605.00 ± 24.93 526.57±56.81526.57 ± 56.81 506.43±30.95506.43 ± 30.95 445.43±19.00445.43 ± 19.00 397.86±54.27397.86 ± 54.27
+
외물0336.43±92.21
+
External object0336.43 ± 92.21
645.71±42.18645.71 ± 42.18 567.43±44.50567.43 ± 44.50 508.57±38.50508.57 ± 38.50 484.29±42.10484.29 ± 42.10 416.43±28.78416.43 ± 28.78 370.29±30.30370.29 ± 30.30

경구내당능 측정 시험 결과, 당뇨군에서 공복 시 384.14±53.22 mg/dL에서 15분 후 668.14±50.76 mg/dL로 올랐고, 120분 후에는 427.86±22.95 mg/dL이었다. 양성대조군 및 시험물질을 경구투여한 군에서는 30분 이후부터 당뇨군보다 투여한 용량에 대비하여 혈당이 낮아짐을 확인할 수 있었다. As a result of oral glucose tolerance test, the diabetic group rose from fasting 384.14 ± 53.22 mg / dL to 668.14 ± 50.76 mg / dL after 15 minutes and 427.86 ± 22.95 mg / dL after 120 minutes. In the control group and the oral administration of the test control group and the test substance it was confirmed that the blood glucose is lower than the dose administered from the diabetic group after 30 minutes.

[실험예 7] 혈중 Glucose, 당화혈색소(HbA1c)Experimental Example 7 Glucose in blood, glycated hemoglobin (HbA1c)

본 실험예에서는 혈청의 glucose와 적혈구 헤모글로빈의 일부인 HbA1c의 농도를 측정하고자 하였다.In this experimental example, the concentration of HbA1c, a part of serum glucose and red blood cell hemoglobin, was measured.

실험 6주째 실험동물을 절식시킨 후 채혈하여 혈액생화학분석기를 이용하여 glucose, HbA1c의 함량을 분석하였다.Six weeks after the experiment, the animals were fasted and blood was collected and analyzed by using a blood biochemical analyzer.

GroupGroup GLUGLU HbA1cHbA1c NCNC 171.49±6.10171.49 ± 6.10 3.20±0.003.20 ± 0.00 HFD+STZHFD + STZ 405.44±130.54405.44 ± 130.54 5.59±1.295.59 ± 1.29 HFD+STZ+
Metformin (200)
HFD + STZ +
Metformin (200)
278.71±69.12278.71 ± 69.12 4.23±0.684.23 ± 0.68
HFD+STZ+여주 외 복합물 (100)HFD + STZ + Lip Yeoju Complex (100) 394.07±145.37394.07 ± 145.37 5.03±1.175.03 ± 1.17 HFD+STZ+여주 외 복합물 (300)HFD + STZ + Let Yeoju Complex (300) 359.31±123.43359.31 ± 123.43 4.89±0.934.89 ± 0.93

실험결과, 혈중 glucose의 경우 정상군, 당뇨군, 양성대조군, 시험물질투여군 각각 171.49±6.10 mg/dl, 405.44±130.54 mg/dl, 278.71±69.12 mg/dl, 394.07±145.37 mg/dl, 359.31±123.43 mg/dl으로 당뇨군에 비해 양성대조군 및 시험물질투여 군의 혈중 glucose가 낮음을 확인하였다.The results of blood glucose were 171.49 ± 6.10 mg / dl, 405.44 ± 130.54 mg / dl, 278.71 ± 69.12 mg / dl, 394.07 ± 145.37 mg / dl, 359.31 ±, respectively. At 123.43 mg / dl, the blood glucose levels of the positive control group and the test substance administration group were lower than those of the diabetic group.

혈중 당화혈색소(HbA1c)의 경우는 정상군, 당뇨군, 시험물질투여군 각각 각각 3.20±0.00%, 5.59±1.29%, 4.23±0.68%, 5.03±1.17%, 4.89±0.93%이었으며 양성대조군 포함 시험물질투여 군에서 당뇨군보다 혈중당화혈색소가 낮아짐을 알 수 있었다.Blood glycated hemoglobin (HbA1c) was 3.20 ± 0.00%, 5.59 ± 1.29%, 4.23 ± 0.68%, 5.03 ± 1.17%, 4.89 ± 0.93%, respectively, in the normal, diabetic, and test substance administration groups, respectively. The glycated hemoglobin level was lower in the administration group than in the diabetic group.

Claims (9)

당뇨 예방 또는 개선용 식품 조성물로서,
상기 조성물은
여주(Momordica charantia L.) 추출물, 구절초(Chrysanthemum zawadskii var. latilobum) 추출물 및 작약(Paeonia lactiflora) 추출물을 유효성분으로 포함하고,
상기 여주 추출물, 구절초 추출물 및 작약 추출물의 함량비율은,
1: 1.5: 7.5인, 제2형 당뇨 예방 또는 개선용 식품 조성물.
As a food composition for preventing or improving diabetes,
The composition is
Momordica charantia L. extract, Chrysanthemum zawadskii var.latilobum extract, and Peony ( Paeonia lactiflora ) extract as an active ingredient,
The content ratio of the bitter gourd extract, gujeolcho extract and peony extract,
1: Food composition for preventing or ameliorating type 2 diabetes, which is 1.5: 7.5.
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KR1020170160760A 2016-11-28 2017-11-28 Composition for preventing or improving diabetes mellitus comprising momrdica charantia (l.) extract, chrysanthemum zawadskii var. latilobum and paeonia lactiflora extract as an effective ingredient KR102064651B1 (en)

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KR102147058B1 (en) * 2019-08-05 2020-08-24 최면 Composition for prevention, improvement or treatment of diabetes with extracts from Scrophularia Buergeriana, Siberian ginseng, Lycii fructus root, Momordica charantia Linnaeus, Rosa rugosa
KR102644056B1 (en) * 2020-06-05 2024-03-06 한국생명공학연구원 Composition for preventing, improving or treating metabolic syndrome comprising β-gentiobiosyl paeoniflorinas as effective ingredients
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