KR100924216B1 - Hepatoprotective composition comprising pectolinarin or pectolinarigenin - Google Patents
Hepatoprotective composition comprising pectolinarin or pectolinarigenin Download PDFInfo
- Publication number
- KR100924216B1 KR100924216B1 KR1020070106338A KR20070106338A KR100924216B1 KR 100924216 B1 KR100924216 B1 KR 100924216B1 KR 1020070106338 A KR1020070106338 A KR 1020070106338A KR 20070106338 A KR20070106338 A KR 20070106338A KR 100924216 B1 KR100924216 B1 KR 100924216B1
- Authority
- KR
- South Korea
- Prior art keywords
- liver
- composition
- fentorariginine
- present
- fentorinarin
- Prior art date
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Abstract
본 발명은 펙토리나린 또는 펙토리나리게닌을 포함하는 간 보호용 조성물에 관한 것이다. 본 발명의 펙토리나린 및 펙토리나리게닌은 D-갈락토사민에 의해 유도된 간손상에서 AST, ALT, ALP 및 LDH의 농도를 감소시키고, 과산화지질 지표인 말론디알데히드의 양을 낮추어 지질 산화를 억제하며, GSH, GR, GCS, GST 및 SOD의 농도를 증가시킴으로써 간보호 효과와 항산화 효과가 우수하다. 따라서, 본 발명의 펙토리나린 및 펙토리나리게닌은 간보호용 의약품 및 건강식품으로 유용하게 사용될 수 있다.The present invention relates to a composition for protecting liver comprising fentorinarin or fentorariginine. Fectorinarin and Fectorinarigenin reduce the concentration of AST, ALT, ALP and LDH in D-galactosamine-induced liver damage and lower the amount of malondialdehyde, which is an indicator of lipid peroxide, to inhibit lipid oxidation In addition, by increasing the concentration of GSH, GR, GCS, GST and SOD, hepatoprotective and antioxidant effects are excellent. Therefore, the fentorinarin and fentorariginine of the present invention can be usefully used as a medicine for liver protection and health food.
Description
본 발명은 펙토리나린 또는 펙토리나리게닌을 포함하는 간 보호용 조성물에 관한 것이다.The present invention relates to a composition for protecting liver comprising fentorinarin or fentorariginine.
간은 인체 내 소화기계와 전신순환계 사이에 위치하여 외부로부터 들어온 독성물질로부터 전신을 방어하고 생체 외 물질의 대사를 담당하고 있다. 생체 내로 들어온 생체 외 물질은 일단 간을 통과하기 때문에, 간은 영양소 외에도 많은 독성물질에 노출될 위험이 높아 다른 장기보다 손상받을 가능성이 많다. 간은 재생능력이 우수한 장기로 약간의 손상에는 충분히 정상으로 회복된다. 그러나 알콜의 과다섭취, 화학물질의 남용, 바이러스성 간염, 담즙 분비정지 등에 의해 지속적으로 손상을 받게 되면 간기능이 저하될 뿐만 아니라 간조직의 일부가 완전히 파괴되고 손상부분은 정상으로 회복되지 못하는 결과를 초래하며, 결국에는 간염, 간경화, 간암 등의 간질환으로 발전하게 된다. 간질환은 초기 단계에는 통증이나 자각증세가 나타나지 않고, 말기에 이르러서야 발견되기 때문에 적절한 시기에 치료가 불가능하고, 그에 따라 사망률이 높은 질환이다.The liver is located between the digestive system and the circulatory system of the human body to protect the body from toxic substances from the outside and is responsible for metabolism of in vitro substances. Since the in vitro material that enters the living body once passes through the liver, the liver is more likely to be damaged than other organs because of the high risk of exposure to many toxic substances besides nutrients. The liver is a good organ with good regenerative capacity and recovers to normal enough for some damage. However, continuous damage caused by excessive ingestion of alcohol, abuse of chemicals, viral hepatitis, and biliary secretion can lead to a decrease in liver function, as well as complete destruction of liver tissue and inability to restore normal damage. And eventually develops liver diseases such as hepatitis, cirrhosis and liver cancer. Liver disease is a disease with high mortality due to the absence of pain or subjective symptoms in the early stages, and since it is found only at the end, it cannot be treated in a timely manner.
또한, 우리의 몸은 산업화에 따른 공해물질, 유독물질에 항상 노출되어 있어 우리의 간은 끊임없이 해독작용에 시달리고 있다. 더욱이 심각한 것은 정신적 스트레스로 인한 간손상이다. 정신적 휴식을 가질 경우 손상된 간세포는 복구되지만 급박한 현대사회에서 정신적 휴식의 여유를 찾을 수 없어 정신적 스트레스, 과음, 흡연으로 간손상을 가중시켜 인체가 방어 해독 작용을 하지 못해 면역 체계에 이상을 가져와 다른 질병의 원인이 되기도 한다.In addition, our bodies are constantly exposed to pollutants and toxic substances due to industrialization, and our liver is constantly suffering from detoxification. What is more serious is liver damage caused by mental stress. If you have mental rest, damaged hepatocytes will be repaired, but in an urgent modern society, you will not be able to afford mental rest, which will increase your liver damage by mental stress, heavy drinking, and smoking. It can also cause illness.
간독성을 일으키는 유발물질에는 사염화탄소(CCl4), D-갈락토사민(D-galactosamine; GalN), 지질다당류(lipopolysaccharide; LPS), 브로모벤젠 등이 있다. 이중, D-갈락토사민은 잘 알려진 간독성 물질로 in vivo와 in vitro에서 간손상을 일으키는 모델로 사용되어 왔다. In vivo에서 D-갈락토사민은 바이러스에 의한 간염 및 약품에 의한 간염과 비슷한 간손상을 일으키는 것으로 연구되었다 (Keppler et al., 1968; MacDonald et al., 1987). 이 간독성은 간세포에서 우리딘 (uridine) 뉴클레오티드의 손실과 UDP 헥소스아민(hexoseamine)의 축적으로 RNA와 단백질 합성을 억제한다(Decker and Keppler, 1974; Keppler et al. 1968). 랫트에서는 낮은 농도의 내독소에 의해 쿠퍼(Kuffer) 세포가 활성화되는데, 이것이 D-갈락토사민 독성과 관련 있다(Galanos et al., 1979; Kasravi et al., 1995; Stachlewitz et al., 1999). 특히 D-갈락토사민은 간에서 TNF-α 민감성을 증가시키며 간손상에 기여한다(Leist et al. 1997).Caustic agents causing hepatotoxicity include carbon tetrachloride (CCl 4 ), D-galactosamine (GalN), lipopolysaccharide (LPS), and bromobenzene. D-galactosamine is a well known hepatotoxic substance and has been used as a model for liver damage in vivo and in vitro. In vivo, D-galactosamine has been studied to cause liver damage similar to hepatitis caused by viruses and hepatitis caused by drugs (Keppler et al., 1968; MacDonald et al., 1987). This hepatotoxicity inhibits RNA and protein synthesis by loss of uridine nucleotides and accumulation of UDP hexoseamine in hepatocytes (Decker and Keppler, 1974; Keppler et al. 1968). In rats, Kuffer cells are activated by low concentrations of endotoxins, which are associated with D-galactosamine toxicity (Galanos et al., 1979; Kasravi et al., 1995; Stachlewitz et al., 1999). . In particular, D-galactosamine increases TNF-α sensitivity in the liver and contributes to liver damage (Leist et al. 1997).
또한, 과산화지질을 억제 또는 방지할 수 있는 기능인 항산화 효과는 간보호 효과 및 항염증 작용이 있다고 보고되어 있어, 항산화 물질(antioxidant compound)은 반응성 산소중간생성물(reactive oxygen intermediate)에 의한 공격에 대항해서In addition, the antioxidant effect, which is a function that inhibits or prevents lipid peroxide, has been reported to have a hepatoprotective effect and an anti-inflammatory action, and thus, an antioxidant compound is used against an attack by a reactive oxygen intermediate.
간과 간세포 보호의 목적으로 사용되고 있다.It is used for the purpose of protecting the liver and liver cells.
따라서, 항산화 메커니즘에 의해 간보호 효과를 나타낼 수 있는 물질에 관한 연구가 많이 진행되고 있으며, 특히 생약재로부터 탐색하려는 연구가 많이 시도되고 있다. 생약재로부터 인간의 질병을 예방 및 치료할 수 있는 신물질의 탐색은 과거부터 많은 과학자들의 연구대상이 되어왔다. 이와 같은 천연 자원의 개발로 현재 사용되고 있는 의약품의 50% 이상이 천연물로부터 유래되었으며, 미국 FDA로부터 승인된 의약품이 120여종으로 시장규모는 약 10조 달러에 이르고 있다. 항 간독성 활성을 갖는 천연물의 탐색 및 개발도 많이 이루어지고 있으나 실제 치료제로 사용중이거나 임상시험을 거친 예는 소수에 불과하다.Therefore, many studies have been conducted on substances capable of exhibiting a hepatoprotective effect by antioxidant mechanisms, and many studies have been attempted to search for herbal medicines. The search for new substances that can prevent and treat human diseases from herbal medicines has been the subject of research by many scientists from the past. The development of these natural resources has led to more than 50% of the drugs currently in use, derived from natural products, and more than 120 approved drugs from the US FDA, with a market size of about $ 10 trillion. There have been many researches and developments of natural products with anti-hepatotoxic activity, but only a few cases have been used or tested in actual treatments.
한편, 고려엉겅퀴(Cirsium setidens)는 국화과에 속하는 다년초로 곤드레 또는 곤달비라고도 불리운다. 고려엉겅퀴는 태백산의 해발 700m 고지에서 자생하는 야생식물로, 한국, 일본, 중국 등 동남아시아뿐만 아니라 지중해 연안, 북미 남서부 등 북반구의 온대부터 한대에 이르기까지 널리 분포한다. 어린잎과 줄기를 식용으로 하며, 단백질, 칼슘 및 비타민 A가 풍부하다. 약리효과로는 이뇨, 해독, 소염, 지혈 작용이 있으며, 폐렴이나 고혈압, 장염, 신장염에도 쓰인다. 특히, 고려엉겅퀴 잎의 생즙은 신경통과 관절염에 좋다고 알려져 있다. 고려엉겅퀴의 주요 활성성분으로는 펙토리나린(pectolinarin)이 있으며, Cirsium subcoriaceum에서 분리한 펙토리나린은 진통효과 및 항염증효과가 있음이 증명되었고(Martinez-Vazquez M, Ramirez Apan TO, Lastra AL, Bye R. A comparative study of the analgesic and anti-inflammatory activities of pectolinarin isolated from Cirsium subcoriaceum and linarin isolated from Buddleia cordata. Planta Med. 1998; 64: 134-137.), Linaria reflexa Desf에서 분리한 펙토리나린은 COR-L23, Caco-2 및 C32 등의 세포주에서 항암효과를 나타내었으며(Tundis R, Deguin B, Loizzo MR, Bonesi M, Statti GA, Tillequin F, Menichini F. Potential antitumor agents: flavones and their derivatives from Linaria reflexa Desf. Bioorg Med Chem Lett. 2005; 15: 4757-4760.), Cirsium japonicum에서 분리한 펙토리나린은 S180과 H22 마우스에서 항암효과가 있음이 밝혀졌다(Liu S, Luo X, Li D, Zhang J, Qiu D, Liu W, She L, Yang Z.Tumor inhibition and improved immunity in mice treated with flavone from Cirsium japonicum DC. Int Immunopharmacol. 2006; 6: 1387-1393. and Liu S, Zhang J, Li D, Liu W, Luo X, Zhang R, Li L, Zhao J. Anticancer activity and quantitative analysis of flavone of Cirsium japonicum DC. Nat Prod Res. 2007; 21: 915-922.).Meanwhile, thistle ( Cirsium) setidens ) is a perennial plant belonging to the family Asteraceae, also called gondre or gondalbi . Korean thistle is a wild plant that grows at an altitude of 700 meters above sea level of Taebaek Mountain. It is widely distributed in temperate and cold regions of the northern hemisphere such as Southeast Asia such as Korea, Japan and China, as well as the Mediterranean coast and southwestern North America. Young leaves and stems are edible and rich in protein, calcium and vitamin A. Pharmacological effect is diuretic, detoxification, anti-inflammatory, hemostatic action, pneumonia, high blood pressure, enteritis, nephritis is also used. In particular, the fresh juice of Korean thistle leaves is known to be good for neuralgia and arthritis. The main active ingredient of Korean thistle is pectolinarin, Cirsium A pektori Naryn separated from subcoriaceu m has been demonstrated that the analgesic and anti-inflammatory effect (Martinez-Vazquez M, Ramirez Apan TO, Lastra AL, Bye R. A comparative study of the analgesic and anti-inflammatory activities of pectolinarin isolated from Cirsium subcoriaceum and linarin isolated from Buddleia cordata.Planta Med. 1998; 64: 134-137.), Linaria Factorinirin isolated from reflexa Desf showed anticancer effects in cell lines such as COR-L23, Caco-2 and C32 (Tundis R, Deguin B, Loizzo MR, Bonesi M, Statti GA, Tillequin F, Menichini F. Potential antitumor agents: flavones and their derivatives from Linaria reflexa Desf.Bioorg Med Chem Lett. 2005; 15: 4757-4760.), Cirsium Pectolinerin isolated from japonicum has been shown to have anticancer effects in S180 and H22 mice (Liu S, Luo X, Li D, Zhang J, Qiu D, Liu W, She L, Yang Z. Tumor inhibition and improved immunity in mice treated with flavone from Cirsium japonicum DC.Int Immunopharmacol. 2006; 6: 1387-1393. and Liu S, Zhang J, Li D, Liu W, Luo X, Zhang R, Li L, Zhao J. Anticancer activity and quantitative analysis of flavone of Cirsium japonicum DC.Nat Prod Res. 2007; 21: 915-922.).
상기한 바와 같이, 펙토리나린의 다양한 약리활성에 대해 알려져 있지만, 간보호 효과에 대해서는 아직까지 알려져 있지 않으며, 이에 대한 연구도 전무한 상태이다.As mentioned above, although the pharmacological activity of the factorinirin is known, the hepatoprotective effect is not known yet, and there is no research on this.
본 발명자들은 펙토리나린 및 이의 배당체인 펙토리나리게닌의 간보호 활성에 대해 연구하던 중, 펙토리나린 및 펙토리나리게닌이 D-갈락토사민에 의해 유도된 간손상에서 AST, ALT, ALP 및 LDH의 농도를 감소시키고, 지질산화를 억제하며, GSH, GR, GCS, GST 및 SOD의 농도를 증가시킴으로써 간보호 효과와 항산화 효과가 우수함을 확인하고 본 발명을 완성하였다. While the present inventors have studied the hepatoprotective activity of fentorinarin and its glycoside, fentorariginine, the concentrations of AST, ALT, ALP and LDH in hepatitis induced by D-galactosamine By reducing the, inhibiting lipid oxidation, increasing the concentrations of GSH, GR, GCS, GST and SOD confirmed that hepatoprotective and antioxidant effects are excellent and completed the present invention.
본 발명은 펙토리나린 또는 펙토리나리게닌을 포함하는 간 보호용 조성물을 제공하고자 한다.The present invention is to provide a composition for protecting liver comprising fentorinarin or fentorariginine.
본 발명은 하기 화학식 1로 표시되는 펙토리나린을 포함하는 간 보호용 조성물을 제공한다.The present invention provides a composition for protecting liver, which comprises a factorinarin represented by the following formula (1).
또한, 본 발명은 하기 화학식 2로 표시되는 펙토리나리게닌을 포함하는 간 보호용 조성물을 제공한다.In another aspect, the present invention provides a composition for liver protection comprising the fentorariginine represented by the following formula (2).
본 발명의 조성물은 약학 조성물 및 식품 조성물을 포함한다.Compositions of the present invention include pharmaceutical compositions and food compositions.
이하, 본 발명에 대해 상세히 설명한다.Hereinafter, the present invention will be described in detail.
본 발명의 조성물의 유효성분인 펙토리나린 및 펙토리나리게닌은 통상적인 모든 방법에 의해 얻을 수 있고, 시판되는 시약을 사용할 수 있으며, 생약재로부터 추출 및 분리하여 얻을 수 있다. 본 발명에서는 펙토리나린 및 펙토리나리게닌을 하기와 같은 방법으로 추출 및 분리하여 얻을 수 있다.The effective ingredients of fentorinarin and fentorariginine of the composition of the present invention can be obtained by all conventional methods, commercially available reagents can be used, and extracted and separated from the herbal medicines. In the present invention can be obtained by extracting and separating the fentorinarin and fentorariginine in the following method.
먼저 고려엉겅퀴 잎을 물, 알콜 또는 물과 알콜의 혼합용매에 첨가하여 환류추출한다(3회 반복). 추출액을 여과한 후 감압농축하고 동결 건조하여 분말 형태의 고려엉겅퀴 잎 추출물을 얻는다. 상기 물과 알콜의 혼합용매는 10 내지 100%의 메탄올 또는 10 내지 100%의 에탄올 중에서 선택될 수 있으며, 바람직하게는 10 내지 100%의 메탄올이다. 상기 고려엉겅퀴 잎 메탄올 추출물을 증류수에 현탁시키고, 클로로포름으로 3회 분배추출한다. 클로로포름 가용성 분획을 진공 하에 건조시켜 클로로포름 분획을 얻는다. 그 다음 남은 수층을 부탄올로 3회 분배추출하고, 부탄올 가용성 분획을 진공 하에 건조시켜 부탄올 분획을 얻는다.First, the Korean thistle leaf is added to water, alcohol or a mixed solvent of water and alcohol to extract reflux (3 times). The extract was filtered, concentrated under reduced pressure, and lyophilized to obtain Korean thistle leaf extract in powder form. The mixed solvent of water and alcohol may be selected from 10 to 100% methanol or 10 to 100% ethanol, preferably 10 to 100% methanol. The Korean thistle leaf methanol extract is suspended in distilled water and extracted three times with chloroform. The chloroform soluble fraction is dried under vacuum to give the chloroform fraction. The remaining aqueous layer is then partitioned and extracted three times with butanol and the butanol soluble fraction is dried in vacuo to give a butanol fraction.
상기 고려엉겅퀴 잎 부탄올 분획을 클로로포름:메탄올:물이 7:3:1인 용매를 사용하여 실리카겔 컬럼 크로마토그래피(SiO2, Art No. 7734, Merck, Germany, 280 g, 5 x 55 ㎝)를 실시하여 3개의 분획으로 분리한다. 이중 두 번째 분획을 진공 하에 건조시키고 메탄올로 재결정하여 화합물 1을 얻고, 펙토리나린으로 동정한다.The Korean thistle leaf butanol fraction was subjected to silica gel column chromatography (SiO 2 , Art No. 7734, Merck, Germany, 280 g, 5 x 55 cm) using a solvent of chloroform: methanol: water 7: 3: 1. To separate into three fractions. The second fraction is dried in vacuo and recrystallized from methanol to give compound 1 and identified as factorininarin.
또한, 상기 펙토리나린을 50% 메탄올 용액 내 5% 황산에 가하고 환류 하에 가수분해시킨 후, 클로로포름으로 3회 분배추출한다. 클로로포름 분획을 증류수로 세척하고 건조하여 농축시킨 후, 잔류물을 메탄올에 녹여 화합물 2를 얻고, 펙토리나리게닌으로 동정한다.In addition, the factorinirin is added to 5% sulfuric acid in a 50% methanol solution, hydrolyzed under reflux, and then partitioned and extracted three times with chloroform. The chloroform fraction is washed with distilled water, dried and concentrated, and then the residue is dissolved in methanol to obtain Compound 2, which is identified as pectoriginalinine.
본 발명의 펙토리나린 및 펙토리나리게닌은 D-갈락토사민에 의해 유도된 간손상에서 AST, ALT, ALP 및 LDH의 농도를 감소시키고, 과산화지질 지표인 말론디알데히드의 양을 낮추어 지질 산화를 억제하며, GSH, GR, GCS, GST 및 SOD의 농도를 증가시킴으로써 간보호 효과와 항산화 효과가 우수하다. 따라서, 본 발명의 펙토리나린 및 펙토리나리게닌은 간보호용 의약품 및 건강식품으로 유용하게 사용될 수 있다.Fectorinarin and Fectorinarigenin reduce the concentration of AST, ALT, ALP and LDH in D-galactosamine-induced liver damage and lower the amount of malondialdehyde, which is an indicator of lipid peroxide, to inhibit lipid oxidation In addition, by increasing the concentration of GSH, GR, GCS, GST and SOD, hepatoprotective and antioxidant effects are excellent. Therefore, the fentorinarin and fentorariginine of the present invention can be usefully used as a medicine for liver protection and health food.
본 발명의 조성물은 펙토리나린 또는 펙토리나리게닌과 함께 간보호 효과를 갖는 공지의 유효성분을 1종 이상 함유할 수 있다.The composition of the present invention may contain at least one known active ingredient having hepatoprotective effect together with atorcrinein or atorcrineignin.
본 발명의 조성물은, 투여를 위해서 상기 기재한 유효성분 이외에 추가로 약학적으로 허용가능한 담체를 1종 이상 포함하여 제조할 수 있다. 약학적으로 허용 가능한 담체는 식염수, 멸균수, 링거액, 완충 식염수, 덱스트로오스 용액, 말토 덱스트린 용액, 글리세롤, 에탄올 및 이들 성분 중 1 성분 이상을 혼합하여 사용할 수 있으며, 필요에 따라 항산화제, 완충액, 정균제 등 다른 통상의 첨가제를 첨가할 수 있다. 또한 희석제, 분산제, 계면활성제, 결합제 및 윤활제를 부가적으로 첨가하여 수용액, 현탁액, 유탁액 등과 같은 주사용 제형, 환약, 캡슐, 과립 또는 정제로 제제화할 수 있다. 더 나아가 당분야의 적정한 방법으로 또는 Remington's Pharmaceutical Science(최근판), Mack Publishing Company, Easton PA에 개시되어 있는 방법을 이용하여 각 질환에 따라 또는 성분에 따라 바람직하게 제제화할 수 있다.The composition of the present invention may be prepared by including one or more pharmaceutically acceptable carriers in addition to the above-described active ingredients for administration. Pharmaceutically acceptable carriers may be used in combination with saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol and one or more of these components, if necessary, as an antioxidant, buffer And other conventional additives such as bacteriostatic agents can be added. Diluents, dispersants, surfactants, binders and lubricants may also be added in addition to formulate into injectable formulations, pills, capsules, granules or tablets such as aqueous solutions, suspensions, emulsions and the like. Furthermore, it may be preferably formulated according to each disease or component by a suitable method in the art or using a method disclosed in Remington's Pharmaceutical Science (Recent Edition), Mack Publishing Company, Easton PA.
본 발명의 조성물은 목적하는 방법에 따라 경구 투여하거나 비경구 투여(예를 들어, 정맥 내, 피하, 복강 내 또는 국소에 적용)할 수 있으며, 투여량은 환자의 체중, 연령, 성별, 건강상태, 식이, 투여시간, 투여방법, 배설율 및 질환의 중증도 등에 따라 그 범위가 다양하다. 상기 펙토리나린 또는 펙토리나리게닌의 일일 투여량은 약 5~20 ㎎/㎏, 바람직하게는 약 10~20 ㎎/㎏이며, 하루 일회 내지 수회에 나누어 투여하는 것이 더욱 바람직하다.The composition of the present invention can be administered orally or parenterally (eg, applied intravenously, subcutaneously, intraperitoneally or topically) according to the desired method, and the dosage is based on the weight, age, sex and health of the patient. The range varies depending on the diet, the time of administration, the method of administration, the rate of excretion and the severity of the disease. The daily dosage of the fentorinarin or fentorariginine is about 5 to 20 mg / kg, preferably about 10 to 20 mg / kg, and more preferably administered once or several times a day.
본 발명의 조성물은 간보호를 위하여 단독으로, 또는 수술, 호르몬 치료, 약물 치료 및 생물학적 반응 조절제를 사용하는 방법들과 병용하여 사용할 수 있다.The composition of the present invention may be used alone or in combination with methods using surgery, hormonal therapy, drug therapy and biological response modifiers for liver protection.
본 발명의 조성물은 간보호를 목적으로 건강식품에 첨가될 수 있다. 본 발명의 펙토리나린 또는 펙토리나리게닌을 식품 첨가물로 사용할 경우, 상기 펙토리나린 또는 펙토리나리게닌을 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용할 수 있고, 통상적인 방법에 따라 적절하게 사용할 수 있다. 유효 성분의 혼합양은 사용 목적(예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다. 일반적으로, 식품 또는 음료의 제조시에는 본 발명의 펙토리나린 또는 펙토리나리게닌은 원료에 대하여 15 중량% 이하, 바람직하게는 10 중량% 이하의 양으로 첨가된다. 그러나, 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하일 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로도 사용될 수 있다.The composition of the present invention may be added to health food for the purpose of liver protection. In the case of using the fentorinarin or fentorinariginin of the present invention as a food additive, the fentorinarin or fentorariginine can be added as it is or used in combination with other foods or food ingredients, and can be suitably used according to a conventional method. The mixed amount of the active ingredient may be suitably determined depending on the purpose of use (prevention, health or therapeutic treatment). In general, in the manufacture of foods or beverages, the fentorinarin or fentorariginine of the present invention is added in an amount of 15 wt% or less, preferably 10 wt% or less with respect to the raw material. However, in the case of long-term intake for health and hygiene or health control, the amount may be below the above range, and the active ingredient may be used in an amount above the above range because there is no problem in terms of safety. .
상기 식품의 종류에는 특별한 제한은 없다. 상기 물질을 첨가할 수 있는 식품의 예로는 육류, 소세지, 빵, 쵸코렛, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알콜 음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강식품을 모두 포함한다.There is no particular limitation on the kind of food. Examples of the food to which the substance can be added include dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, drinks, Alcoholic beverages and vitamin complexes, and the like and include all of the health foods in the conventional sense.
본 발명의 건강음료 조성물은 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물은 포도당, 과당과 같은 모노사카라이드, 말토오스, 수크로오스와 같은 디사카라이드, 및 덱스트린, 시클로덱스트린과 같은 폴리사카라이드, 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 감미제로서는 타우마틴, 스테비아 추출물과 같은 천연 감미제나, 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100㎖당 일반적으로 약 0.01~0.04g, 바람직하게는 약 0.02~0.03g 이다.The health beverage composition of the present invention may contain various flavors or natural carbohydrates, etc. as additional components, as in the general beverage. Natural carbohydrates described above are glucose, monosaccharides such as fructose, malsaccharides, disaccharides such as sucrose, and polysaccharides such as dextrin, cyclodextrin, sugar alcohols such as xylitol, sorbitol, and erythritol. As the sweetening agent, natural sweetening agents such as tautin and stevia extract, synthetic sweetening agents such as saccharin and aspartame, and the like can be used. The ratio of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 ml of the composition of the present invention.
상기 외에 본 발명의 조성물은 여러 가지 영양제, 비타민, 전해질, 풍미제, 착색제, 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. 그 밖에 본 발명의 조성물은 천연 과일쥬스, 과일쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 크게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0.01~0.1 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the composition of the present invention includes various nutrients, vitamins, electrolytes, flavors, coloring agents, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, And a carbonation agent used for the carbonated beverage. In addition, the composition of the present invention may contain a pulp for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components can be used independently or in combination. The proportion of such additives is not critical but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.
이하, 본 발명의 이해를 돕기 위하여 바람직한 실시예를 제시한다. 그러나 하기의 실시예는 본 발명을 보다 쉽게 이해하기 위하여 제공되는 것일 뿐, 실시예에 의해 본 발명의 내용이 한정되는 것은 아니다.Hereinafter, preferred examples are provided to aid in understanding the present invention. However, the following examples are merely provided to more easily understand the present invention, and the contents of the present invention are not limited by the examples.
실시예Example 1 One : 고려엉겅퀴 잎 추출물로부터 : From Korean Thistle Leaf Extract 펙토리나린의Factory 제조 Produce
1. 고려엉겅퀴 잎 추출물의 제조1. Preparation of Korean Thistle Leaf Extract
고려엉겅퀴 잎을 강원도 평창군 진부면에서 채집하였다. 고려엉겅퀴 잎을 음건하고 세절하였다. 세절된 고려엉겅퀴 잎 628g을 둥근 바닥 플라스크에 넣고, 메탄올 3ℓ를 가한 후 환류 하에 5시간씩 3회 추출하였다. 추출액을 여과하고 감압 하에 여과 및 농축한 후 동결건조하여 분말 형태의 고려엉겅퀴 잎 메탄올 추출물 128g을 얻었다. 상기 고려엉겅퀴 잎 메탄올 추출물 108g을 800㎖의 증류수에 현탁시키고, 800㎖의 클로로포름을 가하여 3회 분배추출하였다. 클로로포름 가용성 분획을 진공 하에 건조시켜 클로로포름 분획 44g을 얻었다. 그 다음 남은 수층을 800㎖의 부탄올로 3회 분배추출한 다음, 부탄올 가용성 분획을 진공 하에 건조시켜 부탄올 분획 6g을 얻었다.Korean thistle leaves were collected from Jinbu-myeon, Pyeongchang-gun, Gangwon-do. Korean thistle leaves were dried and shredded. 628 g of shredded Korean thistle leaves were placed in a round bottom flask, and 3 L of methanol was added thereto, followed by extraction three times for 5 hours under reflux. The extract was filtered, filtered and concentrated under reduced pressure, and then lyophilized to obtain 128 g of Korean thistle leaf methanol extract in powder form. 108 g of the Korean thistle leaf methanol extract was suspended in 800 ml of distilled water, and 800 ml of chloroform was added thereto to extract three times. The chloroform soluble fraction was dried under vacuum to give 44 g of chloroform fraction. The remaining aqueous layer was then extracted three times with 800 ml of butanol, and the butanol soluble fraction was dried under vacuum to give 6 g of butanol fraction.
2. 고려엉겅퀴 잎 2. Korean thistle leaf 부탄올Butanol 분획으로부터 From fractions 펙토리나린의Factory 분리 detach
상기 1에서 얻은 고려엉겅퀴 잎 부탄올 분획을 클로로포름:메탄올:물이 7:3:1인 용매를 사용하여 실리카겔 컬럼 크로마토그래피(SiO2, Art No. 7734, Merck, Germany, 280 g, 5 x 55 ㎝)를 실시하여 3개의 분획으로 분리하였다. 이중 두 번째 분획을 진공 하에 건조시키고 메탄올로 재결정하여 흰색 무정형 분말의 화합물 1을 얻었다. 상기 화합물 1의 이화학적 특성은 하기와 같으며, 발표된 문헌의 것과 비교 분석한 결과 펙토리나린으로 동정하였다.The Korean thistle leaf butanol fraction obtained in 1 was subjected to silica gel column chromatography (SiO 2 , Art No. 7734, Merck, Germany, 280 g, 5 x 55 cm using a solvent of chloroform: methanol: water 7: 3: 1). ) Into three fractions. The second fraction was dried in vacuo and recrystallized from methanol to give compound 1 as a white amorphous powder. The physicochemical properties of the compound 1 are as follows and were identified as factorinarin as a result of comparative analysis with that of the published literature.
화합물 1 : Compound 1: 펙토리나린Factorinarin
1) 물질의 성상 : 흰색 무정형 분말,1) Appearance of the substance: white amorphous powder,
2) 녹는점 : 250~253℃,2) Melting Point: 250 ~ 253 ℃
3) 1H NMR (500MHz, pyridine-d 5): 6.86 (1H, s, H-1), no peak (H-8), 8.04 (2H, d, J=9.0 Hz, H-2',6'), 7.25 (2H, d, J=9.0 Hz, H-3',5'), 4.05 (3H, s, H-6), 3.71 (3H, s, H-4'); Sugar moieties, Glc-5.73 (1H, d, J=7.5 Hz, H-1"), 4.34 (1H, m, H-2"), 4.34 (1H, m, H-3"), 4.08 (1H, m, H-4"), 4.27 (1H, m, H-5"), 4.72 (1H, dd-like, Ha-6"), 4.14 (1H, dd-like, Hb-6"), Rha-5.47 (1H, brs, H-1'''), 4.62 (1H, dd, J=1.5, 9.0 Hz, H-2'''), 4.51 (1H, dd, J=3.0, 9.0 Hz, H-3'''), 4.16 (1H, dd-like, H-4'''), 4.27 (1H, d, J=6.5 Hz, H-5'''), 1.55 (3H, d, J=6.5 Hz, H-6''');3) 1 H NMR (500MHz, pyridine- d 5 ): 6.86 (1H, s, H-1), no peak (H-8), 8.04 (2H, d, J = 9.0 Hz, H-2 ', 6 '), 7.25 (2H, d, J = 9.0 Hz, H-3', 5 '), 4.05 (3H, s, H-6), 3.71 (3H, s, H-4'); Sugar moieties, Glc-5.73 (1H, d, J = 7.5 Hz, H-1 "), 4.34 (1H, m, H-2"), 4.34 (1H, m, H-3 "), 4.08 (1H, m, H-4 "), 4.27 (1H, m, H-5"), 4.72 (1H, dd-like, H a- 6 "), 4.14 (1H, dd-like, H b -6"), Rha-5.47 (1H, brs, H-1 '''), 4.62 (1H, dd, J = 1.5, 9.0 Hz, H-2'''), 4.51 (1H, dd, J = 3.0, 9.0 Hz, H-3 '''), 4.16 (1H, dd-like, H-4'''), 4.27 (1H, d, J = 6.5 Hz, H-5 '''), 1.55 (3H, d, J = 6.5 Hz, H-6 ''');
4) 13C NMR (125.5MHz, pyridine-d 5) δ Genin 164.5 (C-2), 104.1 (C-3), 153.0 (C-5), 133.9 (C-6), 157.6 (C-7), 95.0 (C-8), 122.8 (C-1'), 128.6 (C-2',6'), 115.0 (C-3',5'), 162.9 (C-4'), 60.6 (6-OCH3), 55.2 (4'-OCH3); Glc - 102.3 (C-1"), 74.5 (C-2"), 78.3 (C-3"), 71.1 (C-4"), 77.5 (C-5"), 67.4 (C-6"); Rha - 102.2 (C-1'''), 71.9 (C-2'''), 72.7 (C-3'''), 73.8 (C-4'''), 69.6 (C-5'''), 18.3 (C-6''').4) 13 C NMR (125.5 MHz, pyridine- d 5 ) δ Genin 164.5 (C-2), 104.1 (C-3), 153.0 (C-5), 133.9 (C-6), 157.6 (C-7) , 95.0 (C-8), 122.8 (C-1 '), 128.6 (C-2', 6 '), 115.0 (C-3', 5 '), 162.9 (C-4'), 60.6 (6- OCH 3 ), 55.2 (4′-OCH 3 ); Glc-102.3 (C-1 "), 74.5 (C-2"), 78.3 (C-3 "), 71.1 (C-4"), 77.5 (C-5 "), 67.4 (C-6"); Rha-102.2 (C-1 '''), 71.9 (C-2'''), 72.7 (C-3 '''), 73.8 (C-4'''), 69.6 (C-5 ''' ), 18.3 (C-6`` ').
3. 3. 펙토리나린으로부터From factory narin 펙토리나리게닌의Of factorinariginin 제조 Produce
상기 2에서 얻은 펙토리나린 2g을 50% 메탄올 용액 내 5% 황산 200㎖에 가하고 3시간 동안 환류 하에 가수분해시켰다. 반응액을 냉각시킨 후, 클로로포름 200㎖로 3회 분배추출하였다. 클로로포름 분획을 증류수로 두번 세척하고 건조하여 농축시켰다. 잔류물을 메탄올에 녹여 화합물 2를 얻었다. 상기 화합물 2의 이화학적 특성은 하기와 같으며, 발표된 문헌의 것과 비교 분석한 결과 펙토리나리게닌으로 동정하였다[Do, JC, Jung GY, Son GH, Isolation of pectolinarin from the aerial parts of Cirsium nipponicum, Kor. J. Pharmacogn. 25: 73~75 (1994).].2 g of factorinarin obtained in 2 was added to 200 ml of 5% sulfuric acid in a 50% methanol solution and hydrolyzed under reflux for 3 hours. After the reaction solution was cooled, the mixture was extracted three times with 200 ml of chloroform. The chloroform fraction was washed twice with distilled water, dried and concentrated. The residue was taken up in methanol to give compound 2. The physicochemical properties of the compound 2 are as follows, and as a result of comparative analysis with that of the published literature was identified as pectorinariginin [Do, JC, Jung GY, Son GH, Isolation of pectolinarin from the aerial parts of Cirsium nipponicum, Kor. J. Pharmacogn. 25: 73-75 (1994).].
화합물 2 : Compound 2: 펙토리나리게닌Factorinarigenin
1) 물질의 성상 : 귤색(yellow orange) 분말,1) Appearance of material: yellow orange powder,
2) 녹는점 : 200~205℃.2) Melting Point: 200 ~ 205 ℃.
실험예Experimental Example 1 One : 본 발명에 따른 : According to the present invention 펙토리나린Factorinarin 및 And 펙토리나리게닌의Of factorinariginin 간보호Liver protection 효과 및 항산화 효과 Effect and antioxidant effect
본 발명에 따른 펙토리나린 및 펙토리나리게닌이 간보호 효과 및 항산화 효과에 미치는 영향을 알아보기 위하여, 하기와 같은 실험을 수행하였다.In order to determine the effects of ectorinarin and fentorariginine according to the present invention on the hepatoprotective and antioxidant effects, the following experiment was performed.
1. 실험동물1. Experimental Animal
실험동물은 체중 200±10g의 Sprague-Dawley계 웅성 흰쥐를 대한 바이오링크㈜에서 분양받아 일정한 조건(온도: 20±2℃, 습도: 40-60%, 명암 주기: 12 h)으로 2주간 충분하게 적응시켜 사육하였다. 실험동물은 12개의 군으로 나누어 1군당 9마리씩 할당하였으며, 실험 전 24시간 동안 물만 주고 절식하였다. The experimental animals were distributed by Biolink Co., Ltd. for Sprague-Dawley male rats weighing 200 ± 10g and kept at a constant condition (temperature: 20 ± 2 ℃, humidity: 40-60%, contrast cycle: 12 h) for 2 weeks. Adapted to breeding. Experimental animals were divided into 12 groups and 9 animals were assigned to each group, and only water was fasted for 24 hours before the experiment.
2. D-2. D- 갈락토사민(GalN)에To galactosamine (GalN) 의한 by 간손상Liver damage 유도 및 시료 투여 Induction and Sample Dosing
시료 투여 마지막 24시간 전, 실험동물에 생리식염수로 용해시킨 D-갈락토사민(Sigma, St. Louis, MO, USA) 400 mg/kg을 복강 내로 투여하여 간손상을 유도하 였다.Liver damage was induced by intraperitoneal administration of 400 mg / kg of D-galactosamine (Sigma, St. Louis, MO, USA) dissolved in physiological saline to the experimental animals 24 hours prior to the last 24 hours of sample administration.
정상군 및 1개의 간손상 유도군에는 각각 1㎖의 생리식염수를 투여하였고, 6개의 간손상 유도군에는 상기 실시예 1에서 제조한 고려엉겅퀴 잎 메탄올 추출물, 고려엉겅퀴 잎 부탄올 분획, 고려엉겅퀴 잎 클로로포름 분획을 생리식염수로 조제한 10% 트윈 80 용액에 용해시켜 각각 100 ㎎/㎏ 및 200 ㎎/㎏로, 4개의 간손상 유도군에는 상기 실시예 1에서 제조한 펙토리나린 및 펙토리나리게닌을 각각 10 ㎎/㎏ 및 20 ㎎/㎏을 1㎖의 생리식염수에 용해하여 경구 존데(oral jonde)를 사용하여 2주간 경구투여하였다.The normal group and one liver injury induction group were administered with 1 ml of physiological saline, respectively, the six liver damage induction groups, Korean thistle leaf methanol extract prepared in Example 1, Korean thistle leaf butanol fraction, Korean thistle leaf chloroform The fractions were dissolved in a 10% Tween 80 solution prepared with physiological saline, and 100 mg / kg and 200 mg / kg, respectively. / Kg and 20 mg / kg were dissolved in 1 ml of saline and orally administered for 2 weeks using oral jonde.
단백질 농도는 Lowery 방법에 의하여 BSA(bovine serum albumin; Sigma chemical Co., St. Louis, MO, USA)를 사용하여 결정하였으며, 실험에서 얻어진 결과의 통계처리는 평균치±표준편차로 표시하였다. 통계학적 분석은 Duncan's multiple rage test를 이용하여 유의성을 검증하였으며, 유의성은 p<0.05로 표시하였다.Protein concentration was determined by using the Bovine serum albumin (Sigma chemical Co., St. Louis, MO, USA) by the Lowery method, the statistical results of the results obtained in the experiment was expressed as mean ± standard deviation. Statistical analysis was performed using Duncan's multiple rage test, and the significance was expressed as p <0.05.
3. 시료의 채취 및 3. Collection of Samples and 효소원의Enzyme 제조 Produce
실험동물을 CO2로 가볍게 마취시킨 후, 복부 정중선을 따라 개복하고 복부 대동맥에서 혈액을 채취하여 실온에서 60분간 방치한 후 1,000 xg에서 15분간 원심분리하여 혈청을 분리하였다. 분리된 혈청은 AST(aspartate), ALT(alanine transaminase), ALP(alkaline phosphatase) 및 LDH(lactate dehydrogenase) 효소 활성 측정에 사용되었다.After the animal was lightly anesthetized with CO 2 , the abdominal midline was opened, blood was collected from the abdominal aorta, left at room temperature for 60 minutes, and centrifuged at 1,000 xg for 15 minutes to separate serum. The isolated serum was used to measure the enzyme activity of aspartate (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH).
간장은 생리식염수로 관류시켜 조직 내 혈액을 제거하고 적출하여 생리식염수로 씻은 다음 여지로 간에 있는 혈액 및 기타 이물질을 제거한 다음 간조직 1g 당 4배의 0.1M 인산염 완충용액(pH 7.4)을 가하여 빙냉상에서 glass Teflon homogenizer로 마쇄하였다. 이 마쇄액을 냉장 원심분리기로 1,000 xg에서 10분간 원심분리하여 핵 및 미마쇄 부분을 제거한 상층액을 고속원심분리기로 10,000 xg에서 20분간 원심분리하였다. 상층액을 다시 105,000 xg에서 60분간 초고속 원심분리하여 세포질(cytosolic) 분획을 얻었으며, 이를 GSH(glutathione), GST (glutathione-S-transferase), GR(glutathione reductase), GCS(γ-glutamylcysteine synthetase) 및 SOD(superoxide dismutase) 효소 활성 측정에 사용하였다. 하기의 모든 실험은 4℃에서 실행하였다.The liver is perfused with physiological saline to remove blood from the tissue, extracted, washed with physiological saline, and then freed of blood and other foreign substances in the liver, and then added with 4 times 0.1M phosphate buffer solution (pH 7.4) per 1 g of liver tissue. The cold phase was triturated with a glass Teflon homogenizer. The ground liquor was centrifuged at 1,000 xg for 10 minutes using a refrigerated centrifuge, and the supernatant from which the nucleus and uncrushed portions were removed was centrifuged at 10,000 xg for 20 minutes using a high-speed centrifuge. The supernatant was further centrifuged at 105,000 xg for 60 minutes to obtain a cytosolic fraction, which was obtained by GSH (glutathione), GST (glutathione-S-transferase), GR (glutathione reductase), and GCS (γ-glutamylcysteine synthetase). And SOD (superoxide dismutase) enzyme activity was measured. All experiments below were run at 4 ° C.
4. 효소 활성 측정 - 4. Determination of enzyme activity- 간보호Liver protection 효과 effect
4-1. 4-1. ASTAST (( aspartateaspartate ) 및 ) And ALTALT (( alaninealanine transaminasetransaminase )의 측정) Measurement
아미노트랜스퍼라제(aminotransferase)는 아미노기를 전이시키는 효소로 간이 손상되었을 때 임상적으로 측정하여 진단하는데 이용된다. 특히 세포막의 손상이 생겼을 때 세포 내 AST와 ALT가 세포 밖으로 유출된다. 그러므로 혈액 내의 이 수치는 간질환의 진단에 매우 중요하다.Aminotransferase is an enzyme that transfers amino groups and is used to diagnose and diagnose clinically when the liver is damaged. In particular, when cell membrane damage occurs, intracellular AST and ALT flow out of the cell. Therefore, this level in the blood is very important for the diagnosis of liver disease.
Reitman과 Frankel(1957)의 방법에 따라 조제된 아산제약 키트를 사용하여 AST 및 ALT 효소 활성을 측정하였다[Reitman S, Frankel S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol.1957; 28: 56-63.]. AST 기질액(0.0266 ㎎/㎖ L- 아스파르트산, 0.29 ㎎/㎖ α-케토글루탐산) 및 ALT 기질액(0.0178 ㎎/㎖ DL-알라닌, 0.29 ㎎/㎖ α-케토글루탐산)을 각각 1㎖씩 37℃에서 5분간 방치하였다. AST 기질액 및 ALT 기질액에 혈청 0.2㎖를 넣고 37℃에서 AST는 60분간, ALT는 30분간 반응시킨 후 정지용액(stop solution; 0.19 ㎎/㎖ 2,4-디니트로페닐히드라진) 1㎖를 첨가하고 1㎖의 0.4N NaOH를 가하여 혼합한 후 실온에서 10분간 방치하였다. 505 nm에서 흡광도를 측정하여 효소 활성도를 표준 검량선에 준하여 계산하였으며, 혈청 1㎖당 Karmen unit로 표시하였다.The AST and ALT enzyme activities were measured using Asan Pharmaceutical Kit prepared according to the method of Reitman and Frankel (1957) [Reitman S, Frankel S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol. 1957; 28: 56-63.]. 1 ml each of AST substrate solution (0.0266 mg / ml L-aspartic acid, 0.29 mg / ml α-ketoglutamic acid) and ALT substrate solution (0.0178 mg / ml DL-alanine, 0.29 mg / ml α-ketoglutamic acid) 37 It left for 5 minutes at ° C. 0.2 ml of serum was added to the AST substrate solution and ALT substrate solution, and the reaction was carried out at 37 ° C. for 60 minutes and ALT for 30 minutes, followed by 1 ml of stop solution (0.19 mg / ml 2,4-dinitrophenylhydrazine). 1 ml of 0.4N NaOH was added thereto, mixed, and left to stand at room temperature for 10 minutes. The absorbance was measured at 505 nm and the enzyme activity was calculated according to the standard calibration curve and expressed in Karmen units per 1 ml of serum.
4-2. 4-2. ALPALP (( alkalinealkaline phosphatasephosphatase )의 측정) Measurement
ALP는 뉴클레오티드와 단백질의 인산기를 제거하는 가수분해효소로, 일차적으로 간과 뇌에서 생성되며 간의 상태를 알아볼 수 있는 효소이다.ALP is a hydrolase that removes phosphate groups from nucleotides and proteins. It is primarily produced in the liver and brain and is an enzyme that can recognize the condition of the liver.
Roos(1966)의 방법에 따라 조제된 아산제약 키트로 ALP 효소 활성을 측정하였다[Roos K. A simplified AutoAnalyzer procedure for the determination of serum alkaline phosphatase activity. Clin Chim Acta. 1966; 13: 403-405.]. 1mM 페닐 포스페이트를 함유한 2㎖의 0.05M 탄산염 완충용액(carbonate buffer, pH 10.0)을 37℃에서 3분간 방치하였다. ALP 기질액에 혈청 0.05㎖를 가한 후 1㎖의 정지용액(0.19 ㎎/㎖ 2,4-디니트로페닐히드라진)과 1㎖의 0.4N HCl을 첨가하고 혼합한 후 실온에서 10분간 방치하였다. 500 nm에서 흡광도를 측정하여 활성도를 표준 검량선에 준하여 계산하였으며, 혈청 1㎖당 Karmen unit로 표시하였다.ALP enzyme activity was measured with an Asan pharmaceutical kit prepared according to the method of Roos (1966) [Roos K. A simplified AutoAnalyzer procedure for the determination of serum alkaline phosphatase activity. Clin Chim Acta. 1966; 13: 403-405.]. 2 ml of 0.05 M carbonate buffer (pH 10.0) containing 1 mM phenyl phosphate was left at 37 ° C. for 3 minutes. After adding 0.05 ml of serum to the ALP substrate solution, 1 ml of a stop solution (0.19 mg / ml 2,4-dinitrophenylhydrazine) and 1 ml of 0.4N HCl were added, mixed, and left to stand at room temperature for 10 minutes. The absorbance was measured at 500 nm and the activity was calculated according to the standard calibration curve, expressed in Karmen units per 1 ml of serum.
4-3. 4-3. LDHLDH (( lactatelactate dehydrogenasedehydrogenase )의 측정) Measurement
LDH는 조직 손상에서 급성 및 만성의 진행성을 알아보는 일반적 지표로 기 관, 조직, 세포를 진단할 수 있는 중요한 효소이다.LDH is a general indicator of the acute and chronic progression of tissue damage and is an important enzyme for the diagnosis of organs, tissues and cells.
Kim 등(2005)의 방법에 따라 조제된 아산제약 키트로 LDH 효소 활성을 측정하였다[Kim NY, Lee MK, Park MJ, Kim SJ, Park HJ, Choi JW, Kim SH, Cho SY, Lee JS. Momordin Ic and oleanolic acid from Kochiae Fructus reduce carbon tetrachloride-induced hepatotoxicity in rats. J Med Food. 2005; 8: 1777-1783.]. 용액 A[23.1 ㎎/㎖ 리튬 아세테이트, 24.2 ㎎/㎖ 트리스(히드록시메틸)아미노메탄]와 용액 B[57.4 ㎎/㎖ NAD, 0.034 ㎎/㎖ 1'-메톡시-5'-메틸페나지늄 메틸설페이트(1'-methoxy-5'-methylphenazinium methylsulfate; phenazine methosulfate(PMS))]를 같은 부피로 혼합하여 37℃에서 5분간 방치하였다. 이것을 간균질액(100~300 ㎖ 단백질)과 혼합하고 37℃에서 10분간 방치시킨 다음, 0.4N HCl을 가하여 반응을 중지시켰다. 570 nm에서 흡광도를 측정하여 활성도를 표준 검량선에 준하여 계산하였다.LDH enzyme activity was measured by Asan Pharmaceutical kit prepared according to the method of Kim et al. (2005) [Kim NY, Lee MK, Park MJ, Kim SJ, Park HJ, Choi JW, Kim SH, Cho SY, Lee JS. Momordin Ic and oleanolic acid from Kochiae Fructus reduce carbon tetrachloride-induced hepatotoxicity in rats. J Med Food. 2005; 8: 1777-1783.]. Solution A [23.1 mg / ml lithium acetate, 24.2 mg / ml tris (hydroxymethyl) aminomethane] and Solution B [57.4 mg / ml NAD, 0.034 mg / ml 1'-methoxy-5'-methylphenazinium Methyl sulfate (1'-methoxy-5'-methylphenazinium methylsulfate; phenazine methosulfate (PMS))] was mixed in the same volume and left for 5 minutes at 37 ℃. This was mixed with a homogeneous solution (100-300 mL protein) and left at 37 ° C. for 10 minutes, and then 0.4N HCl was added to stop the reaction. The absorbance was measured at 570 nm and the activity was calculated according to the standard calibration curve.
D-갈락토사민에 의해 유도된 간손상에서 본 발명의 펙토리나린 및 펙토리나리게닌의 AST, ALT, ALP 및 LDH 효소 활성도는 표 1에 나타내었다.Table 1 shows the AST, ALT, ALP and LDH enzyme activities of the fentorinarin and fentorariginine of the present invention in liver damage induced by D-galactosamine.
※ 같은 활자가 뒤이어 오는 값은 유의적으로 차이가 없다(p<0.05).※ There is no significant difference between the values following the same letter (p <0.05).
표 1에 나타난 바와 같이, D-갈락토사민에 의해 유도된 간손상에서 본 발명의 펙토리나린은 각각 10mg/kg 및 20mg/kg에서 AST 효소 활성 억제율이 16.5%와 31.7%이고, ALT 효소 활성 억제율은 23.3%와 32.3%이며, ALP 효소 활성 억제율은 14.5%와 31.5%이고, LDH 효소 활성 억제율은 39.6%와 53.2%를 나타내었다. 또한 펙토리나리게닌의 AST, ALT, ALP 및 LDH 효소 활성 억제율은 펙토리나린 보다 약하지만 거의 같은 효과를 나타내었다.As shown in Table 1, in the liver damage induced by D-galactosamine, the fentorinine of the present invention has inhibition rates of AST enzyme activity of 16.5% and 31.7% at 10 mg / kg and 20 mg / kg, respectively, and ALT enzyme inhibition rate. Were 23.3% and 32.3%, and the inhibition rate of ALP enzyme activity was 14.5% and 31.5%, and the inhibition rate of LDH enzyme activity was 39.6% and 53.2%. In addition, the inhibition rate of AST, ALT, ALP, and LDH enzyme activity of pectorinaligin was weaker than that of pectorinarin, but showed almost the same effect.
5. 효소 활성 측정 - 항산화 효과5. Determination of Enzyme Activity-Antioxidant Effect
산화적 스트레스는 D-갈락토사민 투여시 간세포 손상에서 나타나는 일차적인 요인으로 활성산소종(reactive oxygen species, ROS)이 in vivo(Yoshikawa 등, 1982)와 in vitro(Quintero 등, 2002)에서 간접적으로 증가함이 보고되었다. 특히 이러한 활성산소종의 증가는 세포 내 지질을 산화시키거나 GSH 뿐만 아니라 GSH 합성관련 효소를 포함하는 항산화방어시스템에 영향을 미치게 된다. D-갈락토사민에 의해 GSH 수준감소는 GSH 합성억제에 의한 것으로, GSH 합성에 관련된 효소의 감소와 GSH 분해에 관련된 효소의 증가로 일어나는 것으로 보고되었다(McMillan and Jollow 1992).Oxidative stress is the primary cause of hepatocellular injury when D-galactosamine is administered. Inactive oxygen species (ROS) indirectly in vivo (Yoshikawa et al., 1982) and in vitro (Quintero et al., 2002). An increase was reported. In particular, the increase of reactive oxygen species may affect the antioxidant defense system that oxidizes intracellular lipids or contains enzymes related to GSH as well as GSH synthesis. D-galactosamine has been reported to decrease GSH levels by inhibiting GSH synthesis, resulting in a decrease in enzymes involved in GSH synthesis and an increase in enzymes involved in GSH degradation (McMillan and Jollow 1992).
5-1. 과산화지질의 함량 측정5-1. Measurement of Lipid Peroxide Content
Ohkawa 등(1979)의 방법에 따라 지질의 산화 정도는 TBARS(thiobarbituric acid reactive substances)를 이용하여 측정하였다[Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979; 95: 351-358.]. 0.9% NaCl이 포함된 10%의 간균질액 0.4㎖에 1.5㎖의 8.1% SDS, 1.5㎖의 20% 아세테이트 완충용액(pH 3.5) 및 1.5㎖의 0.8% TBA 용액을 첨가한 후 95℃에서 1시간 가열하였다. 반응액을 실온에서 냉각시킨 후 5.0㎖의 n-부탄올-피리딘(15:1)을 첨가하여 추출하고, n-부탄올-피리딘층을 532nm에서 TBARS 양을 측정하여 말론디알데히드(malondialdehyde) nmole/mg protein으로 표시하였다.According to the method of Ohkawa et al. (1979), the degree of oxidation of lipids was measured using thiobarbituric acid reactive substances (TBARS) [Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979; 95: 351-358. To 0.4 ml of 10% homogenate containing 0.9% NaCl, 1.5 ml of 8.1% SDS, 1.5 ml of 20% acetate buffer (pH 3.5) and 1.5 ml of 0.8% TBA solution were added. Heated. After the reaction solution was cooled to room temperature, 5.0 mL of n-butanol-pyridine (15: 1) was added thereto, and the n-butanol-pyridine layer was measured by measuring the amount of TBARS at 532 nm. It is expressed as protein.
5-2. 5-2. GSHGSH (( glutathioneglutathione )의 측정) Measurement
Gaitonde 등(1967)의 방법을 변형하여 비단백질 결합-SH에서 시스테인-SH로 변화된 정도를 측정하였다[Gaitonde MK. A spectrophotometric method for the direct determination of cysteine in the presence of other naturally occurring amino acids. Biochem J. 1967; 104: 627-633.]. 10% 트리클로로아세트산 (trichloroacetic acid)을 균질액에 가하여 원심분리하였다. 0.5㎖의 아세트산과 0.5㎖의 닌히드린(ninhydrin) 시약을 상층액에 첨가한 후 10분간 가열하고 냉각시켰다. 그 다음 즉시 3㎖의 에탄올을 첨가하여 412 nm에서 GSH 양을 결정하였다.The method of Gaitonde et al. (1967) was modified to measure the degree of change from nonprotein binding-SH to cysteine-SH [Gaitonde MK. A spectrophotometric method for the direct determination of cysteine in the presence of other naturally occurring amino acids. Biochem J. 1967; 104: 627-633. 10% trichloroacetic acid was added to the homogenate and centrifuged. 0.5 ml of acetic acid and 0.5 ml of ninhydrin reagent were added to the supernatant, followed by heating and cooling for 10 minutes. Then immediately 3 ml of ethanol was added to determine the amount of GSH at 412 nm.
5-3. 5-3. GSTGST (( glutathioneglutathione -S--S- transferasetransferase )의 측정) Measurement
Habig와 Jakoby(1981)의 방법에 따라 GST 효소 활성을 측정하였다[Habig WH, Jakoby WB. Glutathione S-transferases (rat and human). Methods Enzymol. 1981; 77: 218-231.]. 2.5㎖의 0.1M 인산나트륨 완충용액(pH 7.4)과 0.1㎖의 뒤-미토콘드리아 상층액(post-mitochondrial supernatant) (10% wt/vol)을 총 부피의 3.0㎖가 되도록 반응액을 만들었다. 340 nm에서 흡광도를 측정하고 효소 활성도를 1-클로로-2,4-디니트로벤젠의 nanomole 흡광계수(9.6×103/M/㎝)를 이용하여 산정하였다.GST enzyme activity was measured according to the method of Habig and Jakoby (1981) [Habig WH, Jakoby WB. Glutathione S-transferases (rat and human). Methods Enzymol. 1981; 77: 218-231. The reaction solution was made up to 2.5 ml of 0.1 M sodium phosphate buffer (pH 7.4) and 0.1 ml of post-mitochondrial supernatant (10% wt / vol) to a total volume of 3.0 ml. The absorbance was measured at 340 nm and the enzyme activity was calculated using the nanomole absorption coefficient (9.6 × 10 3 / M / cm) of 1-chloro-2,4-dinitrobenzene.
5-4. 5-4. GRGR (( glutathioneglutathione reductasereductase )의 측정) Measurement
Mize와 Langdon(1962)의 방법에 따라 GR 효소 활성을 측정하였다[Mize CE, Langdon RG. Hepatic glutathione reductase. I. Purification and general kinetic properties. J Biol Chem. 1962; 237: 1589-1595.]. 3.5㎖의 반응액[0.1M 포타슘 포스페이트 완충용액(potassium phosphate buffer, pH 7.5), 0.94 mM EDTA, 4.6 mM 산화된 글루타치온, 0.16 mM NADPH]과 간균질액(100~300 ㎖ 단백질)을 섞어 37℃에서 10분간 반응시켰다. 340 nm에서 흡광도를 측정하여 NADPH의 변화량으로 계산하였다.GR enzyme activity was measured according to the method of Mize and Langdon (1962) [Mize CE, Langdon RG. Hepatic glutathione reductase. I. Purification and general kinetic properties. J Biol Chem. 1962; 237: 1589-1595.]. Mix 3.5 ml reaction solution [0.1 M potassium phosphate buffer (pH 7.5), 0.94 mM EDTA, 4.6 mM oxidized glutathione, 0.16 mM NADPH] and homogenate (100-300 ml protein) at 37 ° C. The reaction was carried out for 10 minutes. Absorbance was measured at 340 nm and calculated as the change in NADPH.
5-5. 5-5. GCSGCS (γ-(γ- glutamylcysteineglutamylcysteine synthetasesynthetase )의 측정) Measurement
Richman와 Meister(1975)의 방법에 따라 GCS 효소 활성을 측정하였다 [Richman PG, Meister A. Regulation of gamma-glutamyl-cysteine synthetase by nonallosteric feedback inhibition by glutathione. J Biol Chem. 1975; 250: 1422-1426.]. 3.5㎖의 반응액[0.1M 트리스·HCl 완충용액(pH 8.0), 8.9 mM L-글루탐산, 0.94 mM EDTA, 3.2 mM MgCl2, 1.35 mM ATP]과 간균질액(100~300 ㎖ 단백질)을 섞어 37℃에서 30분간 반응시켰다. 600 nm에서 흡광도를 측정하여 표준 검량선으로 계산하였다.GCS enzyme activity was measured according to the method of Richman and Meister (1975) [Richman PG, Meister A. Regulation of gamma-glutamyl-cysteine synthetase by nonallosteric feedback inhibition by glutathione. J Biol Chem. 1975; 250: 1422-1426.]. Mix 3.5 mL of reaction solution [0.1M Tris-HCl buffer (pH 8.0), 8.9 mM L-glutamic acid, 0.94 mM EDTA, 3.2 mM MgCl 2 , 1.35 mM ATP] and homogenate (100-300 mL protein) 37 It was made to react at 30 degreeC. Absorbance was measured at 600 nm and calculated with a standard calibration curve.
5-6. 5-6. SODSOD (( superoxidesuperoxide dismutasedismutase )의 측정) Measurement
Marklund S.와 Marklund G.(1974)의 방법에 따라 SOD 효소 활성을 측정하였다[Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem. 1974; 47: 469-474.]. 1㎖의 시토크롬 c 용액(0.2 M 포타슘 포스페이트 완충용액(pH 8.6), 0.1 mM EDTA)을 얼음 욕조에 20분간 방치하였다. 0.5㎖의 염기성 DMSO 또는 비염기성 DMSO를 혼합하여 37℃에서 30분간 방치하였다. 550 nm에서 환원된 시토크롬 c를 측정하였으며, 활성도는 환원된 시토크롬 c가 50% 억제되는 것을 1 unit로 정의하였다.SOD enzyme activity was measured according to the methods of Marklund S. and Marklund G. (1974). Eur J Biochem. 1974; 47: 469-474. 1 ml of cytochrome c solution (0.2 M potassium phosphate buffer (pH 8.6), 0.1 mM EDTA) was left in an ice bath for 20 minutes. 0.5 ml of basic DMSO or non-basic DMSO was mixed and left at 37 ° C. for 30 minutes. Reduced cytochrome c was measured at 550 nm, and activity was defined as 1 unit that 50% inhibition of reduced cytochrome c was suppressed.
D-갈락토사민에 의해 유도된 간손상에서 본 발명의 펙토리나린 및 펙토리나리게닌의 과산화지질의 함량은 도 1에 나타내었으며, GSH, GST, GR, GCS 및 SOD 효소 활성도는 표 2에 나타내었다.In the liver damage induced by D-galactosamine, the contents of lipid peroxides of fentorinarin and fentorariginine of the present invention are shown in FIG. 1, and GSH, GST, GR, GCS and SOD enzyme activities are shown in Table 2. .
※ 같은 활자가 뒤이어 오는 값은 유의적으로 차이가 없다(p<0.05).※ There is no significant difference between the values following the same letter (p <0.05).
도 1에 나타난 바와 같이, 본 발명의 펙토리나린 및 펙토리나리게닌은 D-갈락토사민에 의해 유도된 간손상에서 과산화지질 지표인 말론디알데히드의 양을 낮추어, 지질 산화를 억제함을 알 수 있다.As shown in FIG. 1, it can be seen that the factorinarin and the factorinariginin of the present invention lower the amount of malondialdehyde, an indicator of lipid peroxide in liver damage induced by D-galactosamine, thereby inhibiting lipid oxidation. .
또한 표 2에 나타난 바와 같이, D-갈락토사민에 의해 유도된 간손상에서 본 발명의 펙토리나린 및 펙토리나리게닌은 각각 10mg/kg 및 20mg/kg에서 GR, GCS 효소를 활성화시켜 D-갈락토사민에 의한 GSH의 감소를 억제하였다. 또한, 본 발명의 펙토리나린은 각각 10mg/kg 및 20mg/kg에서 GST 활성이 34.4%와 44.6%, SOD 활성은 40.7%와 50.0%를 증가시켰다. 또한 펙토리나리게닌의 GST 및 SOD 효소 활성은 펙토리나린 보다 약하지만 거의 같은 효과를 나타내었다.In addition, as shown in Table 2, in the liver damage induced by D-galactosamine, the fentorinarine and fentorarigenin of the present invention activates the enzymes GR and GCS at 10 mg / kg and 20 mg / kg, respectively, to D-galacto Inhibition of GSH by samine was inhibited. In addition, the Fectorinarin of the present invention increased the GST activity of 34.4% and 44.6%, SOD activity of 40.7% and 50.0% at 10mg / kg and 20mg / kg, respectively. In addition, the GST and SOD enzyme activity of efectorariginine was weaker than that of efectorinarin, but showed almost the same effect.
따라서, 본 발명의 펙토리나린 및 펙토리나리게닌은 D-갈락토사민에 의해 유도된 간손상에서 간보호 효과 및 항산화 효과가 우수함을 알 수 있다.Therefore, it can be seen that the fentorinarin and fentorariginine of the present invention have excellent hepatoprotective and antioxidant effects in liver damage induced by D-galactosamine.
하기에 본 발명의 조성물을 위한 제제예를 예시한다.Examples of preparations for the compositions of the present invention are illustrated below.
제제예Formulation example 1 One : 약학적 제제의 제조 : Preparation of Pharmaceutical Formulations
1. 산제의 제조1. Preparation of powder
펙토리나린(또는 펙토리나리게닌) 2g2 g of fentorinarin (or fentorariginine)
유당 1g1g lactose
상기의 성분을 혼합하고 기밀포에 충진하여 산제를 제조하였다.The above ingredients were mixed and filled in airtight cloth to prepare a powder.
2. 정제의 제조2. Preparation of Tablets
펙토리나린(또는 펙토리나리게닌) 100㎎Pectorinarin (or Pectorinarigin) 100mg
옥수수전분 100㎎Corn Starch 100mg
유 당 100㎎Lactose 100mg
스테아린산 마그네슘 2㎎2 mg magnesium stearate
상기의 성분을 혼합한 후, 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조하였다.After mixing the above components, tablets were prepared by tableting according to a conventional method for producing tablets.
3. 캡슐제의 제조3. Preparation of Capsule
펙토리나린(또는 펙토리나리게닌) 100㎎Pectorynarine (or Pectoryriginin) 100mg
옥수수전분 100㎎Corn Starch 100mg
유 당 100㎎Lactose 100mg
스테아린산 마그네슘 2㎎2 mg magnesium stearate
상기의 성분을 혼합한 후, 통상의 캡슐제의 제조방법에 따라서 젤라틴 캡슐에 충전하여 캡슐제를 제조하였다.After mixing the above components, the capsule was prepared by filling in gelatin capsules according to the conventional method for producing a capsule.
제제예Formulation example 2 2 : 식품의 제조 : Manufacture of food
1. 조리용 양념의 제조1. Preparation of Cooking Seasonings
펙토리나린(또는 펙토리나리게닌) 20~95 중량%로 건강 증진용 조리용 양념을 제조하였다.20% to 95% by weight of fentorinarin (or fentorrigininin) was prepared for health promotion cooking seasoning.
2. 토마토 케찹 및 소스의 제조2. Preparation of Tomato Ketchup and Sauce
펙토리나린(또는 펙토리나리게닌) 0.2~1.0 중량%를 토마토 케찹 또는 소스에 첨가하여 건강 증진용 토마토 케찹 또는 소스를 제조하였다.Health-promoting tomato ketchup or sauce was prepared by adding 0.2-1.0 wt% of fentorinarin (or factorinariginin) to tomato ketchup or sauce.
3. 밀가루 식품의 제조3. Manufacturing of Flour Foods
펙토리나린(또는 펙토리나리게닌) 0.5~5.0 중량%를 밀가루에 첨가하고, 이 혼합물을 이용하여 빵, 케이크, 쿠키, 크래커 및 면류를 제조하여 건강 증진용 식품을 제조하였다.0.5 to 5.0% by weight of fentorinarin (or fentorariginine) was added to the flour, and bread, cake, cookies, crackers and noodles were prepared using this mixture to prepare health-promoting foods.
4. 스프 및 육즙(gravies)의 제조4. Preparation of soups and gravy
펙토리나린(또는 펙토리나리게닌) 0.1~5.0 중량%를 스프 및 육즙에 첨가하여 건강 증진용 육가공 제품, 면류의 수프 및 육즙을 제조하였다.0.1-5.0% by weight of fentorinarin (or fentorariginine) was added to soups and gravy to prepare health-producing meat products, soups of noodles and gravy.
5. 그라운드 비프(ground beef)의 제조5. Preparation of Ground Beef
펙토리나린(또는 펙토리나리게닌) 10 중량%를 그라운드 비프에 첨가하여 건강 증진용 그라운드 비프를 제조하였다.Health promoting ground beef was prepared by adding 10% by weight of fentorinarin (or fentorariginine) to the ground beef.
6. 유제품(dairy products)의 제조6. Manufacture of Dairy Products
펙토리나린(또는 펙토리나리게닌) 5~10 중량%를 우유에 첨가하고, 상기 우유를 이용하여 버터 및 아이스크림과 같은 다양한 유제품을 제조하였다.5-10% by weight of fentorinarin (or fentorariginine) was added to milk, and the milk was used to prepare various dairy products such as butter and ice cream.
제제예Formulation example 3 3 : 음료의 제조 : Preparation of Beverages
1. 탄산음료의 제조1. Preparation of carbonated drinks
설탕 5~10%, 구연산 0.05~0.3%, 카라멜 0.005~0.02%, 비타민 C 0.1~1%의 첨가물을 혼합하고, 여기에 79~94%의 정제수를 섞어서 시럽을 만들고, 상기 시럽을 85~98℃에서 20~180초간 살균하여 냉각수와 1:4의 비율로 혼합한 다음 탄산가스를 0.5~0.82%를 주입하여 본 발명의 펙토리나린(또는 펙토리나리게닌)을 함유하는 탄산음료를 제조하였다.5-10% of sugar, 0.05-0.3% citric acid, 0.005-0.02% caramel, 0.1-1% of vitamin C are mixed, and 79-94% purified water is mixed to make syrup, and the syrup is 85-98 After sterilizing at 20 ° C. for 20 seconds to 180 seconds, the mixture was mixed with cooling water at a ratio of 1: 4, and then 0.5 to 0.82% of carbon dioxide was injected to prepare a carbonated beverage containing fentorinarin (or fentorariginine) of the present invention.
2. 건강음료의 제조2. Manufacture of health drinks
액상과당(0.5%), 올리고당(2%), 설탕(2%), 식염(0.5%), 물(75%)과 같은 부재료와 펙토리나린(또는 펙토리나리게닌)을 균질하게 배합하여 순간 살균을 한 후 이를 유리병, 패트병 등 소포장 용기에 포장하여 건강음료를 제조하였다.Instant sterilization by homogeneous mixing of ingredients such as liquid fructose (0.5%), oligosaccharide (2%), sugar (2%), salt (0.5%) and water (75%) After that, it was packaged in small packaging containers such as glass bottles and plastic bottles to prepare healthy drinks.
3. 야채쥬스의 제조3. Preparation of Vegetable Juice
펙토리나린(또는 펙토리나리게닌) 5g을 토마토 또는 당근 쥬스 1,000㎖에 가하여 건강 증진용 야채쥬스를 제조하였다.Health supplement vegetable juice was prepared by adding 5 g of factorinarin (or factorinariginin) to 1,000 ml of tomato or carrot juice.
4. 과일쥬스의 제조4. Preparation of Fruit Juice
펙토리나린(또는 펙토리나리게닌) 1g을 사과 또는 포도 쥬스 1,000㎖에 가하여 건강 증진용 과일쥬스를 제조하였다.Health supplement fruit juice was prepared by adding 1 g of ectorinarin (or ecterinariginin) to 1,000 ml of apple or grape juice.
본 발명의 펙토리나린 및 펙토리나리게닌은 D-갈락토사민에 의해 유도된 간손상에서 AST, ALT, ALP 및 LDH의 농도를 감소시키고, 과산화지질 지표인 말론디알데히드의 양을 낮추어 지질 산화를 억제하며, GSH, GR, GCS, GST 및 SOD의 농도를 증가시킴으로써 간보호 효과와 항산화 효과가 우수하다. 따라서, 본 발명의 펙토리나린 및 펙토리나리게닌은 간보호용 의약품 및 건강식품으로 유용하게 사용될 수 있다.Fectorinarin and Fectorinarigenin reduce the concentration of AST, ALT, ALP and LDH in D-galactosamine-induced liver damage and lower the amount of malondialdehyde, which is an indicator of lipid peroxide, to inhibit lipid oxidation In addition, by increasing the concentration of GSH, GR, GCS, GST and SOD, hepatoprotective and antioxidant effects are excellent. Therefore, the fentorinarin and fentorariginine of the present invention can be usefully used as a medicine for liver protection and health food.
도 1은 D-갈락토사민에 의해 유도된 간손상에서 본 발명의 펙토리나린 및 펙토리나리게닌의 과산화지질의 함량을 나타낸 도이다.Figure 1 is a diagram showing the content of lipid peroxide of the fentorinarin and fentorariginine of the present invention in liver damage induced by D-galactosamine.
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