KR20050032927A - Composition comprising chongkukjang or its extract for improving lipid metabolism - Google Patents
Composition comprising chongkukjang or its extract for improving lipid metabolism Download PDFInfo
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- KR20050032927A KR20050032927A KR1020030068920A KR20030068920A KR20050032927A KR 20050032927 A KR20050032927 A KR 20050032927A KR 1020030068920 A KR1020030068920 A KR 1020030068920A KR 20030068920 A KR20030068920 A KR 20030068920A KR 20050032927 A KR20050032927 A KR 20050032927A
- Authority
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- South Korea
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- composition
- cheonggukjang
- cholesterol
- hours
- soybeans
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Classifications
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- 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
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- 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
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/328—Foods, ingredients or supplements having a functional effect on health having effect on glycaemic control and diabetes
-
- 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
- A23V2250/54—Proteins
- A23V2250/548—Vegetable protein
- A23V2250/5488—Soybean protein
Landscapes
- Life Sciences & Earth Sciences (AREA)
- Mycology (AREA)
- Health & Medical Sciences (AREA)
- Nutrition Science (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Medicines Containing Plant Substances (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
Description
본 발명은 청국장 또는 그 추출물을 함유하는 혈중 지질대사 개선제에 관한 것으로, 상세하게는 혈중 중성지질 및 콜레스테롤을 저하시키는 활성을 갖는 본 발명의 청국장 또는 그 추출물을 함유한 지질농도 증가로 인한 질환의 예방 및 치료용 조성물에 관한 것이다.The present invention relates to a blood lipid metabolism improving agent containing Cheonggukjang or its extract, and in particular, the prevention of diseases caused by increasing the lipid concentration containing the cheonggukjang of the present invention or its extract having an activity of lowering blood triglycerides and cholesterol And to therapeutic compositions.
동맥경화, 심근경색 및 뇌졸중과 같은 순환기계 질환은 2001년 한국인 사망요인의 2위(뇌혈관질환)와 3위(심혈관질환)을 차지하고 있다(Korea National Statistical Office : The cause of death Statistics 2001. Annual Report of on the Cause of Death Statistics. Korea National Statistical Office, 2002).Circulatory system diseases such as atherosclerosis, myocardial infarction and stroke accounted for the 2nd place (cerebrovascular disease) and 3rd place (cardiovascular disease) in Korea in 2001 (Korea National Statistical Office: The cause of death Statistics 2001. Annual) Report of on the Cause of Death Statistics.Korea National Statistical Office, 2002).
동맥경화, 심근경색 및 뇌졸중과 같은 순환기계질환은 다른 만성 질환에 비하여 식이에 영향을 많이 받는다고 알려져 있으며 위험인자로는 혈중 콜레스테롤, 혈중 중성지방, 고혈압, 흡연, 혈전, 당뇨, 비만 등이 있다. 그 중 혈중 콜레스테롤, 고혈압 등은 동맥경화와 심근경색 발생의 주요 위험 인자이므로 혈중 콜레스테롤 농도를 정상으로 유지하는 것이 중요하다(Bowman, M.P., et al., J. Nutri., 118, pp555-560, 1988; 조성희, 한국영양식량학회지 23, pp170-179, 1994).Circulatory diseases such as arteriosclerosis, myocardial infarction and stroke are known to be more affected by diet than other chronic diseases. Risk factors include blood cholesterol, blood triglycerides, high blood pressure, smoking, blood clots, diabetes and obesity. . Among these, blood cholesterol and hypertension are important risk factors for atherosclerosis and myocardial infarction. Therefore, it is important to keep blood cholesterol levels normal (Bowman, MP, et al., J. Nutri., 118, pp555-560, 1988; Cho Sung-hee, Korean Journal of Nutrition and Nutrition 23, pp170-179, 1994).
혈중 지질은 중성지방, 콜레스테롤, 인지질, 유리지방산으로 이루어진다. 혈중 콜레스테롤 중 LDL-콜레스테롤은 심혈관질환의 위험인자로 보고되며, HDL-콜레스테롤은 혈관 벽으로부터 콜레스테롤을 제거하는 작용이 있어 심혈관 질환의 예방 인자로 보고되고 있다. 특히 총 콜레스테롤/HDL-콜레스테롤이나 LDL-콜레스테롤/HDL-콜레스테롤비가 총 콜레스테롤 양보다 심혈관 질환의 위험 인자로서 더 정확한 지표가 된다고 하는 연구자들도 다수 있다(황수관 외, 대한스포츠의학회지, 15, 1997). 또한, 혈중 중성지질 농도의 증가는 HDL-콜레스테롤의 농도를 낮추고 키로마이크론 잔유물의 함량을 높여 주는 기작을 통해 관상동맥질환의 주요 원인이 된다는 보고(Goldberg, I.J., J. Lipid Res., 37, pp693-707, 1996)가 있다. 그리고, 혈중 지질은 다른 지질보다 혈관 내피세포를 잘 통과하기 때문에 동맥경화증의 주원인이 되고 식후의 급격한 중성지방의 상승은 뇌졸중의 발생과 밀접한 관계가 있다고 보고(Feldman, R.G. and Albrick, M.J., S. Arch. Neurol., 10, pp91, 1964)되고 있다.Blood lipids consist of triglycerides, cholesterol, phospholipids and free fatty acids. LDL-cholesterol in blood cholesterol has been reported as a risk factor for cardiovascular disease, and HDL-cholesterol has been reported as a preventive factor for cardiovascular disease because it has a function of removing cholesterol from the blood vessel wall. In particular, many researchers have found that total cholesterol / HDL-cholesterol or LDL-cholesterol / HDL-cholesterol ratios are more accurate indicators of cardiovascular disease than total cholesterol (Hwangsu-Kwan et al., Korean Journal of Sports Medicine, 15, 1997). . In addition, an increase in serum triglyceride levels is a major cause of coronary artery disease through mechanisms that lower HDL-cholesterol levels and increase the content of chylomicron residues (Goldberg, IJ ., J. Lipid Res., 37 , pp693-707, 1996). In addition, since blood lipids pass through vascular endothelial cells better than other lipids, it is a major cause of atherosclerosis, and rapid elevation of triglycerides after a meal is closely related to the occurrence of stroke (Feldman, RG and Albrick, MJ, S. Arch. Neurol., 10, pp 91, 1964).
한편, 당뇨병의 경우 인슐린을 비롯한 호르몬 불균형으로 탄수화물을 비롯한 단백질, 지질 및 전해질 대사 등 생리적 대사 조절 기능 이상으로 고혈당의 특징적인 증세를 나타내며(Gonuth, S.M., Ann. Intern. Med., 79, pp812-822, 1973) 이러한 고혈당 증세가 지속되면 혈액순환 장애를 비롯한 심각한 만성적 합병증(Kannel, W.B. and McGee, D.L. JAMA, 241, pp2035-2038, 1979)을 가져오게 된다.On the other hand, in the case of diabetes, hormonal imbalances including insulin show characteristic symptoms of hyperglycemia due to physiological metabolic control functions such as protein, lipid and electrolyte metabolism including carbohydrates (Gonuth, SM, Ann. Intern. Med. , 79 , pp812-). 822, 1973) The persistence of these hyperglycemic symptoms leads to serious chronic complications including blood circulation disorders (Kannel, WB and McGee, DL JAMA, 241 , pp 2035-2038, 1979).
특히, 정상인에 비해서 당뇨환자에 있어서는 동맥경화증, 뇌경색, 뇌혈전, 심근경색과 같은 심혈관계 질환의 발병율이 높다(Fuller, J.H. Lancet 1, pp1373-1376, 1980). 당뇨병환자는 관상동맥질환이나 뇌혈관질환에 의한 사망 위험률이 높고, 이는 고혈압과 고지혈증, 비만 등에 의해 흔히 발병된다(허갑범. 한국영양학회. 초록발표논문집. pp15-18, 1984). 제 2형 당뇨환자 중 67%가 한 종류 또는 그 이상의 지질대사 이상을 가지고 있다고 보고되었다(Harris, M.I. Diabetes Care, 23, pp754-758, 2000). 제 2형 당뇨환자는 중성지방 및 콜레스테롤 농도가 증가하고 및 HDL-콜레스테롤이 감소하는 지질대사의 이상이 일어나며(Goldberg, R.B. Diabetes Care 4, pp561-572, 1981), 이것은 당뇨 합병증인 관상동맥 질환의 원인이 된다(Reaven, J.W. Am. J. Med., 83, pp31-40, 1987). 관상동맥질환은 당뇨환자의 사망요인에 있어서 중요한 원인이 되는 합병증으로 당뇨환자의 사망률 중 최소 60%에 해당한다(Miettinen, H. Diabetes Care 21, pp69-75, 1998). 그러므로 고지혈증 치료제를 개발하여 심혈관질환을 개선시키고자 하는 많은 연구가 진행되어 왔다.In particular, the incidence of cardiovascular diseases such as atherosclerosis, cerebral infarction, cerebral thrombosis, and myocardial infarction is higher in diabetic patients than in normal persons (Fuller, JH Lancet 1 , pp1373-1376, 1980). Diabetes patients have a high risk of death from coronary artery disease or cerebrovascular disease, which are often caused by hypertension, hyperlipidemia, obesity, etc. (Hu-Beom Bum. The Korean Nutrition Society. Abstract, pp. 15-18, 1984). It has been reported that 67% of people with type 2 diabetes have more than one or more types of lipid metabolism (Harris, MI Diabetes Care , 23 , pp754-758, 2000). Type 2 diabetic patients have abnormalities of lipid metabolism with increased triglyceride and cholesterol levels and decreased HDL-cholesterol (Goldberg, RB Diabetes Care 4 , pp561-572, 1981). (Reaven, JW Am. J. Med., 83 , pp 31-40, 1987). Coronary artery disease is a major complication in the mortality of diabetic patients and is at least 60% of diabetes mortality (Miettinen, H. Diabetes Care 21 , pp69-75, 1998). Therefore, many studies have been conducted to improve cardiovascular disease by developing a hyperlipidemic drug.
1950년에서 1960년대에 걸쳐 많은 콜레스테롤 강하제가 개발되어 니코틴산(Goldmith, G.A et al., Arch Intern. Med., 105, pp512-517, 1959), 콜레스티라민, 클로피브레이트(clofibrate), 네오마이신(neomycin), 식물 스테롤(plant sterols)(Pollack, O.J., Circulation, 7, pp702-706, 1953), 트리파라놀 (Hollander, W. and Chobanian. Boston Med. Quart., 10, pp37-44, 1959), D-티로신 (Srar, P. et al., AMA Arch. Intern. Med., 105, pp830-842, 1960), 에스트로겐호르몬 등이 치료에 사용되어 왔으나 혈관 확장, 발열, 위장장애 고요산혈증, 간기능 저하 등의 여러 가지 부작용이 보고되었고, 따라서 부작용이 적은 천연물 및 식품으로부터 콜레스테롤 저하제품을 개발하려는 연구가 활발하게 진행되고 있다.Many cholesterol-lowering agents were developed from the 1950s to the 1960s, with nicotinic acid (Goldmith, GA et al., Arch Intern. Med., 105 , pp512-517, 1959), cholestyramine, clofibrate, neomycin (neomycin), plant sterols (Pollack, OJ, Circulation, 7 , pp702-706, 1953), tripanol (Hollander, W. and Chobanian.Boston Med. Quart., 10, pp37-44, 1959 ), D-tyrosine (Srar, P. et al., AMA Arch. Intern. Med., 105 , pp830-842, 1960), estrogen hormones have been used for the treatment of vasodilation, fever, gastrointestinal disorders hyperuricemia, Various side effects such as decreased liver function have been reported, and therefore, studies to develop cholesterol-lowering products from natural products and foods having few side effects are being actively conducted.
지질대사 개선기능을 가진 식물성분에 관한 연구들이 많이 보고되고 있으며, 이 등(이정선, 이지수, 신현경. 한국영양학회지. 30, pp781-788, 1997)은 치커리 추출물이 당뇨쥐 간의 중성지질 및 인지질의 합성을 증가시키고 체내 콜레스테롤 대사를 항진시킴으로써 혈당조절에 유익한 영향을 미친다고 보고하였으며, 성 등(성낙주, 이수정, 신정혜 등. 한국식품영양과학회, 25, pp986, 1996)은 도라지 추출액이 당뇨쥐의 혈당, 혈청 및 간장의 지질개선에 효과가 있다고 보고하였다.Many studies have been reported on plant components with improved lipid metabolism, and Lee et al. (Lee Jung-sun, Lee Ji-soo, Hyun-Kyung Shin. Korean Journal of Nutrition. 30 , pp781-788, 1997). It has been reported that it has a beneficial effect on glycemic control by increasing the synthesis of cholesterol and increasing cholesterol metabolism in the body, and Sung et al. (Seung Nak-ju, Lee Soo-jeong, Shin Jung-hye, et al., Korean Society of Food and Nutrition, 25 , pp986, 1996). It has been reported to be effective in improving lipid levels of blood sugar, serum and liver.
청국장은 콩을 이용한 우리나라의 전통 기호식품이다. 콩에는 단백질 이외에 생리활성을 가지는 식이섬유, 비타민 E, 인지질, 이소플라본, 페놀, 사포닌, 트립신 저해제, 피틴산 등의 성분이 함유되어 있어(Adlercreuts, H., Mazur, W., Ann. Med., 29, pp95-120, 1997, Kim, O.S., Yang, J.L. and Song, Y.S. Food Industry and Nutrition., 4, pp40-46, 1999), 동맥경화, 심장병, 항암효과 등 만성퇴행성 질환 예방에 효과가 높을 것이라고 기대되며, 특히 이소플라본은 항암효과 이외에 골다공증, 신부전, 심장질환 등과 같은 만성질환의 예방에 탁월한 효과를 나타낸다. 또한 청국장은 발효과정 중에 생성되는 효소들에 의해 콩 껍질이나 세포막을 구성하고 있는 섬유소 및 세포 내에 있는 당질 및 단백질이 분해되면서 소화율이 향상되며 유리지방산이 월등히 많아진다(이계호 외, 한국농화학회지, 1, pp191-199, 1971).Cheonggukjang is a traditional Korean favorite food using soybean. Soybeans contain physiologically active dietary fiber, vitamin E, phospholipids, isoflavones, phenols, saponins, trypsin inhibitors, and phytic acid (Adlercreuts, H., Mazur, W., Ann. Med., 29 , pp95-120, 1997, Kim, OS, Yang, JL and Song, YS Food Industry and Nutrition., 4 , pp40-46, 1999), which may be highly effective in preventing chronic degenerative diseases such as atherosclerosis, heart disease, and anticancer effects. In particular, isoflavones have an excellent effect on the prevention of chronic diseases such as osteoporosis, kidney failure, heart disease, etc. in addition to the anticancer effect. In addition, Cheonggukjang improves digestibility as the enzymes generated during fermentation decomposes the cellulose and proteins in soybean hulls and cell membranes and significantly increases free fatty acids (Lee Kee-Ho et al., Korean Journal of Agricultural Chemistry, 1). , pp 191-199, 1971).
일본의 전통 대두 발효식품인 낫토(natto)에 혈전용해 물질이 들어 있다는 사실이 밝혀졌고 분리된 혈전용해 효소를 낫토키나아제(nattokinase)라 명명하고 경구투여 생체내의 혈전 용해능을 높일 수 있었다고 보고(Sumi, H.H., et al., Experimentia, 43, pp1110, 1987)되었다.Natto, a traditional Japanese soybean fermented food, has been found to contain thrombolytic substances, and the isolated thrombolytic enzyme is called nattokinase and reported to increase the thrombolytic ability in vivo. , HH, et al., Experimentia, 43 , pp1110, 1987).
콩 단백질은 각종 성인병의 원인이 되는 혈중 콜레스테롤을 낮추고 동맥경화, 심근경색, 뇌졸중, 고혈압 등의 예방과 당뇨병 질환을 개선하며 또한 항암 작용도 있는 것으로 보고되었다(Kwon, T.W. and Song, Y.S. Health functions of soybean foods in proceeding of IUFOST '96 reginal symposium on non-nutrition health factors for future foods', Seoul, Korea, 1996). 코스타 등(Costa, R.L., Summa, M.A. Ann. Pharmacother., 34, pp931-935, 2000)은 고지혈증 환자들에게서 대두 단백질의 섭취가 혈중 지질 농도에 좋은 영향을 미친다고 보고하였고, 최(최용순, 한국영양식량학회지, 12, pp673-677, 1993)는 두부 비지의 섭취가 흰쥐의 혈청 HDL-콜레스테롤을 유의적으로 낮추고, 간의 콜레스테롤 농도도 유의적으로 낮춘다고 보고하였다.Soy protein has been reported to lower blood cholesterol, which causes various adult diseases, to prevent atherosclerosis, myocardial infarction, stroke, and high blood pressure, to improve diabetes disease, and to have anti-cancer effects (Kwon, TW and Song, YS Health functions of soybean foods in proceeding of IUFOST '96 reginal symposium on non-nutrition health factors for future foods', Seoul, Korea, 1996). Costa et al. (Costa, RL, Summa, MA Ann. Pharmacother ., 34 , pp931-935, 2000) reported that soy protein intake had a positive effect on blood lipid concentrations in patients with hyperlipidemia. The Korean Journal of Nutrition and Food Science, 12 , pp673-677, 1993) reported that ingestion of tofu busy significantly lowered serum HDL-cholesterol in rats and significantly lowered liver cholesterol levels.
이에 본 발명자는 정상동물, 당뇨동물 및 당뇨환자에게 청국장을 장기간 섭취시키고 체내 지질대사에 미치는 영향을 조사하고, 본 발명의 청국장이 혈중 지질 및 콜레스테롤의 농도를 낮춤을 확인하여 본 발명을 완성하였다.In this regard, the present inventors completed the present invention by examining the effects of long-term intake of cheonggukjang on the body and lipid metabolism in normal animals, diabetic animals and diabetic patients, and confirming that the cheonggukjang of the present invention lowers the concentration of lipid and cholesterol in blood.
본 발명은 지질대사개선에 효과적인 기능성 청국장을 제조하여, 이를 함유하는 지질농도 증가로 인한 질환의 예방 및 치료를 위한 조성물을 제공하고자 한다. The present invention is to provide a composition for the prevention and treatment of diseases caused by increasing the concentration of lipids containing the same by producing a functional Cheonggukjang effective in improving lipid metabolism.
상기 목적을 달성하기 위하여, 본 발명은 세척한 대두를 침지, 탈수, 증자, 방냉 후 바실러스 서브틸리스 균으로 접종 및 발효를 통하여 제조된 기능성 청국장 또는 그 추출물을 함유하는 지질농도 증가로 인한 질환 예방 및 치료용 조성물을 제공한다.In order to achieve the above object, the present invention is to prevent disease caused by increasing the concentration of lipid containing a functional soybean paste or its extract prepared by inoculation and fermentation of Bacillus subtilis bacteria after dipping, dehydration, steaming, and cooling the washed soybeans. And it provides a therapeutic composition.
상기 지질농도의 증가로 인한 질환은 고지혈증, 고혈압, 동맥경화, 심근경색, 뇌졸중 등의 심순환계질환을 포함한다.Diseases caused by the increase in lipid concentration include hyperlipidemia, hypertension, arteriosclerosis, myocardial infarction, cardiovascular diseases such as stroke.
상기 대두는 한국산, 중국산, 일본산 등의 외국산 대두를 포함한다.The soybean includes foreign soybeans such as Korean, Chinese, and Japanese.
이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
본 발명의 기능성 청국장 또는 그 추출물은 하기와 같이 수득될 수 있다.The functional Chunggukjang or extract thereof of the present invention can be obtained as follows.
먼저, 대두를 세척하고 12시간 내지 24시간 동안 부피의 3배 내지 5배의 물에 침지시킨 다음, 10분 내지 2시간동안 탈수시킨 다음, 가압증자기를 이용하여 100 내지 150℃, 바람직하게는 121℃ 에서 10분 내지 2시간, 바람직하게는 15분동안 증자한 후, 온도가 50 내지 70℃가 되도록 방냉한다. 배양된 바실러스 서브틸리스(Bacillus subtilis), 바람직하게는 바실러스 서브틸리스 SNU816, 바실러스 서브틸리스 ATCC9327, 바실러스 서브틸리스 ATCC6633, 바실러스 서브틸리스 ATCC9466, 더욱 바람직하게는 바실러스 서브틸리스 SNU816 균주를 대두 무게의 1-3중량%, 바람직하게는 2중량%로 접종하여 37℃에서 40시간 내지 80시간, 바람직하게는 72시간동안 발효시키고, 부가적으로 동결건조 및 분말화시켜 본 발명의 기능성 청국장을 수득할 수 있다.First, soybeans are washed and soaked in water of 3 to 5 times the volume for 12 to 24 hours, then dehydrated for 10 minutes to 2 hours, and then 100 to 150 ° C. using a pressurized steamer, preferably 121 After steaming for 10 minutes to 2 hours, preferably 15 minutes at < RTI ID = 0.0 > C, < / RTI > Cultured Bacillus subtilis , preferably Bacillus subtilis SNU816, Bacillus subtilis ATCC9327, Bacillus subtilis ATCC6633, Bacillus subtilis ATCC9466, more preferably Bacillus subtilis SNU816 strain is inoculated at 1-3% by weight, preferably 2% by weight of soybean, fermented at 37 ° C. for 40 hours to 80 hours, preferably 72 hours, and added Lyophilized and powdered to obtain the functional cheonggukjang of the present invention.
또한 본 발명의 기능성 청국장은 상기 제법에 추가적으로 당업계의 통상적인 추출방법, 예를 들어 주정 또는 정제수로 온침 또는 냉침 추출하는 방법을 통하여 엑기스 형태로 얻은 후 이를 동결건조와 같은 건조방법을 수행하여 건조추출물형태를 얻음으로써 이를 제품화에 사용이 가능하게 제조될 수 있다.In addition, the functional Cheonggukjang of the present invention is obtained in extract form through a conventional extraction method in the art, for example, a hot or cold extract with spirit or purified water, followed by a drying method such as lyophilization, followed by drying. By obtaining the extract form it can be prepared to be used in commercialization.
본 발명의 상기 방법으로 수득된 기능성 청국장 또는 그 추출물은 정상쥐, 제2형 당뇨동물모델 및 제2형 당뇨환자에게 장기간 섭취시킨 경우, 혈장 중의 중성지방 및 콜레스테롤 측정 시험에서 중성지방, 콜레스테롤 함량을 감소시키는 효과를 보였으며, HDL-콜레스테롤 수치를 높이는 효과를 나타내었다. 또한 전혀 급성 독성을 나타내지 않는 등 부작용이나 독성 등의 문제가 없어, 안전하게 투여할 수 있는 약재로 지질농도 증가로 인한 질환을 예방 및 치료하기 위한 치료제로 이용하거나 기능성 식품의 유효성분으로도 이용할 수 있다.Functional cheonggukjang obtained by the above method of the present invention or extracts thereof in the normal rat, type 2 diabetic animal model and type 2 diabetic patients for a long time, the triglyceride and cholesterol content in the test of the measurement of triglyceride and cholesterol in plasma It has been shown to reduce the effects, and to increase the HDL-cholesterol level. In addition, there are no side effects or toxicity problems such as no acute toxicity at all, and can be safely used as a therapeutic agent for preventing and treating diseases caused by increased lipid concentration or as an active ingredient of functional foods. .
본 발명은 상기 방법으로 수득된 기능성 청국장 또는 그 추출물을 유효성분으로 함유하는 지질농도 증가로 인한 질환 예방 및 치료용 약학조성물을 제공한다. The present invention provides a pharmaceutical composition for preventing and treating diseases caused by increasing lipid concentration, which contains the functional Cheonggukjang obtained by the above method or its extract as an active ingredient.
특히 제 2형 당뇨질환에서, 혈중 지질농도 증가로 인한 심혈관질환의 예방 및 치료용 조성물로 사용할 수 있다.Particularly in type 2 diabetic diseases, it can be used as a composition for the prevention and treatment of cardiovascular diseases due to the increase in blood lipid concentration.
본 발명의 지질농도 증가로 인한 질환 예방 및 치료용 조성물은, 조성물 총 중량에 대하여 상기 청국장 또는 그 추출물을 0.1 ~ 80 % 중량으로 포함한다.The composition for preventing and treating diseases due to the increase in lipid concentration of the present invention, the total weight of the composition comprises 0.1 to 80% by weight of the Cheonggukjang or its extract.
본 발명의 청국장 또는 그 추출물을 포함하는 조성물은 약학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다. The composition comprising the cheonggukjang of the present invention or its extract may further include appropriate carriers, excipients and diluents commonly used in the preparation of pharmaceutical compositions.
또한, 본 발명의 조성물에는 필요에 따라 상기 청국장 또는 그 추출물 이외에 인체의 지질흡수를 억제하여 지질농도 증가로 인한 질환을 예방 및 치료하는데 사용되는 공지 물질 또는 새로운 물질을 추가로 포함하여 상승작용을 발휘할 수 있다.In addition, the composition of the present invention may exhibit synergism by additionally including known substances or new substances used to prevent and treat diseases caused by increasing lipid concentration by inhibiting lipid absorption of the human body in addition to the Cheonggukjang or its extracts as necessary. Can be.
본 발명에 따른 청국장 또는 그 추출물을 포함하는 조성물은, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있으며, 청국장 또는 그 추출물을 포함하는 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 청국장 또는 그 추출물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(calcium carbonate), 수크로스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스티레이트, 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는 데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈 (tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.Cheonggukjang or a composition containing the extract according to the present invention, respectively, according to a conventional method of powder or granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, oral formulations, such as external preparations, suppositories and sterile injectable solutions Carriers, excipients and diluents which may be formulated and used in the composition comprising Cheonggukjang or its extract may include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, Acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil Can be mentioned. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one excipient such as starch, calcium carbonate, water Prepared by mixing sucrose or lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium styrate and talc are also used. Liquid preparations for oral use may include various excipients, such as wetting agents, sweeteners, fragrances, preservatives, etc., in addition to water and liquid paraffin, which are commonly used to include suspensions, solutions, emulsions, and syrups. have. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
본 발명의 청국장 또는 그 추출물의 약학적 투여 형태는 단독으로 또는 타 약학적 활성 분획물과 결합뿐만 아니라 적당한 집합으로 사용될 수 있다. The pharmaceutical dosage forms of Chunggukjang or extracts thereof of the present invention may be used alone or in combination with other pharmaceutically active fractions, as well as in a suitable collection.
본 발명의 청국장 또는 그 추출물의 사용량은 환자의 나이, 성별, 체중에 따라 달라질 수 있으나, 일반적으로 0.01 내지 1000 mg/㎏의 양, 바람직하게는 0.1 내지 100 mg/㎏의 양을 일일 1회 내지 수회로 나누어 투여할 수 있다. 또한 그 청국장 또는 그 추출물의 투여량은 투여경로, 질병의 정도, 성별, 체중, 나이, 합병증 등을 포함한 환자의 상태에 따라 증감될 수 있다. 이 외에 환자의 생활스타일과 같은 환자의 요소와 약리학적 요소 등을 고려하여 환자에게 제공하여야 한다. 따라서, 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다. Cheonggukjang or the extract of the present invention may vary depending on the age, sex, and weight of the patient, but generally in an amount of 0.01 to 1000 mg / kg, preferably in an amount of 0.1 to 100 mg / kg once daily Can be administered in several divided doses. In addition, the dosage of the Cheonggukjang or its extract may be increased or decreased depending on the patient's condition, including the route of administration, degree of disease, sex, weight, age, complications, and the like. In addition, the patient should be provided to the patient in consideration of the patient's factors such as the patient's lifestyle and pharmacological factors. Therefore, the above dosage does not limit the scope of the present invention in any aspect.
본 발명의 약학 조성물은 쥐, 생쥐, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁내 경막 또는 뇌혈관내 (intracerebroventricular) 주사에 의해 투여될 수 있다. The pharmaceutical composition of the present invention can be administered to mammals such as rats, mice, livestock, humans by various routes. All modes of administration can be expected, for example by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.
본 발명은 지질대사 개선 또는 지질농도 증가로 인한 질환의 예방 효과를 나타내는 상기 제조방법으로 제조된 청국장 또는 그 추출물 및 식품학적으로 허용 가능한 식품보조 첨가제를 포함하는 건강기능식품을 제공한다. 본 발명의 건강기능식품은 산제, 과립제, 정제, 캡슐제, 환제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 약학투여형태 또는 건강음료형태가 바람직하다. 기능성 청국장 또는 그 추출물을 첨가할 수 있는 식품으로는, 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합제, 건강기능 식품류 등이 있다. The present invention provides a health functional food comprising Cheonggukjang or its extract and a food supplement acceptable food supplement additive prepared by the manufacturing method showing the prevention effect of the disease due to improved lipid metabolism or increased lipid concentration. The health functional food of the present invention is preferably in the form of a pharmaceutical or health beverage such as powders, granules, tablets, capsules, pills, suspensions, emulsions, syrups, aerosols. Examples of the food to which the functional Cheonggukjang or its extract can be added include various foods, beverages, gums, teas, vitamin complexes, and health functional foods.
또한 지질대사 개선 또는 지질농도 증가로 인한 질환의 예방을 목적으로 식품 또는 음료에 첨가될 수 있다. It may also be added to food or beverages for the purpose of improving the lipid metabolism or preventing diseases caused by increased lipid concentration.
이 때, 식품 또는 음료 중의 상기 청국장 또는 그 추출물의 양은, 일반적으로 본 발명의 건강기능식품 조성물의 경우는 전체 식품 중량의 0.1 내지 80 중량 %, 바람직하게는 1 내지 50 중량 %로 가할 수 있으며, 건강 음료 조성물에는 100㎖를 기준으로 1 ∼ 30 g, 바람직하게는 3 ∼10 g의 비율로 가할 수 있다. At this time, the amount of the Cheonggukjang or its extract in the food or beverage can be added to 0.1 to 80% by weight, preferably 1 to 50% by weight of the total functional food composition of the present invention, It can be added to the health beverage composition in the ratio of 1-30 g, Preferably it is 3-10 g based on 100 ml.
상기 외에 본 발명의 조성물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명의 조성물들은 천연 과일 쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다. In addition to the above, the composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof, alginic acid and its Salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. The compositions of the present invention may also contain pulp for the production of natural fruit juices and fruit juice beverages and vegetable beverages. These components can be used independently or in combination. The proportion of such additives is not so critical but is generally selected from the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.
이하, 본 발명을 실시예에 의해 상세히 설명한다.Hereinafter, the present invention will be described in detail by way of examples.
단, 하기 실시예 및 실험예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실시예 및 실험예에 의해 한정되는 것은 아니다.However, the following Examples and Experimental Examples are merely illustrative of the present invention, and the content of the present invention is not limited by the following Examples and Experimental Examples.
참조예 1. 혈장 총 콜레스테롤 측정Reference Example 1. Measurement of total plasma cholesterol
혈장 총 콜레스테롤의 측정은 살레의 방법(Sale, F.O., et al., Anal. Biochem., 142, pp347-348, 1984)에 기초를 하였다.The measurement of plasma total cholesterol was based on Saleh's method (Sale, FO, et al., Anal. Biochem. , 142 , pp347-348, 1984).
즉, 혈청 중에는 유리형 및 에스테르형 콜레스테롤이 존재하며 에스테르형에 콜레스테롤에스테르 가수분해효소(hydrolase)를 반응시키면 유리형과 지방산으로 분해되고 유리형에 콜레스테롤 산화효소를 반응시키면 H2O2와 δ-콜레스테논(Cholestenone)이 생성된다. 생성된 H2O2에 과산화효소와 4-아미노안티피린 및 페놀을 동시에 반응시키면 산화적 축합반응으로 퀴논이 생성되며 이를 비색하여 콜레스테롤을 정량하는 방법을 사용하여 37℃에서 5분간 반응시킨 후 500nm에서 검체 및 표준으로 흡광도를 측정하여 정량하였다.In other words, serum and free cholesterol are present in serum, and when the esterase reacts with cholesterol ester hydrolase, it is decomposed into free form and fatty acid, and when the free form reacts with cholesterol oxidase, H 2 O 2 and δ- Cholestenone is produced. When the peroxide enzyme, 4-aminoantipyrine and phenol are simultaneously reacted with the produced H 2 O 2 , quinone is produced by oxidative condensation reaction. Absorbance was measured and quantified by sample and standard.
참조예 2. 혈장 중성지방 측정Reference Example 2 Plasma Triglyceride Measurement
혈장 중 중성지방은 부오콜의 방법(Buoccole, G. and David, H. Clin. Chem., 19, pp476, 1973)에 기초를 하여 다음과 같은 방법으로 측정하였다.Triglycerides in plasma were measured by the following method based on Buoccole's method (Buoccole, G. and David, H. Clin. Chem., 19 , pp476, 1973).
중성지질은 트리글리세라이드는 리파아제에 의해서 글리세롤과 지방산으로 분해되고 글리세롤은 다시 글리세롤-1-포스페이트 변화되고 글리세롤-1-포스페이트는 GPO에 의해 분해되어 H2O2가 생성되며, 생성된 H2O2는 아미노아티피린 및 TOOS와 반응하여 산화적 축합반응으로 적색의 퀴논을 생성하며 이를 비색하여 중성지방을 정량하는 방법을 사용하여 37℃에서 5분간 반응시킨 후 546nm에서 검체 및 표준으로 흡광도를 측정하여 정량하였다.Neutral lipid is a triglyceride by the lipase is decomposed into glycerol and fatty acid glycerol is again changed glycerol-1-phosphate glycerol-1-phosphate is cleaved by the GPO H 2 O 2 is produced, and the produced H 2 O 2 Is reacted with aminoatiphyrin and TOOS to produce red quinone by oxidative condensation reaction, and it is reacted for 5 minutes at 37 ℃ by quantifying triglyceride by colorizing and measuring the absorbance with sample and standard at 546nm. Quantification
참조예 3. 통계분석Reference Example 3. Statistical Analysis
하기 모든 결과는 평균±표준오차로 나타내었으며, 대조군과 청국장군 사이의 유의성 검정은 스튜던트 t-테스트(Student's t-test)로 α = 0.05 수준에서 검정하였다.All of the following results were expressed as mean ± standard error, and the significance test between the control group and Cheonggukjang group was tested at the α = 0.05 level by the Student's t-test.
실시예 1. 청국장 제조법Example 1. Cheonggukjang Preparation
실험에 사용된 콩은 국산 대두를 사용하였다. 콩을 세척한 후 18시간 동안 물에 담구어 불린 다음 물빼기를 하고 가압증자기를 이용하여 121℃에서 15분간 증자(autoclave)한 후, 온도가 60℃가 되도록 방냉하였다. 2.4% 영양 한천(nutrient agar) 배지를 121℃에서 15분간 멸균시킨 뒤 패트리 접시에 담아 굳도록 한 다음 바실러스 서브틸리스(Bacillus subtillis)를 4분도말하여 인큐베이터에서 24시간 보관하였다. 0.8%의 액체배지를 제조하여 가압증자기에서 121℃에서 15분간 멸균한 뒤 60℃로 식힌 후, 패트리 접시에 4분도말하였던 바실러스 서브틸리스를 백금이를 이용해 액체배지로 옮겨 37℃에서 48시간동안 배양하였다. 액체배지에서 배양한 바실러스 서브틸리스를 콩 무게의 2%로 접종하여, 인큐베이터에서 37℃에 72시간 동안 발효시킨 후 얻어진 발효물을 동결건조시키고 분말화하여 하기 실험에 사용하였다.The soybeans used in the experiment were domestic soybeans. After washing the beans, soaked in water for 18 hours, soaked, drained and autoclave at 121 ° C. for 15 minutes using a pressurized steamer, and cooled to 60 ° C. 2.4% nutrient agar medium was sterilized at 121 ° C. for 15 minutes and then placed in a petri dish to solidify. Bacillus subtillis was then smeared for 4 minutes and stored in an incubator for 24 hours. 0.8% liquid medium was prepared and sterilized in a pressurized steamer at 121 ° C. for 15 minutes, cooled to 60 ° C., and then transferred to Bacillus subtilis, which had been smeared for 4 minutes in a petri dish, using platinum. Incubated for hours. Bacillus subtilis cultured in a liquid medium was inoculated at 2% of the weight of the beans, fermented at 37 ° C. for 72 hours in an incubator, and the obtained fermented product was lyophilized and powdered and used in the following experiment.
실시예 2. 정상쥐에 있어서 청국장의 혈중 지질 저하효과Example 2 Blood Lipid Lowering Effect of Cheonggukjang in Normal Rats
2-1. 실험동물의 사육2-1. Breeding of Experimental Animals
이유한 스프라그 도올리(Sprague Dawley, SD)계 웅성 흰쥐 (n=20)를 1주일간의 대조 식이(basal diet)로 적응시킨 후 각 군의 평균 체중이 동일하도록 난괴법으로 대조군 및 청국장군으로 두 군으로 나누었다. 각 군에게 AIN-76 식이를 기본으로 하여 제조한 대조 식이 또는 동결 건조한 청국장을 단백질 급원으로 하는 청국장함유 식이를 8주간 자유급식으로(ad libitum) 섭취시켰다.Weaned Sprague Dawley (SD) male rats (n = 20) were adapted to the basal diet for 1 week, and then the control group and Cheonggukjang group were treated by the ovary method so that the average weight of each group was the same. Divided into two groups. Each group was fed a control diet or a freeze-dried Cheonggukjang prepared on the basis of the AIN-76 diet for 8 weeks as ad libitum .
각 식이의 성분 및 함량은 표 1에 나타내었다. 청국장 함유 식이는 동결건조한 청국장을 39.3% 함유하도록 제조하였으며, 대조 식이의 단백질 급원은 카제인(casein), 청국장 함유 식이의 단백질 급원은 청국장으로 하였다. 두 종류 식이의 단백질, 지방, 총 식이섬유의 함량을 동량이 되게 하였고, 복합당과 단순당의 함량도 유사하도록 하였다. The components and contents of each diet are shown in Table 1. Cheonggukjang-containing diets were prepared to contain 39.3% of lyophilized Cheonggukjang. The protein source of the control diet was casein, and the protein source of the diet containing Cheonggukjang was Cheonggukjang. The contents of protein, fat and total fiber of the two diets were equalized, and the contents of complex and simple sugars were similar.
사육실의 온도 및 습도는 20∼25℃, 50∼60%로 유지하였고, 명암은 12시간 간격으로 점등 및 소등을 하였다. 동물 체중과 식이섭취량은 매주 3회 측정하였다.The temperature and humidity of the breeding room were maintained at 20 to 25 ℃, 50 to 60%, the contrast was turned on and off every 12 hours. Animal weight and dietary intake were measured three times weekly.
청국장을 8주간 섭취한 정상쥐에 있어서 식이섭취량 및 체중 증가량을 측정한 결과는 표 2 와 같다. 체중증가량 및 식이섭취량은 대조군과 청국장 섭취군간에 유의적인 차이가 없었다.Table 2 shows the results of measuring dietary intake and weight gain in normal rats ingested for 8 weeks. Body weight gain and dietary intake were not significantly different between the control group and Cheonggukjang intake group.
2-2. 동물 희생 및 콜레스테롤, 중성지방 함량 측정2-2. Animal Sacrifice and Cholesterol and Triglyceride Content Determination
실험동물에게 8주간 식이를 제공하여 사육한 후, 쥐를 14시간 동안 절식시키고 EDTA(ethylene diamine teteracetic acid)를 처리한 주사기로 심장에서 채혈하여 희생시킨 후, 혈액을 채취하여 3000rpm에서 15분 동안 4℃에서 원심분리 시킨 후 혈장(plasma)을 분리하였다. 혈장 총 콜레스테롤 및 중성지방 함량은 참조예 1 및 2의 방법에 따라 측정되었다.After feeding animals for 8 weeks, they were fed for 14 hours, sacrificed by collecting blood from the heart with a syringe treated with ethylene diamine teteracetic acid (EDTA), and collected blood for 15 minutes at 3000 rpm. After centrifugation at ℃ ℃ plasma (plasma) was separated. Plasma total cholesterol and triglyceride content were measured according to the methods of Reference Examples 1 and 2.
청국장군의 혈장 총 콜레스테롤의 함량이 59.97±4.12mg/dL로 나타나, 대조군(76.41±7.94mg/dL)에 비해 유의적으로 낮게 나타났다(p<0.05). 중성지방 함량도 대조군은 99.98±5.87mg/dL로 나타났으며, 청국장군은 87.93±3.07mg/dL로 유의적으로 낮게 나타났다(도 1 참조).The total cholesterol content of Chungkookjang group was 59.97 ± 4.12mg / dL, which was significantly lower than the control group (76.41 ± 7.94mg / dL) (p <0.05). The triglyceride content of the control group was 99.98 ± 5.87 mg / dL, and the Chungkookjang group was significantly lower (87.93 ± 3.07 mg / dL) (see Figure 1).
도 1은 정상쥐에 있어서 대조군과 청국장군의 콜레스테롤과 중성지방의 농도를 측정한 결과도이다.1 is a result of measuring the concentration of cholesterol and triglycerides in the control group and Cheonggukjang in normal mice.
따라서 장기간의 청국장 섭취는 고 중성지방혈증을 감소시켜 동맥경화증 유발 등 심혈관계 질환의 예방에 기여하리라고 볼 수 있다. Therefore, long-term Cheonggukjang intake can reduce hypertriglyceridemia and contribute to the prevention of cardiovascular diseases such as atherosclerosis.
실시예 3 : 당뇨쥐에 있어서 청국장의 지질대사 개선Example 3 Improvement of Lipid Metabolism in Cheonggukjang in Diabetic Rats
3-1. 실험동물3-1. Laboratory animals
건강한 스프라그 도올리(SD)계 흰쥐에게 출생 5일째에 스트렙토조토신 (STZ, Sigma Co., USA, 100mg/kg BW)을 대퇴부 근육에 1회 주사하여 당뇨병을 유발하였다. 스트렙토조토신은 0.1M 시트르산 완충액(citrate buffer, pH 4.5)에 용해시켜 사용하였다. 흰쥐를 생후 3주에 이유시키고, 정제형 식이(chow)를 10주간 자유급식으로(ad libitum) 섭취시켰다. 흰쥐를 밤 동안 12시간 절식시킨 후, 공복상태에서 꼬리 정맥으로부터 채혈하여 간이혈당계(Glucotrend, Germany)로 측정한 혈당 수준이 150mg/㎗ 이상일 때, 당뇨병이 유발된 동물로 제2형 당뇨모델로 하였다(Schaffer, S.W. and Mozaffari, M. CRC Press. pp231-255, 1996).Healthy Sprague-Dawley (SD) rats were induced with diabetes by injecting streptozotocin (STZ, Sigma Co., USA, 100 mg / kg BW) into the femoral muscles on the fifth day of birth. Streptozotocin was used by dissolving in 0.1M citric acid buffer (pH 4.5). Rats were weaned at 3 weeks of age and fed a tableted diet (chow) for 10 weeks in ad libitum . The rats were fasted for 12 hours during the night, and blood was collected from the tail vein in a fasted state, and the blood glucose level measured by the hepatic glucose level (Glucotrend, Germany) was 150 mg / ㎗ or more. (Schaffer, SW and Mozaffari, M. CRC Press. Pp231-255, 1996).
당뇨병이 유발된 흰쥐(n=18)를 각 군의 평균 체중이 같도록 난괴법으로 대조군 및 청국장군으로 두 군으로 나누어 카제인을 단백질 급원으로 하는 AIN-93G 식이와 동결 건조한 청국장을 단백질 급원으로 하는 청국장함유 식이를 8주 동안 자유급식으로 공급하였다. 대조군 식이와 청국장 함유 식이의 단백질, 지방 및 식이섬유 함량이 동일하게 하였고 복합당과 단순당의 비율도 동일하도록 하였고 청국장 식이는 40.1%의 청국장을 함유하도록 하였다(표 3 참조). Diabetes-induced rats (n = 18) were divided into two groups, the control group and the Cheonggukjang group, with the same weight of each group.The dietary source was AIN-93G with casein as the protein source and freeze-dried Cheonggukjang as the protein source. Cheonggukjang-containing diets were provided free of charge for 8 weeks. Protein, fat and fiber content of the control diet and Chungkookjang containing diet were the same, and the ratio of complex sugar and simple sugar was also the same, and the Chungkookjang diet contained 40.1% of Chungkookjang (see Table 3).
모든 동물은 온도 20∼25℃, 습도 50∼60%, 명암주기 12시간으로 조절되는 사육환경에서 실험을 하였다. 동물의 체중 변화 및 식이 섭취량을 사육기간 동안 매주 3회 측정하였다. All animals were tested in a breeding environment with a temperature of 20 to 25 ° C, a humidity of 50 to 60%, and a contrast cycle of 12 hours. Animal weight changes and dietary intake were measured three times a week during the breeding period.
청국장식이를 공급하기 전 대조군 및 청국장군의 체중은 각각 184.9 ± 9.8g, 176.0 ± 10.5g이었고 식이 섭취 8주째 체중은 대조군이 251.6 ± 10.0g, 청국장군이 242.9 ± 10.9g로 두 군 사이에 유의적인 차이가 없었다. 식이 섭취량 및 식이 효율도 두 군 사이에 유의적인 차이가 없었다(표 4 참조).The weight of the control group and Cheongguk-gun was 184.9 ± 9.8g and 176.0 ± 10.5g, respectively. There was no difference. There was no significant difference in dietary intake and dietary efficiency between the two groups (see Table 4).
3-2. 중성지방. 콜레스테롤, HDL-콜레스테롤 측정3-2. Triglycerides. Cholesterol, HDL-Cholesterol Measurement
식이 섭취 8주째 실험동물을 희생하였다. 실험동물은 희생하기 전 14시간 절식시킨 후 이산화탄소 가스로 질식시켜 EDTA(ethylene diamine tetraacetic acid)를 10㎎씩 넣은 주사기로 심장에서 채혈하였다. 혈액은 3,000rpm에서 15분간 원심 분리하여 혈장을 수집하여 -70℃에서 보관하였다. Animals were sacrificed at 8 weeks of diet. The animals were fasted for 14 hours before sacrifice and suffocated with carbon dioxide gas and blood was collected from the heart with a syringe containing 10 mg of EDTA (ethylene diamine tetraacetic acid). Blood was centrifuged at 3,000 rpm for 15 minutes to collect plasma and stored at -70 ° C.
혈장 총 콜레스테롤의 측정은 참고예 1의 살레의 방법을 사용하였고, 혈장 중 중성지방은 참고예 2의 부오콜의 방법을 사용하여 측정하였다.Plasma total cholesterol was measured using the method of Saleh of Reference Example 1, and triglycerides in plasma were measured using the method of Buchhol of Reference Example 2.
HDL(고밀도지단백)은 조직 중의 콜레스테롤을 받아 들여 간으로 운반함으로써 혈당 콜레스테롤 농도를 감소시켜 동맥경화를 예방하는 지단백이다. 혈장 고밀도 콜레스테롤은 다음과 같은 방법으로 실시하였다. 덱스트란 설페이트(Dextran sulfate)와 마그네슘 설페이트(magnesium sulfate)를 이용하여 LDL과 VLDL의 리포단백질(lipoprotein)을 침전시킨 후, 상층에 남아있는 HDL층의 측정하는 방법을 사용하여 37℃에서 15분간 반응시킨 다음, 500nm에서 검체 및 표준으로 흡광도를 측정하여 정량하였다.HDL (High Density Lipoprotein) is a lipoprotein that prevents arteriosclerosis by reducing blood glucose levels by taking cholesterol from tissues and transporting it to the liver. Plasma high density cholesterol was performed by the following method. Precipitate the lipoproteins of LDL and VLDL using dextran sulfate and magnesium sulfate, and then react for 15 minutes at 37 ° C using the method of measuring the HDL layer remaining on the upper layer. Next, the absorbance was measured and quantified by a sample and a standard at 500 nm.
대조군 및 청국장군의 혈장 중성지방과 콜레스테롤, HDL-콜레스테롤의 농도는 표 5에 나타난 바와 같다. The concentrations of plasma triglycerides, cholesterol, and HDL-cholesterol in the control and Cheonggukjang groups are shown in Table 5.
청국장군의 혈장 총 콜레스테롤의 함량이 98.8±8.5mg/dL로 나타나, 대조군(137.4±11.0mg/dL)에 비해 유의적으로 낮게 나타났다(p<0.05). 중성지방 함량도 대조군은 80.8±4.0mg/dL로 나타났으며, 청국장군은 67.3±4.3mg/dL로 유의적으로 낮게 나타났다The total cholesterol content of Chungkookjang was 98.8 ± 8.5mg / dL, which was significantly lower than the control group (137.4 ± 11.0mg / dL) (p <0.05). The triglyceride content of the control group was 80.8 ± 4.0mg / dL, and the Cheongguk-gun group was 67.3 ± 4.3mg / dL.
표 5에서 볼 수 있는 바와 같이, 청국장군이 혈중 중성지방 농도가 67.3 ± 4.3mg/dL, 콜레스테롤 농도가 98.8 ± 8.5mg/dL로 대조군에 비해 유의적으로 감소하였다. HDL-콜레스테롤의 농도는 두 군 사이에 유의적인 차이가 없었다.As can be seen in Table 5, the Chungkookjang group had significantly decreased blood triglyceride concentration of 67.3 ± 4.3 mg / dL and cholesterol concentration of 98.8 ± 8.5 mg / dL compared to the control group. The concentration of HDL-cholesterol was not significantly different between the two groups.
따라서 청국장에 함유된 식이섬유질과 단백질, 그리고 콩의 발효과정에 생성된 물질들이 지질저하효과에 기여한 것으로 사료된다. Therefore, the dietary fiber and protein contained in Chunggukjang and the substances produced during fermentation of soybean contributed to the hypolipidemic effect.
실시예 4 : 당뇨환자에 있어서 지질대사 개선효과Example 4 Improvement of Lipid Metabolism in Diabetic Patients
본 발명의 기능성 청국장을 당뇨환자의 혈중 지질 함량 개선에 효과가 있는지 확인하기 위하여, 제 2형 당뇨환자 9명(남자 4명, 여자 5명, 평균연령 63.4±3.2세)에게 12주간 매일 본 발명의 청국장 100 g을 섭취하도록 하였다. 환자는 실험 기간동안 실험 시작 이전부터 복용해 온 경구혈당강하제를 지속적으로 복용하였으며, 일상적인 식생활 및 생활습관을 유지하도록 하였다. In order to determine whether the functional Cheonggukjang of the present invention is effective in improving blood lipid content in diabetic patients, the present invention was administered to 9 patients with type 2 diabetes (4 males, 5 females, and an average age of 63.4 ± 3.2 years) for 12 weeks 100 g of Cheonggukjang was taken. Patients continued to take oral glucose-lowering medications taken prior to the start of the study and maintained their daily diet and lifestyle.
실험시작 전 환자의 신장과 체중을 측정하여 체질량지수(body mass index, BMI, kg/m2)를 계산하였고, 혈압계로 혈압을 측정하였으며, 바이오임페던스 분석기(Bioimpedance analyzer, 타니카사, 일본)으로 체지방을 측정하였다. 청국장 섭취기간 시작 전 및 종료 후 공복 상태의 환자의 정맥에서 채혈하여 혈장을 분리하였다. 공복 혈장의 중성지방, 콜레스테롤, HDL-콜레스테롤의 농도는 각각 효소법으로 측정하였다.The body mass index (BMI, kg / m 2 ) was calculated by measuring the height and weight of the patient before the start of the experiment, and the blood pressure was measured by a blood pressure monitor, using a bioimpedance analyzer (Tanikas, Japan). Body fat was measured. Plasma was isolated from the vein of a fasting patient before and after the beginning of the Cheonggukjang intake period. The concentrations of triglyceride, cholesterol, and HDL-cholesterol in fasting plasma were measured by enzyme method, respectively.
모든 결과는 평균±표준오차로 나타내었으며, 청국장 섭취기간 전 및 12주간의 섭취기간 종료 후의 측정치에 대한 유의성 검증은 대응표본 T 검정(paired t-test)을 사용하여 실시하였다(α=0.05).All results were expressed as mean ± standard error. The significance test for the measurements before and after the 12-week intake period was A paired t-test was used (α = 0.05).
표 6을 보면, 실험대상자의 평균연령은 63.8±3.9세, 평균 유병기간은 6.5년±1.8 년이었다. 실험대상자의 평균체질량지수는 28.1±4.5 kg/m2, 체지방은 28.4±2.1 %이었으며, 최고 혈압 및 최저혈압은 각각 144.6±8.0 mmHg, 81.5±2.8 mmHg이었다. 당뇨환자 중에서 8명은 경구혈당 강하제로 설폰요소제를, 1명은 비구아나이드를 복용하였다.In Table 6, the mean age of the subjects was 63.8 ± 3.9 years and the mean disease duration was 6.5 years ± 1.8 years. The mean BMI of the test subjects was 28.1 ± 4.5 kg / m 2 and body fat was 28.4 ± 2.1%. The highest and lowest blood pressures were 144.6 ± 8.0 mmHg and 81.5 ± 2.8 mmHg, respectively. Among the diabetic patients, 8 patients received oral hypoglycemic agent and sulfone urea, and 1 patient received biguanide.
당뇨환자의 혈장 지질 농도는 표 7에 나타내었다. 당뇨환자의 공복 혈장 중성지방 농도는 청국장 섭취 전에 171.7±15.0 mg/dL이었으나 섭취 후 150.0±17.0 mg/dL로 유의적으로 감소하였다(21.7±5.1 mg/dL). 공복 혈장 콜레스테롤 농도는 청국장 섭취 전에 215.3±13.5 mg/dL이었으나, 청국장 섭취 12주 후에 유의적으로 감소하여(14.4±6.0 mg/dL) 200.9±12.0 mg/dL로 나타났다. 공복 혈장 HDL-콜레스테롤 농도는 청국장 섭취 전, 후에 각각 38.8±2.5 mg/dL 및 45.2±3.0 mg/dL로 나타나, 청국장의 섭취로 유의적으로 증가하였다. The plasma lipid concentrations of diabetic patients are shown in Table 7. Fasting plasma triglyceride levels in diabetic patients were 171.7 ± 15.0 mg / dL before cheonggukjang intake, but significantly decreased to 150.0 ± 17.0 mg / dL after intake (21.7 ± 5.1 mg / dL). Fasting plasma cholesterol concentration was 215.3 ± 13.5 mg / dL before Cheonggukjang intake, but significantly decreased (14.4 ± 6.0 mg / dL) after 12 weeks of Cheonggukjang intake, showing 200.9 ± 12.0 mg / dL. Fasting plasma HDL-cholesterol concentrations were 38.8 ± 2.5 mg / dL and 45.2 ± 3.0 mg / dL, respectively, before and after cheonggukjang intake, and were significantly increased by intake of cheonggukjang.
본 연구에서는 청국장을 장기간 섭취시킨 경우 당뇨환자의 혈중 중성지방 및 콜레스테롤 농도가 감소하고, HDL-콜레스테롤 농도가 증가되어 당뇨환자의 지질 대사를 개선시키는 것으로 나타났다. In the present study, long-term intake of cheonggukjang reduced blood triglyceride and cholesterol levels in diabetic patients, and increased HDL-cholesterol levels, which improved lipid metabolism in diabetic patients.
본 발명의 청국장은 장기복용 시에는 정상쥐 및 당뇨쥐 그리고 당뇨환자에 있어서 혈장 중성지방과 콜레스테롤 농도를 저하시켰다, 따라서 청국장은 아테롬성 동맥경화증의 예방 및 치료에 유용할 뿐만 아니라, 혈중 지질농도의 증가로 인해 야기되는 각종 순환계질환의 예방 및 치료에도 매우 유용할 것으로 예상된다. Cheonggukjang of the present invention lowered plasma triglyceride and cholesterol concentrations in normal rats, diabetic rats and diabetic patients during long-term use. It is expected to be very useful for the prevention and treatment of various circulatory diseases caused by.
도 1은 정상쥐에 있어서 대조군과 청국장군의 콜레스테롤과 중성지방의 농도를 측정한 결과도이다.1 is a result of measuring the concentration of cholesterol and triglycerides in the control group and Cheonggukjang in normal mice.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101154220B1 (en) * | 2008-11-24 | 2012-06-21 | 한국식품연구원 | Composition comprising the powder of a fermented Chungkukjang or the extracted fraction of a fermented Chungkukjang for treating and preventing ischemia damage disease |
| KR101349140B1 (en) * | 2012-01-30 | 2014-01-10 | 한국식품연구원 | Compositions for Preventing or Treating Metabolic Disease Comprising Jerusalem Artichoke and Cheonggukjang as Active Ingredients |
| KR20170011908A (en) * | 2015-07-24 | 2017-02-02 | 강원대학교산학협력단 | Composition comprising an extract of Cheonggukjang for preventing or treating radiation syndrome |
| KR20170097586A (en) * | 2016-02-18 | 2017-08-28 | 강원대학교산학협력단 | Composition for anti-allergy comprising fermented soybean extract as effective component and production method thereof |
| WO2021045554A1 (en) * | 2019-09-05 | 2021-03-11 | 장영진 | Pharmaceutical composition comprising processed fish product and/or processed soybean product as active ingredient |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101154220B1 (en) * | 2008-11-24 | 2012-06-21 | 한국식품연구원 | Composition comprising the powder of a fermented Chungkukjang or the extracted fraction of a fermented Chungkukjang for treating and preventing ischemia damage disease |
| KR101349140B1 (en) * | 2012-01-30 | 2014-01-10 | 한국식품연구원 | Compositions for Preventing or Treating Metabolic Disease Comprising Jerusalem Artichoke and Cheonggukjang as Active Ingredients |
| KR20170011908A (en) * | 2015-07-24 | 2017-02-02 | 강원대학교산학협력단 | Composition comprising an extract of Cheonggukjang for preventing or treating radiation syndrome |
| KR20170097586A (en) * | 2016-02-18 | 2017-08-28 | 강원대학교산학협력단 | Composition for anti-allergy comprising fermented soybean extract as effective component and production method thereof |
| WO2021045554A1 (en) * | 2019-09-05 | 2021-03-11 | 장영진 | Pharmaceutical composition comprising processed fish product and/or processed soybean product as active ingredient |
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