KR20130043767A - A composition comprising the extract of processed panax genus plant for treating and preventing liver disease and hepato-protective activity - Google Patents
A composition comprising the extract of processed panax genus plant for treating and preventing liver disease and hepato-protective activity Download PDFInfo
- Publication number
- KR20130043767A KR20130043767A KR1020110107852A KR20110107852A KR20130043767A KR 20130043767 A KR20130043767 A KR 20130043767A KR 1020110107852 A KR1020110107852 A KR 1020110107852A KR 20110107852 A KR20110107852 A KR 20110107852A KR 20130043767 A KR20130043767 A KR 20130043767A
- Authority
- KR
- South Korea
- Prior art keywords
- panax
- ginseng
- processed
- extract
- liver disease
- Prior art date
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- 241000208343 Panax Species 0.000 title claims abstract description 40
- 235000002791 Panax Nutrition 0.000 title claims abstract description 31
- 208000019423 liver disease Diseases 0.000 title claims abstract description 22
- 241000196324 Embryophyta Species 0.000 title claims abstract description 9
- 230000002443 hepatoprotective effect Effects 0.000 title claims abstract description 6
- 239000000284 extract Substances 0.000 title claims description 33
- 239000000203 mixture Substances 0.000 title abstract description 41
- 235000008434 ginseng Nutrition 0.000 claims abstract description 60
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- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
- A61K36/258—Panax (ginseng)
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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- A—HUMAN NECESSITIES
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
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- A61K2236/30—Extraction of the material
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Abstract
Description
본 발명의 가공된 파낙스속 식물 추출물을 유효성분으로 함유하는 간보호 및 간질환의 치료 또는 예방용 조성물에 관한 것이다.It relates to a composition for the treatment or prevention of liver protection and liver disease containing the processed Panax genus plant extract of the present invention as an active ingredient.
[문헌 1] Brenneisen, P., Wenk, J., Klotz. L.O., Wlaschek, M., Briviba, K., Krieg, T., Sies, H., Scharffetter-Kochanek, K., Central role of ferrous/ferric iron in the ultraviolet B irradiation-mediated signaling pathway leading to increased interstitial collagenase (matrix-degrading metalloproteinase (MMP)-1) and stromelysin-1 (MMP-3) mRNA levels in cultured human dermal fibroblasts. J. Biol. Chem. 273, 5279-5287, 1998. [Document 1] Brenneisen, P., Wenk, J., Klotz. LO, Wlaschek, M., Briviba, K., Krieg, T., Sies, H., Scharffetter-Kochanek, K., Central role of ferrous / ferric iron in the ultraviolet B-mediated signaling pathway leading to increased interstitial collagenase (MMP-1) and stromelysin-1 (MMP-3) mRNA levels in cultured human dermal fibroblasts. J. Biol. Chem. 273, 5279-5287, 1998.
[문헌 2] Masaki, H., Atsumi, T., Sakurai, H., Detection of hydrogen peroxide and hydroxyl radicals in murine skin fibroblasts under UVB irradiation. Biochem . Biophys . Res . Commun .206,pp.474-479,1995.[Literature 2] Masaki, H., Atsumi, T., Sakurai, H. Detection of hydrogen peroxide and hydroxyl radicals in murine skin fibroblasts under UVB irradiation. Biochem . Biophys . Res . Commun . 206, pp. 474-479, 1995.
[문헌 3] 고려삼의 이해, 고려인삼학회, p 9, 1995; Advances in Ginseng Research, 고려인삼학회, p 127, 1998)[Literature 3] Understanding of Korean ginseng, Korean Ginseng Society, p 9, 1995; Advances in Ginseng Research, Korea Ginseng Society, p 127, 1998)
[문헌 4] 고려인삼의 이해, 고려인삼학회, pp 9-18, 2008). [Reference 4] Understanding Korean Ginseng, Korean Ginseng Society, pp 9-18, 2008).
[문헌 4] Kim W.Y. et al, Journal of Natural Products, vol.63, pp1702-1704, 2000; [Document 4] Kim W.Y. et al., Journal of Natural Products, vol. 63, pp 1702-1704, 2000;
[문헌 5] Kwon S W, et al., J. Chromatogr. A, 921(2), pp 335-339, 2001; [Literature 5] Kwon S W, et al., J. Chromatogr. A, 921 (2), pp 335-339, 2001;
[문헌 6] Park I.H. et. al., Archives of Pharmacal Research, 25, pp.428-432 and 837-841, 2002;[Document 6] Park I.H. et. al., Archives of Pharmacal Research, 25, pp. 428-432 and 837-841, 2002;
[문헌 7] Yong-Sam Keum, Kwang-Kyun Park, Jong-Min Lee, Kyung-soo Chun., Antioxidant and anti-tumor promoting activities of the methanol extract of heat-processed ginseng. J. CancerLetters .150,PP.41-48,2000.[7] Yong-Sam Keum, Kwang-Kyun Park, Jong-Min Lee and Kyung-soo Chun. Antioxidant and anti-tumor promoting activities of the methanol extracts of heat-processed ginseng. J. CancerLetters . 150, pp. 41-48,2000.
[문헌 8] Young C. Kim, So R. Kim, George J. Markelonis, Tae H. Oh., Ginsenosides Rb1 and Rg3 Protect Cultured Rat Cortical Cells From Glutamate-Induced Neurodegeneration. J. NeuroscienceRes .53,PP.426-432,1998.[8] Young C. Kim, So R. Kim, George J. Markelonis, Tae H. Oh., Ginsenosides Rb1 and Rg3 Protect Cultured Rat Cortical Cells From Glutamate-Induced Neurodegeneration. J. Neuroscience Res . 53, pp. 426-432, 1998.
[문헌 9] Keun Young Jung, Dong seon Kim, Platelet Activating Factor Antagonist Activity of Ginsenosides. Biol . Pharm . Bull .21.PP.79-80,1998.[Literature 9] Keun Young Jung, Dong Seon Kim, Platelet Activating Factor Antagonist Activity of Ginsenosides. Biol . Pharm . Bull . 21.PP.79-80, 1998.
[문헌 10] Kim WY, et al., J. Nat . Prod ., 63(12), pp 1702-1704, 2001 ;[Literature 10] Kim WY, et al., J. Nat . Prod . , 63 (12) , pp 1702-1704, 2001;
[문헌 11] Kwon SW, et al., J. Chromatogr . A., 921(2), pp 335-339, 2001 [Document 11] Kwon SW, et al., J. Chromatogr . A. , 921 (2) , pp 335-339, 2001
[문헌 12] 대한민국 특허 10-0192678 약효가 증강된 가공인삼제품, 1999 [Document 12] Korean Patent 10-0192678 Processed Ginseng Product with Enhanced Drug Effect, 1999
본 발명은 가공된 파낙스속 식물 추출물을 유효성분으로 함유하는 간세포보호 및 간질환의 치료 또는 예방용 조성물에 관한 것이다. The present invention relates to a composition for treating or preventing hepatocellular protection and liver disease, which contains the processed Panax genus plant extract as an active ingredient.
세포손상은 세포의 기능을 저해하여 다양한 질환을 유발하는 것으로 알려져 있다. 생체내에서의 지질과산화 현상은 대식세포, 중성과립구 등의 다핵세포구들의 화학적 주화성을 유발하며, 세포 활성화를 통한 류코트리엔, 콜라게나제, 엘라스타제, 산화효소 등의 분비를 촉진시켜 다양한 생체 이상을 유발한다. 과산화지질은 간세포 괴사의 주요한 원인으로도 작용하는데, 주로 세포막의 불포화지방산이 자유기로 활성화된 산소와 반응하여 형성된다. 생체 내에서의 과산화지질의 생성의 원인물질로는 사염화탄소, 삼차-부틸 히드로퍼록사이드(t-BHP) 알콜 등의 환경물질, 유해성 식품첨가물, 아세트아미노펜 같은 비스테로이드성 항염증제뿐만 아니라 UV, X-선과 같은 물리적인 요인, 그 밖에 중금속 등 다양하게 알려져 있다(1-2). 지질과산화에 관여하는 산화적 스트레스는 DNA 돌연변이, 효소의 활성 변화, 수용체 산화를 통한 신호전달체계 교란, 이온 통로 변화를 통한 세포의 삼투압변화 등을 통해 세포를 파괴하고 기능을 억제한다. 따라서, 다양한 화학물질의 대사과정에 관여하는 간세포는 알콜 섭취뿐만 다양한 약물 등에 의해서도 쉽게 과산화지질이 파괴될 수 있다. 따라서, 간 세포를 보호하기 위한 다양한 약물 개발들이 개발되었고, 이는 대부분 간세포로부터 생성된 과산화지질을 포함한 다양한 산화성 유리기를 제거하는 작용을 가지고 있다.Cell damage is known to cause various diseases by inhibiting the function of cells. Lipid peroxidation in vivo causes chemical chemotaxis of multinucleated cells such as macrophages and neutrophils, and stimulates the secretion of leukotriene, collagenase, elastase, oxidase, etc. Cause abnormalities. Lipid peroxide also acts as a major cause of hepatocellular necrosis, which is formed mainly by the reaction of unsaturated fatty acids in the cell membrane with free radicals activated oxygen. Causes of lipid peroxide production in vivo include UV, X-rays, as well as environmental substances such as carbon tetrachloride and tert-butyl hydroperoxide (t-BHP) alcohols, hazardous food additives, and nonsteroidal anti-inflammatory agents such as acetaminophen. The same physical factors and other heavy metals are known in various ways (1-2). Oxidative stress, which is involved in lipid peroxidation, destroys cells and inhibits function through DNA mutations, changes in enzyme activity, disruption of signaling systems through receptor oxidation, and changes in the osmotic pressure of cells through changes in ion channels. Therefore, hepatocytes involved in metabolic processes of various chemicals can be easily destroyed lipid peroxide not only by alcohol consumption but also various drugs. Therefore, various drug developments have been developed to protect liver cells, which have the function of removing various oxidative free radicals including lipid peroxide produced from hepatocytes.
파낙스(Panax)속 식물은 식물 분류학상 오가피과 (Araliaceae)에 속하는 다년생 숙근초로서 지구상에 십여종이 알려져 있다. 대표적인 종으로 고려인삼 (Panax ginseng), 화기삼 (Panax quinquefolia), 전칠삼 (삼칠, Panax notoginseng), 베트남삼 (Panax vietnamensis), 죽절삼 (Panax japonicus) 등이 있으며, (고려삼의 이해, 고려인삼학회, p 9, 1995; Advances in Ginseng Research, 고려인삼학회, p 127, 1998) 기타 파낙스속 식물로는 파낙스 엘레가티오르 (Panax elegatior), 파낙스 완지아누스 (Panax wangianus), 파낙스 비핀나티푸스 (Panax bipinnatifidus), 파낙스 슈도진생 (Panax pseudoginseng) 등이 있다.Panax is a perennial herbaceous plant belonging to the genus Araliaceae in plant taxonomy. Representative species include Korean ginseng ( Panax ginseng ), flower ginseng ( Panax quinquefolia ), ginseng (samchi, Panax notoginseng ), Vietnamese ginseng ( Panax vietnamensis ) and Panax japonicus (People's Understanding, Korean Ginseng Society, p 9, 1995; Advances in Ginseng Research, Korean Ginseng Society, p 127, 1998). Thior ( Panax elegatior ), Panax wanzianus ( Panax wangianus , Panax bipinnatifidus ), Panax pseudoinsins ( Panax pseudoginseng ).
파낙스속 식물 중 가장 유명한 인삼은 예로부터 아시아 지역에서 가장 널리 사용되어온 생약 중의 하나로, 피로회복, 자양강장, 인지기능개선, 기억력증가, 혈액순환개선, 항암, 항당뇨, 성기능개선, 노화방지, 면역력증강, 혈소판 응집억제 등 많은 약리효능이 알려져 있다 (고려인삼의 이해, 고려인삼학회, pp 9-18, 2008). Ginseng, one of the most famous Panax plants, is one of the most widely used herbal medicines in Asia. It has been widely used in Asia for many years. It has been widely used for many purposes such as fatigue, nourishment, improvement of cognitive function, memory, blood circulation improvement, And the inhibition of platelet aggregation are known. (Understanding of Korean Ginseng, Korean Ginseng Society, pp 9-18, 2008).
한편, 파낙스속 식물을 가열 가공 처리하거나 또는 약산으로 처리하면 진세노사이드 구조에서 일부 당과 알콜기가 떨어져나가 약효가 더 강력한 새로운 구조의 진세노사이드, 즉, 진세노사이드 Rg3, Rg5, Rk1, Rk2, Rk3, Rs1, Rs2, Rs3, F4, Rh2, Rh3, Rh4 등이 생성되는 것이 알려져 있다 (Kim W.Y. et al, Journal of Natural Products, vol.63, pp1702-1704, 2000; Kwon S W, et al., J. Chromatogr. A, 921(2), pp 335-339, 2001; Park I.H. et. al., Archives of Pharmacal Research, 25, pp.428-432 and 837-841, 2002) On the other hand, heat-processing or treating a genus of Panax plants with a weak acid removes some sugars and alcohol groups from the ginsenoside structure, and the new structure of ginsenosides having stronger potency, ie, ginsenosides Rg3, Rg5, Rk1, Rk2 , Rk3, Rs1, Rs2, Rs3, F4, Rh2, Rh3, Rh4 and the like are known to be produced (Kim WY et al, Journal of Natural Products, vol. 63, pp1702-1704, 2000; Kwon SW, et al. , J. Chromatogr.A, 921 (2), pp 335-339, 2001; Park IH et. Al., Archives of Pharmacal Research, 25, pp.428-432 and 837-841, 2002)
대한민국 등록특허 제192678호 및 미국 등록특허 제5776460호에는 진세노사이드 (Rg3+Rg5+Rk1)의 함량의 합이 (Rb1+Rb2+Rc+Rd)의 함량의 합보다도 더 커진 가공 파낙스속 식물(이하, 선삼이라 함)에 대하여 기술되어 있으며, 상기 선삼은 인삼(Panaxginseng)을 고열 고압으로 처리하여 약효가 강한 Rg3,Rg5,Rk1의 함량을 획기적으로 높인 가공 인삼이다. 선삼의 약효로는 항암작용(7), 뇌기능 개선작용(8), 혈소판 응집능 차단작용(9) 등이 보고되어있다. Republic of Korea Patent No. 192678 and U.S. Patent No. 5,76,460 include processed panax plants in which the sum of the contents of ginsenosides (Rg3 + Rg5 + Rk1) is greater than the sum of the contents of (Rb1 + Rb2 + Rc + Rd). Hereinafter, the ginseng) is described, wherein the ginseng is a processed ginseng by dramatically increasing the content of Rg 3 , Rg 5 , Rk 1 , which is highly effective by treating ginseng ( Panaxginseng ) at high temperature and high pressure. The efficacy of sun ginseng has been reported anti-cancer action (7), brain function improving action (8), platelet aggregation ability blocking action (9) and the like.
그러나, 상기 문헌들의 어디에도 아직까지 가공된 파낙스속 식물 추출물의 간보호 및 간질환에 대한 치료 효과에 대해서는 전혀 기재되거나 교시된 바가 없다.However, none of the above documents have yet described or taught the therapeutic effect of the processed Panax genus plant extracts on hepatoprotective and hepatic diseases.
본 발명자들은, 가공 인삼인 선삼의 추출물을 이용하여 삼차-부틸 히드로퍼록사이드 (t-BHP)에 의한 간세포의 상해를 억제하는 작용에 대해서 평가하고자 하였다. 이를 위하여 사람의 간세포주인 HepG2 세포에 t-BHP를 처리하여 세포사멸에 대하여 측정하였으며, 산화적 인자인 NO생성과 지질과산화에 미치는 영향을 측정하였고, 세포막 파괴로 유발되는 LDH, GOT, GPT 유리를 측정하여 간보호 및 간질환 치료 및 예방효과를 확인하여 본 발명을 완성하였다.
The present inventors attempted to evaluate the action of inhibiting the injury of hepatocytes by tert-butyl hydroperoxide (t-BHP) using extract of ginseng, a processed ginseng. To this end, hepG2 cells, human hepatocytes, were treated with t-BHP to measure apoptosis, and their effects on NO production and lipid peroxidation, oxidative factors, and LDH, GOT, and GPT glass induced by cell membrane destruction were measured. The present invention was completed by measuring the effect of preventing and treating liver protection and liver disease.
상기 목적을 해결하기 위해 본 발명은 진세노사이드 Rg3, Rk1, Rg5 함량의 합이 진세노사이드 Rb1, Rb2, Rc, Rd의 함량의 합보다 더 높도록 약효성분을 증가시킨 가공된 파낙스속 식물 추출물을 유효성분으로 함유하는 간보호 및 간질환 치료 또는 예방용 약학조성물을 제공한다.
In order to solve the above object, the present invention is processed Panax genus plant extract in which the sum of the ginsenoside Rg3, Rk1, Rg5 content is higher than the sum of the content of ginsenoside Rb1, Rb2, Rc, Rd It provides a pharmaceutical composition for treating or preventing liver protection and liver disease containing as an active ingredient.
본 발명은 진세노사이드 Rg3, Rk1, Rg5 함량의 합이 진세노사이드 Rb1, Rb2, Rc, Rd의 함량의 합보다 더 높도록 약효성분을 증가시킨 가공된 파낙스속 식물 추출물을 유효성분으로 함유하는 간보호 및 간질환 예방 및 개선용 건강기능식품을 제공한다.The present invention comprises a processed Panax genus plant extract having an increased active ingredient as an active ingredient such that the sum of ginsenosides Rg3, Rk1, and Rg5 is higher than the sum of the contents of ginsenosides Rb1, Rb2, Rc, and Rd. Provide health functional food for liver protection and prevention and improvement of liver disease.
본원에서 정의되는 가공된 파낙스속 식물은, 바람직하게는 고려인삼 (Panax ginseng), 화기삼 (Panax quinquefolia), 전칠삼 (삼칠, Panax notoginseng), 베트남삼 (Panax vietnamensis), 죽절삼 (Panax japonicus), 파낙스 엘레가티오르 (Panax elegatior), 파낙스 완지아누스 (Panax wangianus), 파낙스 비핀나티푸스 (Panax bipinnatifidus), 또는 파낙스 슈도진생 (Panax pseudoginseng)을 인위적으로 가공시킨 식물을 포함하며, 보다 바람직하게는 고온에서 가열처리함으로써 약효가 증강된 가공인삼에 관한 것이다. 더욱 구체적으로, 인삼을 120 내지 180℃의 고온에서 0.5 내지 20시간 동안 가열처리하여 진세노사이드 (Rg3+Rg5)/(Rc+Rd+Rb₁+Rb₂)의 비율이 1.0이상이 되도록 약효성분을 증가시킨 가공인삼을 포함한다.
Processed Panax genus plant as defined herein, preferably a ginseng (Panax ginseng), hwagisam (Panax quinquefolia ), Whole Chilsam (samchi, Panax notoginseng ), Vietnamese ginseng ( Panax vietnamensis ), Panax ginseng ( Panax japonicus), Panax elegans tee climb (Panax elegatior), Panax Wan Jia Augustine (Panax wangianus), Panax non-typhoid pinna (Panax bipinnatifidus), or Panax pseudo-ginseng (Panax pseudoginseng ) artificially processed plants, and more preferably relates to processed ginseng with enhanced efficacy by heat treatment at high temperatures. More specifically, the ginseng is heated at a high temperature of 120 to 180 ° C. for 0.5 to 20 hours to increase the active ingredient so that the ratio of ginsenosides (Rg 3 + Rg 5) / (Rc + Rd + RbR + Rb₂) is 1.0 or more. Contains processed ginseng.
상기 추출물은 물, 메탄올, 에탄올, 부탄올 등의 저급 알콜 또는 이들의 혼합용매, 바람직하게는, 물 또는 10 내지 100% 물 및 에탄올 혼합용매, 보다 바람직하게는, 약 50 내지 90% 물 및 에탄올 혼합용매에 가용한 추출물을 포함한다.The extract is a lower alcohol such as water, methanol, ethanol, butanol, or a mixed solvent thereof, preferably water or 10 to 100% water and ethanol mixed solvent, more preferably, about 50 to 90% water and ethanol mixed Extracts soluble in the solvent.
상기 간 질환은 급성간염, 만성간염, 지방간증, 간경화증, 간섬유화증, 및 간암, 바람직하게는 지방간증을 포함하는 것을 특징으로 한다.The liver disease is characterized by including acute hepatitis, chronic hepatitis, fatty liver disease, cirrhosis of the liver, liver fibrosis, and liver cancer, preferably fatty liver disease.
이하 본 발명의 추출물을 수득하는 방법을 보다 상세하게 설명한다. Hereinafter, the method of obtaining the extract of the present invention will be described in more detail.
예를 들어, 파낙스속 식물의 열매, 줄기 또는 뿌리를 각각 세척 및 건조시킨 후, 상기 파낙스속 식물은 120 내지 180℃의 고온에서 0.5 내지 20시간 동안 가열처리한 후에 상기 개개 시료 중량의 약 1배 내지 30배, 바람직하게는 약 5배 내지 15배 (w/v) 부피의 물, C1 내지 C4의 저급 알콜 또는 이들의 혼합용매로, 바람직하게는 물 또는 에탄올, 보다 바람직하게는 물 또는 50 내지 90% 에탄올을 추출용매로 하여, 약 70 내지 120℃, 바람직하게는 80 내지 110℃의 반응온도에서 약 1 내지 6시간, 바람직하게는 3 내지 5시간 동안 가열추출법, 초음파 추출법, 환류 추출법 등의 통상적인 추출방법, 바람직하게는 환류 추출법으로 1 내지 10회, 바람직하게는 2 내지 7회 반복 추출하는 제 2단계; 상기 단계에서 수득한 추출액을 여과 및 감압 농축하는 제 3단계를 통하여 본 발명의 가공된 파낙스속 식물 추출물을 수득가능하다.
For example, after washing and drying the fruits, stems or roots of the Panax plants, respectively, the Panax plants are heat treated at a high temperature of 120 to 180 ° C. for 0.5 to 20 hours and then about 1 times the weight of the individual samples. To 30 times, preferably about 5 to 15 times (w / v) volume of water, C 1 to C 4 lower alcohols or mixed solvents thereof, preferably water or ethanol, more preferably water or Heat extraction method, ultrasonic extraction method, reflux extraction method for about 1 to 6 hours, preferably 3 to 5 hours at a reaction temperature of about 70 to 120 ℃, preferably 80 to 110 ℃ using 50 to 90% ethanol as the extraction solvent A second step of repeated
또한 본 발명은 상기한 제조방법 및 상기 제조방법으로 제조된 가공된 파낙스속 식물 추출물을 유효성분으로 함유하는 간보호 및 간질환의 치료 및 예방을 위한 약학 조성물 및 건강기능식품을 제공한다. The present invention also provides a pharmaceutical composition and health functional food for the treatment and prevention of liver protection and liver disease containing the above production method and processed Panax genus plant extract prepared by the production method as an active ingredient.
상기에서 제조된 추출물은 사람의 간세포주인 HepG2 세포에 t-BHP를 처리하여 세포사멸에 대하여 측정하였으며, 산화적 인자인 NO생성과 지질과산화에 미치는 영향을 측정하였고, 세포막 파괴로 유발되는 LDH, GOT, GPT 유리정도를 측정한 결과, 탁월한 간세포 보호 및 간질환의 치료 및 예방에 유용함을 확인하였다.The extracts prepared above were measured for apoptosis by treatment of HepG2 cells, human hepatocytes, with t-BHP, and their effects on NO production and lipid peroxidation, oxidative factors, and LDH and GOT induced by cell membrane destruction. As a result of measuring the degree of GPT release, it was confirmed that it is useful for the protection of hepatocytes and the treatment and prevention of liver disease.
본 발명의 조성물은, 조성물 총 중량에 대하여 상기 생약 추출물을 0.1 내지 50% 중량으로 포함한다.The composition of the present invention comprises 0.1 to 50% by weight of the herbal extract based on the total weight of the composition.
그러나 상기와 같은 조성은 반드시 이에 한정되는 것은 아니고, 환자의 상태 및 질환의 종류 및 진행 정도에 따라 변할 수 있다.However, the composition is not limited thereto, and may vary depending on the condition of the patient, the type of disease, and the progress of the disease.
본 발명의 추출물을 포함하는 조성물은 약학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다.Compositions comprising the extract of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of pharmaceutical compositions.
본 발명에 따른 추출물을 포함하는 조성물은, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있으며, 이에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 마그네슘 스테아레이트 및 광물유를 들 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 추출물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(calcium carbonate), 수크로스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.The composition containing the extract according to the present invention may be formulated in the form of powders, granules, tablets, capsules, oral preparations such as suspensions, emulsions, syrups and aerosols, external preparations, suppositories and sterilized injection solutions, Examples of carriers, excipients and diluents that can be included in the composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium Silicates, cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, magnesium stearate and mineral oil. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and the solid preparations may include at least one excipient such as starch, calcium carbonate, sucrose in the extract. ) Or lactose, gelatin and the like are mixed. In addition to simple excipients, lubricants such as magnesium stearate talc are also used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
본 발명의 추출물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 그러나 바람직한 효과를 위해서, 추출물은 1일 0.01 mg/kg 내지 10 g/kg으로, 바람직하게는 1 mg/kg 내지 1 g/kg으로 투여하는 것이 좋다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수 있다. 그러므로 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.Preferred dosages of the extracts of the present invention vary depending 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 extract is preferably administered at a dose of 0.01 mg / kg to 10 g / kg per day, preferably 1 mg / kg to 1 g / kg per day. The administration may be carried out once a day or divided into several doses. Therefore, the dose is not intended to limit the scope of the present invention in any aspect.
본 발명의 조성물은 쥐, 생쥐, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구 및 직장, 또는 정맥 등의 방법을 통하여 투여할 수 있다. The composition of the present invention may be administered to mammals such as rats, mice, livestock, humans, and the like in various routes. All modes of administration may be expected, including, for example, oral and rectal, or intravenous.
또한 본 발명은 가공된 파낙스속 식물 추출물을 유효성분으로 함유하는 간보호 및 간질환의 예방 및 개선용 건강기능식품을 제공한다. In another aspect, the present invention provides a functional food for the prevention and improvement of liver protection and liver disease containing the processed Panax genus plant extract as an active ingredient.
본 발명의 추출물을 포함하는 건강기능식품은 간질환의 예방 및 개선을 위한 약제, 식품 및 음료 등에 다양하게 이용될 수 있다. 본 발명의 추출물을 첨가할 수 있는 식품으로는, 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합제, 건강보조 식품류 등이 있고, 분말, 과립, 정제, 캡슐 또는 음료인 형태로 사용할 수 있다.Health functional foods including the extract of the present invention can be used in a variety of drugs, foods and beverages for the prevention and improvement of liver disease. Examples of the foods to which the extract of the present invention can be added include various foods, beverages, gums, tea, vitamin complexes, health supplements and the like, and they can be used as powders, granules, tablets, capsules or beverages have.
따라서, 또한, 본 발명은 간보호 및 간질환 개선효과를 갖는 가공된 파낙스속 식물 추출물을 유효성분으로 함유하는 식품 및 식품첨가제를 제공한다.Accordingly, the present invention also provides a food and food additive containing the processed Panax genus plant extract as an active ingredient having an effect of protecting liver and improving liver disease.
본 발명의 추출물은 간질환의 예방 및 개선을 목적으로 식품 또는 음료에 첨가될 수 있다. 이 때, 식품 또는 음료 중의 상기 추출물의 양은 일반적으로 본 발명의 건강식품 조성물은 전체 식품 중량의 0.01 내지 15 중량%로 가할 수 있으며, 건강 음료 조성물은 100 ml를 기준으로 0.02 내지 10 g, 바람직하게는 0.3 내지 1 g의 비율로 가할 수 있다. The extract of the present invention can be added to food or beverage for the purpose of prevention and improvement of liver disease. At this time, the amount of the extract in the food or beverage is generally added to the health food composition of the present invention to 0.01 to 15% by weight of the total food weight, the health beverage composition is 0.02 to 10 g based on 100 ml, preferably Can be added at a ratio of 0.3 to 1 g.
본 발명의 건강 음료 조성물은 지시된 비율로 필수 성분으로서 상기 추출물의 혼합물을 함유하는 것 외에 액체성분에는 특별한 제한점은 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등의 디사카라이드, 예를 들어 말토스, 슈크로스 등의 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진등)) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 ml당 일반적으로 약 1 내지 20 g, 바람직하게는 약 5 내지 12 g이다. The health beverage composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient, such as ordinary beverages, in addition to containing a mixture of the above extract as an essential ingredient in the indicated ratios, have. Examples of the above-mentioned natural carbohydrates include monosaccharides such as disaccharides such as glucose and fructose such as maltose, sucrose and the like and polysaccharides such as dextrin, cyclodextrin and the like Sugar, and sugar alcohols such as xylitol, sorbitol, and erythritol. As natural flavors other than those described above, natural flavors (such as tau martin, stevia extract (e.g., rebaudioside A, glycyrrhizin)) and synthetic flavors (saccharin, aspartame, etc.) have. The proportion of such natural carbohydrates is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.
상기 외에 본 발명의 조성물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명의 조성물들은 천연 과일 쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.
In addition to the above-mentioned composition, the composition of the present invention can be used as a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and intermediates (cheese, chocolate etc.), pectic acid and its salts, Salts, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages and the like. In addition, the compositions of the present invention may contain flesh for the production of natural fruit juices and fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.
상기와 같이, 본 발명의 가공된 파낙스속 식물 추출물을 유효성분으로 함유하는 조성물은 사람의 간세포주인 HepG2 세포에 t-BHP를 처리하여 세포사멸에 대한 효과실험 및 산화적 인자인 NO생성과 지질과산화에 미치는 영향 실험과 세포막 파괴로 유발되는 LDH, GOT, GPT 유리정도를 측정한 결과, 탁월한 간세포 보호 및 간질환의 치료 및 예방에 유용하게 쓰일 수 있다.
As described above, the composition containing the processed Panax genus plant extract of the present invention as an active ingredient treatment effect t-BHP to HepG2 cells, a human liver cell line, the effect on cell death and NO production and lipid peroxidation of oxidative factors Effects of LDH, GOT, and GPT release caused by cell membrane destruction can be useful for protecting liver cells and treating and preventing liver disease.
도 1은 본 발명의 가공인삼 추출물 (SG)의 간세포 사멸 억제 효과를 나타낸 도이며 (여기에서 *P>0.01, t-BHP, SG 모두 처리하지 않은 것과 비교; **P>0.05, t-BHP만 처리한 것과 비교; # P>0.01, t-BHP만 처리한 것과 비교를 나타낸 것임);
도 2는 본 발명의 가공인삼 추출물 (SG)의 간 세포막 파괴 억제 효과를 나타낸 도이며 (여기에서 *P>0.01, t-BHP만 처리한 것과 비교; ** P>0.05, t-BHP만 처리한 것과 비교를 나타낸 것임);
도 3은 본 발명의 가공인삼 추출물 (SG)의 간세포로 부터 GOT 유리 억제 효과를 나타낸 도이며 (여기에서, *P>0.01, t-BHP, SG 모두 처리하지 않은 것과 비교; **P>0.05, t-BHP만 처리한 것과 비교를 나타낸 것임);
도 4은 본 발명의 가공인삼 추출물 (SG)의 SG의 간세포로 부터 GPT 유리 억제 효과를 나타낸 도이며 (여기에서 *P>0.05, t-BHP 만 처리한 것과 비교; **P>0.01, t-BHP만 처리한 것과 비교를 나타낸 것임);
도 5은 본 발명의 가공인삼 추출물 (SG)의 간 세포 과산화지질 생성 억제 효과를 나타낸 도이다 (여기에서 *P>0.05, t-BHP만 처리한 것과 비교; ** P>0.01, t-BHP만 처리한 것과 비교를 나타낸 것임).1 is a diagram showing the inhibitory effect of hepatic cell death of the processed ginseng extract (SG) of the present invention (where * P> 0.01, t-BHP, SG not compared with all treated; ** P> 0.05, t-BHP Compared with only treatment, #P> 0.01, showing comparison with only treatment with t-BHP);
Figure 2 is a diagram showing the inhibitory effect of hepatic cell membrane destruction of the processed ginseng extract (SG) of the present invention (where * P> 0.01, compared with only t-BHP; ** P> 0.05, t-BHP only treatment Comparison with one);
Figure 3 is a diagram showing the effect of inhibiting GOT free from hepatocytes of the processed ginseng extract (SG) of the present invention (where * P> 0.01, t-BHP, SG all compared with not treated; ** P> 0.05 , a comparison with the treatment with only t-BHP);
Figure 4 is a diagram showing the effect of inhibiting GPT free from hepatocytes of SG of the processed ginseng extract (SG) of the present invention (where * P> 0.05, compared with the treatment with t-BHP; ** P> 0.01, t A comparison with the treatment with only BHP);
Figure 5 is a diagram showing the inhibitory effect of hepatic cell peroxidation production of the processed ginseng extract (SG) of the present invention (where * P> 0.05, compared with only t-BHP; ** P> 0.01, t-BHP Only comparisons with treatments).
이하, 본 발명을 하기 실시예 및 실험예에 의하여 상세히 설명한다. 단, 이는 본 발명을 예시하는 것일 뿐, 본 발명의 내용은 이에 의해 한정되는 것은 아니다.
Hereinafter, the present invention will be described in detail with reference to the following examples and experimental examples. However, it should be understood that the present invention is not limited thereto.
실시예Example 1. 가공 인삼 추출물의 제조 1. Preparation of processed ginseng extract
김 등의 방법 (Kim WY, et al., J. Nat . Prod ., 63(12), pp 1702-1704, 2001 ; Kwon SW, et al., J. Chromatogr . A., 921(2), pp 335-339, 2001)에 의하여 특수가공인삼을 제조하였다. Kim et al. (Kim WY, et al., J. Nat . Prod . , 63 (12) , pp 1702-1704, 2001; Kwon SW, et al., J. Chromatogr.A . , 921 (2) , pp. 335-339, 2001).
즉, 건조된 인삼(금산 인삼시장)을 잘게 자른 후, 120℃, 15 기압에서 4시간 동안 수증기를 이용하여 가열하였다. 가공된 인삼(이하 선삼이라 함) 1 kg에 80% 에탄올 2 L를 가하고 수욕상에서 4시간 이상 환류 추출하여 얻어진 추출물을 감압 농축한 다음 동결 건조하여 추출분말 약 300 g 을 수득하였다. 실험 시에는 선삼 추출물(이하 SG라 함)을 DMSO(Sigma D-2650)를 이용하여 배지에 녹인 후, pore size 0.45 ㎛의 여과지를 통과시킨 후 사용하였다. 실험에 사용한 선삼 추출물의 (Rg3 + Rg5 + Rk1)/(Rb1 + Rb2 + Rc + Rd)= 6.1 이었다.That is, dried ginseng (Gumsan ginseng market) was finely chopped, and heated using steam at 120 ° C. and 15 atm for 4 hours. 2 L of 80% ethanol was added to 1 kg of processed ginseng (hereinafter referred to as ginseng), and the extract obtained by reflux extraction for 4 hours or more in a water bath was concentrated under reduced pressure and freeze-dried to obtain about 300 g of an extract powder. In the experiment, the ginseng extract (hereinafter referred to as SG) was dissolved in a medium using DMSO (Sigma D-2650), and used after passing a filter paper having a pore size of 0.45 μm. (Rg3 + Rg5 + Rk1) / (Rb1 + Rb2 + Rc + Rd) = 6.1 of the ginseng extract used in the experiment.
실시예Example 2. 2. 선삼Ginseng 추출물의 사포닌 함량 분석 Analysis of saponin content of extract
실시예 1에서 얻은 본 발명에 따라 제조된 가공인삼에 함유된 인삼사포닌 성분을 다음과 같은 방법에 의해 분석하였다. The ginseng saponin component contained in the processed ginseng prepared in Example 1 according to the present invention was analyzed by the following method.
40㎖ 용적의 스테인레스 스틸 용기 4개에 각각 백삼 5g과 물 5㎖를 가한 후 밀폐하여 각각 110℃에서 2시간, 120℃에서 2시간 및 3시간 및 130℃에서 2시간 동안 가열하였다. 가열이 끝난 가공인삼, 및 시판품인 백삼 및 홍삼 각 5g 씩을 취하여 메탄올 100㎖씩으로 3회 추출하고 농축시킨 후에 물에 현탁시키고 에테르 100㎖씩으로 3회 추출하였다. 남은 수층을 부탄올 100㎖씩으로 3회 추출한 후에 부탄올 분획을 농축시키고, 수득된 농축물을 메탄올에 용해시켜 HPLC(컬럼: LiChro- sorb NH₂, 이동상: CH₃CN/H₂O/i-PrOH=80/5/15→80/20/15, 검출기: ELSD(Evaporative light scattering detector))로 분석하였다. 측정된 결과는 다음 표 1에 기재된 바와 같다. Four 40 ml stainless steel vessels were added with 5 g of white ginseng and 5 ml of water, respectively, and then sealed and heated at 110 ° C. for 2 hours, 120 ° C. for 2 hours and 3 hours, and 130 ° C. for 2 hours. 5 g of each of the processed ginseng and the commercially produced white ginseng and red ginseng were taken, extracted three times with 100 ml of methanol, concentrated, suspended in water, and extracted three times with 100 ml of ether. The remaining aqueous layer was extracted three times with 100 mL of butanol, and then the butanol fraction was concentrated. → 80/20/15, detector: analyzed by ELSD (Evaporative light scattering detector). The measured results are shown in Table 1 below.
샘플Saponin
Sample
(Rc+Rd+Rb1+Rb2)(Rg 3 + Rg 5) /
(Rc + Rd + Rb 1 + Rb 2)
상기 표 1에 기재된 결과로부터 알 수 있는 바와 같이, 본 발명에 따라 가열처리하여 수득한 가공인삼은 수삼, 백삼 및 홍삼 등에는 거의 또는 전혀 존재하지 않는 인삼 사포닌인 Rg 및 Rg 성분의 함량이 현저히 증가하여 우수한 약효를 나타낸다. As can be seen from the results shown in the above Table 1, the processed ginseng obtained by the heat treatment according to the present invention significantly increases the contents of Rg and Rg components, which are ginseng saponins which are almost or completely absent from fresh ginseng, white ginseng and red ginseng And exhibits excellent drug efficacy.
상기한 바와 같은 결과에 따라 인삼에 대한 가열온도의 변화에 따른 사포닌 성분, 특히 진세노사이드 Rg 및 Rg의 함량 변화를 더욱 구체적으로 확인하기 위하여 가열을 100℃, 110℃, 120℃, 130℃, 150℃, 160℃, 180℃ 및 200℃에서 2시간씩 행하여 얻어진 인삼들의 Rg 및 Rg 함량을 측정하여 가열처리하지 않은 인삼(수삼)에서의 함량과 비교하여 보았다. 그 결과는 다음 표 2에 기재한 바와 같다. According to the results as described above, in order to more specifically confirm the change in the content of saponin components, in particular ginsenoside Rg and Rg according to the change in the heating temperature for ginseng, heating is 100 ℃, 110 ℃, 120 ℃, 130 ℃, Rg and Rg content of ginseng obtained by 2 hours at 150 ° C., 160 ° C., 180 ° C. and 200 ° C. was measured and compared with the content in ginseng (salt) that was not heated. The results are shown in Table 2 below.
(시간)
종류Heating temperature
(time)
Kinds
(수삼)Untreated
(Fresh ginseng)
2시간100
2 hours
2시간110
2
2시간120
2 hours
2시간130
2 hours
2시간150
2 hours
2시간160
2 hours
2시간180
2 hours
2시간200
2 hours
주) 각각의 성분함량은 사용한 수삼의 양에 대한 함량 %로 나타낸 것이다.
Note) Each ingredient content is expressed as% of the amount of fresh ginseng used.
상기에서 보는 바와 같이 본 발명에서와 같이 120 내지 180℃에서 가열처리된 가공인삼의 경우에 Rg 및 Rg와 같은 진세노사이드의 함량이 비처리 수삼이나 홍삼(100℃ 가열)의 경우에 비해 현저히 증가하였음을 알 수 있다. 실험에 사용한 선삼 추출물의 (Rg3 + Rg5 + Rk1)/(Rb1 + Rb2 + Rc + Rd)= 6.1 이었다.As seen above, the content of ginsenosides such as Rg and Rg is significantly increased in the case of processed ginseng heated at 120 to 180 ° C as in the present invention compared to the case of untreated ginseng or red ginseng (100 ° C heating). It can be seen that. (Rg3 + Rg5 + Rk1) / (Rb1 + Rb2 + Rc + Rd) = 6.1 of the ginseng extract used in the experiment.
참고예 1. 실험 준비Reference Example 1. Experiment Preparation
1-1. 1-1. 시약reagent
MTT, 1,3,3,3-테트라에톡시프로판, 삼차-부틸 히드로퍼록사이드 (tert-butylhydroxyperoxide (t-BHP))는 시그마 (St. Louis, MO)사에서 구입하였고, 젖산 탈수소 효소 활성 측정 키트와 지오티, 지피티측정 키트는 ㈜바이오 크리니칼 시스템사에서 구입하였다. 2-티오바르비투르산 (TBA)는 TKOYO KASEI KOGYO사 (Toshima, kita-Ku, Tokyo, JAPAN)에서 구입하였다. MTT, 1,3,3,3-tetraethoxypropane and tert-butylhydroxyperoxide (t-BHP) were purchased from Sigma (St. Louis, MO) and measured for lactic acid dehydrogenase activity. Kits, geoti, and phyti measurement kits were purchased from Bio Clinical System. 2-thiobarbituric acid (TBA) was purchased from TKOYO KASEI KOGYO (Toshima, kita-Ku, Tokyo, JAPAN).
1-2. 세포 배양1-2. Cell culture
실험에 사용된 세포는 인간 간 세포주인 HepG2 를 한국 세포주 은행에서 구입하여 사용하였다. 세포를 10% FBS (Lonza, Walkersville, MD USA)이 함유된 DMEM 배지에서 (WelGENE, Daegu, KOREA) 배양하였다. 배양기의 온도는 37°C이며, 5% 이산화탄소 농도를 유지시켰다. 이틀째, 배양 접시에 세포가 80% 정도 채워지면 새로운 배양 접시로 옮겼다.
The cells used in the experiment were HepG2, a human liver cell line, purchased from Korea Cell Line Bank. Cells were cultured in DMEM medium containing 10% FBS (Lonza, Walkersville, MD USA) (WelGENE, Daegu, KOREA). The temperature of the incubator is 37 ° C and maintained at 5% carbon dioxide concentration. On the second day, when the culture dish was about 80% full, the cells were transferred to a new culture dish.
참고예 2. 통계처리Reference Example 2. Statistics Processing
모든 실험 결과는 일원변량 분석을 이용하여 통계 처리하였고, 유의성이 인정될 경우 Student-Newman-Keuls Test를 사용하여 p < 0.05 수준 이하에서 유의성 검정을 실시하였다.
All experimental results were statistically analyzed using one-way ANOVA, and significance was assessed at p <0.05 level using Student-Newman-Keuls Test.
실험예 1. 간세포 생존율 측정 실험Experimental Example 1. Experiment of measuring liver cell survival rate
상기 실시예에서 얻은 선삼 추출물의 간세포에 생존율에 미치는 효과를 실험하기 위하여 문헌에 개시된 방법을 응용하여 하기와 같이 실험을 수행하였다.(Sohn JH, Han KL, Lee SH, Hwang JK. Protective effects of panduratin A against oxidative damage of tert-butylhydroperoxide in human HepG2 cells. Biol Pharm Bull. 2005 ; 28(6):1083-60) In order to test the effect on the viability of hepatic ginseng extract obtained in the above example was performed by applying the method disclosed in the literature as follows (Sohn JH, Han KL, Lee SH, Hwang JK. Protective effects of panduratin A against oxidative damage of tert-butylhydroperoxide in human HepG2 cells.Biol Pharm Bull. 2005; 28 (6): 1083-60)
상기 참고예에서 얻은 간세포를 96-웰 플레이트에 5 X 105개 정도 분주하여 12시간 배양 후, 혈청이 없는 DMEM 배지에 각각의 농도가 되도록 SG시료를 처리하고 배양하였다. 30분 후, 삼차-부틸 히드로퍼록사이드를 넣어주거나 또는 넣어주지 않는 조건에서 3시간 동안 배양하였다. 처리가 끝나면, 식염수로 세포를 1회 세척하고, 0.5 mg/mL 농도의 MTT 용액을 100 ml 가하고 빛을 차단시켜 37°C 배양기에서 3시간 동안 반응시켰다. 반응 후에는 세포를 식염수로 1회 세척하고, 100 ml의 DMSO를 넣어 반응액을 추출한 다음, 마이크로 플레이트 리더(GENios A5082, TECAN,Maennedort, Switzerland)를 이용해 530 nm 파장에서 흡광도를 측정하였다.
Hepatocytes obtained in the reference example were dispensed about 5 X 10 5 in a 96-well plate and cultured for 12 hours, and then treated with SG samples so as to have respective concentrations in DMEM medium without serum. After 30 minutes, incubated for 3 hours under or without tert-butyl hydroperoxide. After the treatment, the cells were washed once with saline, 100 ml of 0.5 mg / mL MTT solution was added thereto, and the reaction was performed for 3 hours in a 37 ° C incubator by blocking the light. After the reaction, the cells were washed once with saline, 100 ml of DMSO was added to extract the reaction solution, and the absorbance was measured at 530 nm using a microplate reader (GENios A5082, TECAN, Maennedort, Switzerland).
혈청이 없는 DMEM배지에 각각 0, 5, 10, 20 ㎍/mL이 되도록 SG를 넣어 30분 간 전처리 후, 1.25 mM 삼차-부틸 히드로과산화물을 가하여 3시간 동안 5% 이산화탄소 배양기에서 배양하였다. 1.25 mM 농도의 삼차-부틸 히드로과산화물을 처리하면, 처리하지 않았을 때와 비교해 약 50%의 세포손상이 관찰된다 (도 1.). 그러나 SG의 농도를 0, 5, 10 그리고 20 ㎍/mL이 되도록 첨가해주면, SG의 농도가 높을수록 세포 손상이 줄어드는 것을 볼 수 있었다. t-BHP를 처리하여 50% 감소된 세포 생존율은 20 μ/mL의 SG를 첨가했을 때, 약 78.6%까지 회복되는 것을 관찰하였다. SG는 농도에 비례하여 삼차-부틸 히드로과산화물에 의해 손상된 간세포의 생존율을 증가시킴을 확인하였다.
After SG was added to DMEM medium without serum to be 0, 5, 10, and 20 ㎍ / mL, respectively, and pretreated for 30 minutes, 1.25 mM tert-butyl hydroperoxide was added and incubated in a 5% carbon dioxide incubator for 3 hours. Treatment of tertiary-butyl hydroperoxide at a concentration of 1.25 mM resulted in about 50% cell damage compared to that without treatment (FIG. 1). However, when the concentration of SG was added to 0, 5, 10 and 20 ㎍ / mL, the higher the concentration of SG was found to reduce the cell damage. 50% reduction in cell viability after treatment with t-BHP was observed to recover to about 78.6% when 20 μ / mL of SG was added. SG was found to increase the survival rate of hepatocytes damaged by tert-butyl hydroperoxide in proportion to concentration.
실험예Experimental Example 2. 간세포 2. Hepatocytes LDHLDH 유리에 미치는 영향 측정 실험 Glass impact test
상기 실시예에서 얻은 선삼 추출물의 간세포 LDH 유리 미치는 영향을 실험하기 위하여 문헌에 개시된 방법을 응용하여 하기와 같이 실험을 수행하였다.(Lima CF, Fernandes-Ferreira M, Pereira-Wilson C. Phenolic compounds protect HepG2 cells from oxidative damage: relevance of glutathione levels. Life Sci. 2006;79(21):2056-68)In order to examine the effect of hepatocellular LDH release of the ginseng extract obtained in the above example, the experiment was performed by applying the method disclosed in the literature (Lima CF, Fernandes-Ferreira M, Pereira-Wilson C. Phenolic compounds protect HepG2). cells from oxidative damage: relevance of glutathione levels.Life Sci. 2006; 79 (21): 2056-68)
LDH 효소의 활성 측정을 위하여 간세포를 96-웰 플레이트에 5X105개 정도 분주하여 12시간 배양 후, 혈청이 없는 배지에 각각의 농도가 되도록 SG를 처리하고 배양하였다. 30분 후, 삼차-부틸 히드로과산화물을 넣어주고 3시간 동안 배양하였다. 처리가 끝나면, 20 ml의 배양액에 젖산 리튬 기질액과 NAD, 니트로테트라졸륨블루, 1-메톡시 PMS가 포함된 정색시약을 50 ml 가한 후 37°C에서 10 분간 반응시킨다. 반응이 완료되면 100 ml의 염산 용액을 넣어 반응을 정지시키고, 60분 이내에 마이크로 플레이트 리더를 이용해 570 nm 파장에서 흡광도를 측정하였다. LDH 효소의 활성치는 LDH 효소 표준액의 흡광도를 이용해 W.U (Wroblewski 단위)로 표시하였다.In order to measure the activity of LDH enzyme, hepatocytes were divided into 5 × 10 5 cells in a 96-well plate and cultured for 12 hours, and then treated with SG and cultured to each concentration in a medium without serum. After 30 minutes, tert-butyl hydroperoxide was added and incubated for 3 hours. After the treatment, 50 ml of a colorant reagent containing lithium lactate substrate, NAD, nitrotetrazolium blue, and 1-methoxy PMS was added to 20 ml of the culture solution and reacted at 37 ° C for 10 minutes. After the reaction was completed, 100 ml of hydrochloric acid solution was added to stop the reaction, and the absorbance was measured at 570 nm using a microplate reader within 60 minutes. The activity value of the LDH enzyme was expressed in WU (Wroblewski units) using the absorbance of the LDH enzyme standard solution.
LDH (lactate dehydrogenase) 효소는 세포질에 존재하는 효소로 통상은 세포막을 통과하지 않으나 세포막이 손상되면 세포 외, 즉 배양액으로 방출된다. 배양액 내의 젖산탈수소 효소는 키트 내 기질액 중의 젖산을 탈수소화하고 피루빈산과 NAD를 생성하게 되며, 생성된 NAD에 의해 반응액 중의 니트로테트라졸륨 블루가 환원되어 디포르마잔을 생성한다. 반응이 완료되면 마이크로 플레이트 리더를 이용해 반응물인 디포르마잔의 색도를 측정한다. MTT 측정에서 얻은 데이터를 근거로, 약 50%의 세포 사멸을 일으키는 1.25 mM 삼차-부틸 히드로과산화물을 간 세포에 처리하여 세포 외로 방출된 젖산탈수소 효소의 활성을 관찰하였다 (도 2 참조). 삼차-부틸 히드로과산화물을 처리하지 않은 세포군 (26.3 W.U)에 비해 약 5배 정도 (108.5 W.U)의 젖산탈수소 효소 활성이 배양액에서 증가하였으며, 여기에 SG를 5, 10 그리고 20 g/mL의 농도로 처리하면 농도에 비례하여 각각 74.5 (유의 확률 0.01 미만), 70.5 (유의 확률 0.01 미만) 그리고 41.3 W.U (유의 확률 0.05 미만; 1.25 mM t-BHP만 처리한 세포군과 비교 시)로 감소하였다. 즉, 삼차-부틸 히드로과산화물에 의한 HepG2 세포의 산화적 손상이 SG에 의해 억제되었다.
LDH (lactate dehydrogenase) enzyme is an enzyme present in the cytoplasm that normally does not pass through the cell membrane, but when the cell membrane is damaged, it is released extracellularly, that is, into the culture medium. The lactic acid dehydrogenase in the culture solution dehydrogenates the lactic acid in the substrate solution in the kit to produce pyruvic acid and NAD, and the produced NAD reduces nitrotezozolium blue in the reaction solution to produce deformazan. After the reaction is completed, the chromaticity of the reactant deformazan is measured using a microplate reader. Based on the data obtained from the MTT measurement, hepatic cells were treated with 1.25 mM tert-butyl hydroperoxide, which caused about 50% cell death, to observe the activity of lactate dehydrogenase released extracellularly (see FIG. 2). About 5 times (108.5 WU) of lactate dehydrogenase activity was increased in the culture compared to the tri-butyl hydroperoxide-treated cell population (26.3 WU), and the concentration of SG was increased to 5, 10 and 20 g / mL. Treatment reduced to 74.5 (significance less than 0.01), 70.5 (significance less than 0.01), and 41.3 WU (significance less than 0.05; relative to cells treated with 1.25 mM t-BHP only) relative to concentration. That is, oxidative damage of HepG2 cells by tert-butyl hydroperoxide was inhibited by SG.
실험예Experimental Example 3. 간세포로부터 3. from liver cells GOTGOT 및 And GPTGPT 유리에 미치는 영향 측정 실험 Glass impact test
상기 실시예에서 얻은 선삼 추출물의 간세포로부터 GOT 및 GPT 유리에 미치는 영향을 실험하기 위하여 문헌에 개시된 방법을 응용하여 하기와 같이 실험을 수행하였다.(Lima CF, Fernandes-Ferreira M, Pereira-Wilson C. Phenolic compounds protect HepG2 cells from oxidative damage: relevance of glutathione levels. Life Sci. 2006;79(21):2056-68)In order to examine the effect on the GOT and GPT release from the hepatocytes of the ginseng extract obtained in the above examples, the experiment was performed as follows (Lima CF, Fernandes-Ferreira M, Pereira-Wilson C.). Phenolic compounds protect HepG2 cells from oxidative damage: relevance of glutathione levels.Life Sci. 2006; 79 (21): 2056-68)
세포막 파괴를 측정하기 위하여 배지에서 GOT, GPT를 측정하였다. 간세포를 96-웰 플레이트에 5X105개 정도 분주하여 12시간 배양 후, 혈청이 없는 배지에 각각의 농도가 되도록 SG를 처리하고 배양하였다. 30분 후, 삼차-부틸 히드로퍼록사이드를 넣어주고 3시간 동안 배양하였다. 다시 50 ml의 배양액에 지오티용 기질액 (알파-케토글루타레이트산과 L-아스파르트산)과 지피티용 기질액 (알파-케토글루타레이트산과 L-알라닌)을 각각 30 ml씩 넣고 37°C에서 일정시간 반응시켰다. 반응 생성물에 2,4-디니트로페닐히드라진 정색시약(Sigma-aldrich)을 30 ml씩 넣고 실온에서 방치하였다. 20분 후, 100 ml의 수산화나트륨 용액을 넣고 다시 실온에서 10분 간 방치하여 발색시킨다. 60분 이내에 마이크로 플레이트 리더(iGNOS, TECAN)를 이용해 505 nm 파장에서 흡광도를 측정하였다. GOT, GPT 활성은 표준 검량선을 이용하여 Karmen/mL 단위로 표시하였다.GOT and GPT were measured in the medium to measure cell membrane destruction. Hepatocytes were divided into 5 × 10 5 cells in a 96-well plate and cultured for 12 hours, and then treated with SG and cultured in a serum-free medium. After 30 minutes, tert-butyl hydroperoxide was added and incubated for 3 hours. In 50 ml of the culture solution, add 30 ml of geotid substrate solution (alpha-ketoglutarate and L-aspartic acid) and gefiti substrate solution (alpha-ketoglutarate and L-alanine), respectively, at 37 ° C. Reaction was continued for a while. 30 ml of 2,4-dinitrophenylhydrazine color reagent (Sigma-aldrich) was added to the reaction product and allowed to stand at room temperature. After 20 minutes, 100 ml of sodium hydroxide solution was added and left to stand at room temperature for 10 minutes for color development. Within 60 minutes absorbance was measured at a wavelength of 505 nm using a microplate reader (iGNOS, TECAN). GOT and GPT activities were expressed in Karmen / mL using standard calibration curves.
지오티(GOT)는 간세포에 있는 효소로서, 삼차-부틸 히드로과산화물에 의해 간 세포가 손상을 입으면 배양액으로 나오게 된다. 그러므로, 배양액 중의 지오티 활성치 증가는 곧 세포의 간세포의 손상을 의미한다. 배양액에 키트 내의 지오티용 기질액 (알파-케토글루타레이트산과 L-아스파르트산)을 넣고 반응시키면, 지오티에 의해 기질이 옥살로아세트산 및 피루빈산을 생성하게 된다. 생성된 옥살로아세트산 및 피루빈산에 의해 키트 내 정색시약(영동시약) 중의 2,4-디니트로페닐히드라진이 히드라진으로 변화되고, 여기에 수산화나트륨 용액을 넣어 반응액을 등갈색으로 발색시켜 색도를 기기(iGNOS, TECAN)를 이용하여 측정하였다. 1.25 mM 삼차-부틸 히드로과산화물을 간 세포에 처리하여 세포 외로 방출된 지오티 효소의 활성을 관찰한 결과 (도 3), 삼차-부틸 히드로과산화물을 처리하지 않은 세포군 (3 Karmen/mL)에 비해 약 10배 정도 (33 Karmen/mL)의 지오티 활성이 배양액에서 증가하였으며, 여기에 SG를 5, 10 그리고 20 g/mL의 농도로 처리하면 농도에 따라 각각 17.5 (유의 확률 0.05 미만), 12 (유의 확률 0.05 미만) 그리고 7.5 Karmen/mL (유의 확률 0.05 미만; 1.25 mM 삼차-부틸 히드로과산화물을 만 처리한 세포군과 비교 시)로 감소하였다. 이로써, 간 세포에서 삼차-부틸 히드로과산화물에 의한 지오티의 세포 외 방출이 SG에 의해 억제됨을 확인하였다.GOT is an enzyme in hepatocytes, which is released into culture when hepatic cells are damaged by tert-butyl hydroperoxide. Therefore, the increase in the activity of geothyroidism in the culture medium implies the damage of the hepatocytes of the cells. When the reaction solution is added to the culture solution for the geoty substrate solution (alpha-ketoglutarate acid and L-aspartic acid) in the kit, the substrate generates oxaloacetic acid and pyruvic acid by geoty. The resulting oxaloacetic acid and pyruvic acid change the 2,4-dinitrophenylhydrazine in the color reagent (young reagent) into the hydrazine in the kit, and sodium hydroxide solution is added thereto to develop the reaction solution to light brown color. Was measured using an instrument (iGNOS, TECAN). 1.25 mM tert-butyl hydroperoxide was treated to liver cells to observe the activity of the extracellularly released geotyse enzymes (Fig. 3), compared with the cell group not treated with tert-butyl hydroperoxide (3 Karmen / mL). About 10-fold (33 Karmen / mL) geotypic activity was increased in the culture, where SG was treated at concentrations of 5, 10 and 20 g / mL, depending on the concentration of 17.5 (probability below 0.05) and 12 ( Significant probability less than 0.05) and 7.5 Karmen / mL (significant probability less than 0.05; compared with cell groups treated only with 1.25 mM tert-butyl hydroperoxide). As a result, it was confirmed that the extracellular release of geoty by tertiary-butyl hydroperoxide was inhibited by SG in liver cells.
지피티(GPT)는 간세포에 있는 효소로서, 지오티나 젖산탈수소 효소와 마찬가지로 삼차-부틸 히드로과산화물에 의해 간 세포가 손상을 입으면 배양액으로 나오게 된다. 그러므로, 배양액 중의 지피티 활성치 증가는 곧 세포의 간세포의 손상을 의미한다. 배양액에 키트 내의 지피티용 기질액 (알파-케토글루타레이트산과 L-알라닌)을 넣고 반응 시키면, 지피티에 의해 기질이 옥살로아세트산 및 피루빈산을 생성하게 된다. 지오티 측정과 같은 원리에 따라 색도를 측정하여 간세포 손상의 정도를 확인할 수 있다. 1.25 mM 삼차-부틸 히드로과산화물을 간 세포에 처리하여 세포 외로 방출된 지피티 효소의 활성을 관찰한 결과 (도 4), 삼차-부틸 히드로과산화물을 처리하지 않은 세포군 (3 Karmen/mL)에 비해 약 8배 정도 (24 Karmen/mL)의 지피티 활성이 배양액에서 증가하였으며, 여기에 SG를 5, 10 그리고 20 g/mL의 농도로 처리하면 농도에 따라 각각 20 (유의 확률 0.05 미만), 17.5 (유의 확률 0.05 미만) 그리고 11 Karmen/mL (유의 확률 0.01 미만; 1.25 mM 삼차-부틸 히드로과산화물만 처리한 세포군과 비교 시)로 감소하였다. 즉, SG는 삼차-부틸 히드로과산화물에 의한 HepG2의 세포 손상을 감소시켰다. GPT is an enzyme in hepatocytes and, like geotin and lactic acid dehydrogenase, when liver cells are damaged by tert-butyl hydroperoxide, they are released into the culture medium. Therefore, the increase in the activity of pipi activity in the culture medium means damage of the hepatocytes of the cells. When the substrate solution for gephyti (alpha-ketoglutarate acid and L-alanine) in the kit was added to the culture solution and reacted, the substrate produced oxaloacetic acid and pyruvic acid by zipi. You can determine the extent of hepatocellular damage by measuring the chromaticity according to the same principle as the geotye measurement. Treatment of 1.25 mM tert-butyl hydroperoxide to liver cells observed the activity of the zipi enzyme released extracellularly (FIG. 4), compared to the cell group not treated with tert-butyl hydroperoxide (3 Karmen / mL). Eighty times (24 Karmen / mL) zipi activity was increased in the culture, where SG was treated at concentrations of 5, 10 and 20 g / mL, depending on the concentration of 20 (below 0.05 probability) and 17.5 ( Significant probability less than 0.05) and 11 Karmen / mL (significance less than 0.01; compared with cell groups treated only with 1.25 mM tert-butyl hydroperoxide). In other words, SG reduced the cellular damage of HepG2 by tert-butyl hydroperoxide.
실험예Experimental Example 4. 간세포의 과산화지질 생성량 측정 실험 4. Measurement of lipid peroxide production in hepatocytes
상기 실시예에서 얻은 선삼 추출물의 간세포의 과산화지질 생성량에 미치는 영향을 실험하기 위하여 문헌에 개시된 방법을 응용하여 하기와 같이 실험을 수행하였다.(Noh et al. 2010. Antioxidant effects of the chestnut (Castanea crenata) inner shell extract in t-BHP-treated HepG2 cells, and CCl4- and high-fat diet-treated mice.Food and Chemical Toxicology 48,3177-83) In order to examine the effect of the ginseng extract obtained in the above example on the amount of lipid peroxide production of hepatocytes, the experiment was performed by applying the method disclosed in the literature (Noh et al. 2010. Antioxidant effects of the chestnut (Castanea crenata) ) inner shell extract in t -BHP-treated HepG2 cells, and CCl 4 -and high-fat diet-treated mice.Food and Chemical Toxicology 48,3177-83)
간세포를 96-웰 플레이트에 5X105개 정도 분주하여 12시간 배양 후, 혈청이 없는 배지에 각각의 농도가 되도록 SG를 처리하고 30분 배양하였다. 삼차-부틸 히드로과산화물을 넣어주고 3시간 배양한 후 배양액을 제거하고, 150 ml의 6% 트리톤 X-100을 5분간 처리하였다. 여기에 20 ml의 트리클로로아세트산 용액과 섞어 얼음에서 15분간 방치한 다음, 1,500 rpm에서 15분간 저온에서 원심분리하였다. 원심분리에서 얻어진 상등액 120 ml에 같은 양의 0.67% 티오바르비투르산 용액을 가하고 10분간 끓인 후, 실온에서 식히고, 마이크로 플레이트 리더를 이용해 535 nm 파장에서 색도를 측정하였다. 검량선은 표준물질인 1,1,3,3-테트라에톡시프로판을 이용하여 작성하였으며, 지질과산화 정도는 티오바르비투르산 반응물(TBARS)의 몰농도로 나타내었다. Hepatocytes were divided into 5 × 10 5 cells in a 96-well plate and cultured for 12 hours, and then treated with SG in a serum-free medium at different concentrations and incubated for 30 minutes. After tertiary-butyl hydroperoxide was added and incubated for 3 hours, the culture solution was removed, and 150 ml of 6% Triton X-100 was treated for 5 minutes. It was mixed with 20 ml of trichloroacetic acid solution and left for 15 minutes on ice, followed by centrifugation at low temperature for 15 minutes at 1,500 rpm. An equal amount of 0.67% thiobarbituric acid solution was added to 120 ml of the supernatant obtained by centrifugation, boiled for 10 minutes, cooled at room temperature, and chromaticity was measured at 535 nm using a microplate reader. The calibration curve was prepared using standard 1,1,3,3-tetraethoxypropane, and the degree of lipid peroxidation was expressed by the molar concentration of thiobarbituric acid reactant (TBARS).
지질과산화는 동, 식물에서 잘 알려진 세포손상 메카니즘으로 세포나 조직이 산화적 스트레스를 겪으면 증가한다. 특히, 세포막의 불포화지질은 가장 과산화화 되기 쉬운 것으로 알려졌으며, 그 결과로 자연스럽게 발생하는 산물이 말론디알데히드 (MDA) 이다. 티오바르비투르산 반응산물 (TBARS) 측정법은 지질 과산화화의 대표적 측정 방법으로서, 말론디알데히드가 티오바르비투르산과 반응하여 부가생성물을 형성하며 이의 색도를 측정함으로써 지질 과산화화 정도를 측정한다. 색도가 증가할수록 지질 과산화화는 증가하고, 산화적 스트레스에 의한 세포 및 조직의 손상이 일어났다고 예상할 수 있다. 간 세포에 각각 0, 5, 10, 20 ㎍/mL 농도의 SG를 전처리하고, 1.25 mM 농도의 삼차-부틸 히드로과산화물을 넣어준 후, 세포 용해물을 티오바르비투르산 용액과 반응시켜 티오바르비투르산 반응물의 농도를 관찰한 결과 (도 5), 삼차-부틸 히드로과산화물을 처리하지 않은 세포군 (0.01 mM)에 비해 크게 (0.39 mM) 증가하였으며, 여기에 SG를 5, 10 ㎍/mL의 농도로 처리하면 농도에 따라 각각 0.37 mM (유의 확률 0.05 미만), 0.3 mM (유의 확률 0.01 미만)로 감소하였고, 20 ㎍/mL SG 처리 시에는 0.17 mM (유의 확률 0.01 미만; 1.25 mM 삼차-부틸 히드로과산화물만 처리한 세포군과 비교 시)로 약 69% 감소하였다. 즉, 삼차-부틸 히드로과산화물에 의해 야기된 간 세포 내 지질 과산화화는 SG를 처리하여 억제할 수 있음을 확인하였다.
Lipid peroxidation is a well-known cell damage mechanism in animals and plants that increases when cells or tissues undergo oxidative stress. In particular, unsaturated lipids in cell membranes are known to be most peroxidized, and the resulting naturally occurring product is malondialdehyde (MDA). The thiobarbituric acid reaction product (TBARS) assay is a representative measurement method of lipid peroxidation, in which malondialdehyde reacts with thiobarbituric acid to form an adduct and measures the degree of lipid peroxidation by measuring its chromaticity. Lipid peroxidation increases with increasing chromaticity, and it can be expected that cell and tissue damage caused by oxidative stress has occurred. After pretreatment of SG at 0, 5, 10, and 20 ㎍ / mL concentrations to liver cells, and the addition of 1.25 mM tert-butyl hydroperoxide, the cell lysates were reacted with thiobarbituric acid solution. Observation of the concentration of the acid reactant (FIG. 5) showed a significant increase (0.39 mM) compared to the cell group without treatment with tert-butyl hydroperoxide (0.09 mM), where the SG concentration was 5, 10 μg / mL. Treatment reduced to 0.37 mM (below 0.05 probability) and 0.3 mM (below 0.01 probability) depending on concentration, and 0.17 mM (below 0.01 probability; 1.25 mM tert-butyl hydroperoxide with 20 μg / mL SG treatment). Compared to the cell group treated only) by about 69%. That is, it was confirmed that lipid peroxidation in liver cells caused by tert-butyl hydroperoxide can be suppressed by treating SG.
실험예Experimental Example 5. 5. 단회투여독성Single dose toxicity 시험 exam
마우스를 사용하여 상기 실시예에서 제조한 가공인삼 추출물을 이용하여 단회투여독성 시험을 실시하였다. 단회투여독성 시험 결과, 상기 추출의 경우 ICH에서 정하고 있는 투여 가능 용량인 2 g/kg에서 2주간 사망예를 전혀 관찰할 수 없었으며, 체중 증가, 사료 섭취량 등에서 전혀 유의한 이상을 발견할 수 없었다. 따라서 본 발명의 각 추출물은 안전한 약물임을 알 수 있었다. A single dose toxicity test was performed using the processed ginseng extract prepared in Example using a mouse. As a result of the single dose toxicity test, no mortality was observed for 2 weeks at 2 g / kg, which is the dose prescribed by ICH, and no significant abnormality was found in weight gain and feed intake. . Therefore, each extract of the present invention was found to be a safe drug.
하기에 본 발명의 추출물을 함유하는 조성물의 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.
Hereinafter, formulation examples of the composition containing the extract of the present invention will be described, but the present invention is not intended to be limited thereto but is specifically described.
제제예Formulation example 1. One. 산제의Sanje 제조 Produce
SG 추출물 20 mgSG Extract 20 mg
유당 100 mg
탈크 10 mg
상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 제조한다.
The above components are mixed and filled in airtight bags to prepare powders.
제제예Formulation example 2. 정제의 제조 2. Preparation of tablets
SG 추출물 10 mgSG Extract 10 mg
옥수수전분 100 mg
유당 100 mg
스테아린산 마그네슘 2 mgMagnesium stearate 2 mg
상기의 성분들을 혼합한 후 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조한다.
After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.
제제예Formulation example 3. 캅셀제의 제조 3. Preparation of capsules
SG 추출물 10 mgSG Extract 10 mg
결정성 셀룰로오스 3 mgCrystalline cellulose 3 mg
락토오스 14.8 mgLactose 14.8 mg
마그네슘 스테아레이트 0.2 mgMagnesium stearate 0.2 mg
통상의 캅셀제 제조방법에 따라 상기의 성분을 혼합하고 젤라틴 캡슐에 충전하여 캅셀제를 제조한다.
The above components are mixed in accordance with a conventional method for producing a capsule, and filled in a gelatin capsule to prepare a capsule.
제제예Formulation example 4. 주사제의 제조 4. Preparation of injections
SG 추출물 10 mgSG Extract 10 mg
만니톨 180 mgMannitol 180 mg
주사용 멸균 증류수 2974 mgSterile distilled water for injection 2974 mg
Na2HPO4 ,12H2O 26 mgNa 2 HPO 4 , 12H 2 O 26 mg
통상의 주사제의 제조방법에 따라 1 앰플당 (2 ㎖) 상기의 성분 함량으로 제조한다.
(2 ml) per ampoule in accordance with the usual injection method.
제제예Formulation example 5. 5. 액제의Liquid 제조 Produce
SG 추출물 20 mgSG Extract 20 mg
이성화당 10 g10 g per isomer
만니톨 5 g5 g mannitol
정제수 적량Purified water quantity
통상의 액제의 제조방법에 따라 정제수에 각각의 성분을 가하여 용해시키고 레몬향을 적량 가한 다음 상기의 성분을 혼합한 다음 정제수를 가하여 전체를 정제수를 가하여 전체 100 ml로 조절한 후 갈색병에 충진하여 멸균시켜 액제를 제조한다.
Each component was added and dissolved in purified water according to the usual liquid preparation method, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was added with purified water to adjust the total volume to 100 ml, And sterilized to prepare a liquid preparation.
제제예Formulation example 6. 건강 식품의 제조 6. Manufacture of health food
SG 추출물 1000 mgSG Extract 1000 mg
비타민 혼합물 적량Vitamin mixture quantity
비타민 A 아세테이트 70 ㎍70 [mu] g of vitamin A acetate
비타민 E 1.0 ㎎Vitamin E 1.0 mg
비타민 B1 0.13 ㎎0.13 mg vitamin B1
비타민 B2 0.15 ㎎0.15 mg of vitamin B2
비타민 B6 0.5 ㎎0.5 mg vitamin B6
비타민 B12 0.2 ㎍0.2 [mu] g vitamin B12
비타민 C 10 ㎎10 mg vitamin C
비오틴 10 ㎍Biotin 10 μg
니코틴산아미드 1.7 ㎎Nicotinic acid amide 1.7 mg
엽산 50 ㎍50 ㎍ of folic acid
판토텐산 칼슘 0.5 ㎎Calcium pantothenate 0.5 mg
무기질 혼합물 적량Mineral mixture quantity
황산제1철 1.75 ㎎1.75 mg of ferrous sulfate
산화아연 0.82 ㎎0.82 mg of zinc oxide
탄산마그네슘 25.3 ㎎Magnesium carbonate 25.3 mg
제1인산칼륨 15 ㎎15 mg of potassium phosphate monobasic
제2인산칼슘 55 ㎎Secondary calcium phosphate 55 mg
구연산칼륨 90 ㎎
탄산칼슘 100 ㎎100 mg of calcium carbonate
염화마그네슘 24.8 ㎎Magnesium chloride 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강식품 조성물 제조에 사용할 수 있다.
Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.
제제예Formulation example 7. 건강 음료의 제조 7. Manufacture of health drinks
SG 추출물 1000 mgSG Extract 1000 mg
구연산 1000 ㎎Citric acid 1000 mg
올리고당 100 g100 g of oligosaccharide
매실농축액 2 gPlum concentrate 2 g
타우린 1 gTaurine 1 g
정제수를 가하여 전체 900 ㎖Purified water was added to a total of 900 ml
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간동안 85℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2ℓ 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강음료 조성물 제조에 사용한다. The above components were mixed according to a conventional health drink manufacturing method, and the mixture was heated at 85 DEG C for about 1 hour with stirring, and the solution thus prepared was filtered to obtain a sterilized 2-liter container, which was sealed and sterilized, ≪ / RTI >
상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 수요계층, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.
Although the composition ratio is a composition that is relatively suitable for the preferred beverage in a preferred embodiment, the compounding ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.
Claims (9)
Hepatoprotective, containing as an active ingredient, a processed Panax genus plant extract with an increased active ingredient such that the sum of the ginsenosides Rg3, Rk1, and Rg5 is higher than the sum of the contents of the ginsenosides Rb1, Rb2, Rc, and Rd; Pharmaceutical composition for treating or preventing liver disease.
상기 파낙스속 식물은 고려인삼 (Panax ginseng), 화기삼 (Panax quinquefolia), 전칠삼 (삼칠, Panax notoginseng), 베트남삼 (Panax vietnamensis), 죽절삼 (Panax japonicus), 파낙스 엘레가티오르 (Panax elegatior), 파낙스 완지아누스 (Panax wangianus), 파낙스 비핀나티푸스 (Panax bipinnatifidus), 또는 파낙스 슈도진생 (Panax pseudoginseng)을 인위적으로 가공시킨 식물을 특징으로 하는 약학조성물.
The method of claim 1,
The Panax genus plants include Panax ginseng , Panax quinquefolia , Panax notoginseng , Panax vietnamensis , Panax vietnamensis , Panax japonicus , Panax elegatior , Panax Wan Jia Augustine (Panax wangianus), Panax non-typhoid pinna (Panax bipinnatifidus), or Panax pseudo-ginseng (Panax pseudoginseng ) is artificially processed.
상기 파낙스속 식물은 인삼을 120 내지 180℃의 고온에서 0.5 내지 20시간 동안 가열처리하여 진세노사이드 (Rg3+Rg5)/(Rc+Rd+Rb1+Rb2)의 비율이 1.0이상이 되도록 약효성분을 증가시킨 가공인삼임을 특징으로 하는 약학조성물.
The method of claim 1,
The Panax genus plants are treated with ginseng at a high temperature of 120 to 180 ° C. for 0.5 to 20 hours so that the ratio of ginsenosides (Rg 3 + Rg 5) / (Rc + Rd + Rb 1 + Rb 2 ) is 1.0 or more. Pharmaceutical composition characterized by processed ginseng with increased ingredients.
상기 추출물은 물, 메탄올, 에탄올, 부탄올 등의 저급 알콜 또는 이들의 혼합용매인 약학 조성물.
The method of claim 1,
Wherein the extract is water, a lower alcohol such as methanol, ethanol, butanol, or a mixed solvent thereof.
The pharmaceutical composition of claim 1, wherein the liver disease is acute hepatitis, chronic hepatitis, fatty liver disease, liver cirrhosis, liver fibrosis, and liver cancer.
Hepatoprotective, containing as an active ingredient, a processed Panax genus plant extract with an increased active ingredient such that the sum of the ginsenosides Rg3, Rk1, and Rg5 is higher than the sum of the contents of the ginsenosides Rb1, Rb2, Rc, and Rd; Health functional food for preventing and improving liver disease.
7. The dietary supplement of claim 6 which is a powder, granule, tablet, capsule or beverage.
Ginsenoside Rg3, Rk1, Rg5 content with liver protection and liver disease improvement is higher than the sum of the ginsenosides Rb1, Rb2, Rc, Rd content of the processed Panax genus plant extract Food or food additives containing as an active ingredient.
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CN104644660A (en) * | 2013-11-22 | 2015-05-27 | 富力 | Application of 20(R)-ginsenoside Rg3 in preparation of medicament for relieving or/and treating fatty liver |
KR20190000863A (en) * | 2018-12-21 | 2019-01-03 | 재단법인 금산국제인삼약초연구소 | Composition for treating liver diseases contain ginseng extracts |
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CN104644660A (en) * | 2013-11-22 | 2015-05-27 | 富力 | Application of 20(R)-ginsenoside Rg3 in preparation of medicament for relieving or/and treating fatty liver |
KR20190000863A (en) * | 2018-12-21 | 2019-01-03 | 재단법인 금산국제인삼약초연구소 | Composition for treating liver diseases contain ginseng extracts |
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