KR20210081164A - Pharmaceutical compositions containing Dansameum water extract for prevention or treatment of non-alcoholic fatty liver diseases - Google Patents
Pharmaceutical compositions containing Dansameum water extract for prevention or treatment of non-alcoholic fatty liver diseases Download PDFInfo
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- KR20210081164A KR20210081164A KR1020190173430A KR20190173430A KR20210081164A KR 20210081164 A KR20210081164 A KR 20210081164A KR 1020190173430 A KR1020190173430 A KR 1020190173430A KR 20190173430 A KR20190173430 A KR 20190173430A KR 20210081164 A KR20210081164 A KR 20210081164A
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- fatty liver
- extract
- alcoholic fatty
- alcoholic
- pharmaceutical composition
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Abstract
Description
본 발명의 조성물은 지방세포의 지질 축적 억제 효과와 동시에 비알코올성 지방간 질환과 관련되는 다양한 기전에 관여함으로써 비알콜성 지방간의 예방 또는 치료에 우수한 효과를 나타내는 단삼음 추출물을 유효성분으로 포함하는 비알콜성 지방간의 예방 또는 치료용 약학 조성물에 관한 것이다.The composition of the present invention contains, as an active ingredient, a dansaneum extract, which exhibits an excellent effect in the prevention or treatment of nonalcoholic fatty liver by being involved in various mechanisms related to nonalcoholic fatty liver disease while simultaneously inhibiting lipid accumulation in adipocytes. It relates to a pharmaceutical composition for preventing or treating sexual fatty liver.
지방간은 중성지방이 간세포에 저장되어 간 무게의 5% 이상 과도하게 축적된 상태를 의미하며, 그 원인에 따라 알코올성 지방간과 비알코올성 지방간으로 구분될 수 있다.Fatty liver refers to a state in which triglycerides are stored in hepatocytes and excessively accumulated over 5% of the liver weight, and can be classified into alcoholic fatty liver and non-alcoholic fatty liver depending on the cause.
상기 알코올성 지방간은 과도한 알코올 섭취, 유전적 요인(예컨대, 알코올 분해효소의 유전 다형성 등), 환경적인 요인(예컨대, 성별, 영양상태, C형 간염바이러스 감염 등)에 의하여 주로 발생하며, 향후 간염 또는 간경변증으로 진행될 수 있으며, 간 암 또는 간 부전까지 진행되어 사망에 이르기도 한다. The alcoholic fatty liver is mainly caused by excessive alcohol intake, genetic factors (eg, genetic polymorphism of alcohol-degrading enzyme, etc.), and environmental factors (eg, sex, nutritional status, hepatitis C virus infection, etc.). It can progress to cirrhosis, liver cancer or liver failure, leading to death.
비알콜성 지방간(non-alcoholic fatty liver disease, NAFLD) 병변은 간에 유해할 정도로 인정되는 알콜 섭취 병력이 없음에도 불구하고 간 조직 검사에서 알콜성 간염의 특징적인 소견인 단순 지방간(non-alcoholic fatty liver, NAFL), 지방간염(non-alcoholic steatohepatits, NASH), 지방간염과 동반된 섬유화증, 간경변증을 포함하는 소견을 보인다. 특히, 비알콜성 지방간염의 경우 간경변이나 간세포암으로 진전될 가능성이 높다고 알려져 적극적인 치료를 요한다. Non-alcoholic fatty liver disease (NAFLD) lesions are non-alcoholic fatty liver, a characteristic finding of alcoholic hepatitis in liver biopsy despite no history of alcohol intake recognized as harmful to the liver. , NAFL), non-alcoholic steatohepatits (NASH), fibrosis associated with steatohepatitis, and liver cirrhosis. In particular, nonalcoholic steatohepatitis is known to be highly likely to progress to cirrhosis or hepatocellular carcinoma, requiring active treatment.
NAFLD의 유병률 분석은 환자의 확진을 위해 조직검사가 필수적이어서 정확한 분석은 어려우나 미국에서 성인 13,500명 대상연구에서 18세 이상의 성인 중 23.5%의 유병률을 보고하고 있고, 국내에서도 유병률의 증가추세를 인지하고 있다. It is difficult to analyze the prevalence of NAFLD precisely because a biopsy is essential for confirming the patient, but a study of 13,500 adults in the United States reported a prevalence of 23.5% among
또한, NAFLD은 대부분 인슐린 저항성 악화, 비만, 당뇨병, 고지혈증 등의 합병증을 동반한다. 더욱이, NAFLD와 심혈관계 질환의 관련성을 명확히 하지는 않고 있으나, NAFLD가 동맥경화의 과정에 영향을 준다는 가설도 여러 연구에서 제기되고 있다. In addition, most of NAFLD is accompanied by complications such as worsening of insulin resistance, obesity, diabetes, and hyperlipidemia. Moreover, although the relationship between NAFLD and cardiovascular disease has not been clearly established, several studies have also suggested the hypothesis that NAFLD influences the process of atherosclerosis.
현재까지 NAFLD에 대한 임상적 적용은 적극적인 운동량의 증가와 식이조절을 우선시하고 있으나, 환자의 대부분의 경우 운동량과 식이조절은 매우 어렵다. 지방간 치료제인 폴리엔포스파티딜콜린(polyene phosphatidylcholine)이나, 고지혈증 치료제인 클로피브레이트(clofibrate)로 대표되는 피브레이트(fibrate)계 약제가 사용되고 있는 실정이지만, 상기 치료제들을 비알코올성 지방간 환자에게 장기간 투여시 안전성 및 효능에 대한 임상자료가 많이 부족한 실정이고, 게다가, 치료제의 복용후에도 부작용 또한 많은 것이 애로사항이다. To date, clinical application of NAFLD prioritizes active exercise and dietary control, but in most patients, exercise and diet control are very difficult. Although fibrate-based agents, such as polyene phosphatidylcholine, a treatment for fatty liver, and clofibrate, a treatment for hyperlipidemia, are being used, safety and efficacy when administering these treatments to patients with nonalcoholic fatty liver for a long period of time There is a lack of clinical data on the drug, and in addition, there are many side effects even after taking the treatment.
치료용 약학 조성물을 개발하기 위해서, 치료의 작용점 연구와 독성을 동반한 부작용 저해 연구는 매우 중요하다. 바이오 마커 측면에서, NAFLD는 비만과 연관된 간조직의 지방 축적(LXR-α, PPAR-γ, SREBP1, ACC1, FAS, SCD1과 CD36) 이후 염증성의 진행은 간세포에서 NF-κB 경로를 활성화시키고, 염증인자인 IL-6, TNF-a, 그리고 IL-1β 등의 분비를 촉진시켜 전신적인 인슐린 저항성을 악화시키게 된다고 알려져 있다. In order to develop a therapeutic pharmaceutical composition, a study on the point of action of treatment and a study on inhibition of side effects accompanied by toxicity are very important. In terms of biomarkers, NAFLD is associated with obesity-associated hepatic fat accumulation (LXR-α, PPAR-γ, SREBP1, ACC1, FAS, SCD1 and CD36), followed by inflammatory progression by activating the NF-κB pathway in hepatocytes, and It is known to exacerbate systemic insulin resistance by promoting secretion of factors such as IL-6, TNF-a, and IL-1β.
중의학에서 처방되어 한의학에서도 처방 되어 지는 단삼음(丹蔘飮)은 단삼을 주약으로 단향과 사인을 좌사약으로 배합한 처방으로, 심통과 위완부의 제반 통증에 사용하며, 특히 부인에게 효능이 좋은 것으로 알려져 있다. Dansameum (丹蔘飮), which is prescribed in Chinese medicine and also prescribed in oriental medicine, is a prescription that combines danhyang and sine as a suppository with dansam as the main drug. It is used for heartache and various pains in the upper arm. It is especially effective for women. it is known
하지만, 지금까지의 연구는 본 추출물을 비알콜성 지방간 질환 치료나 동맥경화의 치료를 대상으로 하는 임상 시험과 비임상 시험에서는 전무한 실정이다. 따라서, 본 발명은 본 추출물을 세포수준과 동물모델을 적용하여 분자수준에서의 변화를 분석하였고, 비알콜성 지방간 질환 치료나 동맥경화의 치료용 약학조성물로서의 기능을 규명한 연구결과를 제시한다. However, studies so far have not been conducted in clinical trials and non-clinical trials targeting this extract for the treatment of non-alcoholic fatty liver disease or arteriosclerosis. Therefore, the present invention presents the study results of analyzing the change at the molecular level by applying the extract at the cellular level and in an animal model, and identifying the function of the extract as a pharmaceutical composition for the treatment of non-alcoholic fatty liver disease or arteriosclerosis.
현재 시판되고 있는 치료제들을 비알코올성 지방간 환자에게 장기간 투여 시 안전성 및 효능에 대한 임상자료가 많이 부족한 실정이고, 게다가, 치료제의 복용후에도 부작용 또한 많은 애로사항이다. 본 발명자들은 거듭된 연구를 통하여 본 약학조성물을 비알콜성 지방간 질환 예방 또는 치료용 약학적 조성물으로서 이용될 단삼음 추출물을 개발하고자 하는 것이다.Clinical data on the safety and efficacy of currently marketed therapeutic agents for long-term administration to patients with nonalcoholic fatty liver are lacking, and in addition, side effects are also a problem even after taking the therapeutic agent. The present inventors intend to develop a Dansaneum extract to be used as a pharmaceutical composition for preventing or treating non-alcoholic fatty liver disease with this pharmaceutical composition through repeated research.
본 발명은 상기와 같은 문제점을 고려하여 지방세포의 지질 축적 억제 효과를 나타냄과 동시에 신호전달 매개 단백질과 염증 발현 인자 억제 효능에 우수한 효과를 나타내는 단삼음 열수출물의 수용성 분획물을 포함하는 비알콜성 지방간 질환 예방 또는 치료용 약학적 조성물을 제공하는 것이다.In consideration of the above problems, the present invention provides a non-alcoholic fatty liver comprising a water-soluble fraction of dansaeum extract that exhibits an effect of inhibiting lipid accumulation in adipocytes and at the same time exhibiting an excellent effect in inhibiting signal transduction proteins and inflammatory expression factors. To provide a pharmaceutical composition for preventing or treating diseases.
상기 과제를 해결하기 위한 수단으로서, 본 발명은 단삼음 추출물을 유효성분으로 포함하는 비알콜성 지방간 질환 예방 또는 치료용 약학 조성물을 제공하는 것이다.As a means for solving the above problems, the present invention is to provide a pharmaceutical composition for preventing or treating non-alcoholic fatty liver disease comprising an extract of dansa ginseng as an active ingredient.
본 발명은 단삼음 추출물이 단삼, 단향, 사인으로부터 유래한 것을 특징으로 하는 비알콜성 지방간 질환 예방 또는 치료용 약학 조성물을 제공하는 것이다.The present invention is to provide a pharmaceutical composition for preventing or treating non-alcoholic fatty liver disease, characterized in that the extract of Dansameum extract is derived from Dansam, Danhyang, and sine.
본 발명은 단삼음 추출물이 단삼, 단향, 사인에 대해 증류수를 가하여 열수 추출한 후, 여과하고 동결건조하여 수득된 것임을 특징으로 하는 비알콜성 지방간 질환 예방 또는 치료용 약학 조성물을 제공하는 것이다.The present invention is to provide a pharmaceutical composition for preventing or treating non-alcoholic fatty liver disease, characterized in that the extract of Dansameum extract is obtained by adding distilled water to dansam, danhyang, and sine, followed by hot water extraction, followed by filtration and freeze-drying.
본 발명은 단삼음 추출물이 도 1에 표시된 고성능 액체 크로마토그래피 분석 패턴을 갖는 것을 특징으로 하는 비알콜성 지방간 질환 예방 또는 치료용 약학 조성물을 제공하는 것이다.The present invention is to provide a pharmaceutical composition for preventing or treating non-alcoholic fatty liver disease, characterized in that the dansaeum extract has a high-performance liquid chromatography analysis pattern shown in FIG. 1 .
본 발명은 단삼음 추출물이 유효성분 표지물질인 로즈마린산(rosmarinic acid), 살비아놀산(salvianolic acid), 탄시논 IIA(tanshinone IIA)을 포함하는 비알콜성 지방간 질환 예방 또는 치료용 약학 조성물을 제공하는 것이다.The present invention provides a pharmaceutical composition for preventing or treating non-alcoholic fatty liver disease, wherein the extract of Dansaneum extract contains rosmarinic acid, salvianolic acid, and tanshinone IIA as active ingredient markers will be.
본 발명은 단삼음 추출물이 지질 축적으로 인한 간조직의 변형 및 지방축적을 감소시키고, 혈중 지질함량을 감소시키는 것을 특징으로 하는 비알콜성 지방간 질환 예방 또는 치료용 약학 조성물을 제공하는 것이다.The present invention is to provide a pharmaceutical composition for preventing or treating non-alcoholic fatty liver disease, characterized in that the extract of Dansameum reduces liver tissue deformation and fat accumulation due to lipid accumulation, and reduces blood lipid content.
본 발명은 비알콜성 지방간 질환이 비알콜성 단순성 지방간, 비알콜성 지방간염, 지방간염과 동반된 섬유화증 또는 비알콜성 간경변인 것을 특징으로 하는 비알콜성 지방간 질환 예방 또는 치료용 약학 조성물을 제공하는 것이다.The present invention provides a pharmaceutical composition for preventing or treating nonalcoholic fatty liver disease, characterized in that the nonalcoholic fatty liver disease is nonalcoholic simple fatty liver, nonalcoholic steatohepatitis, fibrosis or nonalcoholic cirrhosis accompanying steatohepatitis. will provide
본 발명은 단삼음 추출물의 용법이 1일 240㎎/kg이하로 12주간 경구 복용하는 것을 특징으로 하는 비알콜성 지방간 질환의 예방 또는 치료용 약학조성물을 제공하는 것이다.The present invention is to provide a pharmaceutical composition for the prevention or treatment of non-alcoholic fatty liver disease, characterized in that the usage of the Dansameum extract is taken orally for 12 weeks at 240 mg/kg or less per day.
상기 과제를 해결하기 위한 다른 수단으로서, 본 발명은 단삼음 추출물을 유효성분으로 포함하는 것을 특징으로 하는 비알콜성 지방간 개선용 식품 조성물을 제공하는 것이다.As another means for solving the above problems, the present invention is to provide a food composition for improving non-alcoholic fatty liver, characterized in that it comprises a dansaeum extract as an active ingredient.
본 발명은 단삼음 추출물이 단삼, 단향, 사인으로부터 유래한 것을 특징으로 하는 비알콜성 지방간 개선용 식품 조성물을 제공을 제공하는 것이다.The present invention is to provide a food composition for improving non-alcoholic fatty liver, characterized in that Dansameum extract is derived from Dansam, Danhyang, and sine.
본 발명은 상기 단삼음 추출물이 단삼, 단향, 사인에 대해 증류수를 가하여 열수 추출한 후, 여과하고 동결건조하여 수득된 것임을 특징으로 하는 비알콜성 지방간 개선용 식품 조성물을 제공을 제공하는 것이다.The present invention is to provide a food composition for improving non-alcoholic fatty liver, characterized in that the extract of Dansameum extract is obtained by adding distilled water to Danginseng, Danhyang, and sine, followed by hot water extraction, followed by filtration and freeze-drying.
본 발명은 단삼음 추출물이 도 1에 표시된 고성능 액체 크로마토그래피 분석 패턴을 갖는 것을 특징으로 하는 비알콜성 지방간 개선용 식품 조성물을 제공한다.The present invention provides a food composition for improving non-alcoholic fatty liver, characterized in that the dansaeum extract has a high-performance liquid chromatography analysis pattern shown in FIG. 1 .
본 발명은 단삼음 추출물이 유효성분 표지물질인 로즈마린산(rosmarinic acid), 살비아놀산(salvianolic acid), 탄시논 IIA(tanshinone IIA)을 포함하는 비알콜성 지방간 개선용 식품 조성물을 제공을 제공하는 것이다.The present invention provides a food composition for improving non-alcoholic fatty liver, wherein the extract of Dansaneum extract contains rosmarinic acid, salvianolic acid, and tanshinone IIA as active ingredient markers. .
본 발명은 단삼음 추출물이 지질 축적으로 인한 간조직의 변형 및 지방축적을 감소시키고, 혈중 지질함량을 감소시키는 것을 특징으로 하는 비알콜성 지방간 개선용 식품 조성물을 제공을 제공하는 것이다.The present invention is to provide a food composition for improving non-alcoholic fatty liver, characterized in that the extract of Dansameum reduces liver tissue deformation and fat accumulation due to lipid accumulation, and reduces blood lipid content.
본 발명은 비알콜성 지방간 질환이 비알콜성 단순성 지방간, 비알콜성 지방간염, 지방간염과 동반된 섬유화증 또는 비알콜성 간경변인 것을 특징으로 하는 비알콜성 지방간 개선용 식품 조성물을 제공을 제공하는 것이다.The present invention provides a food composition for improving nonalcoholic fatty liver, characterized in that the nonalcoholic fatty liver disease is nonalcoholic simple fatty liver, nonalcoholic steatohepatitis, fibrosis or nonalcoholic cirrhosis accompanying steatohepatitis. will do
본 발명으로 경제적으로도 저렴하면서도 비알콜성 지방간의 치료와 동맥경화의 치료 효과가 우수한 새로운 비알콜성 지방간의 예방 및 치료를 위한 치료제 혹은 약학 조성물을 얻을 수 있다.According to the present invention, it is possible to obtain a novel therapeutic agent or pharmaceutical composition for the prevention and treatment of non-alcoholic fatty liver which is economically inexpensive and has excellent therapeutic effects for the treatment of non-alcoholic fatty liver and arteriosclerosis.
본 조성물은 지질 축적으로 인한 간조직의 변형 및 지방축적을 감소시키고, 혈중 지질함량을 감소시키며, 간 병변의 진행 과정상의 분자수준에서 NF-κB 경로를 활성화경로를 차단하여 염증인자인 IL-6, TNF-a, 그리고 IL-1b를 하향 조절하며, 지방 합성 경로 (LXR-α, PPAR-γ, SREBP1, ACC1, FAS, SCD1과 CD36)를 포함한 세포 산화 환원 상태를 하향 조정하는 것으로, 비알콜성 지방간 질환 예방 또는 치료용으로 사용가능한 약학 조성물에 관한 것이다.This composition reduces the transformation of liver tissue and fat accumulation due to lipid accumulation, reduces the lipid content in blood, and blocks the NF-κB pathway at the molecular level during the progression of liver lesions, thereby blocking the activation pathway of IL-6, an inflammatory factor. , downregulates TNF-a, and IL-1b, and downregulates cellular redox status, including lipogenesis pathways (LXR-α, PPAR-γ, SREBP1, ACC1, FAS, SCD1 and CD36). It relates to a pharmaceutical composition usable for preventing or treating fatty liver disease.
더욱이, 본 발명의 유효성분은 천연 식물로부터 수득된 추출물이므로 인체에 유해하지 않으며 종래 약물에서 나타나는 부작용이 최소화되거나 없다.Moreover, since the active ingredient of the present invention is an extract obtained from a natural plant, it is not harmful to the human body, and side effects appearing in conventional drugs are minimized or absent.
본 발명에 따른 조성물은 비알코올성 지방간 질환을 예방 또는 치료하는 약학 조성물로, 본 발명의 또다른 측면에서, 본 발명은 단삼음 추출물을 유효성분으로 포함하는, 비알콜성 지방간 질환의 개선 또는 예방용 식품 조성물을 제공한다. The composition according to the present invention is a pharmaceutical composition for preventing or treating non-alcoholic fatty liver disease, and in another aspect of the present invention, the present invention is for improving or preventing non-alcoholic fatty liver disease, comprising an extract of Dansaneum extract as an active ingredient A food composition is provided.
도1은 단삼을 추출물에서 HPLC로 유효성분의 함량을 분석한 도를 나타낸다.
도2는 팔미틱에시드 단삼음의 효과를 확인 한 도이다. 팔미틱에시드 0.5mM과 단삼음 100㎍과 200㎍을 24시간 동안 처리 하였다. 도2의 a는 나일(Nile)염색으로 축적된 지질을 붉은색으로 나타낸다. 도2의 b는 a의 붉은색의 강도를 나타낸 그래프이다.
도3은 팔미틱에시드로 유도된 HepG2에서 지질축적 인자들의 mRNA 발현을 확인한 도이다. 구체적으로 HepG2에 단삼음과 팔미틱에시드를 처리하고 24시간 뒤에 RNA를 추출하여 RT-PCR로 mRNA의 발현을 확인 하였다.
도4는 단삼음의 12주간 고지방식이로 유도한 비알콜성지방간 APOE 결손 마우스에서의 지질 축적인자들의 변화를 확인한 도이다. 단삼음은 240㎎/kg을 12주간 매일 섭취하였고, APOE 결손 마우스의 간을 획득하여 간조직에서의 변화를 확인 하였다. 도4의 a와 b는 간의 조직학적 모양과 지질의 축적정도를 확인한 결과이다. 도4의 d는 면역조직화학염색을 통하여 간조직에서의 지질축적 인자들의 단백질 발현을 확인한 도이다. 도4의 e에서 h는 각각의 단백질의 발현을 정량화한 그래프이다.
도5는 단삼음이 팔미틱에시드에 의해 유도된 HepG2세포에서와 고지방식이 APOE 결손 마우스에서의 단백질 발현에 미치는 영향을 보여주는 도이다. 구체적으로, 도5의 a와 b는 HepG2에 단삼음과 팔미틱에시드를 처리하고 24시간 뒤에 단백질을 추출하여 확인하고 정량하여 그래프로 나타내었다. 도5의 c와 d는 고지방식이 APOE 결손 마우스에서 신호전달에 중요한 마커인 인산화된 JNK의 단백질 발현을 확인하고 정량화한 그래프이다.
도6은 단삼음이 팔미틱에시드로 유도된 HepG2세포의 염증인자 발현에 미치는 영향을 보여주는 도이다. 팔미틱에시드와 단삼음을 동시에 처리 한 후, RNA와 단백질을 회수 하여 각각의 인자들의 발현을 확인하고 정량화한 도이다.
도7은 단삼음이 고지방식이로 유도된 비알콜성 지방간 마우스모델에서 ROS 발생과 염증인자들의 조절에 미치는 영향을 확인한 도이다.
이하에서는 구체적인 실시예들을 들어 본 발명의 실시예에 따른 단삼음 추출물을 포함하는 조성물에 대해서 설명한다. 그러나 이하의 실시예들에 의하여 본 발명의 기술사상이 제한되는 것은 아니다.1 shows the analysis of the content of active ingredients in the extract of dandelion ginseng by HPLC.
Figure 2 is a diagram confirming the effect of palmitic acid single sameum. 0.5 mM of palmitic acid and 100 μg and 200 μg of Dansaeum were treated for 24 hours. Figure 2a shows lipids accumulated by Nile staining in red. Figure 2b is a graph showing the intensity of the red color of a.
3 is a diagram confirming the mRNA expression of lipid accumulation factors in HepG2 induced with palmitic acid. Specifically, HepG2 was treated with dansaeum and palmitic acid, and RNA was extracted 24 hours later, and mRNA expression was confirmed by RT-PCR.
4 is a diagram confirming changes in lipid accumulation factors in non-alcoholic fatty liver APOE-deficient mice induced by a 12-week high-fat diet of Dansaeum. Dansaeum was ingested at a dose of 240 mg/kg daily for 12 weeks, and liver tissue was obtained by obtaining the liver of an APOE-deficient mouse. 4 a and b are the results of confirming the histological shape of the liver and the degree of accumulation of lipids. 4 d is a diagram confirming the protein expression of lipid accumulation factors in liver tissue through immunohistochemical staining. In FIG. 4E , h is a graph quantifying the expression of each protein.
FIG. 5 is a diagram showing the effect of dansaeum on protein expression in HepG2 cells induced by palmitic acid and high-fat diet in APOE-deficient mice. Specifically, in Figure 5 a and b, HepG2 was treated with dansaeum and palmitic acid, and after 24 hours, the protein was extracted, confirmed, quantified, and presented as a graph. 5 c and d are graphs confirming and quantifying the protein expression of phosphorylated JNK, an important marker for signal transduction in high-fat diet APOE-deficient mice.
6 is a diagram showing the effect of dansaeum on the expression of inflammatory factors in HepG2 cells induced with palmitic acid. After simultaneous treatment with palmitic acid and dansaeum, RNA and protein were recovered to confirm and quantify the expression of each factor.
7 is a diagram confirming the effect of dansaeum on the generation of ROS and the regulation of inflammatory factors in a non-alcoholic fatty liver mouse model induced by a high-fat diet.
Hereinafter, a composition comprising a Dansaeum extract according to an embodiment of the present invention will be described with reference to specific examples. However, the technical spirit of the present invention is not limited by the following examples.
현재 시판되고 있는 치료제들을 비알코올성 지방간 환자에게 장기간 투여 시 안전성 및 효능에 대한 임상자료가 많이 부족한 실정이고, 게다가, 치료제의 복용후에도 부작용 또한 많은 애로사항이다. 본 발명자들은 연구를 거듭한 결과 본 약학조성물을 비알콜성 지방간 질환 예방 또는 치료용 약학적 조성물으로서 이용될 단삼음 추출물을 개발하였다.Clinical data on the safety and efficacy of currently marketed therapeutic agents for long-term administration to patients with nonalcoholic fatty liver are lacking, and in addition, side effects are also a problem even after taking the therapeutic agent. As a result of repeated research, the present inventors developed a Dansaneum extract to be used as a pharmaceutical composition for preventing or treating non-alcoholic fatty liver disease.
본 발명은 상기와 같은 문제점을 고려하여 지방세포의 지질 축적 억제 효과를 나타냄과 동시에 신호전달 매개 단백질과 염증 발현 인자 억제 효능에 우수한 효과를 나타내는 단삼음 열수출물의 수용성 분획물을 포함하는 비알콜성 지방간 질환 예방 또는 치료용 약학적 조성물을 제공하는 것이다.In consideration of the above problems, the present invention provides a non-alcoholic fatty liver comprising a water-soluble fraction of dansaeum extract that exhibits an effect of inhibiting lipid accumulation in adipocytes and at the same time exhibiting an excellent effect in inhibiting signal transduction proteins and inflammatory expression factors. To provide a pharmaceutical composition for preventing or treating diseases.
본 발명은 비알코올성 지방간 질환을 유의적으로 예방 또는 치료할 수 있는 단삼음 추출물을 유효성분으로 포함하는 조성물을 제공한다. The present invention provides a composition comprising, as an active ingredient, a dansaeum extract capable of significantly preventing or treating non-alcoholic fatty liver disease.
본 발명에서 사용되는 용어 "치료"는 본 발명에 따른 조성물의 투여에 의해 비알코올성 지방간 질환의 증상이 호전 또는 완치되는 모든 행위를 의미한다.As used herein, the term “treatment” refers to any action in which symptoms of nonalcoholic fatty liver disease are improved or cured by administration of the composition according to the present invention.
본 발명에서 사용되는 용어 "예방"은 본 발명에 따른 조성물의 투여에 의해 비알코올성 지방간 질환이 억제 또는 지연되는 모든 행위를 의미한다. As used herein, the term “prevention” refers to any action in which non-alcoholic fatty liver disease is inhibited or delayed by administration of the composition according to the present invention.
본 발명에 따른 약학 조성물은 하나 이상의 약학적으로 허용되는 담체, 부형제 또는 희석제를 추가로 함유할 수 있다. 사용가능한 담체, 부형제 또는 희석제로는, 락토즈, 덱스트로즈, 수크로즈, 솔비톨, 만니톨, 자이리톨, 에리스리톨, 말리톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로즈, 폴리비닐피롤리돈, 물, 메틸하이드록시벤조에이트, 프로필하이드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유가 있으며, 이중 선택되는 하나 이상을 사용할 수 있다. 또한, 치료 및 예방제가 약제인 경우 충진제, 항응집제, 윤활제, 습윤제, 향료, 유화제 또는 방부제 등이 추가적으로 포함될 수 있다.The pharmaceutical composition according to the present invention may further contain one or more pharmaceutically acceptable carriers, excipients or diluents. Usable carriers, excipients or diluents include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, malitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose. , microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil, and at least one selected from among them may be used. In addition, when the therapeutic and prophylactic agent is a pharmaceutical, a filler, an anti-aggregant, a lubricant, a wetting agent, a fragrance, an emulsifier, or a preservative may be additionally included.
본 발명의 약학 조성물은 상술한 바와 같은 투여 경로에 따라 경구 투여용 또는 비경구 투여용 제제로 제형화 할 수 있다. 기 조성물의 제형은 사용방법이나 유효성을 고려하여 다양하게 결정될 수 있다.The pharmaceutical composition of the present invention may be formulated as a formulation for oral administration or parenteral administration according to the administration route as described above. The formulation of the base composition may be variously determined in consideration of the method of use or effectiveness.
경구 투여용 제제의 경우에 본 발명의 조성물은 분말, 과립, 정제, 환제, 당의정제, 캡슐제, 액제, 겔제, 시럽제, 슬러리제, 현탁액 등으로 당업계에 공지된 방법을 이용하여 제형화될 수 있다.In the case of a formulation for oral administration, the composition of the present invention may be formulated as a powder, granule, tablet, pill, dragee, capsule, liquid, gel, syrup, slurry, suspension, etc. using methods known in the art. can
비경구 투여용 제제의 경우에는 주사제, 크림제, 로션제, 외용연고제, 오일제, 보습제, 겔제, 에어로졸 및 비강흡입제의 형태로 당업계에 공지된 방법으로 제형화할 수 있다.Formulations for parenteral administration may be formulated in the form of injections, creams, lotions, external ointments, oils, moisturizers, gels, aerosols and nasal inhalants by methods known in the art.
본 발명에 따른 활성 성분은 식품 형태로도 투여될 수 있다. 식품 조성물의 제형은 특별히 한정되지 않으며, 예를 들어 정제, 과립제, 분말제, 드링크제와 같은 액제, 겔 또는 바 등으로 제형화될 수 있다.The active ingredient according to the invention can also be administered in food form. The formulation of the food composition is not particularly limited, and may be formulated as, for example, tablets, granules, powders, liquids such as drinks, gels or bars.
본 발명의 약학 조성물의 총 유효량은 단일 투여량(single dose)으로 환자에게 투여될 수 있으며, 다중 투여량(multiple dose)으로 장기간 투여되는 분할 치료 방법(fractionated treatment protocol)에 의해 투여될 수 있다. 본 발명의 약학 조성물은 질환의 증상에 따라 유효성분의 함량을 달리할 수 있다.The total effective amount of the pharmaceutical composition of the present invention may be administered to a patient as a single dose, and may be administered by a fractionated treatment protocol in which multiple doses are administered for a long period of time. The pharmaceutical composition of the present invention may vary the content of the active ingredient according to the symptoms of the disease.
본 발명의 조성물을 개체에게 투여하는 단계를 포함하는 비알코올성 지방간 질환의 치료 또는 예방 방법을 제공한다.It provides a method for treating or preventing non-alcoholic fatty liver disease, comprising administering the composition of the present invention to a subject.
본 발명은 단삼음 추출물을 포함하는 비알콜성 지방간 질환 예방 또는 치료용 약학 조성물에 관한 것으로, 보다 상세하게는 로스마린산(rosmarinic acid), 살비아놀산(salvianolic acid), 탄시논 IIA(tanshinone IIA)을 함유하는 단삼음 추출물의 수용성 분획물을 포함하는 비알콜성 지방간 질환 예방 또는 치료용 약학 조성물을 제공하는 것이다.The present invention relates to a pharmaceutical composition for preventing or treating non-alcoholic fatty liver disease comprising an extract of dansaeum extract, and more particularly, rosmarinic acid, salvianolic acid, tanshinone IIA (tanshinone IIA) ) to provide a pharmaceutical composition for preventing or treating non-alcoholic fatty liver disease, comprising a water-soluble fraction of Dansaeum extract containing.
[실시 예 1: 단삼음 추출물 제조][Example 1: Preparation of Dansaneum extract]
본 실시예에서는 하기와 같이 단삼음 추출물을 제조하였다. 실험을 실시하기 위해, 단삼(40g), 단향(4g), 사인(4g)을 증류수에 넣고 3시간 동안 90℃내지 100℃에서 가열하여 열수 추출하였다. 이후 추출물을 여과하여 동결 건조기에 감압 건조시킨다. 이후 추출물은 인산완충식염수(phosphate-buffered saline, PBS)에 녹여 사용하였다. In this example, a dansaeum extract was prepared as follows. To conduct the experiment, ginseng (40g), danhyang (4g), and sage (4g) were put in distilled water and heated at 90°C to 100°C for 3 hours to extract hot water. Then, the extract is filtered and dried under reduced pressure in a freeze dryer. Thereafter, the extract was dissolved in phosphate-buffered saline (PBS) and used.
[실시 예 2: 단삼음 추출물의 고성능 액체 크로마토그래피(High performance liquid chromatograpy, HPLC) 분석] [Example 2: High performance liquid chromatography (HPLC) analysis of dandelion extracts]
실시예 1에서 제조한 단삼음 추출물의 표준 물질의 존재 및 함량을 확인하기 위하여, 고성능 액체 크로마토그래피를 이용한 화학적 분석(chemical fingerprinting)을 하기와 같이 수행하였다.In order to confirm the presence and content of the standard material of the Dansaeum extract prepared in Example 1, chemical fingerprinting using high-performance liquid chromatography was performed as follows.
고성능 액체 크로마토그래피는 Elite Lachrom HPLC system (Hitachi Co., Japan)을 사용하였고, L-2130 pump, L-2200 auto-sampler, L-2350 column oven, L-2455 diode array UV/VIS detetctor로 구성되어 있으며, 컬럼은 OptimaPak C18 (5㎛, 100A, 4.6mm × 250mm, RStech Co., Korea)을 사용하였고, 컬럼 오븐은 30℃를 유지하였다. 이동상은 고성능 액체 크로마토그래피용 물과 아세토니트릴(actonitrile)의 혼합용매의 비율을 변화시킨 gradient solvent system(5 내지 100% 아세토니트릴 혼합용매, 시간: 60분, 유속: 1㎖/min)을 사용하였고, 구체적으로, 표준 화합물들 (마그놀올(magnolol)과 호노키올(honokiol))과 후박추출물의 분말의 무게를 정확히 측정한 다음, 메탄올에 녹여 100mg/ml의 농도로 조제하였으며, 0.45㎛ filter로 여과한 후 10㎕를 주입하여 분석하였다. 이때, 광다이오드 배열 검출기(Photo-Diode Array Detector:DAD)의 UV 파장은 후박추출물의 모든 피크가 고르게 잘 분포한 230nm를 선택하였다. Elite Lachrom HPLC system (Hitachi Co., Japan) was used for high-performance liquid chromatography, and it was composed of L-2130 pump, L-2200 auto-sampler, L-2350 column oven, and L-2455 diode array UV/VIS detetctor. and OptimaPak C18 (5㎛, 100A, 4.6mm × 250mm, RStech Co., Korea) was used as the column, and the column oven was maintained at 30°C. For the mobile phase, a gradient solvent system (5 to 100% acetonitrile mixed solvent, time: 60 minutes, flow rate: 1 ml/min) was used in which the ratio of the mixed solvent of water and acetonitrile for high-performance liquid chromatography was changed. , Specifically, the weight of the powder of the standard compounds (magnolol and honokiol) and the peppercorn extract was accurately measured, and then dissolved in methanol to prepare a concentration of 100 mg/ml, and filtered through a 0.45 μm filter After that, 10 μl was injected and analyzed. At this time, the UV wavelength of the Photo-Diode Array Detector (DAD) was selected to be 230 nm, in which all the peaks of the hull extract are evenly and well distributed.
그 결과, 도1에 나타낸 바와 같이, 단삼음 추출물에는 로즈마린산(rosmarinic acid), 살비아놀산(rosmarinic acid), 탄시논 IIA(tanshinone IIA)가 지표 물질로서 존재함을 확인할 수 있었다. As a result, as shown in FIG. 1 , it was confirmed that rosmarinic acid, salvianolic acid, and tanshinone IIA were present as indicator substances in the Dansaeum extract.
[실시 예 3: 지방세포의 지질 축적 억제 효과][Example 3: Effect of inhibiting lipid accumulation in adipocytes]
(1) 인체간암세포에서의 지질 축적 억제 (1) Inhibition of lipid accumulation in human liver cancer cells
실시예 1에서 제조된 단삼음을 간에서의 지질 축적 억제 효능을 확인하기 위해 나일(Nile) 염색법을 사용하였다. 인체간암세포 (HepG2)를 6-well plate에 배양한 후, 팔미틱에시드(palmitic acid)를 처리하거나 100㎍과 200㎍의 단삼음을 처리하였다. 도 2에서 보듯이, 팔미틱에시드는 지방축적을 시키는 반면에, 100㎍과 200㎍ 단삼음은 세포의 지방 축적을 억제시키는 것을 알 수 있었다. The Nile staining method was used to confirm the efficacy of inhibiting lipid accumulation in the liver of dansaeum prepared in Example 1. Human liver cancer cells (HepG2) were cultured in a 6-well plate, and then treated with palmitic acid or 100 μg and 200 μg of single ginseng. As shown in FIG. 2 , it was found that palmitic acid inhibited fat accumulation in cells, whereas 100㎍ and 200㎍ dansameum inhibited the accumulation of fat.
(2)지방세포의 지질관련 인자 억제 효과 (2) Inhibitory effect of lipid-related factors in adipocytes
HepG2의 지질 축적과 관련 유전자들의 발현을 확인하기 위해서, 도3와 같이 연쇄중합반응 효소(reverse transformation polymerase chain reaction; RT-PCR)를 이용하여 지방합성과 연관된 인자의 RNA발현을 확인하였다. LXR-α, PPAR-γ, SEREBP1, ACC-1, FAS, SCD1과 CD36의 RNA 발현은 단삼음에 의해 억제가 되었다. In order to confirm the lipid accumulation of HepG2 and the expression of related genes, RNA expression of factors related to lipogenesis was confirmed using a reverse transformation polymerase chain reaction (RT-PCR) as shown in FIG. 3 . RNA expression of LXR-α, PPAR-γ, SEREBP1, ACC-1, FAS, SCD1 and CD36 was inhibited by monotone.
[실시예 4: 고지방식이를 한 ApoE 결손 마우스의 간에서의 지질 축적 억제 효과 ][Example 4: Inhibition of lipid accumulation in the liver of ApoE-deficient mice fed a high-fat diet]
12주동안 ApoE 결손 마우스에게 고지방식이로 비알콜성 지방간 모델을 제작하였고, 12주동안 단삼음 240㎎/kg을 주어 지질 축적 억제 효과를 확인하였다. 또한, 간에서의 지질축적 유도 인자들의 발현은 간조직에서 면역조직화학법을 이용하여 단백질의 발현을 확인하였다.A non-alcoholic fatty liver model was prepared on a high-fat diet in ApoE-deficient mice for 12 weeks, and lipid accumulation inhibitory effect was confirmed by giving Dansameum 240 mg/kg for 12 weeks. In addition, expression of lipid accumulation inducing factors in the liver was confirmed by immunohistochemistry in liver tissue.
도3은 고지방식이로 인해 유도된 비알콜성지방간 모델의 조직학적 분석과 지질 축적을 확인하였고, 지질 유도인자의 단백질인 LXR-α, PPAR-γ, SREBP-1과 CD36의 발현 또한 단삼음에 의해 발현이 감소함을 알 수 있었다. 3 is a histological analysis and lipid accumulation in the non-alcoholic fatty liver model induced by a high-fat diet, and the expression of LXR-α, PPAR-γ, SREBP-1 and CD36, which are lipid-inducing factor proteins, is also suppressed. It was found that the expression was decreased by
따라서, 실시예 2와 실시예 3에서 나타난 지질의 축적은 단삼음이 지질축적 인자를 억제함으로 인해 조절됨을 알 수 있었다. Therefore, it can be seen that the accumulation of lipids shown in Examples 2 and 3 is regulated due to the suppression of the lipid accumulation factor in Dansameum.
[실시예 5: 단삼음의 고지방식이를 한 ApoE 결손 마우스의 중성지방함량 감소 효과][Example 5: Effect of reducing triglyceride content in ApoE-deficient mice fed a high-fat diet of ginseng]
APOE 결손 마우스(대조군), 고지방을 12주동안 식이한 마우스(고지방식이군)와 단삼음과 고지방식이를 동시에 한 ApoE 결손 마우스(단삼음처리군)로 군을 나누어 중성지방함량을 측정하였다. 표1과 같이, 마우스의 몸무게는 고지방식이군이 대조군과 비교하여 유의하게 증가하였고 반면에 단삼음 처리군은 대조군과 비슷한 몸무게를 보였다. 또한, 중성지방 함량을 고지방식이군은 대조군 대비 299㎎/dL까지 올라간 반면, 단삼음 처리군은 대조군과 유사한 양의 콜레스테롤 수치를 보였다. The triglyceride content was measured by dividing the groups into APOE-deficient mice (control group), mice fed a high-fat diet for 12 weeks (high-fat diet group), and ApoE-deficient mice fed a monotone and high-fat diet at the same time (sample salt treatment group). As shown in Table 1, the weight of the mice in the high-fat diet group was significantly increased compared to the control group, whereas the monotone treatment group showed a similar body weight to the control group. In addition, the triglyceride content of the high-fat diet group increased to 299 mg/dL compared to the control group, whereas the dansaeum treatment group showed a cholesterol level similar to that of the control group.
[실시예 6: 신호전달 매개 단백질과 염증 발현 인자 억제 효능 ][Example 6: Efficacy of Inhibiting Signal Transduction Mediating Protein and Inflammatory Expression Factor]
c-Jun N-terminal kinase (JNK)는 비알코올성 지방간이 일어날 때 활성화되는 카이네즈로 신호전달에 중요한 역할을 한다. 따라서, 팔미틱에시드로 유도된 HepG2세포에서 단삼음이 JNK의 인산화를 조절하는지 확인하였다. 도5와 같이 100㎍과 200㎍의 단삼음은 JNK의 인산화를 유의하게 조절하는 것을 알 수 있었다. 또한, 고지방식이를 한 ApoE 결손 마우스에서도 단삼음에 의해 JNK의 인산화가 감소됨을 확인할 수 있었다. c-Jun N-terminal kinase (JNK) is a kinase activated when nonalcoholic fatty liver occurs and plays an important role in signal transduction. Therefore, it was confirmed whether Dansaemeum regulates the phosphorylation of JNK in HepG2 cells induced with palmitic acid. As shown in FIG. 5, it was found that 100 μg and 200 μg of single sameum significantly regulated the phosphorylation of JNK. In addition, it was confirmed that the phosphorylation of JNK was reduced by dansaeum in ApoE-deficient mice fed a high-fat diet.
비알콜성 지방간이 발생하면 염증 수치도 증가하게 된다. 따라서 팔미틱에시드로 유도된 HepG2에서 단삼음의 염증 억제 효능을 확인하고자 하였다. 도6와 같이, 팔미틱에시드와 고지방식이로 인해 염증인자인 IL-1β, IL-6, p-NF-κB의 발현이 증가한 반면, 단삼음으로 인해 발현이 억제되는 것을 확인할 수 있었다. When nonalcoholic fatty liver develops, the level of inflammation also increases. Therefore, the purpose of this study was to confirm the anti-inflammatory effect of dansaeum in HepG2 induced with palmitic acid. As shown in FIG. 6 , it was confirmed that the expression of inflammatory factors IL-1β, IL-6, and p-NF-κB was increased due to palmitic acid and a high-fat diet, whereas the expression was suppressed by dansaeum.
또한, 도 7과 같이 고지방식이를 한 ApoE 결손 마우스에서 증가된 ROS의 발현을 단삼음에 의해 억제됨을 확인할 수 있었고, 염증 인자들인 IL-1β, IL-6와 TNF-α, NF-κB의 발현이 단삼음에 의해 감소됨을 확인하였다. In addition, as shown in FIG. 7 , it was confirmed that the increased expression of ROS in ApoE-deficient mice fed a high-fat diet was suppressed by single sameum, and the inflammatory factors IL-1β, IL-6, TNF-α, and NF-κB It was confirmed that the expression was reduced by single sameum.
Claims (15)
상기 단삼음 추출물은 단삼, 단향, 사인으로부터 유래한 것을 특징으로 하는 비알콜성 지방간 질환 예방 또는 치료용 약학 조성물.According to claim 1,
The Dansameum extract is a pharmaceutical composition for preventing or treating non-alcoholic fatty liver disease, characterized in that it is derived from Danginseng, Danhyang, and sine.
상기 단삼음 추출물은 단삼, 단향, 사인에 대해 증류수를 가하여 열수 추출한 후, 여과하고 동결건조하여 수득된 것임을 특징으로 하는 비알콜성 지방간 질환 예방 또는 치료용 약학 조성물.According to claim 1,
The dansameum extract is a pharmaceutical composition for preventing or treating non-alcoholic fatty liver disease, characterized in that it is obtained by adding distilled water to dansam, danhyang, and sine, followed by hot water extraction, filtration and freeze-drying.
상기 단삼음 추출물은 도 1에 표시된 고성능 액체 크로마토그래피 분석 패턴을 갖는 것을 특징으로 하는 비알콜성 지방간 질환 예방 또는 치료용 약학 조성물.
[도 1]
The dansaeum extract is a pharmaceutical composition for preventing or treating non-alcoholic fatty liver disease, characterized in that it has a high-performance liquid chromatography analysis pattern shown in FIG.
[Fig. 1]
상기 단삼음 추출물은 유효성분 표지물질인 로즈마린산(rosmarinic acid), 살비아놀산(salvianolic acid), 탄시논 IIA(tanshinone IIA)을 포함하는 비알콜성 지방간 질환 예방 또는 치료용 약학 조성물.According to claim 1,
The dansaeum extract is a pharmaceutical composition for preventing or treating non-alcoholic fatty liver disease, comprising rosmarinic acid, salvianolic acid, and tanshinone IIA as active ingredient markers.
상기 단삼음 추출물은 지질 축적으로 인한 간조직의 변형 및 지방축적을 감소시키고, 혈중 지질함량을 감소시키는 것을 특징으로 하는 비알콜성 지방간 질환 예방 또는 치료용 약학 조성물.According to claim 1,
The Dansaeum extract is a pharmaceutical composition for preventing or treating non-alcoholic fatty liver disease, characterized in that it reduces the transformation and fat accumulation in liver tissue due to lipid accumulation, and reduces the lipid content in the blood.
상기 비알콜성 지방간 질환은 비알콜성 단순성 지방간, 비알콜성 지방간염, 지방간염과 동반된 섬유화증 또는 비알콜성 간경변인 것을 특징으로 하는 비알콜성 지방간 질환 예방 또는 치료용 약학 조성물.According to claim 1,
The non-alcoholic fatty liver disease is a non-alcoholic fatty liver disease prevention or treatment pharmaceutical composition, characterized in that non-alcoholic simple fatty liver, non-alcoholic steatohepatitis, fibrosis or non-alcoholic cirrhosis accompanied by steatohepatitis.
상기 단삼음 추출물의 용법은 1일 240㎎/kg이하로 12주간 경구 복용하는 것을 특징으로 하는 비알콜성 지방간 질환의 예방 또는 치료용 약학조성물.According to claim 1,
The usage of the Dansameum extract is a pharmaceutical composition for the prevention or treatment of non-alcoholic fatty liver disease, characterized in that it is orally taken for 12 weeks at 240 mg/kg or less per day.
상기 단삼음 추출물은 단삼, 단향, 사인으로부터 유래한 것을 특징으로 하는 비알콜성 지방간 개선용 식품 조성물.10. The method of claim 9,
The dansameum extract is a food composition for improving non-alcoholic fatty liver, characterized in that it is derived from dansam, danhyang, and sine.
상기 단삼음 추출물은 단삼, 단향, 사인에 대해 증류수를 가하여 열수 추출한 후, 여과하고 동결건조하여 수득된 것임을 특징으로 하는 비알콜성 지방간 개선용 식품 조성물.10. The method of claim 9,
The dansameum extract is a non-alcoholic fatty liver improvement food composition, characterized in that it is obtained by adding distilled water to dansam, danhyang, and sine, followed by hot water extraction, filtration and freeze-drying.
상기 단삼음 추출물은 도 1에 표시된 고성능 액체 크로마토그래피 분석 패턴을 갖는 것을 특징으로 하는 비알콜성 지방간 개선용 식품 조성물.
[도 1]
The dansaeum extract is a food composition for improving non-alcoholic fatty liver, characterized in that it has a high-performance liquid chromatography analysis pattern shown in FIG.
[Fig. 1]
상기 단삼음 추출물은 유효성분 표지물질인 로즈마린산(rosmarinic acid), 살비아놀산(salvianolic acid), 탄시논 IIA(tanshinone IIA)을 포함하는 비알콜성 지방간 개선용 식품 조성물.10. The method of claim 9,
The Dansaeum extract is a non-alcoholic fatty liver improvement food composition comprising active ingredient markers, rosmarinic acid, salvianolic acid, and tanshinone IIA.
상기 단삼음 추출물은 지질 축적으로 인한 간조직의 변형 및 지방축적을 감소시키고, 혈중 지질함량을 감소시키는 것을 특징으로 하는 비알콜성 지방간 개선용 식품 조성물.10. The method of claim 9,
The Dansameum extract is a food composition for improving non-alcoholic fatty liver, characterized in that it reduces liver tissue deformation and fat accumulation due to lipid accumulation, and reduces blood lipid content.
상기 비알콜성 지방간 질환은 비알콜성 단순성 지방간, 비알콜성 지방간염, 지방간염과 동반된 섬유화증 또는 비알콜성 간경변인 것을 특징으로 하는 비알콜성 지방간 개선용 식품 조성물.10. The method of claim 9,
The non-alcoholic fatty liver disease is non-alcoholic fatty liver improvement food composition, characterized in that non-alcoholic simple fatty liver, non-alcoholic steatohepatitis, fibrosis or non-alcoholic cirrhosis accompanied with steatohepatitis.
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| KR20180055945A (en) | 2016-11-16 | 2018-05-28 | 영진약품 주식회사 | Composition for Improving hepatic function Including Extract of Salvia Militorhiza Bunge and Method for Preparation of the Same |
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| WO2024048998A1 (en) * | 2022-09-02 | 2024-03-07 | 한국 한의학 연구원 | Composition for prevention, alleviation, or treatment of bone disease, containing salvianolic acid as active ingredient |
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