KR100479736B1 - A food for preventing fatty liver comprising powdered-mixture or an extract from natural herbs - Google Patents
A food for preventing fatty liver comprising powdered-mixture or an extract from natural herbs Download PDFInfo
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- KR100479736B1 KR100479736B1 KR10-2002-0037063A KR20020037063A KR100479736B1 KR 100479736 B1 KR100479736 B1 KR 100479736B1 KR 20020037063 A KR20020037063 A KR 20020037063A KR 100479736 B1 KR100479736 B1 KR 100479736B1
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- Prior art keywords
- mixed powder
- mixtures
- liver
- cholesterol
- leaves
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Classifications
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/20—Natural extracts
- A23V2250/21—Plant extracts
- A23V2250/212—Garlic
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/20—Natural extracts
- A23V2250/21—Plant extracts
- A23V2250/2124—Ginseng
Abstract
본 발명은 천연 식물체 유래의 혈중 지질농도 관련 질환과 간질환의 예방 및 치료용 혼합분말, 추출물 및 이를 포함하는 식품으로서, 인삼; 마늘; 대추; 양파; 감잎; 귤피; 구기자꽃, 잎 또는 이의 혼합물; 메밀꽃, 잎 또는 이의 혼합물을 수세건조후 분말화하여 혼합분말을 제조하거나 또는 인삼; 마늘; 대추; 양파; 감잎; 귤피; 구기자꽃, 잎 또는 이의 혼합물; 메밀꽃, 잎 또는 이의 혼합물을 혼합하여 열수추출하여 혼합 추출물을 얻은 후 상기 혼합분말을 스프라그 다우리 흰쥐에게 투여하여 혈중 총콜레스테롤, HDL-콜레스테롤 및 중성 지질 함량을 측정함으로써 심장순환기 질환발생 억제효과를 확인하고, 상기 쥐의 혈장 GOT 및 GPT를 측정하여 간질환의 예방 및 치료효과를 확인한 뒤 상기 혼합분말을 토끼에 투여하여 대동맥내의 지방선을 분석하여 동맥경화 억제 효과를 확인한 다음, 상기 토끼의 간내 지방함유세포의 분포비율을 측정하여 지방간 형성 저해력을 확인하고, 본 발명 혼합 분말의 경구독성시험을 실시한 뒤 상기 혼합분말 또는 추출물을 포함하는 식품을 제조함으로써, 혈중 콜레스테롤 및 중성 지질 농도를 크게 낮추며 동맥 내피에 대식세포-지질층이 침착되는 것을 강력이 억제하고 간 세포의 손상 및 지방간화를 강력히 억제하는 혈중 지질농도 관련 질환과 간질화의 예방 및 치료 효과가 있는 식품을 제공하는 뛰어난 효과가 있다.The present invention is a mixed powder, extract and food comprising the same for preventing and treating blood lipid concentration-related diseases and liver diseases derived from natural plants, ginseng; garlic; Jujube; onion; Persimmon leaf; Tangerines; Wolfberry, leaves or mixtures thereof; Buckwheat flowers, leaves or mixtures thereof are washed with water and dried to make powdered powder or ginseng; garlic; Jujube; onion; Persimmon leaf; Tangerines; Wolfberry, leaves or mixtures thereof; Buckwheat flowers, leaves or mixtures thereof were extracted with hot water to obtain a mixed extract, and then the mixed powder was administered to Sprague Dawley rats to measure the total cholesterol, HDL-cholesterol and neutral lipids in the blood to inhibit the cardiovascular disease. After confirming the effect of preventing and treating liver disease by measuring the plasma GOT and GPT of the rat, the mixed powder was administered to the rabbit to analyze the fatty gland in the aorta to confirm the inhibitory effect of atherosclerosis, and then to the intrahepatic fat of the rabbit. By measuring the distribution ratio of the containing cells to determine the inhibitory effect of fatty liver formation, and after performing the oral toxicity test of the mixed powder of the present invention by preparing a food containing the mixed powder or extract, blood cholesterol and neutral lipids significantly lower the blood artery Hepatic cells that strongly inhibit the deposition of macrophage-lipid layers on the endothelium There are excellent effect of providing food is the prevention and treatment of liver damage and Tuesday strongly suppressed serum lipid levels related diseases and epilepsy Tuesday to.
Description
본 발명은 천연 식물체 유래의 혈중 지질농도 관련 질환과 간질환의 예방 및 치료용 혼합분말, 추출물 및 이를 포함하는 식품에 관한 것이다. 더욱 상세하게는, 본 발명은 천연 식물체를 일정비율로 혼합하여 제조한 혈중 지질농도 관련 질환과 간질환의 예방 및 치료용 혼합분말과 천연 식물체를 혼합하여 열수 추출하여 얻은 혈중 지질농도 관련 질환과 간질환의 예방 및 치료용 추출물 및 상기 혼합분말 또는 추출물을 함유하는 식품에 관한 것이다.The present invention relates to a mixed powder, extract and food comprising the same for preventing and treating blood lipid concentration-related diseases and liver diseases derived from natural plants. More specifically, the present invention is a blood lipid concentration-related disease and liver blood lipid concentration-related diseases prepared by mixing a natural plant with a certain ratio and liver lipid disease-related disease and liver obtained by hot water extraction It relates to extracts for the prevention and treatment of diseases and foods containing the mixed powder or extract.
관상동맥성 심혈관 질환은 현재 모든 사망원인의 30% 이상을 차지하고 있으며 미국, 유럽 등 선진국에서는 심각한 문제가 되고 있다. 한편 개발도상국에서도 식생활의 서구화, 운동부족 등의 영향을 받아 심장병이 증가하고 있는 추세에 있다. 혈중 콜레스테롤의 양이 높을 경우 혈관벽에 지방과 더불어 대식세포(macrophage), 포말세포(foam cell) 등이 생성 침착되고 플라크(plaque)를 형성하여 혈액순환을 저해하는 동맥경화증세가 오기 쉬운 것으로 알려져 있다(Ross, R., Nature, 362, 801-809(1993)).Coronary cardiovascular disease currently accounts for more than 30% of all deaths and is a serious problem in developed countries such as the United States and Europe. Meanwhile, in developing countries, heart disease is on the rise due to westernization of diet and lack of exercise. If the amount of cholesterol in the blood is high, macrophage, foam cells, etc. are formed and deposited in the blood vessel walls, and plaques are formed, and atherosclerosis, which inhibits the blood circulation, is known to be prone to occur. Ross, R., Nature, 362 , 801-809 (1993)).
혈중 콜레스테롤의 양을 줄이는 방법중의 하나는 콜레스테롤의 흡수를 억제하는 방법이 있다. 아실코에이:콜레스테롤-o-아실트랜스퍼레이즈(acyl CoA: cholesterol-o-acyltransferase, ACAT)는 인체조직 속에서 콜레스테롤을 콜레스테릴 에스터로 전환시켜주는 효소이다. 실험적이나 임상학적인 동맥경화 현상에서 대식세포(macrophage)나 평활근(smooth muscle) 세포 유래 포말세포들의 형성은 아주 중요한 인자이다. 포말세포들은 ACAT 작용에 의해 형성되고 혈액 속의 LDL에 의해 운반되는 콜레스테롤 에스터를 많이 함유하고 있다. 동맥 혈관 벽에 있는 포말세포들은 ACAT 활성의 증가와 더불어 발견되는 경우가 많기 때문에, ACAT 저해제는 동맥경화 예방제가 될 가능성이 높다. 또한 간 속의 ACAT 활성을 저해 할 경우 혈액속에 유통되는 LDL-콜레스테롤 수준을 낮출 수 있을 것이다(Witiak, D. T. and D. R. Feller(eds), Anti lipidemic Drugs: Medicinal, Chemical, and Biochemical Aspects, Elsevier, pp159-195(1991)).One way to reduce the amount of cholesterol in the blood is to inhibit the absorption of cholesterol. Acyl CoA: Cholesterol-o-acyltransferase (ACL) is an enzyme that converts cholesterol into cholesteryl esters in human tissues. The formation of macrophage or smooth muscle cell-derived foam cells is an important factor in experimental and clinical atherosclerosis. Foam cells contain large amounts of cholesterol esters formed by ACAT and carried by LDL in the blood. Because foam cells in the arterial vessel walls are often found with increased ACAT activity, ACAT inhibitors are likely to be protective agents of atherosclerosis. Inhibition of ACAT activity in the liver may also lower LDL-cholesterol levels in the blood (Witiak, DT and DR Feller (eds), Anti lipidemic Drugs: Medicinal, Chemical, and Biochemical Aspects , Elsevier, pp159-195 (1991)).
혈중 콜레스테롤의 양을 줄이는 다른 방법으로는 지단백질간에 콜레스테롤 전이를 매개하는 콜레스테롤 에스터 전달 단백질(cholesterol ester transfer protein, CETP)의 작용을 억제하거나 간에서 콜레스테롤 생합성에 관련하는 효소인 3-하이드록시-3-메틸글루타릴 조효소 A(HMG-CoA) 환원효소의 작용을 억제하는 방법등이 있다. HMG-CoA 환원효소는 스테롤이나 이소프레노이드계 화합물의 생합성 경로의 중간단계인 메발론산(mevalonic acid) 합성을 매개하는 효소로, 이 효소의 활성을 감소시킬 경우 콜레스테롤의 생합성 속도를 늦추어 고콜레스테롤혈증(hypercholesterolemia) 치료에 효과적으로 이용될 수 있다(William, W. P., Cardiovascular Pharmacology, Kanu Chatterjee(ed), Wolfe Pullishing, 8.6-8.7 (1994)). 현재 사용되고 있는 HMG-CoA 환원효소 활성 저해제는 페니실리움 속 또는 아스퍼질러스 속에서 유래된 것으로 미국 메르크사가 개발한 로바스타틴(lovastatin)과 심바스타틴(simvastatin) 및 일본 산쿄사가 개발한 프라바스타틴(pravastatin) 등이 있다. 그러나 스타틴(statin)류가 중추신경계에 부작용을 주고(Saheki, A.T. et al., Pharm. Res., 11, 304-311 (1994)), 로바스타틴과 심바스타틴은 간의 LDL 수용체의 활성을 증가시킴으로써 혈중 LDL 콜레스테롤을 낮추지만 여러 효소의 양 증가, 크레아틴 키나제(creatine kinase)의 증가, 횡문근변성(rhabdomyolysis) 등의 부작용이 있는 것으로 보고되고 있다(Farmer, J.A. et al., Baillers-clin. Endocrinol. Metab., 9, 825-847 (1995)).Other ways to reduce the amount of cholesterol in the blood include 3-hydroxy-3-, an enzyme that inhibits the action of cholesterol ester transfer protein (CETP) that mediates cholesterol transfer between lipoproteins or is involved in cholesterol biosynthesis in the liver. There is a method for inhibiting the action of methyl glutaryl coenzyme A (HMG-CoA) reductase. HMG-CoA reductase is an enzyme that mediates the synthesis of mevalonic acid, an intermediate step in the biosynthetic pathway of sterols and isoprenoid compounds. Hypercholesterolemia is caused by slowing the rate of cholesterol synthesis by decreasing the activity of this enzyme. (hypercholesterolemia) can be used effectively (William, WP, Cardiovascular Pharmacology , Kanu Chatterjee (ed), Wolfe Pullishing, 8.6-8.7 (1994)). HMG-CoA reductase activity inhibitors currently in use are derived from the genus Penicillium or Aspergillus, such as lovastatin and simvastatin developed by Merck, USA, and pravastatin, developed by Sankyo, Japan. There is this. However, statins have adverse effects on the central nervous system (Saheki, AT et al., Pharm. Res. , 11 , 304-311 (1994)), and lovastatin and simvastatin increase LDL receptor activity in the blood by increasing liver LDL receptor activity. Although it lowers cholesterol, it has been reported to have side effects such as increased amount of various enzymes, increased creatine kinase, and rhabdomyolysis (Farmer, JA et al., Baillers-clin. Endocrinol. Metab ., 9 , 825-847 (1995)).
한편, 간은 지방 성분이 포함된 음식 또는 알콜의 과다 섭취, 및 B형 또는 C형 간염 바이러스의 감염에 의해 그 기능이 저하되고, 이 상태가 방치될 경우 간염, 간경변증, 간암 등으로 진행된다. 특히 음식을 통한 과다한 지방 섭취 또는 과도한 알콜 섭취는 간 조직에 지질이 쌓이는 지방간을 유발하며, 이때 혈청 속의 GOT(glutamate-oxaloacetate transaminase), GPT(glutamate-pyruvate transami- nase), γGTP(γ-glutamyl transpeptidase) 등이 증가하게 된다(T. Banciu, et al., Med. Interne., 20, 69-71(1982); 및 A. Par, et al., Acta. Med. Acad. Sci. Hung., 33, 309-319(1976)). 하야시(Hayashi) 등은 녹차 추출액이 쥐 혈청 GOT 및 GPT의 증가를 예방함으로써 쥐 간 기능을 개선한다고 보고하고 있다(M. Hayashi, et al., Nippon Yakuri gaku Zasshi, 100, 391-399(1992)).On the other hand, the liver is deteriorated due to excessive intake of food or alcohol containing fat components and infection of hepatitis B or C virus, and when left untreated, hepatitis, cirrhosis, liver cancer, and the like progress. In particular, excessive fat intake or excessive alcohol intake causes fatty liver to accumulate lipids in liver tissue. (T. Banciu, et al., Med. Interne. , 20 , 69-71 (1982); and A. Par, et al., Acta. Med. Acad. Sci. Hung. , 33) . , 309-319 (1976). Hayashi et al. Report that green tea extract improves rat liver function by preventing an increase in rat serum GOT and GPT (M. Hayashi, et al., Nippon Yakuri gaku Zasshi , 100 , 391-399 (1992). ).
본 발명자들은 이미 바이오플라보노이드인 헤스페리딘, 헤스페레틴, 나린진 및 나린제닌과 이들이 풍부하게 함유된 감귤류 과피 추출물이 혈중 콜레스테롤을 현저하게 감소시키고 ACAT 활성을 저해하며 동맥 내피 표면에 거대세포-지질 복합체가 형성되거나 침착하는 것을 강력히 억제하며 간 질환에 대해 치료 및 예방 효과가 있다는 사실을 발견하여 특허출원한 바 있다(WO98/16220, WO98/16221, 한국 특허출원 제 98-10888 호, 한국 특허출원 제 98-10889 호).The present inventors have already found that the bioflavonoids hesperidin, hesperetin, naringin and naringenin and citrus peel extracts rich in them significantly reduce blood cholesterol, inhibit ACAT activity, and form giant cell-lipid complexes on the arterial endothelial surface. Has been patented and found to have strong therapeutic and preventive effects on liver disease (WO 98/16220, WO 98/16221, Korean Patent Application No. 98-10888, Korean Patent Application No. 98-). 10889).
본 발명자들은 상기와 같은 점을 감안하여 인삼; 마늘; 대추; 양파; 감잎; 귤피; 구기자꽃, 잎 또는 이의 혼합물; 메밀꽃, 잎 또는 이의 혼합물을 건조시켜 분말화하여 일정비율로 혼합하여 혼합분말을 제조하거나 또는 인삼; 마늘; 대추; 양파; 감잎; 귤피; 구기자꽃, 잎 또는 이의 혼합물; 메밀꽃, 잎 또는 이의 혼합물을 혼합하여 열수추출하여 혼합 추출물을 얻은 후 상기 혼합분말을 스프라그 다우리 흰쥐에게 투여하여 혈중 총콜레스테롤, HDL-콜레스테롤 및 중성 지질 함량을 측정함으로써 심장순환기 질환발생 억제효과를 확인하고, 상기 쥐의 혈장 GOT 및 GPT를 측정하여 간질환의 예방 및 치료효과를 확인한 뒤 상기 혼합분말을 토끼에 투여하여 대동맥내의 지방선을 분석하여 동맥경화 억제 효과를 확인한 다음, 상기 토끼의 간내 지방함유세포의 분포비율을 측정하여 지방간 형성 저해력을 확인하고, 본 발명 혼합분말의 경구독성시험을 실시한 뒤 상기 혼합분말 또는 추출물을 포함하는 식품을 제조함으로써 본 발명을 완성하였다.The present inventors in view of the above points ginseng; garlic; Jujube; onion; Persimmon leaf; Tangerines; Wolfberry, leaves or mixtures thereof; Buckwheat flowers, leaves or mixtures thereof are dried and powdered and mixed at a predetermined ratio to prepare a mixed powder or ginseng; garlic; Jujube; onion; Persimmon leaf; Tangerines; Wolfberry, leaves or mixtures thereof; Buckwheat flowers, leaves or mixtures thereof were extracted with hot water to obtain a mixed extract, and then the mixed powder was administered to Sprague Dawley rats to measure the total cholesterol, HDL-cholesterol and neutral lipids in the blood to inhibit the cardiovascular disease. After confirming the effect of preventing and treating liver disease by measuring the plasma GOT and GPT of the rat, the mixed powder was administered to the rabbit to analyze the fatty gland in the aorta to confirm the inhibitory effect of atherosclerosis, and then to the intrahepatic fat of the rabbit. The distribution ratio of the containing cells was measured to confirm the inhibition of fatty liver formation, and after the oral toxicity test of the mixed powder of the present invention, the present invention was completed by preparing a food containing the mixed powder or extract.
따라서, 본 발명의 목적은 천연 식물체를 수세건조후 마쇄하여 얻은 천연 식물체 분말을 일정비율로 혼합하여 제조한 혈중 지질농도 관련 질환과 간질환의 예방 및 치료용 혼합분말을 제공하는 것이다.Accordingly, it is an object of the present invention to provide a mixed powder for preventing and treating blood lipid concentration-related diseases and liver diseases prepared by mixing natural plant powders obtained by grinding natural plants after washing with water at a certain ratio.
본 발명의 다른 목적은 천연 식물체를 혼합하여 열수 추출하여 얻은 혈중 지질농도 관련 질환과 간질환의 예방 및 치료용 추출물을 제공하는 것이다.Another object of the present invention is to provide an extract for the prevention and treatment of blood lipid concentration-related diseases and liver diseases obtained by hot water extraction by mixing natural plants.
본 발명의 또 다른 목적은 천연 식물체의 혼합분말 또는 열수추출물을 유효성분으로 포함하는 식품을 제공하는 것이다.Still another object of the present invention is to provide a food comprising a mixed powder or hot water extract of a natural plant as an active ingredient.
본 발명의 상기 목적은 인삼; 마늘; 대추; 양파; 감잎; 귤피; 구기자꽃, 잎 또는 이의 혼합물; 메밀꽃, 잎 또는 이의 혼합물을 건조시켜 분말화하여 일정비율로 혼합하여 혼합분말을 제조하거나 또는 인삼; 마늘; 대추; 양파; 감잎; 귤피; 구기자꽃, 잎 또는 이의 혼합물; 메밀꽃, 잎 또는 이의 혼합물을 혼합하여 열수추출하여 혼합 추출물을 얻은 후 상기 혼합분말을 스프라그 다우리 흰쥐에게 투여하여 혈중 총콜레스테롤, HDL-콜레스테롤 및 중성 지질 함량을 측정함으로써 심장순환기 질환발생 억제효과를 확인하고, 상기 쥐의 혈장 GOT 및 GPT를 측정하여 간질환의 예방 및 치료효과를 확인한 뒤 상기 혼합분말을 토끼에 투여하여 대동맥내의 지방선을 분석하여 동맥경화 억제 효과를 확인한 다음, 상기 토끼의 간내 지방함유세포의 분포비율을 측정하여 지방간 형성 저해력을 확인하고, 본 발명 혼합분말의 경구독성시험을 실시한 뒤 상기 혼합분말 또는 추출물을 포함하는 식품을 제조함으로써 달성하였다.The object of the present invention is ginseng; garlic; Jujube; onion; Persimmon leaf; Tangerines; Wolfberry, leaves or mixtures thereof; Buckwheat flowers, leaves or mixtures thereof are dried and powdered and mixed at a predetermined ratio to prepare a mixed powder or ginseng; garlic; Jujube; onion; Persimmon leaf; Tangerines; Wolfberry, leaves or mixtures thereof; Buckwheat flowers, leaves or mixtures thereof were extracted with hot water to obtain a mixed extract, and then the mixed powder was administered to Sprague Dawley rats to measure the total cholesterol, HDL-cholesterol and neutral lipids in the blood to inhibit the cardiovascular disease. After confirming the effect of preventing and treating liver disease by measuring the plasma GOT and GPT of the rat, the mixed powder was administered to the rabbit to analyze the fatty gland in the aorta to confirm the inhibitory effect of atherosclerosis, and then to the intrahepatic fat of the rabbit. By measuring the distribution ratio of the containing cells to confirm the inhibition of fatty liver formation, and by performing the oral toxicity test of the mixed powder of the present invention was achieved by preparing a food containing the mixed powder or extract.
이하 본 발명의 구성을 설명한다.Hereinafter, the configuration of the present invention.
본 발명은 인삼; 마늘; 대추; 양파; 감잎; 귤피; 구기자꽃, 잎 또는 이의 혼합물; 메밀꽃, 잎 또는 이의 혼합물을 건조시켜 분말화하여 일정비율로 혼합하여 혼합분말을 제조하는 단계: 인삼; 마늘; 대추; 양파; 감잎; 귤피; 구기자꽃, 잎 또는 이의 혼합물; 메밀꽃, 잎 또는 이의 혼합물을 혼합하여 열수추출하여 혼합 추출물을 얻는 단계: 상기 혼합분말을 스프라그 다우리 흰쥐에게 투여한 후 혈중 총콜레스테롤, HDL-콜레스테롤 및 중성 지질 함량을 측정하여 심장순환기 질환발생 억제효과를 확인하고 상기 쥐의 혈장 GOT 및 GPT를 측정하여 간질환의 예방 및 치료효과를 확인하는 단계: 상기 혼합분말을 토끼에 투여하여 대동맥내의 지방선을 분석하여 동맥경화 억제 효과를 확인하는 단계: 상기 토끼의 간내 지방함유세포의 분포비율을 측정하여 지방간 형성 저해력을 확인하는 단계: 본 발명 혼합분말의 경구독성시험을 실시하는 단계: 상기 혼합분말 또는 추출물을 포함하는 식품을 제조하는 단계로 구성된다.The present invention ginseng; garlic; Jujube; onion; Persimmon leaf; Tangerines; Wolfberry, leaves or mixtures thereof; Drying buckwheat flowers, leaves or mixtures thereof, powdering and mixing at a predetermined ratio to prepare a mixed powder: ginseng; garlic; Jujube; onion; Persimmon leaf; Tangerines; Wolfberry, leaves or mixtures thereof; Obtaining a mixed extract by hot water extraction by mixing buckwheat flowers, leaves or mixtures thereof: After administration of the mixed powder to Sprague Dawley rats, the content of blood total cholesterol, HDL-cholesterol and neutral lipids is measured to suppress cardiovascular disease. Confirming the effect and confirming the prevention and treatment effect of liver disease by measuring the plasma GOT and GPT of the rat: administering the mixed powder to the rabbit to analyze the fatty gland in the aorta to confirm the effect of inhibiting atherosclerosis: Determining the inhibitory ability of fatty liver formation by measuring the distribution ratio of the liver-containing fat cells in rabbits: Performing an oral toxicity test of the mixed powder of the present invention: Comprising the step of preparing a food containing the mixed powder or extract .
본 발명에서는 인삼; 마늘; 대추; 양파; 감잎; 귤피; 구기자꽃, 잎 또는 이의 혼합물; 메밀꽃, 잎 또는 이의 혼합물을 수세건조시킨 후 분말화하여 얻은 혼합분말 또는 상기 천연 식물체의 혼합물의 열수추출물을 활성성분으로서 약학적으로 허용되는 담체와 함께 포함되는 혈중 중성지방 및 콜레스테롤 농도 저하를 통하여 동맥경화 예방 및 치료와 및 간 기능 보호용 약학 조성물이 제공된다. 또한, 인삼; 마늘; 대추; 양파; 감잎; 귤피; 구기자꽃, 잎 또는 이의 혼합물; 메밀꽃, 잎 또는 이의 혼합물을 수세건조시킨 후 분말화하여 얻은 혼합분말 또는 상기 천연 식물체의 혼합물의 열수추출물을 활성성분으로서 포함하는 혈중 중성지방 및 콜레스테롤 농도 저하를 통하여 동맥경화 예방 및 치료와 간 기능 보호용 식품 조성물 및 음료 조성물이 제공된다.In the present invention, ginseng; garlic; Jujube; onion; Persimmon leaf; Tangerines; Wolfberry, leaves or mixtures thereof; Washing and drying the buckwheat flowers, leaves or mixtures thereof, and powdered mixed powders or hot water extracts of the mixtures of the natural plant as an active ingredient to reduce the concentration of triglycerides and cholesterol in the blood Pharmaceutical compositions for preventing and treating sclerosis and for protecting liver function are provided. Also, ginseng; garlic; Jujube; onion; Persimmon leaf; Tangerines; Wolfberry, leaves or mixtures thereof; For preventing and treating atherosclerosis and protecting liver function by lowering the concentration of triglycerides and cholesterol in blood containing buckwheat flowers, leaves or mixtures thereof after washing with water and powdered mixed powders or hot water extracts of the mixtures of natural plants as active ingredients Food compositions and beverage compositions are provided.
인삼; 마늘; 대추; 양파; 감잎; 귤피; 구기자꽃, 잎 또는 이의 혼합물; 메밀꽃, 잎 또는 이의 혼합물로부터 활성성분을 추출하는 방법은 다음과 같다. 즉, 인삼; 마늘; 대추; 양파; 감잎; 귤피; 구기자꽃, 잎 또는 이의 혼합물; 메밀꽃, 잎 또는 이의 혼합물을 일정비율로 혼합하여 물로 깨끗이 씻은 후, 혼합물 1kg당 2 내지 5 L 의 70 내지 95%의 에탄올 또는 물을 가하고 70 내지 120 ℃에서 30분 내지 3 시간 가열하여 활성물질을 추출할 수 있다. 일반적으로 물 또는 에탄올을 이용하여 활성물질을 추출할 경우, 반응시간, 반응온도, 알콜농도등에 따라 추출물의 조성이 변할 수 있다. 상기와 같이 얻은 추출물은 탁월한 혈중 콜레스테롤 및 중성지방 농도 저하 효과를 나타내므로, 혈중 지질 관련 질환의 예방 및 치료에 유용하다.Ginseng; garlic; Jujube; onion; Persimmon leaf; Tangerines; Wolfberry, leaves or mixtures thereof; The method of extracting the active ingredient from buckwheat flowers, leaves or mixtures thereof is as follows. Ginseng; garlic; Jujube; onion; Persimmon leaf; Tangerines; Wolfberry, leaves or mixtures thereof; After mixing buckwheat flowers, leaves or mixtures thereof in a certain ratio and washing them with water, add 2 to 5 L of 70 to 95% ethanol or water per kg of the mixture and heat them at 70 to 120 ° C for 30 minutes to 3 hours. Can be extracted. In general, when the active material is extracted using water or ethanol, the composition of the extract may change depending on the reaction time, reaction temperature, alcohol concentration. The extract obtained as described above exhibits an excellent blood cholesterol and triglyceride concentration lowering effect, and thus is useful for the prevention and treatment of blood lipid-related diseases.
본 발명에서 혈중 지질 관련 질환이란, 고지혈증, 고콜레스테롤혈증, 동맥경화, 지방간 등 고농도의 혈중 지질이 한 원인이 되는 질병들을 말한다. 따라서, 본 발명에서는 활성성분으로서 인삼; 마늘; 대추; 양파; 감잎; 귤피; 구기자꽃, 잎 또는 이의 혼합물; 메밀꽃, 잎 또는 이의 혼합물로부터 얻은 혼합분말 또는 이들 혼합물의 추출물, 또는 이에 약학적으로 허용 가능한 부형제, 담체 또는 희석제를 포함하는, 혈중 지질 농도 저하를 통한 혈중 지질 농도 관련 질환의 예방 및 치료용, 또는 간 기능 보호용 약학 조성물을 제공한다. In the present invention, blood lipid-related diseases refer to diseases caused by high concentrations of blood lipids such as hyperlipidemia, hypercholesterolemia, arteriosclerosis, and fatty liver. Therefore, ginseng as an active ingredient in the present invention; garlic; Jujube; onion; Persimmon leaf; Tangerines; Wolfberry, leaves or mixtures thereof; For the prevention and treatment of diseases related to blood lipid concentration through lowering blood lipid concentration, including mixed powder obtained from buckwheat flowers, leaves or mixtures thereof or extracts of these mixtures, or pharmaceutically acceptable excipients, carriers or diluents; or It provides a pharmaceutical composition for protecting liver function.
본 발명의 조성물을 이용하여 통상적인 방법에 따라 약학 제형을 제조할 수 있다. 제형은 정제, 알약, 분말, 새세이, 엘릭서, 현탁액, 에멀젼, 용액, 시럽, 에어로졸, 연질 및 경질 젤라틴 캅셀, 멸균 주사용액, 멸균 포장 분말 등의 형태일 수 있다. The pharmaceutical formulations can be prepared according to conventional methods using the compositions of the present invention. The formulation may be in the form of tablets, pills, powders, assays, elixirs, suspensions, emulsions, solutions, syrups, aerosols, soft and hard gelatin capsules, sterile injectable solutions, sterile packaged powders and the like.
적당한 담체, 부형제 및 희석제의 예로는, 락토즈, 덱스트로즈, 수크로즈, 솔비톨, 만니톨, 전분, 아카시아 검, 알긴산염, 젤라틴, 칼슐 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로즈, 폴리비닐피롤리돈, 물, 메틸하이드록시벤조에이트, 프로필하이드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. 제형은 충진제, 항응집제, 윤활제, 습윤제, 향료, 유화제, 방부제 등을 추가로 포함할 수 있다. 본 발명의 조성물은 포유동물에 투여된 후 활성 성분의 신속, 지속 또는 지연된 방출을 제공할 수 있도록 당업계에 공지된 방법을 사용하여 제형화할 수 있다. Examples of suitable carriers, excipients and diluents include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia gum, alginate, gelatin, kale phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, poly Vinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. The formulation may further comprise fillers, anti-coagulants, lubricants, wetting agents, fragrances, emulsifiers, preservatives and the like. Compositions of the invention can be formulated using methods known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to a mammal.
본 발명의 약학적 조성물은 경구, 경피, 피하, 정맥내 또는 근육내를 포함한 여러 경로를 통해 투여될 수 있다. 사람의 경우 본 발명 혼합분말 혹은 열수추출물의 통상적인 1일 투여량은 20 내지 400 ㎎/㎏ 체중, 바람직하게는 80 내지 200 ㎎/㎏ 체중의 범위일 수 있고, 1회 또는 수회로 나누어 투여할 수 있다. 그러나, 활성 성분의 실제 투여량은 치료할 질환, 선택된 투여 경로, 환자의 연령, 성별 및 체중, 및 환자의 증상의 중증도 등의 여러 관련 인자에 비추어 결정되어야 하는 것으로 이해되어야 하며, 따라서, 상기 투여량은 어떠한 방법으로도 본 발명의 범위를 한정하는 것이 아니다. The pharmaceutical compositions of the present invention can be administered via several routes including oral, transdermal, subcutaneous, intravenous or intramuscular. For humans, the usual daily dosage of the mixed powder or hot water extract of the present invention may range from 20 to 400 mg / kg body weight, preferably from 80 to 200 mg / kg body weight, to be administered once or in several portions. Can be. However, it is to be understood that the actual dosage of the active ingredient should be determined in view of several relevant factors such as the disease to be treated, the route of administration chosen, the age, sex and weight of the patient, and the severity of the patient's symptoms, and thus the dosage Does not limit the scope of the invention in any way.
인삼; 마늘; 대추; 양파; 감잎; 귤피; 구기자꽃, 잎 또는 이의 혼합물; 메밀꽃, 잎 또는 이의 혼합물을 수세건조시켜 분말화하여 얻은 혼합분말 또는 상기 천연 식물체의 혼합추출물은 또한 혈중 지질 농도 저하를 통한 동맥경화 예방 및 치료 또는 간 기능 보호를 목적으로 식품 또는 음료에 첨가제 또는 식품 보조제로서 혼입될 수 있다. 상기 식품 또는 음료로는, 육류; 야채 쥬스(예를 들어, 당근 쥬스 및 토마토 쥬스등) 및 과일쥬스(예를 들어, 오렌지쥬스, 포도쥬스, 파인애플쥬스, 사과쥬스 및 바나나쥬스등); 초콜렛; 스넥류; 면류(라면, 칼국수, 소면, 우동등); 과자류; 피자; 빵, 케익, 크래커, 쿠키, 비스킷, 누들 등과 같이 곡물 분말로 만들어진 식품류; 껌류; 우유, 치즈, 요구르트 및 아이스크림과 같은 유제품; 스프; 육즙; 페이스트, 케찹 및 양념류(다시다, 조미료등)쏘스류; 차; 알콜성 음료류; 탄산 음료류; 비타민 복합체; 및 다양한 건강 식품류 등이 있다. 이 경우, 식품 또는 음료 중 본 발명의 혼합분말이나 이의 추출물의 함량은 0.01 내지 20 중량%, 바람직하게는 0.1 내지 10 중량%의 범위일 수 있다. 하기 실시예는 본 발명을 더욱 상세히 설명하고자 하는 것이며 본 발명의 범위가 이에 한정되지는 않는다. 또한, 고체 중 고체, 액체 중 액체, 및 액체 중 고체에 대한 하기 백분율은 각각 중량/중량, 부피/부피 및 중량/부피에 기초한 것이며, 모든 반응은 별도의 특별한 표시가 없는 한 실온에서 수행되었다.Ginseng; garlic; Jujube; onion; Persimmon leaf; Tangerines; Wolfberry, leaves or mixtures thereof; The mixed powder obtained by buckling the buckwheat flower, the leaf or the mixture thereof by washing with water and powdered or the mixed extract of the natural plant is also an additive or food additive to the food or beverage for the purpose of preventing and treating atherosclerosis or lowering liver function by lowering blood lipid concentration. It may be incorporated as an adjuvant. As the food or beverage, meat; Vegetable juices (eg, carrot juice, tomato juice, etc.) and fruit juices (eg, orange juice, grape juice, pineapple juice, apple juice, banana juice, etc.); Chocolate; Snacks; Noodles (ramen noodles, kalguksu, noodles, udon noodles); confectionery; Pizza; Food products made of grain powder such as bread, cakes, crackers, cookies, biscuits, noodle, etc .; Gums; Dairy products such as milk, cheese, yogurt and ice cream; soup; Juicy; Pastes, ketchups and spices (again, seasonings, etc.); car; Alcoholic beverages; Carbonated beverages; Vitamin complexes; And various health foods. In this case, the content of the mixed powder or extract thereof of the present invention in food or beverage may be in the range of 0.01 to 20% by weight, preferably 0.1 to 10% by weight. The following examples are intended to illustrate the invention in more detail, but the scope of the invention is not limited thereto. In addition, the following percentages for solids in solids, liquids in liquids, and solids in liquids are based on weight / weight, volume / volume and weight / volume, respectively, and all reactions were performed at room temperature unless otherwise indicated.
실시예 1 : 인삼; 마늘; 대추; 양파; 감잎; 귤피; 구기자꽃, 잎 또는 이의 혼합물; 메밀꽃, 잎 또는 이의 혼합물의 혼합분말의 제조Example 1: Ginseng; garlic; Jujube; onion; Persimmon leaf; Tangerines; Wolfberry, leaves or mixtures thereof; Preparation of mixed powder of buckwheat flower, leaf or mixture thereof
인삼; 마늘; 대추; 양파; 감잎; 귤피; 구기자꽃, 잎 또는 이의 혼합물; 메밀꽃, 잎 또는 이의 혼합물을 물로 깨끗이 씻은 후 그늘 상태의 상온에서 건조한 후, 100 내지 300 메쉬로 분쇄하여 분말화한 후, 상기에서 얻은 분말화된 인삼 12.5 중량%, 마늘 17.5 중량%, 대추 12.5 중량%, 양파 7.5 중량%, 감잎 11.5 중량%, 귤피(혹은 진피) 5.5 중량%, 구기자잎, 꽃 또는 이의 혼합물 16.5 중량% 및 메밀꽃, 잎 또는 이의 혼합물 16.5 중량%를 혼합하여 혼합분말을 얻었다. Ginseng; garlic; Jujube; onion; Persimmon leaf; Tangerines; Wolfberry, leaves or mixtures thereof; After washing buckwheat flowers, leaves or mixtures thereof with water and drying at room temperature in the shade, pulverized to 100 to 300 mesh, and then powdered ginseng 12.5% by weight, 17.5% by weight of garlic, 12.5% by weight of jujube %, 7.5 wt% onion, 11.5 wt% persimmon leaf, 5.5 wt% tangerine (or dermis), 16.5 wt% of goji leaves, flowers or mixtures thereof and 16.5 wt% of buckwheat flowers, leaves or mixtures thereof were mixed to obtain a mixed powder.
실시예 2 : 인삼; 마늘; 대추; 양파; 감잎; 귤피; 구기자꽃, 잎 또는 이의 혼합물; 메밀꽃, 잎 또는 이의 혼합물의 열수추출물의 제조Example 2 Ginseng; garlic; Jujube; onion; Persimmon leaf; Tangerines; Wolfberry, leaves or mixtures thereof; Preparation of Hot Water Extract of Buckwheat Flower, Leaf, or Mixtures thereof
인삼; 마늘; 대추; 양파; 감잎; 귤피; 구기자꽃, 잎 또는 이의 혼합물; 메밀꽃, 잎 또는 이의 혼합물을 물로 깨끗이 씻은 후, 인삼 12.5 중량%, 마늘 17.5 중량%, 대추 12.5 중량%, 양파 7.5 중량%, 감잎 11.5 중량%, 귤피(혹은 진피) 5.5 중량%, 구기자잎, 꽃 또는 이의 혼합물 16.5 중량% 및 메밀꽃, 잎 또는 이의 혼합물 16.5 중량%를 혼합한 후, 여기에 3.5 L의 물을 가하고 100℃에서 2 시간동안 끓인 후 여과하여 추출액 및 고상 잔류물을 얻었다. 고상 잔류물을 동일한 방법으로 1회 더 추출하였다. 수득된 추출액을 합하고 감압 농축하여 혼합 추출물을 얻었다.Ginseng; garlic; Jujube; onion; Persimmon leaf; Tangerines; Wolfberry, leaves or mixtures thereof; After washing buckwheat flowers, leaves or mixtures thereof with water, ginseng 12.5%, garlic 17.5%, jujube 12.5%, onion 7.5%, persimmon leaf 11.5%, tangerine (or dermis) 5.5%, goji berry, flower Or 16.5% by weight of the mixture thereof and 16.5% by weight of buckwheat flowers, leaves or mixtures thereof, and then 3.5 L of water was added thereto, boiled at 100 ° C. for 2 hours, and filtered to obtain an extract and a solid residue. The solid residue was extracted once more in the same way. The obtained extracts were combined and concentrated under reduced pressure to obtain a mixed extract.
실시예 3 : 인삼; 마늘; 대추; 양파; 감잎; 귤피; 구기자꽃, 잎 또는 이의 혼합물; 메밀꽃, 잎 또는 이의 혼합물로 제조한 혼합분말의 고지혈증 예방 효과 제 1단계 : 쥐에 대한 로바스타틴 및 본 발명 혼합조성물의 투여
3주령의 스프라그 다우리(Sprague Dawley) 흰쥐 30마리를 충북 음성군의 대한실험동물센터로부터 구입하여 1주일간 제일제당 실험동물 사료로 사육하고, 4주령(체중: 90∼110g)이 되었을 때, 난괴법(ramdomized block design)에 의해 3개의 그룹으로 나누었다. 두 그룹의 쥐들에게 각각 3가지의 서로 다른 고콜레스테롤 식이, 즉 정상식이(AIN-76 실험동물 식이; ICN Biochemicals, Cleveland, OH, U. S. A.)에 1% 콜레스테롤이 함유된 실험동물 식이(대조군), 2mg/kg 체중 로바스타틴(중외제약)과 1 % 콜레스테롤을 함유한 AIN-76(ICN Biochemicals, Cleveland, OH, U. S. A.) 실험동물 식이(로바스타틴군) 및 1% 콜레스테롤과 1% 본 발명 혼합분말이 함유된 실험동물 식이를 각각 섭취시켰다. 3그룹의 쥐들에게 섭취시킨 식이의 조성이 하기 표 1에 나타나 있다.
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실시예 4 : 본 발명 혼합조성물의 토끼 동맥경화 억제 효과Example 4 Rabbit Arteriosclerosis Inhibitory Effect of the Mixed Composition of the Present Invention
제 1단계 : 토끼에 대한 본 발명 혼합조성물의 투여First step: administration of the mixed composition of the present invention to a rabbit
체중 2.0∼2.3 kg의 건강한 수컷 뉴질랜드 백색종(New Zealand White) 토끼를 연암원예축산대학으로부터 분양받아 온도 20 ±2℃, 습도 55 ±10 % 및 12 시간 명/암 주기로 조절되는 사육환경하에서 실험에 사용하였다. 실험군은 수분(7.6 %), 조단백질(22.8 %), 조지방(2.8 %), 조회분(8.8 %), 조섬유(14.4 %) 및 가용성 무질소물(43.7 %) 등으로 구성된 토끼용 고형사료(RC4 diet, Oriental Yeast Co., Japan)에 1 % 콜레스테롤이 첨가된 사료만을 섭취시키는 대조군과 로바스타틴(lovastatin) 또는 본 발명 혼합조성물을 일정비율로 혼합하여 투여하는 두 개의 실험군을 포함하여 총 3개 군으로 나누었으며, 8주 동안 사료와 물은 충분히 자유롭게 섭취할 수 있도록 하였다. 각 실험군의 사료조성과 실험조건은 표 4에 나타내었다.Healthy male New Zealand White rabbits weighing 2.0 to 2.3 kg are fed from Yeonam Horticulture and Livestock University and tested in a breeding environment controlled at a temperature of 20 ± 2 ° C, a humidity of 55 ± 10% and a 12 hour light / dark cycle. Used. The experimental group consisted of rabbit solid feed (RC4) consisting of water (7.6%), crude protein (22.8%), crude fat (2.8%), crude ash (8.8%), crude fiber (14.4%), and soluble nitrogen (43.7%). diet, Oriental Yeast Co., Japan) to a total of three groups, including a control group that consumes only 1% cholesterol-added feed, and two experimental groups in which lovastatin or the mixed composition of the present invention is mixed and administered at a predetermined ratio. The food and water were taken freely for eight weeks. Feed composition and experimental conditions of each experimental group are shown in Table 4.
제 2단계 : 대동맥내 지방선 분석Step 2: Analyzing Fat Glands in the Aorta
제 1단계에서 사육된 토끼를 희생시키고 흉부를 절개하였다. 대동맥궁을 따라 하방으로 횡경막 부위까지 절취한 후, 대동맥 주변의 지방을 잘 제거하고 중앙부위를 종축 방향을 따라 절개한 다음 두번째 늑간동맥 기시부에서 7번째 늑간동맥 기시부까지를 잘라내어 10 % 중성 완충 포르말린에 24시간 고정하였다. 이어서 동맥내벽의 지방선(fatty streak) 염색을 위하여 절취한 대동맥을 디쉬 위에 핀으로 고정한 다음 에스퍼 등의 방법(Esper, E. et al., J. Lab Clin Med, 121: 103-110(1993))에 따라 프로필렌 글리콜로 각각 2분씩 3회 수세하고 프로필렌 글리콜에 녹인 오일 레드 오(ORO) 포화용액으로 옮겨 30분간 염색한 다음, 85 % 프로필렌 글리콜로 각각 3분씩 2회 수세하여 여분의 염색액을 제거하였다. 이어서 생리식염수로 1회 세척하고 사진촬영을 한 다음 사진을 얻어 염색된 부위를 투사(tracing)하고 화상분석기(LEICA, Q-600, Germany)로 단위 대동맥 면적에 대한 염색부위(지방선 부위)의 비율(%)을 계산하였으며, 컴퓨터 통계프로그램 (Microsoft excel, version 7.0)을 이용하여 각 실험군간의 유의성 차이를 분석 검정 (student t-test)하였다.The rabbits raised in the first stage were sacrificed and the thoracic incision was made. After cutting down to the diaphragm area along the aortic arch, the fat around the aorta is well removed, the central area is incised along the longitudinal axis, and the second intercostal artery is cut from the seventh intercostal artery to the 10% neutral buffered formalin. Fixed 24 hours. Then the method of Esper, etc., and then lock the cutout for the aortic jibangseon (fatty streak) dyeing of the arterial wall with a pin on the dish (Esper, E. et al, J. Lab Clin Med, 121:. 103-110 (1993)) Wash with propylene glycol three times for 2 minutes each, transfer to saturated oil red OOR solution dissolved in propylene glycol for 30 minutes, and then wash twice with 85% propylene glycol for 3 minutes each to remove excess dye. It was. Then wash once with physiological saline, take a picture, take a picture, tracing the stained area, and using an image analyzer (LEICA, Q-600, Germany) the ratio of the stained area (fatty gland area) to the unit aortic area (%) Was calculated, and the significance difference between each experimental group was analyzed (student t- test) by using computer statistics program (Microsoft excel, version 7.0).
그 결과, 대조군과 비교하여 로바스타틴과 본 발명 혼합조성물을 투여한 2개의 실험군에서 지방선 부위의 비율이 모두 유의성 있게 감소된 양상을 나타내었으며, 본 발명 혼합조성물을 투여한 군이 로바스타틴을 투여한 군보다 더욱 효과적으로 지방선을 억제하는 것으로 나타났다(표 5). As a result, the ratio of the fat line area was significantly decreased in the two experimental groups administered the lovastatin and the mixed composition of the present invention, compared to the control group, and the group administered the mixed composition of the present invention was higher than the group administered the lovastatin. It has been shown to inhibit fat lines more effectively (Table 5).
[주] a) 측정값은 '평균±표준편차'로 나타내었음.NOTE: The measured values are expressed as 'mean ± standard deviation'.
b) 대조군에 비하여 통계학적으로 유의한 차이 (T-test, p < 0.01)를 보였음.b) There was a statistically significant difference (T-test, p <0.01) compared to the control.
도 1a, 1b 및 1c는 각각 대조군, 로바스타틴 투여군 및 본 발명 혼합조성물 투여군 토끼의 동맥 내피 사진이다. 도 1a에서 보듯이, 대조군은 동맥내피 표면에 많은 대식세포-지질복합체 형성에 의해 죽상경화반이 침착되어 있는데 반하여, 도 1b와 1c에서 보듯이, 로바스타틴 투여군과 본 발명 혼합조성물 투여군은 동맥내피의 표면이 깨끗하며 여기에 대식세포-지질 복합체가 형성되지 못하고 있다. 따라서 본 발명의 혼합조성물은 혈중 콜레스테롤이 매우 높은 조건하에서도 동맥경화 예방 효과가 강력하다는 것을 알 수 있다.Figures 1a, 1b and 1c is an arterial endothelial photograph of the control group, lovastatin administration group and the present invention mixed composition administration group rabbits. As shown in Figure 1a, the control group is deposited atherosclerotic plaque by the formation of a large number of macrophage-lipid complexes on the surface of the arterial endothelium, as shown in Figures 1b and 1c, the lovastatin-administered group and the present invention of the mixed composition administration group of the arterial endothelium The surface is clean and no macrophage-lipid complexes are formed there. Therefore, it can be seen that the mixed composition of the present invention has a strong effect of preventing atherosclerosis even under very high blood cholesterol.
제 3단계 : 조직학적 관찰Step 3: histological observation
토끼의 각 장기와 조직에 대한 영향을 조사하기 위하여, 동물부검시 대동맥, 심장, 폐, 간, 신장 및 근육 등을 절취하여 특이소견의 유무를 육안으로 확인하였다. 그 후, 각 장기를 10 % 중성 포르말린에 넣어 24시간 이상 고정시킨 후, 흐르는 물로 충분히 수세하고 70 %, 80 %, 90 % 및 100 % 에탄올을 이용하여 단계적으로 탈수시킨 다음 파라핀 투과과정을 거쳐 포매기 (SHANDON, Histocentre 2, USA)로 포매하였다. 포매된 조직은 박절편기 (LEICA, RM2045, Germany)로 약 4 ㎛의 두께로 조직절편을 제작하여 H & E (Hematoxylin & eosin) 염색을 하고 자일렌(xylene)으로 투명화 과정을 거쳐 퍼마운트(permount)로 봉입하여 광학현미경으로 관찰하였다.To examine the effects on rabbit organs and tissues, the aorta, heart, lung, liver, kidney and muscles were excised at the time of animal necropsy, and the presence of specific findings was visually checked. Each organ is then fixed in at least 10% neutral formalin for at least 24 hours, followed by rinsing with running water and dewatering stepwise using 70%, 80%, 90% and 100% ethanol, followed by paraffin permeation. Maggie (SHANDON, Histocentre 2, USA). The embedded tissues were fabricated into thin sections (LEICA, RM2045, Germany) with a thickness of about 4 μm, stained with H & E (Hematoxylin & eosin), and then transparent with xylene and permounted. ) And observed with an optical microscope.
실시예 5 : 본 발명 혼합조성물의 간 보호 효과Example 5 Liver Protective Effect of the Invention Mixture Composition
고콜레스테롤 식이와 각 시험물질들의 투여가 간조직에 미치는 영향을 정량적으로 알아보기 위하여 포그트 등의 방법(Fogt F. and Nanji A. A., Toxicology and Applied Pharmacology, 136, 87-93(1996))과 키간 등의 방법(Keegan A. et al., Journal of Hepatology, 23, 591-600(1995))을 참고하여, 실시예 4 (제 3단계)의 방법으로 제조한 각 실험군의 간조직 표본을 현미경으로 관찰한 후, 간 중심정맥을 기준으로 간소엽내 비정상 지방함유세포의 분포비율 정도에 따라 1+ (0∼25 %), 2+ (26∼50 %), 3+ (51∼75 %) 및 4+ (75∼100 %)로 분류하고 점수를 산정하였으며, 컴퓨터 통계프로그램 (Microsoft excel, version 7.0)을 이용하여 각 실험군간의 유의성 차이를 분석 검정 (student t-test)하였다.To quantitatively investigate the effect of high cholesterol diet and the administration of each test substance on liver tissue, Fogg F. and Nanji AA, Toxicology and Applied Pharmacology , 136 , 87-93 (1996) Observing the liver tissue samples of each experimental group prepared by the method of Example 4 (Step 3) with reference to the method of Keegan A. et al., Journal of Hepatology , 23 , 591-600 (1995). 1+ (0-25%), 2+ (26-50%), 3+ (51-75%) and 4, depending on the degree of distribution of abnormal fat-containing cells in the hepatic lobe, based on the central hepatic vein. The scores were categorized as + (75-100%), and the statistical differences (student t- test) were analyzed by computer statistics program (Microsoft excel, version 7.0).
그 결과, 지방변성 세포의 분포비율은 본 발명 혼합조성물을 투여한 실험군에서 유의미하게 (p < 0.05) 감소하였다 (표 6).As a result, the distribution ratio of the denatured cells was significantly reduced ( p <0.05) in the experimental group to which the mixed composition of the present invention was administered (Table 6).
도 2a, 2b 및 2c는 각각 대조군, 로바스타틴 투여군 및 본 발명 혼합조성물 투여군 토끼의 간 해부 사진이다. 도 2a 및 2b에서 보듯이, 대조군 토끼의 간에는 중심 정맥 주변부에 지방질이 과도하게 함유된 세포들이 존재하고, 로바스타틴 투여군 토끼의 간에도 중심 정맥 주변부와 주변의 모든 세포가 지방간 세포를 형성하고 있다. 이에 반하여, 도 2c에서 보듯이, 본 발명 혼합조성물 투여군 토끼의 간에는 거의 모든 간 세포가 정상적이다. 따라서, 본 발명의 혼합조성물은 지방간 형성을 강력히 저해함을 알 수 있다.Figure 2a, 2b and 2c is a picture of the liver anatomy of the control group, lovastatin administration group and the present invention of the mixed composition administration group rabbits, respectively. As shown in Figures 2a and 2b, the control rabbit's liver contains cells containing excessive fat in the periphery of the central vein, and all the cells in the periphery and the periphery of the central vein form the liver of the lovastatin-treated rabbit. In contrast, as shown in Figure 2c, almost all liver cells are normal in the liver of the rabbit mixture administration group of the present invention. Therefore, it can be seen that the mixed composition of the present invention strongly inhibits fatty liver formation.
실시예 6 : 본 발명 혼합분말의 독성시험Example 6: Toxicity test of the mixed powder of the present invention
본 발명 혼합분말의 경구독성시험을 다음과 같이 실시하였다. 4 주령의 특정 병원체 부재(specific pathogens free) ICR 마우스로서 암컷 12마리와 숫컷 12 마리(암수 각각 3마리/용량군)를 온도 22±3℃, 습도 55±10%, 조명 12L/12D의 동물실내에서 사육하였다. 마우스는 실험에 사용되기 전 1주일 정도 순화시켰다. 실험동물용 사료{(주)제일제당, 마우스 및 랫드용} 및 음수는 멸균한 후 공급하였으며 자유섭취시켰다.Oral toxicity test of the mixed powder of the present invention was carried out as follows. 12 females and 12 males (3 males and 3 females each) were used as specific pathogens free ICR mice at 4 weeks of age in an animal room of 22 ± 3 ° C, 55 ± 10% humidity, and 12L / 12D illumination. Breeding in. Mice were allowed to acclimate for about a week before being used in the experiment. Feed for experimental animals (for CheilJedang Co., Ltd., mice and rats) and negative water were supplied after sterilization and freely ingested.
본 발명 혼합분말을 0.5 % 트윈 80을 용매로 하여 100 mg/mL 농도로 조제한 후, 마우스 체중 20 g 당 0.2 mL(1 g/kg), 0.4 mL(2 g/kg) 또는 0.8 mL(4 g/kg)씩 경구 투여하였다. 시료는 1 g/kg 및 2 g/kg 용량군은 1회 경구 투여하였고, 4 g/kg 용량군은 2회 경구 투여하였으며, 투여 후 7일 동안 다음과 같이 부작용 또는 치사 여부를 관찰하였다. 즉, 투여당일은 투여 후 1시간, 4시간, 8시간, 12시간 뒤에 그리고 투여 익일부터 7일째까지는 매일 오전, 오후 1회 이상씩 일반증상의 변화 및 사망동물의 유무를 관찰하였다. 또한, 투여 7일째에 동물을 치사시켜 해부한 후 육안으로 내부 장기를 검사하였다. 투여당일부터 1일 간격으로 체중의 변화를 측정하여 본 발명 혼합조성물에 의한 동물의 체중 감소 현상을 관찰하였다.The mixed powder of the present invention was prepared at a concentration of 100 mg / mL using 0.5% Tween 80 as a solvent, and then 0.2 mL (1 g / kg), 0.4 mL (2 g / kg) or 0.8 mL (4 g per 20 g of mouse body weight. / kg) orally. The samples were orally administered once in the 1 g / kg and 2 g / kg dose groups, and twice orally in the 4 g / kg dose group, and observed for side effects or lethality for 7 days after administration. That is, on the day of administration, changes in general symptoms and the presence or absence of dead animals were observed at least once in the morning, at least once every afternoon from 1 hour, 4 hours, 8 hours, 12 hours after the administration and from the next day until the 7th day. In addition, on the 7th day of administration, animals were killed and dissected, and the internal organs were visually examined. The change in body weight was measured at the interval of 1 day from the day of administration, and the weight loss phenomenon of the animals by the mixed composition of the present invention was observed.
그 결과, 급성 경구독성의 경우에는 본 발명 혼합조성물은 1 g/kg, 2 g/kg, 4 g/kg의 용량에서 7일 동안 치사동물이 관찰되지 않았다. 7일 후 생존동물에 대한 부검을 실시한 바, 특별한 병변 육안 소견이 없었으며, 투여 익일부터 7일간 어떠한 체중의 감소 없이 정상적인 체중의 증가가 관찰되었다.As a result, in the case of acute oral toxicity, the mixed composition of the present invention was not observed for 7 days at a dose of 1 g / kg, 2 g / kg, 4 g / kg. An autopsy of the surviving animals was performed 7 days later, and there were no gross lesions, and normal body weight gain was observed without any weight loss for 7 days after the administration.
결론적으로 본 발명 혼합조성물은 상기의 농도로 경구 투여시 LD50값은 암수마우스에서 4 g/kg 체중 이상에 존재하는 것으로 추정되었다.In conclusion, in the mixed composition of the present invention, the LD 50 value was estimated to exist at 4 g / kg or more in male and female mice when administered orally at the above concentration.
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제제 예1: 약학적 제제의 제조Formulation Example 1: Preparation of Pharmaceutical Formulation
다음의 성분들을 혼합하여 경질 젤라틴 캅셀에 충진함으로써 캅셀제를 제조하였다:Capsules were prepared by mixing the following ingredients to fill hard gelatine capsules:
양(mg/캅셀)Amount (mg / capsule)
활성 성분(본 발명 혼합분말) 200Active Ingredient (Inventive Mixed Powder) 200
건조 전분 30Dry starch 30
마그네슘 스테아레이트 20 Magnesium Stearate 20
총 250 mg250 mg total
제제예 2: 본 발명 혼합분말을 포함하는 식품Formulation Example 2 Food Containing the Mixed Powder of the Present Invention
본 발명의 혼합분말 또는 열수추출물을 포함하는 식품들을 다음과 같이 제조하였다.Foods containing the mixed powder or hot water extract of the present invention were prepared as follows.
(1) 조리용 양념의 제조(1) Preparation of seasonings for cooking
종래 조리용 양념 100 중량부에 대하여 본 발명 혼합분말 20 내지 95.0 중량%를 첨가하여 건강 증진용 조리용 양념을 수득하였다.20 to 95.0% by weight of the mixed powder of the present invention was added to 100 parts by weight of the conventional cooking seasoning to obtain a cooking seasoning for health promotion.
(2) 토마토 케찹 및 소스의 제조(2) Preparation of Tomato Ketchup and Sauce
본 발명 혼합분말을 토마토 케찹 또는 소스에 0.2-1.0 중량%의 양으로 첨가하여 건강 증진용 토마토 케찹 또는 소스를 수득하였다. The mixed powder of the present invention was added to tomato ketchup or sauce in an amount of 0.2-1.0% by weight to obtain tomato ketchup or sauce for health promotion.
(3) 밀가루 식품의 제조(3) Preparation of flour food
본 발명 혼합분말을 밀가루에 0.5-5.0 중량%의 양으로 첨가하고, 이 혼합물을 이용하여 빵, 케이크, 쿠키, 크래커 및 면류를 제조하여 건강 증진용 식품을 수득하였다.The mixed powder of the present invention was added to the flour in an amount of 0.5-5.0 wt%, and bread, cake, cookies, crackers and noodles were prepared using the mixture to obtain a food for health promotion.
(4) 스프 및 육즙(gravies)의 제조(4) Preparation of soups and gravy
본 발명 혼합분말을 스프 및 육즙에 0.1-5.0 중량%의 양으로 첨가하여 건강 증진용 육가공제품 및 면류의 수프 및 육즙을 수득하였다.The mixed powder of the present invention was added to the soup and the juice in an amount of 0.1-5.0% by weight to obtain soups and gravy of processed meat products and noodles for health promotion.
(5) 그라운드 비프(ground beef)의 제조(5) Preparation of ground beef
본 발명 혼합분말을 그라운드 비프에 10 중량%의 양으로 첨가하여 건강 증진용 그라운드 비프를 수득하였다.The mixed powder of the present invention was added to the ground beef in an amount of 10% by weight to obtain a ground beef for health promotion.
(6) 유제품(dairy products)의 제조(6) Manufacture of dairy products
본 발명 혼합분말을 우유에 5-10 중량%의 양으로 첨가하고 이 우유를 이용하여 버 터 및 아이스크림과 같은 다양한 유제품을 제조하였다.The mixed powder of the present invention was added to the milk in an amount of 5-10% by weight to prepare various dairy products such as butter and ice cream.
제제예 3: 본 발명 열수추출물을 포함하는 음료Formulation Example 3 Beverage Containing the Hot Water Extract of the Present Invention
(1) 야채쥬스의 제조(1) Preparation of vegetable juice
본 발명 열수추출물 5 mL을 토마토 또는 당근 쥬스 1000 mL에 가하여 건강 증진용 야채쥬스를 수득하였다. 5 mL of the hot water extract of the present invention was added to 1000 mL of tomato or carrot juice to obtain a vegetable juice for health promotion.
(2) 과일쥬스의 제조(2) Preparation of fruit juice
본 발명 열수추출물 1 mL을 사과 또는 포도 쥬스 1000 mL에 가하여 건강 증진용 과일쥬스를 수득하였다.1 mL of the hot water extract of the present invention was added to 1000 mL of apple or grape juice to obtain a fruit juice for health promotion.
이상, 상기 실시예를 통하여 설명한 바와 같이 본 발명의 천연 식물체 유래의 혈중 지질농도 관련 질환과 간질환의 예방 및 치료용 혼합분말 및 열수추출물은 혈중 콜레스테롤 및 중성 지질 농도를 크게 낮추며 동맥 내피에 대식세포-지질층이 침착되는 것을 강력이 억제하고 간 세포의 손상 및 지방간화를 강력히 억제함으로써 혈중 지질농도 관련 질환과 간질화의 예방 및 치료효과가 매우 뛰어나 의약품산업 및 건강식품산업상 매우 유용한 발명인 것이다.As described above, the mixed powders and hot water extracts for preventing and treating blood lipid concentration-related diseases and liver diseases derived from natural plants of the present invention significantly lower blood cholesterol and neutral lipid concentrations, and give macrophages to arterial endothelium. -It is a very useful invention in the pharmaceutical industry and the health food industry because it strongly inhibits the deposition of the lipid layer and strongly inhibits the damage of liver cells and fatty liver, thereby preventing and treating blood lipid-related diseases and epilepsy.
도 1a는 대조군 식이를 투여하여 사육한 토끼의 동맥 내피 사진이다.Figure 1a is an arterial endothelial picture of a rabbit reared by administration of a control diet.
도 1b는 로바스타틴 투여군 식이를 투여하여 사육한 토끼의 동맥 내피 사진이다.Figure 1b is an arterial endothelial picture of a rabbit reared by administration of the lovastatin administration group diet.
도 1c는 본 발명 천연식물체 유래의 조성물 투여군 식이를 투여하여 사육한 토끼의 동맥 내피 사진이다.Figure 1c is a photograph of the arterial endothelial of a rabbit reared by administering a composition administration group diet derived from the natural plant of the present invention.
도 2a는 대조군 식이를 투여하여 사육한 토끼의 간 해부 사진이다.Figure 2a is a liver liver picture of a rabbit reared by administration of a control diet.
도 2b는 로바스타틴 투여군 식이를 투여하여 사육한 토끼의 간 해부 사진이다.Figure 2b is a liver liver picture of a rabbit reared by administering the lovastatin administration group diet.
도 2c는 본 발명 천연식물체 유래의 조성물 투여군 식이를 투여하여 사육한 토끼의 간 해부 사진이다.Figure 2c is a liver liver picture of a rabbit reared by administering the composition administration group diet derived from the natural plant of the present invention.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR0160087B1 (en) * | 1995-12-22 | 1998-11-16 | 김강권 | Process for preparing tea from boxthron leaves |
| KR0182592B1 (en) * | 1996-05-02 | 1999-03-20 | 이능희 | Favorite food made of buckwheat leaf |
| KR19980027074A (en) * | 1996-10-14 | 1998-07-15 | 박원훈 | Cardiovascular disease prevention and treatment composition comprising citrus peel extract, hesperidin or naringin purified therefrom |
| JPH11182592A (en) * | 1997-12-16 | 1999-07-06 | Nsk Warner Kk | Tube pressurizing type brake band |
| WO1999052380A1 (en) * | 1998-04-08 | 1999-10-21 | Korea Institute Of Science And Technology | Health-improving spice composition |
| KR19990079683A (en) * | 1998-04-08 | 1999-11-05 | 박호군 | Functional health food containing citrus rind powder or rind extract |
| KR20000026393A (en) * | 1998-10-20 | 2000-05-15 | 박호군 | Composition for increasing serum high density lipoprotein containing bioflavonoids |
| KR20030083347A (en) * | 2002-04-22 | 2003-10-30 | 이동길 | Composition of uncooked or cooked food |
| KR101147916B1 (en) * | 2007-10-11 | 2012-05-25 | 주식회사 만도 | Solenoid valve for brake system |
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|---|---|
| KR20040001743A (en) | 2004-01-07 |
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