KR102123838B1 - lactobacillus for lowering blood glucose MG5012 - Google Patents
lactobacillus for lowering blood glucose MG5012 Download PDFInfo
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- KR102123838B1 KR102123838B1 KR1020190168222A KR20190168222A KR102123838B1 KR 102123838 B1 KR102123838 B1 KR 102123838B1 KR 1020190168222 A KR1020190168222 A KR 1020190168222A KR 20190168222 A KR20190168222 A KR 20190168222A KR 102123838 B1 KR102123838 B1 KR 102123838B1
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- South Korea
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- strain
- lactobacillus paracasei
- diabetes
- cell
- strains
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Abstract
Description
본 발명은 혈당 저하 효과를 갖는 락토바실러스 균주, 균주 배양액 및 균주의 무세포 상등액에 관한 것이며, 이를 포함하는 혈당 저하용 조성물, 당뇨병 예방 또는 치료용 약학적 조성물, 당뇨병 예방 또는 개선용 건강기능식품 및 당뇨병 예방 또는 개선용 의약외품 조성물에 관한 것이다.The present invention relates to a cell-free supernatant of a Lactobacillus strain, a strain culture, and a strain having a blood sugar lowering effect, a composition for lowering blood sugar, a pharmaceutical composition for preventing or treating diabetes, a health functional food for preventing or improving diabetes, and It relates to a quasi-drug composition for preventing or improving diabetes.
서구화된 식생활과 운동부족으로 인해 각종 생활관련 성인병의 발병률이 높아지고 있는데, 특히, 식생활의 변화는 사람의 소화관 미생물총에 변화를 가져오고, 이로 인해 소화관 내에 소화관 미생물총이 생산하는 내독소가 증가하게 된다. 소화관 내에 내독소가 증가하는 경우 소화관 염증이 유발되고 내독소의 체내로의 흡수가 높아지며 대식세포의 지방조직 등으로의 이동을 촉진하여 비만 또는 고혈당을 유발하게 된다. 따라서 소화관 미생물총이 생산하는 내독소를 제어하는 것을 통해, 혈당을 제어할 수 있고, 궁극적으로 당뇨병을 개선하거나 치료할 수 있을 것으로 알려져 있다. Due to the westernized diet and lack of exercise, the incidence of various lifestyle-related adult diseases is increasing. In particular, changes in diet cause changes in the microflora of the human digestive tract, thereby increasing the endotoxin produced by the microflora of the digestive tract within the digestive tract. do. When the endotoxin increases in the digestive tract, inflammation of the digestive tract is induced, absorption of the endotoxin into the body is increased, and the movement of macrophages to adipose tissue is promoted, leading to obesity or hyperglycemia. Therefore, it is known that by controlling the endotoxin produced by the microflora of the digestive tract, blood sugar can be controlled, and ultimately, diabetes can be improved or treated.
당뇨병은 대표적인 만성질환으로 포도당을 비롯한 여러 대사 장애로 망막, 신장 및 신경 등의 미세혈관 합병증과 중풍, 협심증, 심근경색증 및 말초 혈관 질환 등의 대혈관 합병증을 초래하는 만성적인 질병이다. 혈당 조절을 위한 약물요법은 인슐린 및 화학물질을 사용하고 있어 약물 복용에 따른 부작용과 환자의 내성이 끊임없이 문제가 되고 있다. Diabetes mellitus is a chronic disease that causes microvascular complications such as retina, kidney and nerve, and large vessel complications such as paralysis, angina, myocardial infarction, and peripheral vascular disease due to various metabolic disorders including glucose. Drug therapy for blood sugar control uses insulin and chemicals, so side effects of drug use and patient resistance are constantly becoming a problem.
당뇨병은 췌장 세포에서 분비되는 인슐린의 분비 장애 및 작용 부족에 의해 유발된 대사 장애로, 포도당의 과잉생산, 체지방의 분해 및 단백질의 낭비를 수반하고 글루카곤의 분비를 비정상적으로 항진시켜 대사상의 혼란을 야기 시킨다. 당뇨병의 경우 인슐린을 비롯한 호르몬 불균형으로 탄수화물을 비롯한 단백질, 지질 및 전해질 대사 등 생리적 대사 조절 기능 이상으로 고혈당의 특징적인 증세를 나타내며, 이러한 고혈당 증세가 지속되면 혈액순환 장애, 망막손상, 신경세포 손상, 신장 기능 저하 및 혈관 합병증을 유발한다.Diabetes mellitus is a metabolic disorder caused by impaired insulin secretion and lack of action secreted by pancreatic cells, which is accompanied by overproduction of glucose, decomposition of body fat, and wasted protein and abnormally promotes glucagon secretion, causing metabolic disruption Order. In the case of diabetes, the imbalance of hormones, including insulin, is a characteristic symptom of hyperglycemia with abnormal physiological metabolic functions such as protein, lipid, and electrolyte metabolism including carbohydrate, and if such hyperglycemia symptoms persist, blood circulation disorder, retinal damage, nerve cell damage, Causes kidney function decline and vascular complications.
당뇨병은 크게 2가지 유형, 즉 제1형 당뇨병과 제2형 당뇨병으로 분류되고 있는데, 1형 당뇨병은 혈액 내의 글루코스 조절 호르몬인 인슐린(Insulin)의 분비 결핍으로 야기되며, 주로 10 내지 20대의 젊은 연령층에서 발병된다. 제2형 당뇨병은 주로 40대 이후에 발병되며, 당뇨병 환자의 대부분을 차지한다. 제2형 당뇨병의 병인으로 췌장 베타세포에서 인슐린 분비의 장애와 표적세포에서 인슐린 작용의 결함(인슐린 저항성)이 모두 관찰된다. 인슐린저항성은 말초조직에서 인슐린의 작용이 저하된 상태로 제2형 당뇨병을 유발하는 주된 원인이 된다.Diabetes is largely classified into two types, namely
당뇨병 치료에 있어서 가장 중요한 목표는 혈당치를 가능한 정상치에 가깝게 조절하는 것인데 치료 방법으로 약물요법, 식이요법 및 운동요법이 있다. 현재 당뇨병환자에게 사용되는 경구혈당강하제로 α-글루코시다제(α-glucosidase) 억제제, 설포닐우레아(sulfonylurea) 제제 및 비구아니드(biguanide) 제제가 있으며, α-글루코시다제 억제제는 섭취한 식이 중의 탄수화물의 소화와 흡수를 지연시켜 식후 혈당 및 혈중 인슐린의 상승을 감소시킴으로써 당뇨병의 치료효과를 나타낸다. α-글루코시다제 저해제는 고인슐린혈증이나 저혈당을 유발하지 않고, 인슐린분비를 촉진시키며 글루카곤 분비를 억제하는 글루카곤-유사-펩티드-1(glucagon-likepeptide-1)의 소장에서의 분비를 촉진하는 장점을 가지고 있다.The most important goal in the treatment of diabetes is to control blood sugar levels as close to normal as possible, and treatment methods include drug therapy, diet therapy, and exercise therapy. Oral hypoglycemic agents currently used in diabetic patients include α-glucosidase inhibitors, sulfonylurea agents and biguanide agents, and α-glucosidase inhibitors intake It delays the digestion and absorption of carbohydrates in the liver and reduces the rise in blood sugar and insulin in the blood after eating, thereby showing the therapeutic effect of diabetes. α-glucosidase inhibitor does not induce hyperinsulinemia or hypoglycemia, and promotes insulin secretion and inhibits glucagon secretion, thereby promoting glucagon-likepeptide-1 secretion in the small intestine. Have
현재 임상에서 사용하고 있는 것으로는 아카보스(acarbose), 보길리보스(voglibose) 및 미글리톨(miglitol) 등이 있으나, α-글루코시다제 저해제를 장기 복용한 경우 일부 환자에 있어서 복부 팽만감, 구토 또는 설사 등 부작용을 나타낼 수 있어 그 사용이 제한될 수 있다.Currently used in clinical trials include acarbose, voglibose, and miglitol, but in the case of long-term use of α-glucosidase inhibitors, abdominal bloating, vomiting, or diarrhea in some patients Side effects may be present, and their use may be limited.
따라서, 당뇨병 치료에 있어 식이가 가능하며 부작용이 적은 천연물을 이용하여 당뇨병을 예방, 개선 또는 치료에 대한 연구 및 복부 비만, 고지혈증, 당뇨병, 고혈압 등을 예방하거나 치료 효과가 있는 물질에 대한 개발이 요구되고 있다.Therefore, research on prevention, improvement or treatment of diabetes by using natural products that are dietary and have fewer side effects in the treatment of diabetes, and development of substances that prevent or treat abdominal obesity, hyperlipidemia, diabetes, hypertension, etc. Is becoming.
삭제delete
이에 본 발명자들은 당뇨병의 발생 및 재발 위험을 막고, 현재 당뇨병 치료제로 사용되는 약물에 대한 대안으로 프로바이오틱스를 연구한 결과, 유산균 중 우수한 α-glucosidase 억제 효과를 지니는 다양한 종의 유산균주를 선별하고 특성을 확인하여, 높은 혈당 조절 능력을 지니는 유산균주를 확보함으로써 본 발명을 완성하였다.Accordingly, the present inventors prevented the risk of developing and recurring diabetes and, as a result of studying probiotics as an alternative to drugs currently used as a therapeutic agent for diabetes, selected and characterized the lactic acid bacteria of various species having excellent α-glucosidase inhibitory effect among lactic acid bacteria. By confirming, the present invention was completed by securing a lactic acid bacteria strain having high blood sugar control ability.
따라서, 본 발명의 목적은 혈당 저하 활성을 갖는 락토바실러스 균주, 상기 균주의 배양액 및 상기 균주의 무세포 상등액을 제공하는 것이다.Accordingly, an object of the present invention is to provide a lactobacillus strain having a blood sugar lowering activity, a culture solution of the strain and a cell-free supernatant of the strain.
또한, 본 발명의 목적은 상기 균주, 배양액 또는 상등액을 포함하는 혈당 저하용 조성물 또는 당뇨병 예방 또는 개선용 조성물을 제공하는 것이다.In addition, an object of the present invention is to provide a composition for preventing or improving diabetes or a composition for lowering blood sugar, including the strain, culture solution, or supernatant.
상기 목적을 달성하기 위하여, 본 발명은 혈당 저하 활성을 갖는 락토바실러스 파라카세이(Lactobacillus paracasei) MG5012 균주를 제공한다.In order to achieve the above object, the present invention provides a Lactobacillus paracasei MG5012 strain having a hypoglycemic activity.
또한, 본 발명은 상기 균주, 상기 균주의 배양액 및 상기 균주의 무세포 상등액으로 이루어진 군에서 선택된 1종 이상을 포함하는 조성물을 제공한다.In addition, the present invention provides a composition comprising at least one selected from the group consisting of the strain, the culture solution of the strain and the cell-free supernatant of the strain.
또한, 본 발명은 상기 조성물을 포함하는 혈당 저하용 건강기능식품 조성물을 제공한다.In addition, the present invention provides a health functional food composition for lowering blood sugar containing the composition.
또한, 본 발명은 상기 조성물을 포함하는 당뇨병 예방 또는 치료용 약학적 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for preventing or treating diabetes comprising the composition.
또한, 본 발명은 상기 조성물을 포함하는 당뇨병 예방 또는 개선용 건강기능식품 조성물을 제공한다.In addition, the present invention provides a health functional food composition for preventing or improving diabetes comprising the composition.
또한, 본 발명은 상기 조성물을 포함하는 당뇨병 예방 또는 개선용 의약외품 조성물을 제공한다.In addition, the present invention provides a quasi-drug composition for preventing or improving diabetes comprising the composition.
본 발명의 락토바실러스 파라카세이 MG5012 균주는 혈당 저하 활성이 뛰어나며, 내산성, 내담즙성, 자가 응집능 및 상피 세포 부착능이 뛰어나 프로바이오틱스에 적합하므로 당뇨병 예방 또는 치료용 조성물 등으로 다양하게 활용될 수 있다.The Lactobacillus paracasei MG5012 strain of the present invention is excellent in blood sugar lowering activity, has excellent acid resistance, bile resistance, self-aggregation ability and epithelial cell adhesion ability and is suitable for probiotics, and thus can be used in various ways as a composition for preventing or treating diabetes.
도 1은 MG4296 균주 및 MG5012 균주의 계통도를 나타낸 도이다.
도 2는 MG4296 균주 및 MG5012 균주의 내당능성을 측정하기 위한, 혈당 곡선을 나타낸 도이다.
도 3은 MG5012 균주의 인슐린 저항성 개선 효과를 측정하기 위해, MG5012 균주 처리에 따른 3T3-L1 세포의 포도당 소비량을 측정한 도이다.
도 4는 MG4296과 MG5012 균주를 처리한 당뇨 동물 모델에 MG4296 또는 MG5012을 처리하고, 12주 동안 매주 체중을 측정한 것을 나타낸 도이다.
도 5는 MG4296과 MG5012 균주를 처리한 당뇨 동물 모델에 글루코스 용액을 복강 내 주사하고, 0분, 15분, 30분, 60분, 90분 및 120분에 혈당을 측정한 것을 나타낸 도이다.1 is a diagram showing a phylogenetic diagram of MG4296 strain and MG5012 strain.
2 is a diagram showing a blood sugar curve for measuring glucose tolerance of the MG4296 strain and the MG5012 strain.
FIG. 3 is a graph measuring glucose consumption of 3T3-L1 cells according to treatment with MG5012 strain in order to measure the effect of improving the insulin resistance of MG5012 strain.
FIG. 4 is a diagram showing that MG4296 or MG5012 was treated in a diabetic animal model treated with MG4296 and MG5012 strains, and body weight was measured weekly for 12 weeks.
5 is a diagram showing the glucose solution intraperitoneally injected into a diabetic animal model treated with MG4296 and MG5012 strains, and measuring blood glucose at 0, 15, 30, 60, 90, and 120 minutes.
본 발명은 혈당 저하 활성을 갖는 락토바실러스 파라카세이(Lactobacillus paracasei) MG5012 균주를 제공한다.The present invention provides a Lactobacillus paracasei MG5012 strain having hypoglycemic activity.
본 발명의 락토바실러스 파라카세이 MG5012 균주는 우수한 α-글루코시데이즈(α-glucosidase) 저해활성, α-아밀레이즈(α-amylase) 저해활성 및 인슐린 저항성 개선 효과에 기초하여 혈당 저하 활성이 우수하며, 내산성, 내담즙성, 자가응집성 및 장 내 상피 세포 부착능이 뛰어나다.The Lactobacillus paracasei MG5012 strain of the present invention has excellent blood glucose lowering activity based on excellent α-glucosidase inhibitory activity, α-amylase inhibitory activity and insulin resistance improving effect, It has excellent acid-resistance, bile-resistance, self-aggregation, and ability to attach epithelial cells in the intestine.
이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
상기 락토바실러스 파라카세이 MG5012 균주는 혈당 저하 활성을 갖는 균주이다.The Lactobacillus paracasei MG5012 strain is a strain having hypoglycemic activity.
본 발명에서 용어, "혈당 저하 활성"은 혈액 내 포도당 농도를 나타내는 수치인 혈당을 낮추는 효과를 일컫는 것이다. 인체는 항상성을 유지하기 위하여 혈당 수치를 일정한 범위 내에 유지하는 것이 바람직하다. 고혈당은 혈당치가 비정상적으로 높은 상태를 의미하는 것으로, 식사 후 일시적으로 나타나는 고혈당은 자연적인 현상으로 생리적 고혈당이라고 한다. 그러나, 이를 벗어나는 범위로 혈당치가 증가하거나 고혈당 상태가 지속되는 것은 당뇨가 발병하였거나, 당뇨로 진행할 가능성이 있거나, 당뇨가 발병하였으나 미발견된 상태일 가능성이 높다. 미국식약청 규정상 정상혈당수치는 100 mg/dl 미만의 공복혈당 및 140 mg/dl 미만의 식후 2시간 혈당으로 규정하고 있으며, 126 mg/dl 이상의 공복혈당 및 200 mg/dl 이상의 식후 2시간 혈당을 나타내는 경우를 당뇨병이라 진단한다. 한편, WHO는 110 mg/dl 미만의 공복혈당을 정상수준으로 정의하고 있다. 당뇨병으로 진단되는 수치 미만일 지라도 정상상태보다 높은 고혈당 상태가 지속되는 경우 지방간을 유발하여 중증 간질환으로 진행할 위험성을 증가시키며 심혈관 질환 및 이의 합병증을 유발할 수 있다. 체내에서는 정상 혈당수준을 유지하기 위하여 글루카곤, 아드레날린, 인슐린, 갑상선 호르몬 등이 작용한다. 이러한 호르몬의 분비 및/또는 활성에 이상이 발생하면 고혈당이 발생할 수 있다. 또한 과다한 당의 섭취, 운동부족 및/또는 스트레스도 고혈당의 원인이 된다. 본 발명의 락토바실러스 파라카세이 MG5012 균주는 α-글루코시데이즈(α-glucosidase) 저해활성, α-아밀레이즈(α-amylase) 저해활성 및 인슐린 저항성 개선 효과에 기초한 혈당 저하 효과를 나타내므로, 고혈당으로 인해 유발되는 질환에 대한 예방 및 개선 효과를 가질 수 있다.In the present invention, the term, "blood sugar lowering activity" refers to the effect of lowering blood sugar, which is a value indicating the concentration of glucose in the blood. It is desirable for the human body to maintain blood sugar levels within a certain range in order to maintain homeostasis. Hyperglycemia refers to an abnormally high blood sugar level. Hyperglycemia, which appears temporarily after eating, is a natural phenomenon and is called physiological hyperglycemia. However, an increase in blood glucose level or a persistent hyperglycemic state in a range beyond this is likely to have diabetes, may progress to diabetes, or may have diabetes, but is undiscovered. According to the US Food and Drug Administration, normal blood sugar levels are defined as fasting blood glucose of less than 100 mg/dl and 2 hour postprandial blood sugar of less than 140 mg/dl, and fasting blood glucose of 126 mg/dl or more and 2 hour postprandial blood sugar of 200 mg/dl or more. Diabetes is diagnosed. Meanwhile, WHO defines fasting blood glucose of less than 110 mg/dl as a normal level. Even if the level diagnosed as diabetes is high, a high blood sugar level higher than the normal state may cause fatty liver to increase the risk of progressing to severe liver disease and cause cardiovascular disease and complications thereof. In the body, glucagon, adrenaline, insulin, and thyroid hormones act to maintain normal blood sugar levels. If an abnormality occurs in the secretion and/or activity of these hormones, hyperglycemia may occur. In addition, excessive sugar intake, lack of exercise and/or stress can also contribute to high blood sugar. Since the Lactobacillus paracasei MG5012 strain of the present invention exhibits a hypoglycemic effect based on α-glucosidase inhibitory activity, α-amylase inhibitory activity and insulin resistance improving effect, it is a hyperglycemia. It may have a preventive and improved effect on the disease caused.
본 발명에서 용어, "락토바실러스"는 자연계에 널리 분포하는 당류를 발효하여 에너지를 획득하여 다량의 유산을 생성하는 세균으로 형태적으로는 그람 양성 무포자 간균으로 다형성을 나타낸다. 본 발명에 따른 혈당 저하 활성이 뛰어나며, 내산성, 내담즙성, 자가응집성 및 상피 세포 부착능이 뛰어난 락토바실러스 플란타룸 MG4296 균주는 각각 한국생명공학연구원에 2019.03.26일자로 기탁하여 기탁번호 KCTC13830BP를 부여받았다. 본 발명에 따른 혈당 저하 활성이 뛰어나며, 내산성, 내담즙성, 자가응집성 및 상피 세포 부착능이 뛰어난 락토바실러스 파라카세이 MG5012 균주는 한국생명공학연구원에 2019.03.26일자로 기탁하여 기탁번호 KCTC13831BP를 부여받았다. 본 발명자들은 락토바실러스 파라카세이 MG5012 균주를 하기와 같이 규명하였다.In the present invention, the term "lactobacillus" is a bacterium that generates a large amount of lactic acid by obtaining energy by fermenting sugars widely distributed in nature, and morphologically refers to polymorphism as Gram-positive apoptotic bacilli. The Lactobacillus plantarum MG4296 strain, which has excellent blood glucose lowering activity according to the present invention, and is excellent in acid resistance, bile resistance, self-aggregation, and epithelial cell adhesion, was deposited with the Korea Research Institute of Bioscience and Biotechnology on March 26, 2019, and assigned a deposit number KCTC13830BP received. Lactobacillus paracasei MG5012 strain excellent in blood glucose lowering activity according to the present invention, excellent in acid resistance, bile resistance, self-aggregation and epithelial cell adhesion was deposited with the Korea Research Institute of Bioscience and Biotechnology on March 26, 2019, and was given a deposit number KCTC13831BP. The present inventors have identified the Lactobacillus paracasei MG5012 strain as follows.
본 발명에 따른 락토바실러스 균주를 분리하기 위하여 유산균 237개의 균주 중에서 혈당 강화 활성이 가장 뛰어난 균주 2종류를 선별하여 이를 동정한 결과, 락토바실러스 플란타룸 MG4296 균주 및 락토바실러스 파라카세이 MG5012인 것을 동정하였다.In order to separate the Lactobacillus strain according to the present invention, two strains having the highest blood sugar enhancing activity among 237 lactic acid bacteria were selected and identified, and as a result, Lactobacillus plantarum MG4296 strain and Lactobacillus paracasei MG5012 were identified. .
본 발명의 상기 락토바실러스 파라카세이 MG5012 균주는 혈당 저하 활성이 우수하다.The Lactobacillus paracasei MG5012 strain of the present invention is excellent in blood glucose lowering activity.
본 발명의 상기 락토바실러스 파라카세이 MG5012 균주는 α-글루코시데이즈(α-glucosidase) 저해 활성이 우수하다.The Lactobacillus paracasei MG5012 strain of the present invention has excellent α-glucosidase inhibitory activity.
α-글루코시데이즈의 활성이 저해되면, 당의 소화와 흡수가 지연되어 식후 고혈당을 낮출 수 있다.When the activity of α-glucosidase is inhibited, the digestion and absorption of sugars may be delayed, which may lower hyperglycemia after eating.
본 발명의 상기 락토바실러스 파라카세이 MG5012 균주는 α-아밀레이즈(α-amylase) 저해 활성이 우수하다.The Lactobacillus paracasei MG5012 strain of the present invention has excellent α-amylase inhibitory activity.
α-아밀레이즈의 활성이 저해되면, 소장에서 전분의 소화가 저해되어 포도당의 흡수가 지연됨으로써, 고혈당을 낮출 수 있다.When the activity of α-amylase is inhibited, the digestion of starch in the small intestine is inhibited, and absorption of glucose is delayed, thereby lowering hyperglycemia.
본 발명의 상기 락토바실러스 파라카세이 MG5012 균주는 인슐린 저항성 개선 효과가 우수하다.The Lactobacillus paracasei MG5012 strain of the present invention is excellent in improving insulin resistance.
본 발명의 상기 락토바실러스 파라카세이 MG5012 균주는 고지방 식이에 의해 유발되는 인슐린 저항성을 억제하는 효과가 있는 것일 수 있다.The Lactobacillus paracasei MG5012 strain of the present invention may have an effect of inhibiting insulin resistance caused by a high fat diet.
본 발명의 상기 균주는 내산성을 가질 수 있다. 바람직하게는 pH 2 내지 7에서 안정하며, 더 바람직하게는 위가 비워지는 시간(gastric emptying time)인 2 내지 3시간 동안 체내 위액 조건인 pH 2 내지 7에서 안정하다.The strain of the present invention may have acid resistance. It is preferably stable at
또한 상기 균주는 내담즙성을 가질 수 있다. 바람직하게 담즙염에 안정하고, 더 바람직하게는 0.1 내지 1% 담즙염에서 안정하며, 더욱더 바람직하게는 0.1 내지 0.5% 담즙염에서 안정하다.In addition, the strain may have bile resistance. It is preferably stable in bile salts, more preferably in 0.1 to 1% bile salts, even more preferably in 0.1 to 0.5% bile salts.
본 발명의 락토바실러스 파라카세이 MG5012 균주는 자가응집능력(autoaggregation ability)이 우수하고, 세포 표면 소수성이 높아 상피 세포 부착능이 높을 수 있다. 따라서 장의 연축운동에 의한 프로바이오틱스의 제거를 방지하고 장에서 효과적으로 상피세포에 콜로니를 형성하여 장에 잘 정착할 수 있다. 이러한 세포 정착능은 프로바이오틱스의 효과를 유지시키는데 효과적이다.The Lactobacillus paracasei MG5012 strain of the present invention has excellent autoaggregation ability, high cell surface hydrophobicity and high epithelial cell adhesion. Therefore, it is possible to prevent the removal of probiotics by the spasm movement of the intestine and to colonize the epithelial cells effectively in the intestine to settle well in the intestine. This cell fixing ability is effective in maintaining the effect of probiotics.
세포 표면 소수성은 세포 표면에 단백질이 존재하는 것을 의미하며, 세포 표면 친수성은 세포 표면에 다당류가 많은 것을 의미한다. 세포 표면에 단백질이 많아질수록 자가응집 능력과 세포 부착능이 우수하다. 본 발명의 락토바실러스 파라카세이 MG5012 균주는 자일렌 부착능이 높아 세포 표면이 소수성을 나타낼 수 있으며, 자가응집 능력과 세포 부착능이 우수할 수 있다. Cell surface hydrophobicity means that the protein is present on the cell surface, and cell surface hydrophilicity means that there are many polysaccharides on the cell surface. The more protein on the cell surface, the better the self-aggregation ability and cell adhesion ability. The Lactobacillus paracasei MG5012 strain of the present invention has high xylene adhesion, so that the cell surface may exhibit hydrophobicity, and may have excellent self-aggregation ability and cell adhesion ability.
본 발명의 락토바실러스 파라카세이 MG5012 균주는 반코마이신(vancomycin), 카나마이신(kanamycin) 및 클린다마이신(clindamycin)에 항생제 내성을 가질 수 있으며, 암피실린(ampicillin), 겐타마이신(gentamycin), 스트렙토마이신(streptomycin), 테트라사이클린(tetracyclin), 에리스로마이신(erythromycin) 및 클로람페니콜(chloramphenicol)에 항생제 감수성을 가질 수 있다.The Lactobacillus paracasei MG5012 strain of the present invention can have antibiotic resistance to vancomycin, kanamycin and clindamycin, ampicillin, gentamicin, streptomycin, tetra It can have antibiotic sensitivity to tetracyclin, erythromycin and chloramphenicol.
본 발명의 락토바실러스 파라카세이 MG5012 균주는 에스터레이즈(C4)(Esterase (C4)), 에스터레이즈 리페이즈(C8)(Esterase Lipase (C8)), 류신 아릴아미데이즈(Leucine arylamidase), 발린 아릴아미데이즈(Valine arylamidase), 애시드 포스파테이즈(Acid phosphatase), 나프톨-AS-BI-포스포하이드로레이즈(Naphtol-AS-BI-phosphohydrolase), β-글루코시데이즈(β-glucosidase), α-글루코시데이즈(α-glucosidase)에 효소 활성을 나타내는 것일 수 있다.Lactobacillus paracasei MG5012 strain of the present invention is esterase (C4) (Esterase (C4)), esterase lipase (C8) (Esterase Lipase (C8)), leucine arylamidase, valine arylamidase (Valine arylamidase), Acid phosphatase, Naphtol-AS-BI-phosphohydrolase, β-glucosidase, α-glucosidase (α-glucosidase) may exhibit enzyme activity.
본 발명의 락토바실러스 파라카세이 MG5012 균주는 D-리보스, D-아도니톨, D-갈락토스, D-글루코스, D-프럭토스, D-만노스, L-소르보스, 만니톨, D-소르비톨, 메틸 α D-글루코피라노시드, N-아세틸글루코스아민, 아미그달린, 아르부틴, 에스쿨린, 살리신, D-셀로비오스, D-말토스, D-사카로스, D-트레할로스, 이눌린, D-멜레지토스, 겐티비오스, D-투라노스, D-릭소스, D-타가토스에 대해서 발효 특성을 나타내는 것일 수 있다.The Lactobacillus paracasei MG5012 strain of the present invention is D-ribose, D-adonitol, D-galactose, D-glucose, D-fructose, D-mannose, L-sorbose, mannitol, D-sorbitol, methyl α D-glucopyranoside, N-acetylglucosamine, amidaline, arbutin, esculin, salicin, D-cellobiose, D-maltose, D-saccharose, D-trehalose, inulin, D-melezitose, It may be that it exhibits fermentation properties for gentibios, D-turanose, D-rixos, and D-tagatose.
또한, 본 발명은 상기 균주, 상기 균주의 배양액 및 상기 균주의 무세포 상등액으로 이루어진 군에서 선택된 1종 이상을 포함하는 조성물을 제공한다.In addition, the present invention provides a composition comprising at least one selected from the group consisting of the strain, the culture solution of the strain and the cell-free supernatant of the strain.
본 발명의 상기 조성물은 혈당을 저하하기 위한 용도 및 더 나아가 당뇨병의 예방, 치료, 개선 또는 발병 지연의 용도로 사용될 수 있는데, 여기서 당뇨병은 인슐린 의존형 당뇨병(제1형 당뇨병)과 인슐린 비의존형 당뇨병(제2형 당뇨병)을 포함하는 의미이며, 나아가 다른 질병 등으로 인하여 췌장이 손상됨에 따라 발생하는 당뇨병 예컨대, 갑상선 기능 항진증, 부신피질 기능 항진증, 성장호르몬 과다증 또는 카테콜라민 과다증에 의한 당뇨병, 임신성 당뇨병을 포함하는 의미이다.The composition of the present invention can be used for the purpose of lowering blood sugar and further preventing, treating, improving or delaying the development of diabetes, wherein diabetes is insulin-dependent diabetes (
본 발명의 상기 조성물은 그 유효성분을 혈당 저하 활성을 나타낼 수 있는 한 용도, 제형, 배합 목적 등에 따라 임의의 양(유효량)으로 포함할 수 있는데, 통상적인 유효량은 조성물 전체 중량을 기준으로 할 때 0.001 중량 % 내지 99.990 중량 % 범위 내에서 결정될 것이다. 여기서 "유효량"이란 혈당 저하 활성을 유도할 수 있는 유효성분의 양을 말한다. 이러한 유효량은 당업자의 통상의 능력 범위 내에서 실험적으로 결정될 수 있다. 본 발명의 조성물이 적용(처방)될 수 있는 대상은 포유동물 및 사람이며, 특히 사람인 경우가 바람직하다.The composition of the present invention may include the active ingredient in any amount (effective amount) according to the use, formulation, blending purpose, etc., as long as it can exhibit hypoglycemic activity, the typical effective amount is based on the total weight of the composition It will be determined within the range of 0.001% by weight to 99.990% by weight. Here, the "effective amount" refers to the amount of active ingredients that can induce hypoglycemic activity. Such an effective amount can be determined empirically within the ordinary skill in the art. Subjects to which the composition of the present invention can be applied (prescribed) are mammals and humans, particularly human beings.
또한, 본 발명은 상기 조성물을 포함하는 혈당 저하용 건강기능식품 조성물을 제공한다.In addition, the present invention provides a health functional food composition for lowering blood sugar containing the composition.
또한, 본 발명은 상기 조성물을 포함하는 당뇨병 예방 또는 치료용 약학적 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for preventing or treating diabetes comprising the composition.
또한, 본 발명은 상기 조성물을 포함하는 당뇨병 예방 또는 개선용 건강기능식품 조성물을 제공한다.In addition, the present invention provides a health functional food composition for preventing or improving diabetes comprising the composition.
또한, 본 발명은 상기 조성물을 포함하는 당뇨병 예방 또는 개선용 의약외품 조성물을 제공한다.In addition, the present invention provides a quasi-drug composition for preventing or improving diabetes comprising the composition.
본 발명에서 용어, '예방'이란, 본 발명에 따른 조성물을 개체에 투여하여 당뇨병의 발병을 억제하거나 지연시키는 모든 행위를 의미할 수 있다.In the present invention, the term,'prevention' may mean all actions to suppress or delay the onset of diabetes by administering the composition according to the present invention to an individual.
본 발명에서 용어, '치료'란, 본 발명에 따른 조성물을 당뇨병의 발병 의심 개체에 투여하여 당뇨병의 증세가 호전되도록 하거나 이롭게 되도록 하는 모든 행위를 의미할 수 있다.In the present invention, the term,'treatment', may mean all actions to improve or benefit the symptoms of diabetes by administering the composition according to the present invention to a subject suspected of developing diabetes.
상기 혈당 저하용 건강기능식품 조성물, 당뇨병 예방 또는 치료용 약학적 조성물, 당뇨병 예방 또는 개선용 건강기능식품 조성물 또는 의약외품 조성물은 상기 균주, 균주 배양액 또는 무세포 상등액을 유효성분으로 단독으로 포함할 수 있고, 이외 제형, 사용방법 및 사용목적에 따라 추가성분 즉, 약제학적으로 허용되거나 영양학적으로 허용되는 담체, 부형제, 희석제 또는 부성분을 추가로 포함할 수 있다. The health functional food composition for lowering blood sugar, a pharmaceutical composition for preventing or treating diabetes, a health functional food composition for preventing or improving diabetes, or a quasi-drug composition may contain the strain, strain culture solution, or cell-free supernatant as an active ingredient alone. Depending on the formulation, method of use and purpose of use, it may further include additional ingredients, pharmaceutically acceptable or nutritionally acceptable carriers, excipients, diluents or auxiliary ingredients.
보다 상세하게는 상기 혈당 저하용 건강기능식품 조성물, 당뇨병 예방 또는 치료용 약학적 조성물, 당뇨병 예방 또는 개선용 건강기능식품 조성물 또는 의약외품 조성물은 상기 유효성분 외에 추가로 영양제, 비타민, 전해질, 풍미제, 착색제, 중진제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산 음료에 사용되는 탄산화제 등을 추가로 함유할 수 있다.More specifically, the health functional food composition for lowering blood sugar, a pharmaceutical composition for preventing or treating diabetes, a health functional food composition for preventing or improving diabetes, or a quasi-drug composition, in addition to the above-mentioned active ingredients, a nutrient, vitamin, electrolyte, flavor, Colorants, intermediates, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohol, carbonic acid used in carbonated beverages, etc. may be further contained. .
또한, 상기 담체, 부형제 또는 희석제는 락토스, 덱스트로스, 수크로스, 솔비톨, 만니톨, 자이리톨, 에리스리톨, 말티톨, 전분, 아키시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로오스, 메틸 셀룰로오스, 미정질 셀루로오스, 폴리비닐 피롤리돈, 물, 메틸하이드록시벤조에이트, 프로필하이드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유, 덱스트린, 칼슘카보네이드, 프로필렌글리콜, 리퀴드 파라핀, 생리식염수로 이루어진 군에서 선택된 1 이상일 수 있으나, 이에 한정되는 것은 아니며 통상의 담체, 부형제 또는 희석제 모두 사용가능하다. 상기 성분들은 상기 유효성분인 약학적 조성물에 독립적으로 또는 조합하여 추가될 수 있다.In addition, the carrier, excipient or diluent is lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, aquisia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline In the group consisting of cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, dextrin, calcium carbonate, propylene glycol, liquid paraffin, and physiological saline It may be one or more selected, but is not limited thereto, and any common carrier, excipient, or diluent may be used. The ingredients may be added to the pharmaceutical composition, which is the active ingredient, independently or in combination.
또한, 상기 당뇨병 예방 또는 치료용 약학적 조성물은 약제화하는 경우, 통상의 충진제, 증량제, 결합제, 붕해제, 계면활성제, 항응집제, 윤활제, 습윤제, 향료, 유화제 또는 방부제 등을 더욱 포함할 수 있으며, 일 예로 경구 또는 비경구로 사용할 수 있다.In addition, the pharmaceutical composition for preventing or treating diabetes may further include a conventional filler, extender, binder, disintegrant, surfactant, anti-agglomerate, lubricant, wetting agent, fragrance, emulsifier or preservative, etc. , For example, can be used orally or parenterally.
본 발명에 따른 당뇨병 예방 또는 치료용 약학적 조성물의 투여량은, 투여방법, 복용자의 연령, 성별 및 체중, 및 질환의 중증도 등을 고려하여 당업자에 의해 적절하게 선택될 수 있다. 일예로, 본 발명의 당뇨병 예방 또는 치료용 약학적 조성물은 약학적 조성물을 기준으로 할 때, 0.0001 mg/kg 내지 1000 mg/kg으로, 보다 효과적이기 위해서는 0.01mg/kg 내지 100 mg/kg으로 투여할 수 있다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.The dosage of the pharmaceutical composition for preventing or treating diabetes according to the present invention may be appropriately selected by a person skilled in the art in consideration of the administration method, the age, sex and weight of the patient, and the severity of the disease. In one example, the pharmaceutical composition for preventing or treating diabetes according to the present invention is administered at 0.0001 mg/kg to 1000 mg/kg, based on the pharmaceutical composition, at 0.01 mg/kg to 100 mg/kg to be more effective can do. The administration may be administered once a day, or may be divided into several times. The above dosage does not limit the scope of the present invention in any way.
또한, 본 발명의 당뇨병 예방 또는 치료용 약학적 조성물은, 조성물 이외에 공지의 혈당 저하 활성을 갖는 화합물 또는 식물 추출물을 더욱 포함할 수 있으며, 조성물 100 중량부에 대하여 각각 5 중량부 내지 20 중량부로 포함될 수 있다.In addition, the pharmaceutical composition for preventing or treating diabetes of the present invention may further include a compound or a plant extract having a known hypoglycemic activity in addition to the composition, and may be included in 5 to 20 parts by weight, respectively, based on 100 parts by weight of the composition. Can be.
본 발명의 상기 건강기능식품 조성물은 인간을 포함한 동물에 직접 적용될 수 있다. 상기 동물은 식물에 대응하는 생물군으로 주로 유기물을 영양분으로 섭취하며, 소화나 배설 및 호흡기관이 분화되어 있는 것을 말하고, 바람직하게는 척추동물, 더욱 바람직하게는 포유류일 수 있다. 상기 포유류는 바람직하게는 인간일 수 있다.The health functional food composition of the present invention can be applied directly to animals, including humans. The animal is a bio-group corresponding to the plant, and mainly consumes organic matter as nutrients, and refers to digestion, excretion, and respiratory system differentiation. Preferably, it may be a vertebrate, more preferably a mammal. The mammal may preferably be a human.
본 발명의 조성물을 첨가할 수 있는 건강기능식품으로는 예를 들어, 각종 식품류, 음료, 껌, 캔디, 차, 비타민 복합제, 기능성 식품 등이 있다. 추가로, 본 발명에서 식품에는 특수영양식품(예, 조제유류, 영, 유아식 등), 식육가공품, 어육제품, 두부류, 묵류, 면류(예, 라면류, 국수류 등), 건강보조식품, 조미식품(예, 간장, 된장, 고추장, 혼합장 등), 소스류, 과자류(예, 스넥류), 유가공품(예, 발효유, 치즈 등), 기타 가공식품, 김치, 절임 식품(각종 김치류, 장아찌 등), 음료(예, 과실, 채소류 음료, 두유류, 발효음료류, 아이스크림류 등), 천연조미료(예, 라면 스프 등), 비타민 복합제, 알코올 음료, 주류 및 그 밖의 건강보조식품류를 포함하나 이에 한정되지 않는다. 상기 식품, 음료 또는 식품첨가제는 통상의 제조방법으로 제조될 수 있다.Health functional foods to which the composition of the present invention can be added include, for example, various foods, beverages, chewing gum, candy, tea, vitamin complexes, and functional foods. In addition, in the present invention, the food products include special nutritional foods (e.g., prepared dairy products, English, baby foods, etc.), processed meat products, fish meat products, tofus, jelly, noodles (e.g. ramen, noodles, etc.), health supplements, seasoned foods ( Yes, soy sauce, miso, red pepper paste, mixed sauce, etc., sauces, confectionery (e.g., snacks), dairy products (e.g. fermented milk, cheese, etc.), other processed foods, kimchi, pickled foods (various kimchi, pickles, etc.), drinks ( Examples include, but are not limited to, fruits, vegetable beverages, soy milk, fermented beverages, ice cream, etc., natural seasonings (eg, ramen soup, etc.), vitamin complexes, alcoholic beverages, alcoholic beverages, and other health supplements. The food, beverage or food additive may be prepared by a conventional manufacturing method.
본 발명에서 건강기능식품이란 식품에 물리적, 생화학적, 생물공학적 수법 등을 이용하여 해당 식품의 기능을 특정 목적에 작용, 발현하도록 부가가치를 부여한 식품군이나 식품 조성이 갖는 생체방어리듬조절, 질병방지와 회복 등에 관한 체조절기능을 생체에 대하여 충분히 발현하도록 설계하여 가공한 식품을 의미하며, 바람직하게는 본 발명의 건강기능식품은 혈당 저하 또는 당뇨병의 예방 또는 개선에 관한 생체조절기능을 생체에 대하여 충분히 발현할 수 있는 식품을 의미한다. 상기 건강기능식품에는 식품학적으로 허용 가능한 식품 보조 첨가제를 포함할 수 있으며, 건강기능식품의 제조에 통상적으로 사용되는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다.In the present invention, the health functional food is a food group or food composition that provides added value to act and express the function of the food by using physical, biochemical, or biotechnological techniques, etc. Means a food that has been designed and processed to sufficiently express the body control function related to recovery, and preferably, the health functional food of the present invention provides sufficient biocontrol functions for preventing or improving blood sugar or diabetes. It means food that can be expressed. The dietary supplement may include a food-acceptable food supplement additive, and may further include suitable carriers, excipients, and diluents commonly used in the manufacture of dietary supplements.
본 발명의 락토바실러스 파라카세이 MG5012 균주를 의약외품 조성물로 사용할 경우, 상기 균주, 균주 배양액 또는 무세포 상등액을 그대로 첨가하거나 다른 의약외품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효성분의 혼합양은 사용 목적 (예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다.When the Lactobacillus paracasei MG5012 strain of the present invention is used as a quasi-drug composition, the strain, strain culture solution, or cell-free supernatant may be added as it is or used with other quasi-drug components, and may be suitably used according to a conventional method. The mixing amount of the active ingredient can be appropriately determined according to the purpose of use (prevention, health or therapeutic treatment).
바람직하게는, 상기 의약외품 조성물은 소독청결제, 샤워폼, 가그린, 물티슈, 세제비누, 핸드워시, 가습기 충진제, 마스크, 연고제 또는 필터충진제일 수 있다.Preferably, the quasi-drug composition may be a disinfecting cleaner, shower foam, gagreen, wipes, detergent soap, hand wash, humidifier filler, mask, ointment or filter filler.
본 발명의 락토바실러스 플란타룸 MG4296균주와 락토바실러스 파라카세이 MG5012균주는 유사한 성질을 가지고 있어 보다 우수한 혈당 저하 활성을 위해 병용 사용이 가능하며, 상기 두 균주를 병용 사용하는 경우, 각각의 균주를 단독 사용하였을 때 나타나는 항균효과 대비 예측할 수 없는 현저한 효과를 달성할 수 있다.The Lactobacillus plantarum MG4296 strain of the present invention and the Lactobacillus paracasei MG5012 strain have similar properties, and thus can be used in combination for better blood sugar lowering activity, and when the two strains are used in combination, each strain alone When used, it is possible to achieve a remarkable unexpected effect compared to the antibacterial effect.
중복되는 내용은 본 명세서의 복잡성을 고려하여 생락하며, 본 명세서에서 달리 정의되지 않은 용어들은 본 발명이 속하는 기술분야에서 통상적으로 사용되는 의미를 갖는 것이다.Duplicate contents are omitted in consideration of the complexity of the present specification, and terms that are not otherwise defined herein have meanings commonly used in the technical field to which the present invention pertains.
본 명세서에서 달리 정의되지 않은 용어들은 본 발명이 속하는 기술분야에서 통상적으로 사용되는 의미를 갖는 것이다.Terms that are not otherwise defined herein have meanings commonly used in the art.
이하, 본 발명을 실시예에 의해 상세히 설명한다. 단 하기 실시예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실시예에 의해 한정되는 것은 아니다.Hereinafter, the present invention will be described in detail by examples. However, the following examples are merely illustrative of the present invention, and the contents of the present invention are not limited by the following examples.
실시예 1. 유산균 균주의 α-글루코시데이즈(Glucosidase) 효소 활성 저해 효과 스크리닝Example 1. Screening of the inhibitory effect of α-glucosidase enzyme activity of lactic acid bacteria strains
1.1 α-글루코시데이즈(Glucosidase) 효소 활성 저해 효과 스크리닝을 위한 시료의 준비1.1 Preparation of a sample for screening of α-glucosidase enzyme activity inhibitory effect
유산균주는 ㈜메디오젠 (Mediogen Co. Ltd, Chungju, Korea)으로부터 공급받아 사용하였다. 널리 알려진 유산균인 L. rhamnosus GG (L.GG)를 양성 대조군으로 이용하였으며, 이를 포함한 총 237종의 유산균주가 사용되었다. 이들 유산균주의 α-글루코시데이즈 및 α-아밀레이즈 효소에 대한 활성 저해 활성 평가를 위해 유산균주 시료를 제조하였다. 유산균주를 MRS 배지에 접종하여 37℃에서 15시간 배양한 배양액을 원심분리 (2,700 rpm, 15분, 4℃)한 후, 상등액을 0.2㎛ syringe 필터로 여과하였다. 여과된 배양 상등액 (cell free supernatant, CFS)을 시료로 사용하였다. Lactic acid bacteria were supplied from Mediogen Co. Ltd, Chungju, Korea. L. rhamnosus GG ( L.GG ), a well-known lactic acid bacteria, was used as a positive control, and a total of 237 lactic acid strains including this were used. Lactobacillus strain samples were prepared to evaluate the activity inhibitory activity of α-glucosidase and α-amylase enzymes of these lactic acid strains. After inoculating the lactic acid bacteria into MRS medium, the culture medium cultured at 37° C. for 15 hours was centrifuged (2,700 rpm, 15 minutes, 4° C.), and the supernatant was filtered through a 0.2 μm syringe filter. The filtered culture supernatant (cell free supernatant, CFS) was used as a sample.
1.2 α-글루코시데이즈(Glucosidase) 효소 활성 저해 효과 스크리닝 실험1.2 Screening experiment for inhibiting α-glucosidase enzyme activity
구체적으로 다음과 같은 방법으로 수행하였다. 0.01 M PBS (pH 7.0) 150μL, 0.02M ρ-nitrophenyl α-D-glucopyranoside (PNPG, Sigma-Aldirch Chemical Co., St, Louis, MO, USA) 75μL 및 유산균 배양 상등액 (CFS) 25μL를 혼합하여 37℃에서 10분간 배양하였다. 그 후 PBS에 희석한 0.17 units/mL의 α-글루코시데이즈 (Sigma-Aldirch Chemical Co., St, Louis, MO, USA) 50μL를 첨가한 후, 37℃에서 10분 동안 배양하였다. 배양액에 0.1 M Na2CO3 1mL를 첨가하여 반응을 종결시켰다. 방출된 ρ-nitrophenol(PNP)의 양을 405 ㎚에서 흡광도를 측정하였다. 효소 활성의 저해도는 다음 식에 의하여 산출하였다. Specifically, it was performed in the following manner. 150 μL of 0.01 M PBS (pH 7.0), 75 μL of 0.02M ρ-nitrophenyl α-D-glucopyranoside (PNPG, Sigma-Aldirch Chemical Co., St, Louis, MO, USA) and 25 μL of lactic acid bacteria culture supernatant (CFS) 37 Incubated for 10 minutes at ℃. Thereafter, 50 μL of α-glucosidase (Sigma-Aldirch Chemical Co., St, Louis, MO, USA) at 0.17 units/mL diluted in PBS was added, followed by incubation at 37° C. for 10 minutes. The reaction was terminated by adding 1 mL of 0.1 M Na 2 CO 3 to the culture. The amount of released ρ-nitrophenol (PNP) was measured at 405 nm. The degree of inhibition of enzyme activity was calculated by the following equation.
저해도(%) = [1-(C-D)/(A-B)]×100 Inhibition (%) = [1-(C-D)/(A-B)]×100
A : α-글루코시데이즈 첨가 및 유산균 상등액 미혼합 처리군의 흡광도 A: Absorption of α-glucosidase and lactic acid bacteria supernatant non-mixed treatment group
B : α-글루코시데이즈 미첨가 및 유산균 상등액 미혼합 처리군의 흡광도 B: Absorbance of the treatment group without α-glucosidase and without lactic acid bacteria supernatant
C : α-글루코시데이즈 첨가 및 유산균 상등액 혼합 처리군의 흡광도 C: Absorbance of α-glucosidase added and lactic acid bacteria supernatant mixed treatment group
D : α-글루코시데이즈 미첨가 및 유산균 상등액 혼합 처리군의 흡광도D: Absorption of α-glucosidase-free and lactic acid bacteria supernatant mixed treatment group
상기 식을 이용하여 인체 유래 유산균 300여 종과 양성 대조군 L.GG 균주의 α-글루코시데이즈 저해도를 비교하였으며, α-글루코시데이즈 저해도가 우수한 락토바실러스 플란타룸 (L.plantarum) 균주 69종 및 락토바실러스 파라카세이 (L.paracasei) 균주 36종을 선별하였다. 선별한 락토바실러스 플란타룸 균주를 표 1에 나타내고, 락토바실러스 파라카세이 균주를 표 2에 나타내었다.Lactobacillus plantarum ( L.plantarum ) strains with superior α-glucosidase inhibition were compared by comparing the inhibition of α-glucosidase with over 300 species of lactic acid bacteria derived from the human body and the positive control L.GG strain using the above formula. 69 species and Lactobacillus paracasei (36 species) strains were selected. The selected Lactobacillus plantarum strains are shown in Table 1, and the Lactobacillus paracasei strains are shown in Table 2.
[표 1][Table 1]
[표 2][Table 2]
표 1 및 표 2에 나타낸 바와 같이, MG4296, MG5012 균주가 L.plantarum 균주 및 L.paracaei 균주 대비 우수한 α-글루코시데이즈 저해활성을 나타내는 것을 확인하였으며, 양성 대조군 L.GG의 α-글루코시데이즈 저해 활성은 36.7±7.3%인 것으로 측정되어, MG4296, MG5012 균주는 양성 대조군 대비 훨씬 우수한 α-글루코시데이즈 저해활성을 나타내는 것을 확인하였다.As shown in Table 1 and Table 2, it was confirmed that the MG4296 and MG5012 strains show superior α-glucosidase inhibitory activity compared to the L.plantarum strain and L.paracaei strain, and α-glucosidase of the positive control L.GG The inhibitory activity was measured to be 36.7±7.3%, and thus it was confirmed that the MG4296 and MG5012 strains showed much better α-glucosidase inhibitory activity than the positive control group.
실시예 2. 유산균 균주의 α-아밀레이즈(Amylase) 효소 활성 저해 효과의 측정Example 2. Measurement of the inhibitory effect of α-amylase enzyme activity of lactic acid bacteria strains
실시예 1의 α-글루코시데이즈 저해활성을 측정 결과를 토대로, L.GG 보다 α-글루코시데이즈 저해활성이 우수한 것으로 나타난 29종의 유산균주를 선별하고, 선별한 유산균주를 대상으로, α-아밀레이즈(Amylase) 효소 활성 저해 효과를 확인하기 위한 실험을 실시하였다. 구체적으로 다음과 같은 방법으로 수행하였다. 실시예 1.1과 같은 방법으로 준비한 유산균 배양 상등액 250μL에 α-아밀레이즈(Sigma-Aldirch Chemical Co., St, Louis, MO, USA) 용액(0.5 mg/mL) 250μL를 혼합하여 25℃에서 10분간 반응시켰다. 반응액에 0.02M 소듐 포스페이트(sodium phosphate) 완충액에 용해한 1% 전분 (Samchun Pure Chemical Co., Pyeongtaek, Korea) 용액(starch solution) 250μL를 넣고, 25℃에서 10분간 더 반응시켰다. 그 후, 반응액에 96mM 3,5-디니트로살리실산(DNS, 30% sodium potassium tartrate in 0.5 M NaOH)(Sigma-Aldirch Chemical Co., St, Louis, MO, USA) 500μL를 넣고 반응을 종결시켰다. 종결시킨 반응액을 100℃에서 5분간 끓여 발색을 시킨 후, 충분히 냉각시킨다. 냉각시킨 반응액에 4배 가량의 증류수를 가한 후, ELISA (Spectra Max190, Molecular Devices, US)를 사용하여 540nm에서 흡광도를 측정하였다. α-아밀레이즈 효소 활성의 저해도는 다음 식에 의하여 산출하였다. Based on the results of measuring the α-glucosidase inhibitory activity of Example 1, 29 kinds of lactic acid strains that were shown to have better α-glucosidase inhibitory activity than L.GG were selected, and the selected lactic acid strains were targeted, α -Amylase (Amylase) An experiment was conducted to confirm the inhibitory effect of enzyme activity. Specifically, it was performed in the following manner. 250 μL of α-amylase (Sigma-Aldirch Chemical Co., St, Louis, MO, USA) solution (0.5 mg/mL) was mixed with 250 μL of lactic acid bacteria culture supernatant prepared in the same manner as in Example 1.1 and reacted at 25° C. for 10 minutes. Ordered. 250 μL of a 1% starch (Samchun Pure Chemical Co., Pyeongtaek, Korea) solution dissolved in 0.02M sodium phosphate buffer was added to the reaction solution, and further reacted at 25° C. for 10 minutes. Then, 500 μL of 96
저해도 (%) = [(A-B)/A]×100, Inhibition (%) = [(A-B)/A]×100,
A : 유산균 상등액 미혼합군의 흡광도A: Absorbance of non-mixed lactic acid bacteria supernatant
B : 유산균 상등액 혼합군의 흡광도B: absorbance of the lactic acid bacteria supernatant mixed group
상기 식을 이용하여 실시예 1에서 선별한 유산균주 29종과 양성 대조군 L.GG 균주의 α-아밀레이즈 저해도를 비교하였으며 이를 표 3에 나타내었다.Using the above formula, the α-amylase inhibition of the 29 lactic acid strains selected in Example 1 and the positive control L.GG strain was compared and shown in Table 3.
[표 3][Table 3]
표 3에 나타낸 바와 같이, MG4296균주는 30개 균주의 α-아밀레이즈 저해도 평균값보다 높고, L.GG 균주와 동등한 정도의 α-아밀레이즈 저해도 값을 갖는 것을 확인하였으며, MG5012균주는 30개 균주의 α-아밀레이즈 저해도 평균값보다 높고, L.GG 균주보다 높은 α-아밀레이즈 저해도 값을 갖는 것을 확인하였다. 따라서 MG4296 및 MG5012균주는 모두 우수한 α-아밀레이즈 저해도를 갖는 것을 확인하였다As shown in Table 3, the strain MG4296 is higher than the average value is also raised α- amyl inhibition of 30 strains, it was confirmed that it has a raised α- amyl inhibition values approximately equal to the L.GG strain,
실시예 3.Example 3. MG4296와 MG5012 균주의 동정Identification of MG4296 and MG5012 strains
3.1 MG4296와 MG5012 균주의 염기서열 분석 및 계통수 확인3.1 Sequence analysis and phylogenetic identification of MG4296 and MG5012 strains
MG4296와 MG5012 균주의 universal rRNA 유전자 프라이머(27F, 1492R)를 이용한 16S rRNA 유전자 염기서열 분석을 진행하여 동정하였으며, 각 과정은 Sol-gent(Daejeon, Korea)를 통하여 수행하였다. 분석된 염기서열은 National Center for Biotechnology Institute(NCBI)의 Basic Local Alignment Search Tool(Blast)을 이용하여 Genebank database와 비교하여 동정하고, MEGA 7.0 소프트웨어의 neighborjoining method를 이용하여 계통수를 작성하였다. 분석한 MG4296 균주의 16s rRNA 염기서열을 서열번호 1로 나타내었고, MG5012 균주의 16s rRNA염기서열을 서열번호 2로 나타내었다. MG4296와 MG5012 균주의 계통수를 도 1에 나타내었다. 16S rRNA gene sequence analysis using universal rRNA gene primers (27F, 1492R) of MG4296 and MG5012 strains was performed and identified, and each process was performed through Sol-gent (Daejeon, Korea). The analyzed sequencing was identified by comparison with the Genebank database using the Basic Local Alignment Search Tool (Blast) of the National Center for Biotechnology Institute (NCBI), and phylogenetic trees were prepared using the neighborjoining method of MEGA 7.0 software. The 16s rRNA base sequence of the analyzed MG4296 strain was represented by SEQ ID NO: 1, and the 16s rRNA base sequence of the MG5012 strain was represented by SEQ ID NO: 2. Phylogenetic trees of MG4296 and MG5012 strains are shown in FIG. 1.
도 1에 나타낸 바와 같이, α-글루코시데이즈 및 α-아밀레이즈 저해 활성이 우수한 두 균주는 16S rRNA 염기서열 분석 결과 락토바실러스 플란타룸(Lactobacillus plantarum) MG4296와 락토바실러스 파라카세이(Lactobacillus paracasei) MG5012로 동정하였다. 동정한 락토바실러스 플란타룸(Lactobacillus plantarum) MG4296을 2019년 03월 26일 생물자원센터 (Korean collection for type culture, 한국)에 기탁하고 수탁번호 KCTC13830BP를 부여받았고, 락토바실러스 파라카세이(Lactobacillus paracasei) MG5012를 2019년 03월 26일 생물자원센터 (Korean collection for type culture, 한국)에 기탁하고 수탁번호 KCTC13831BP를 부여받았다.As shown in FIG. 1, two strains having excellent α-glucosidase and α-amylase inhibitory activity showed 16S rRNA sequencing results of Lactobacillus plantarum MG4296 and Lactobacillus paracasei MG5012 It was identified as. Lactobacillus plantarum MG4296 was deposited with the Korean Society for Biological Resource Center (Korean collection for type culture, Korea) on March 26, 2019, and assigned the accession number KCTC13830BP, Lactobacillus paracasei MG5012 Was deposited on March 26, 2019 at the Korean Resource Center for Biological Resources (Korean collection for type culture, Korea), and was assigned an accession number KCTC13831BP.
실시예 4.Example 4. MG4296와 MG5012 균주의 내당능성의 측정Measurement of glucose tolerance of MG4296 and MG5012 strains
α-glucosidase 효소 활성 억제능을 보인 신규 후보로 선별된 유산균 2종 MG4296, MG5012 및 양성대조군 유산균 L. GG을 대상으로 동물모델에서의 내당능성을 확인하기 위한 경구 당 부하시험(oral glucose tolerance test)를 실시하였다. 구체적으로 MG4296, MG5012 유산균을 실험군으로 설정하였고, 양성대조군 유산균으로 L. GG을 설정하였으며, 음성대조군으로 부형제 투여군을 설정하였다. 16시간 절식시킨 ICR 마우스에 1Х108CFU/두의 유산균을 200μl PBS에 녹여 경구투여하고, 1시간 후 2g/kg의 포도당을 경구투여로 섭취시킨 뒤, 30분, 60분, 90분 및 120분에 혈당 측정기(ACCU-CHEK®Performa, Roche Diagnostics, Mannheim, Germany)를 이용하여 혈당을 측정하였다. 혈당 측정 결과를 도 2에 나타내었다.Oral glucose tolerance test for confirming glucose tolerance in animal models of two lactic acid bacteria, MG4296, MG5012, and the positive control lactic acid bacteria L. GG , selected as new candidates showing α-glucosidase enzyme activity inhibitory activity It was carried out. Specifically, MG4296 and MG5012 lactic acid bacteria were set as the experimental group, L. GG was set as the positive control lactic acid bacteria, and the excipient administration group was set as the negative control. After dissolving 1Х10 8 CFU/two lactobacillus in 200μl PBS in ICR mice fasted for 16 hours, orally administered them, and after 1 hour, 2 g/kg glucose was taken orally, and then 30 minutes, 60 minutes, 90 minutes and 120 minutes. Blood glucose was measured using a blood glucose meter (ACCU-CHEK ® Performa, Roche Diagnostics, Mannheim, Germany). The results of blood sugar measurement are shown in FIG. 2.
도 2에 나타낸 바와 같이, 포도당 투여 후 60, 90분에서 혈당 수준은 부형제 투여 음성 대조군에 비하여 L.GG 및 MG4296, MG5012 실험군에서 통계 유의적으로 혈당 상승폭이 낮은 경향을 확인하였다. 따라서, 신규 유산균 균주 MG4296, MG5012의 투여는 혈당 저하 효력이 있어, 당 내성의 증가에 도움을 줄 수 있는 유산균 균주임을 확인하였다.2, the glucose administration after 60, blood glucose level at 90 minutes was confirmed L.GG and MG4296, statistically significant tendency to lower the blood glucose rise in the experimental group compared to the vehicle administration MG5012 negative control. Therefore, it was confirmed that the administration of the new lactic acid bacteria strains MG4296 and MG5012 has a glycemic lowering effect, which can help increase sugar resistance.
실시예 5.Example 5. MG5012 균주의 인슐린 저항성 개선 효과의 확인Confirmation of the effect of improving the insulin resistance of the MG5012 strain
지방세포주인 마우스 3T3-L1 세포주에서의 포도당 이용률을 측정하여 인슐린 저항성의 개선 여부를 알 수 있다. 지방세포 3T3-L1을 MDI 분화유도용액으로 분화시킨 후 각각 포도당 1 mg/ml 및 MG5012균주 추출물(CFE)을 처리하여 세포배양 중 소비된 포도당의 함량을 키트를 이용하여 정량하였다. 구체적인 실험방법은 아래와 같다.It is possible to determine whether insulin resistance is improved by measuring glucose utilization rate in the adipocyte cell line 3T3-L1 cell line. Adipose cells 3T3-L1 were differentiated with MDI differentiation inducing solution, and then treated with
5.1 유산균 추출물(CFE)의 제조5.1 Preparation of lactic acid bacteria extract (CFE)
MG5012 및 L.GG 균주를 각각 MRS 배지에 접종하여 37℃에서 15시간 배양한 배양액을 원심분리 (2,700 rpm, 15분, 4℃)한 후, 균주 펠렛을 회수하고, PBS로 2회 세척하였다. 세척한 균주를 동결건조한 후 PBS에 재현탁하고 현탁액을 0.2㎛ syringe 필터로 여과하였다. 여과된 유산균 추출물 (cell free extract, CFE)을 시료로 사용하였다. 유산균 균수는 각각 1×108 또는 2×108 CFU/ml 농도로 맞춰 처리하였다.MG5012 and L.GG The strains were inoculated into MRS medium, and the culture medium cultured at 37°C for 15 hours was centrifuged (2,700 rpm, 15 minutes, 4°C), and the strain pellets were recovered and washed twice with PBS. The washed strain was lyophilized and then resuspended in PBS and the suspension was filtered through a 0.2 μm syringe filter. Filtered lactic acid bacteria extract (cell free extract, CFE) was used as a sample. The number of lactic acid bacteria was treated at a concentration of 1×10 8 or 2×10 8 CFU/ml, respectively.
5.2 MG5012 균주의 인슐린 저항성 개선 효과의 측정5.2 Measurement of the effect of improving the insulin resistance of the MG5012 strain
대조군으로 MDI 분화유도물질 미처리 및 유산균 추출물 미처리군, MDI 분화유도물질 처리 및 유산균 추출물 미처리군을 각각 설정하였으며, 실험군으로 MDI 분화유도물질 처리 및 각각의 실시예 5.1에서 준비한 유산균 추출물 처리군을 설정하였다. 실험방법은 다음과 같은 방법으로 실시하였다. 3T3-L1를 10% FBS를 포함한 DMEM를 사용하여 배양한 후 6 웰 플레이트에 3×105 cells/well로 시딩(seeding) 한 후 배양하였다. 세포 분화 유도 물질 (MDI)인 인슐린 (10 μg/mL), 덱사메사손 (1 μM), 3-이소부틸-1-메틸잔틴 (3-Isobutyl-1-methylxanthine) (0.5 mM) 및 시료를 포함한 10% FBS DMEM 배지로 교환한 후 2일간 배양하였다. 2일 후 세포에 각각의 시료와 인슐린 (10 μg/mL)만 포함한 10% FBS DMEM 배지로 교환한 후 2일간 더 배양하였다. 세포 안정화를 시키기 위해 10% FBS DMEM 배지로 교환한 후 2일간 더 배양하였다. 2일 배양 후 10% FBS, 1% 피루브산 나트륨(sodium pyruvate), 항생제가 포함된 무-글루코스(glucose-free) DMEM 배지로 교환한 후 모든 시험군에 포도당 1 mg/ml를 처리한 후 2일 배양하였다. 2일 배양한 후 배양액은 1,000 rpm, 5분간 원심분리하여, 배양액 내에 존재하는 세포를 제거하였다. 이때 배양액은 측정 전까지 -80℃에 보관하였다. 분화 유도된 3T3-L1 세포배지 내의 포도당 함량은 Glucose assay kit (GAGO-20, Sigma-aldrich Co., Ltd)을 사용하여 측정한 후 정량하였으며, 정량 결과를 도 3에 나타내었다.As a control group, MDI differentiation-inducing substance untreated and lactic acid bacteria extract-untreated group, MDI differentiation-inducing substance treatment and lactic-acid-bacteria extract-untreated group were respectively set, and MDI differentiation-inducing substance treatment and lactic acid bacteria extract-treated group prepared in Example 5.1 were set as the experimental group. . The experimental method was conducted as follows. 3T3-L1 was cultured using DMEM containing 10% FBS, and then seeded at 3×10 5 cells/well in a 6-well plate and cultured. Including cell differentiation inducer (MDI) insulin (10 μg/mL), dexamethasone (1 μM), 3-isobutyl-1-methylxanthine (0.5 mM) and sample After replacing with 10% FBS DMEM medium, the cells were cultured for 2 days. After 2 days, cells were exchanged with 10% FBS DMEM medium containing only each sample and insulin (10 μg/mL), and then cultured for 2 days. In order to stabilize the cells, the cells were exchanged with 10% FBS DMEM medium and further cultured for 2 days. After 2 days incubation, after replacing with 10% FBS, 1% sodium pyruvate, and glucose-free DMEM medium containing antibiotics, 2 days after treatment with 1 mg/ml glucose in all test groups Cultured. After culturing for 2 days, the culture medium was centrifuged at 1,000 rpm for 5 minutes to remove cells present in the culture medium. At this time, the culture medium was stored at -80°C until measurement. Glucose content in the differentiation-induced 3T3-L1 cell medium was measured and quantified using a Glucose assay kit (GAGO-20, Sigma-aldrich Co., Ltd), and the quantitative results are shown in FIG. 3.
도 3에 나타낸 바와 같이, MDI 분화유도물질 처리 및 유산균 추출물 미처리군과 각 실험군의 소비량을 비교한 결과, 유산균 균수 처리양의 증가에 따라 포도당의 소비량이 증가하는 경향을 나타내었다. 이와 같은 포도당 소비량의 증가는 세포의 인슐린 저항성이 개선되어 포도당의 세포 내 유입이 증가됨을 의미한다. 따라서, MG5012 균주는 양 의존적(dose dependant)으로 인슐린 저항성 개선효과가 있음을 확인하였다.As shown in Figure 3, as a result of comparing the consumption of MDI differentiation-inducing substance treatment and lactic acid bacteria extract-treated group and each experimental group, the consumption of glucose increased as the amount of lactic acid bacteria treatment increased. Such an increase in glucose consumption means that the insulin resistance of the cell is improved, and thus the influx of glucose into the cell is increased. Therefore, it was confirmed that the strain MG5012 has an effect of improving insulin resistance in a dose dependent manner.
실시예 6. MG4296와 MG5012 균주의 내산성 및 내담즙성의 확인Example 6. Confirmation of acid resistance and bile resistance of MG4296 and MG5012 strains
장내 환경과 같은 산성 및 담즙염에 대한 MG4296와 MG5012 균주의 생존력을 확인하기 위한 실험을 실시하였다.Experiments were conducted to confirm the viability of the MG4296 and MG5012 strains against acid and bile salts, such as the intestinal environment.
6.1 MG4296와 MG5012 균주의 내산성 확인 실험6.1 Experiment to confirm acid resistance of MG4296 and MG5012 strains
본 발명의 유산균 MG4296와 MG5012 균주의 내산성을 확인하기 위한 실험을 다음과 같이 실시하였다. MG4296와 MG5012 균주를 MRS 평판배지에 획선도말하여 37℃에 24시간 배양한 뒤, 생성된 집락을 MRS 액체배지에 접종하여 배양(37℃, 18시간)하였다. 이후 배양액은 원심분리(4000×g, 4℃, 5분)한 후, phosphate-buffer saline(PBS, pH7.4)를 이용하여 2번 세척하였다. 세척한 균체는 OD600 1.0 (108-109 CFU/mL)으로 조정하여 유산균 희석액을 제조하였다. 유산균 희석액 1ml를 pH 2 또는 pH 7인 9ml PBS에 첨가 후, 진탕한 뒤 37℃에 3시간 배양한 후 생균수를 확인하였으며, 생균수 확인 결과를 표 4에 나타내었다.The experiment for confirming the acid resistance of the lactic acid bacteria MG4296 and MG5012 strain of the present invention was carried out as follows. The strains MG4296 and MG5012 were streaked on MRS plate medium and incubated at 37°C for 24 hours, and then the resulting colonies were inoculated in MRS liquid medium (37°C, 18 hours). After the culture was centrifuged (4000 × g, 4 ℃, 5 minutes), washed twice with phosphate-buffer saline (PBS, pH7.4). The washed cells were adjusted to OD 600 1.0 (10 8 -10 9 CFU/mL) to prepare a lactic acid bacteria dilution. After adding 1 ml of the lactic acid bacteria dilution solution to 9 ml PBS of
[표 4][Table 4]
표 4에 나타낸 바와 같이, MG4296, MG5012 두 균주 모두 pH 2에서 3시간 후 104CFU/mL 이상의 생균수를 유지하는 것을 확인하였다. 일반적으로 유산균은 pH 2에서 3시간 동안 104CFU/mL 이상의 생균수를 유지하면 내산성이 우수한 것으로 판단하는 바, 본 발명의 MG4296 및 MG5012 모두 내산성이 우수함을 확인하였다.As shown in Table 4, it was confirmed that both strains of MG4296 and MG5012 maintained a viable cell count of 10 4 CFU/mL or more after 3 hours at
6.2 MG4296와 MG5012 균주의 내담즙성 확인 실험6.2 Experiment to confirm bile resistance of MG4296 and MG5012 strains
MG4296와 MG5012의 담즙염에 대한 내성을 확인하기 1~3% 소 담즙(oxgall)을 포함한 MRS 배지에 실시예 6.1에서 제조한 유산균 희석액을 1% 접종하고 37℃에서 24시간 배양한 후 생균수를 확인하였으며, 그 결과를 표 5에 나타내었다.To confirm the resistance to biliary salts of MG4296 and MG5012, 1% of lactic acid bacteria prepared in Example 6.1 was inoculated in MRS medium containing 1% to 3% bovine bile (oxgall), incubated at 37° C. for 24 hours, and the number of live bacteria was counted. It was confirmed, and the results are shown in Table 5.
[표 5][Table 5]
표 5에 나타낸 바와 같이, MG4296과 MG5012는 0.5% 담즙염 농도에서도 각각 6.86log CFU/mL, 7.41log CFU/mL의 매우 높은 생균수를 유지하는 것을 확인하였다. 일반적으로 담즙염에 대한 내성을 확인하기 위해 0.3% 담즙염 농도를 통해 내성을 확인하며, 기존의 연구결과에 따르면 0.3% 담즙염에서 유산균의 생균수가 4log CFU/mL이하인 경우에 담즙염에 민감하다고 알려져 있는 것을 고려할 때, MG4296과 MG5012는 더 높은 농도의 담즙염에서도 더 높은 생균수를 유지하는 바, 우수한 내담즙성을 가지는 것을 확인하였다.As shown in Table 5, it was confirmed that MG4296 and MG5012 maintained very high viable cell counts of 6.86log CFU/mL and 7.41log CFU/mL, respectively, at 0.5% bile salt concentration. In general, in order to confirm resistance to bile salts, resistance is confirmed through 0.3% bile salt concentration, and according to existing research, it is sensitive to bile salts when the number of live bacteria of lactic acid bacteria is less than 4log CFU/mL in 0.3% bile salts. Considering what is known, it was confirmed that MG4296 and MG5012 have excellent bile resistance because they maintain a higher number of viable cells even at higher concentrations of bile salts.
실시예 7. MG4296와 MG5012 균주의 장 정착성의 확인Example 7. Confirmation of intestinal fixation of MG4296 and MG5012 strains
자가응집성(Autoaggregation)과 소수성(hydrophobicity)은 미생물의 상피 세포 부착능을 간접적으로 확인할 수 있는 방법으로, Kos의 연구에 의하면, 자가응집능력과 세포 표면 소수성이 높은 균주가 실제 세포 부착능력 또한 높다고 알려져 있다. Autoaggregation and hydrophobicity are methods that can indirectly determine the ability of microorganisms to adhere to epithelial cells.According to Kos' research, strains with high self-aggregation and cell surface hydrophobicity are also known to have high cell adhesion. have.
7.1 MG4296와 MG5012 균주의 자가응집성(Autoaggregation) 확인7.1 Autoaggregation of MG4296 and MG5012 strains
장내 세포 부착능을 간접적으로 확인하기 위하여 Kassa의 연구를 변형하여 자가응집성(autoaggregation) 실험을 진행하였다. MRS 배지에 18시간 배양한 유산균 배양액을 새로운 10 mL MRS 배지에 2% 접종한 뒤, 18시간 배양하여 실험에 사용하였다. 배양한 유산균은 원심분리 (4,000×g, 4℃, 5분)한 후, PBS에 2번 세척하였고, 균체는 OD600 1.0으로 조정하였다. 균주 현탁액 5mL을 10초간 진탕한 뒤 실험 시작 직후 (A0)와 현탁액을 방치한 1시간, 3시간 또는 5시간 후 (A), 각각 0.1mL의 상등액을 취해 0.9mL PBS와 혼합한 뒤 600nm에서 흡광도를 측정하였고, 다음 계산식에 따라 자가응집(autoaggregation)비율을 계산하였으며, 그 결과를 표 6에 나타내었다.In order to indirectly confirm the intestinal cell adhesion ability, Kassa's study was modified to conduct an autoaggregation experiment. The lactic acid bacteria culture solution cultured for 18 hours in MRS medium was inoculated to 2% in a new 10 mL MRS medium, and cultured for 18 hours to be used in the experiment. The cultured lactic acid bacteria were centrifuged (4,000×g, 4° C., 5 minutes), washed twice in PBS, and the cells were adjusted to OD 600 1.0. After shaking the 5mL strain suspension for 10 seconds, immediately after the start of the experiment (A0) and after 1, 3 or 5 hours of leaving the suspension (A), 0.1 mL of supernatant was taken and mixed with 0.9mL PBS, and absorbance at 600nm. Was measured, and the autoaggregation ratio was calculated according to the following equation, and the results are shown in Table 6.
[표 6][Table 6]
표 6에 나타낸 바와 같이, MG4296와 MG5012 균주에 대한 현탁액 5시간 방치 후 자가응집능은 각각 95.7%, 48.3%였다. Malik의 연구에 따르면, L. Plantarum CMPG5300의 in vitro상의 자가응집이 약 67%일 때 질 상피세포에서의 부착능은 50% 이상임을 확인하였으며, 자가응집능이 높은 균주는 세포 표면에 바이오필름을 형성하는 능력이 우수함을 보였다. 위 연구에서 L. plantarum CMPG5300을 제외한 다른 8개 균주의 자가응집능이 20% 이하임을 감안하면 MG4296과 MG5012 균주의 자가응집능은 우수한 것으로 확인하였다.As shown in Table 6, after 5 hours of suspension for the MG4296 and MG5012 strains, the self-aggregation ability was 95.7% and 48.3%, respectively. According to a study by Malik, when the in vitro autoagglutination of L. Plantarum CMPG5300 was about 67%, the adhesion capacity in the vaginal epithelial cells was 50% or more, and the high autoagglutination strain formed a biofilm on the cell surface. The ability to do was excellent. In the above study, considering that the self-aggregation ability of 8 strains other than L. plantarum CMPG5300 was 20% or less, the self-aggregation ability of the MG4296 and MG5012 strains was confirmed to be excellent.
7.2 MG4296와 MG5012 균주의 소수성(Hydrophobicity) 확인7.2 Identification of Hydrophobicity of MG4296 and MG5012 Strains
장내 세포 부착능력을 간접적으로 확인하기 위한 방법으로 KOS의 용매에 대한 미생물 부착(microbial adhesion to solvents, MATS)실험 방법을 변형하여 소수성(hydrophobicity)을 확인하였다. MG4296와 MG5012 균주를 MRS 배지에 배양(37℃, 18시간)한 후, 원심분리 (4,000 ×g, 4℃, 15분)하여 PBS에 2번 세척하였다. 균체는 PBS를 이용하여 OD600 1.0 (A0)으로 현탁한 뒤 1mL의 자일렌(xylene), 클로로포름(chloroform), 에틸아세테이트(ethylacetate)에 현탁액 3mL을 각각 분주하였다. 각 시험관은 1분간 진탕한 후, 5분간 상온에 방치하였다. 이후 수용액을 회수하여 600nm에서 흡광도를 측정(A)하였으며, 다음 계산식에 따라 용매 부착능을 계산하였고, 그 결과를 표 7에 나타내었다.As a method for indirectly confirming the ability to attach cells in the intestine, the method of testing microbial adhesion to solvents (MATS) of the KOS solvent was modified to confirm the hydrophobicity. Strains MG4296 and MG5012 After incubation in MRS medium (37° C., 18 hours), centrifugation (4,000 × g, 4° C., 15 minutes) was performed and washed twice with PBS. The cells were suspended with OD 600 1.0 (A0) using PBS, and then 3 mL of the suspension was dispensed into 1 mL of xylene, chloroform, and ethylacetate. Each test tube was shaken for 1 minute and then left at room temperature for 5 minutes. Thereafter, the aqueous solution was recovered, and absorbance was measured (A) at 600 nm, and the solvent adhesion ability was calculated according to the following formula, and the results are shown in Table 7.
[표 7][Table 7]
표 7에 나타낸 바와 같이, 세포의 소수성을 알 수 있는 자일렌 부착능은 MG4296 균주가 42.1%, MG5012 균주가 72.7%로 높은 소수성을 나타내었다. 세포 표면 소수성은 세포 표면에 단백질이 존재하는 것을 의미하고, 친수성 특징을 나타낼 경우 다당류가 많은 것을 의미하며, 단백질이 많아질수록 자가응집 능력과 세포 부착능이 뛰어나게 된다. 세포부착능이 뛰어난 균주는 세포에 자리를 잡아 병원균의 세포 부착을 억제하여 감염을 막는 특성을 가진다. 선별된 두 균주는 높은 자가응집능력과 자일렌 부착능을 통해 장 내 상피세포부착능 역시 높을 것으로 확인되며, 향후 장 내 부착하여 안정적으로 혈당 저하 효과를 유지할 수 있을 것을 확인하였다. As shown in Table 7, the xylene adhesion ability to know the hydrophobicity of the cell was 42.1% for the MG4296 strain and 72.7% for the MG5012 strain. Cell surface hydrophobicity means that the protein is present on the cell surface, and if it exhibits hydrophilic characteristics, it means that there are many polysaccharides. The more proteins, the better the self-aggregation ability and cell adhesion ability. Strains with excellent cell adhesion have the property of blocking the infection by inhibiting cell adhesion of pathogens by locating the cells. The two selected strains were confirmed to have high epithelial cell adhesion ability in the intestine through high self-aggregation ability and xylene adhesion ability, and it was confirmed that they could stably maintain the hypoglycemic effect by attaching them in the future.
또한, 표 7에 나타난 바와 같이, 세포 표면 특성을 확인하기 위하여 진행한 클로로포름과 에틸아세테이트 부착능 확인 결과, MG4296와 MG5012 균주 모두 산성 용매인 클로로포름(전자수용체)에 더 높은 부착능을 나타내었다. 이를 통해 MG4296와 MG5012 균주는 세포표면에 전자공여체를 수용하고 있음을 확인하였다.In addition, as shown in Table 7, the results of chloroform and ethyl acetate adhesion confirmed to confirm the cell surface properties, both MG4296 and MG5012 strains It showed a higher adhesion to the acidic solvent chloroform (electroreceptor). Through this, it was confirmed that the MG4296 and MG5012 strains accept electron donors on the cell surface.
실시예 8. MG4296와 MG5012 균주의 항생제 감수성 테스트Example 8. Antimicrobial susceptibility test of MG4296 and MG5012 strains
MG4296와 MG5012 균주의 항생제 감수성 실험은 Clinical and Laboratory Standard Institute (CLSI) 가이드라인을 따라 BHI (Brain Heart Infusion Agar) 평판배지를 이용하여 수행하였다. MG4296, MG5012 균주는 MRS 배지에 1% 접종한 뒤, 18시간 배양하였으며 배양액은 원심분리 (4,000 × g, 4℃, 5분)한 후, PBS에 2번 세척하였다. 이후 McFarland turbidity standard 0.5로 균액의 탁도를 맞춘 뒤 멸균된 면봉을 이용하여 BHI 평판배지에 균주를 도말하였다. 배지가 마른 뒤 항생제 디스크를 균액이 도말된 배지 위에 놓고 37℃에서 24시간 배양하였으며, 생성된 억제환의 크기를 mm 단위로 측정하여 표준 지표에 따라 sensitive, intermediate, resistant 3단계로 판정하였다. 항생제는 암피실린(ampicillin, 10μg), 겐타마이신(gentamicin, 10μg), 카나마이신(kanamycin, 30μg), 스트렙토마이신(streptomycin, 10μg), 테트라사이클린(tetracycline, 30μg), 에리스로마이신(erythromycin, 15μg), 반코마이신(vancomycin, 30μg), 클로람페니콜(chloramphenicol, 30μg), 클린다마이신(clindamycin, 2μg)에 대해 확인하였으며 그 결과를 표 8에 나타내었다.Antimicrobial susceptibility experiments of MG4296 and MG5012 strains were performed using BHI (Brain Heart Infusion Agar) plate medium following the Clinical and Laboratory Standard Institute (CLSI) guidelines. MG4296 and MG5012 strains were inoculated with 1% in MRS medium, cultured for 18 hours, and the culture medium was centrifuged (4,000 × g, 4°C, 5 minutes), and then washed twice in PBS. Thereafter, the turbidity of the fungus was adjusted to McFarland turbidity standard 0.5, and the strain was plated on a BHI plate medium using a sterile cotton swab. After the medium was dried, the antibiotic disk was placed on the medium on which the fungus was smeared and cultured at 37°C for 24 hours, and the size of the resulting inhibitory ring was measured in mm to determine the sensitive, intermediate, and resistant three steps according to standard indicators. Antibiotics include ampicillin (10 μg), gentamicin (10 μg), kanamycin (30 μg), streptomycin (10 μg), tetracycline (30 μg), erythromycin (15 μg), and erythromycin (15 μg) vancomycin, 30μg), chloramphenicol (30μg), clindamycin (clindamycin, 2μg) was confirmed and the results are shown in Table 8.
[표 8][Table 8]
표 8에 나타난 바와 같이, MG4296, MG5012 두 균주 모두 반코마이신, 카나마이신, 클린다마이신에는 내성을 나타내는 것을 확인하였으며, 암피실린, 겐타마이신, 스트렙토마이신, 에리스로마이신, 테트라사이클린, 클로람페니콜에는 항생제 감수성이 있는 것을 확인하였다.As shown in Table 8, it was confirmed that both strains of MG4296 and MG5012 showed resistance to vancomycin, kanamycin, and clindamycin, and that ampicillin, gentamicin, streptomycin, erythromycin, tetracycline, and chloramphenicol had antibiotic sensitivity.
실시예 9. MG4296와 MG5012 균주의 효소 활성의 측정Example 9. Measurement of enzyme activity of MG4296 and MG5012 strains
MG4296 균주 또는 MG5012균주를 MRS 평판배지에 획선도말하여 37℃에 24시간 배양한 뒤, 생성된 집락을 MRS 액체배지에 접종하여 정치 배양 (37℃, 18시간)하였다. 이후 배양액은 원심분리 (4000 ×g, 4℃, 5분)한 후, 인산완충식염수(phosphate-buffer saline, PBS, pH 7.4)를 이용하여 2회 세척하였다. 세척한 균체는 Suspension medium 2mL (BioMerieux, France)을 이용하여 5-6 McFarland로 탁도를 조정한 뒤 시험에 사용하였다. 균액은 API ZYM 스트립의 튜브에 분주하고 37℃, 4시간 배양한 뒤 ZYM A와 ZYM B 시약(BioMerieux, France)을 각각 한방울 첨가하였다. 10분 뒤 색 변화를 통한 효소 활성을 확인하였으며, 효소 활성 결과를 표 9에 나타내었다.MG4296 strain or MG5012 strain was streaked on MRS plate medium and incubated at 37°C for 24 hours, and then the resulting colonies were inoculated in MRS liquid medium and allowed to stand still (37°C, 18 hours). After the culture was centrifuged (4000 × g, 4 ℃, 5 minutes), washed twice with phosphate-buffered saline (phosphate-buffer saline, PBS, pH 7.4). The washed cells were used for the test after adjusting the turbidity with 5-6 McFarland using 2 mL of Suspension medium (BioMerieux, France). The bacterial solution was dispensed into a tube of the API ZYM strip, incubated at 37°C for 4 hours, and then a drop of each of the ZYM A and ZYM B reagents (BioMerieux, France) was added. After 10 minutes, the enzyme activity through color change was confirmed, and the enzyme activity results are shown in Table 9.
[표 9][Table 9]
표 9에 나타낸 바와 같이, MG4296은 류신 아릴아미데이즈(Leucine arylamidase), 애시드 포스파테이즈(Acid phosphatase), β-글루쿠로니데이즈(β-glucuronidase), β-글루코시데이즈(β-glucosidase), N-아세틸-β-글루코사미니데이즈(N-acetyl-β-glucosaminidase)에 효소 활성을 나타내는 것을 확인하였다. As shown in Table 9, MG4296 is leucine arylamidase, acid phosphatase, β-glucuronidase, β-glucosidase, It was confirmed that it shows enzyme activity in N-acetyl-β-glucosaminidase (N-acetyl-β-glucosaminidase).
또한, MG5012는 에스터레이즈(C4)(Esterase (C4)), 에스터레이즈 리페이즈(C8)(Esterase Lipase (C8)), 류신 아릴아미데이즈(Leucine arylamidase), 발린 아릴아미데이즈(Valine arylamidase), 애시드 포스파테이즈(Acid phosphatase), 나프톨-AS-BI-포스포하이드로레이즈(Naphtol-AS-BI-phosphohydrolase), β-글루코시데이즈(β-glucosidase), α-글루코시데이즈(α-glucosidase)에 효소 활성을 나타내는 것을 확인하였다.In addition, MG5012 is esterase (C4) (Esterase (C4)), esterase lipase (C8) (Esterase Lipase (C8)), leucine arylamidase, valine arylamidase, acid Phosphatase, Naphtol-AS-BI-phosphohydrolase, β-glucosidase, α-glucosidase It was confirmed that it exhibits enzyme activity.
실시예 10.Example 10. MG4296와 MG5012 균주의 API 당 발효 특성 확인Confirmation of fermentation characteristics per API of MG4296 and MG5012 strains
MG4296 균주 또는 MG5012균주를 MRS 평판배지에 획선도말하여 37℃에 24시간 배양한 뒤, 생성된 집락을 MRS 액체배지에 접종하여 정치 배양 (37℃, 18시간)하였다. 이후 배양액은 원심분리 (4000 ×g, 4℃, 5분)한 후, 인산완충식염수(phosphate-buffer saline, PBS, pH 7.4)를 이용하여 2회 세척하였다. 세척한 균체는 API 50CHL medium 10mL (BioMerieux, France)을 이용하여 2 McFarland로 탁도를 조정한 뒤 시험에 사용하였다. 균을 부유시킨 API50 CHL배지를 스트립의 튜브에 분주하고 미네랄 오일을 첨가하여 큐플을 혐기조건으로 만든다. 37℃, 48시간 배양한 뒤 결과를 표 10에 나타내었다.MG4296 strain or MG5012 strain was streaked on MRS plate medium and incubated at 37°C for 24 hours, and then the resulting colonies were inoculated in MRS liquid medium and allowed to stand still (37°C, 18 hours). After the culture was centrifuged (4000 × g, 4 ℃, 5 minutes), washed twice with phosphate-buffered saline (phosphate-buffer saline, PBS, pH 7.4). The washed cells were used for the test after adjusting the turbidity with 2 McFarland using API 50CHL medium 10mL (BioMerieux, France). The API50 CHL medium in which the bacteria are suspended is dispensed into a tube of the strip, and mineral oil is added to make the cuppe anaerobically. Table 10 shows the results after incubation at 37°C for 48 hours.
[표 10]Table 10
표 10에 나타낸 바와 같이, MG4296 균주는 D-리보오스, D-갈락토스, D-글루코스, D-프럭토스, D-만노스, 만니톨, D-소르비톨, 메틸 α D-만노피라노시드, N-아세틸글루코스아민, 아미그달린, 아르부틴, 에스쿨린, 살리신, D-셀로비오스, D-말토스, D-락토스, D-멜리비오스, D-사카로스, D-트레할로스, D-라피노스, 겐티비오스, 포타슘 글루네이트에 대해서 발효 특성을 나타내는 것을 확인하였다.As shown in Table 10, strains MG4296 are D-ribose, D-galactose, D-glucose, D-fructose, D-mannose, mannitol, D-sorbitol, methyl α D-mannopyranoside, N-acetylglucose Amine, amidaline, arbutin, esculin, salicin, D-cellobiose, D-maltose, D-lactose, D-melibiose, D-saccharose, D-trehalose, D-rapinose, gentibiose, potassium glue It was confirmed that the nate exhibited fermentation characteristics.
MG5012 균주는 D-리보스, D-아도니톨, D-갈락토스, D-글루코스, D-프럭토스, D-만노스, L-소르보스, 만니톨, D-소르비톨, 메틸 α D-글루코피라노시드, N-아세틸글루코스아민, 아미그달린, 아르부틴, 에스쿨린, 살리신, D-셀로비오스, D-말토스, D-사카로스, D-트레할로스, 이눌린, D-멜레지토스, 겐티비오스, D-투라노스, D-릭소스, D-타가토스에 대해서 발효 특성을 나타내는 것을 확인하였다.The MG5012 strains are D-ribose, D-adonitol, D-galactose, D-glucose, D-fructose, D-mannose, L-sorbose, mannitol, D-sorbitol, methyl α D-glucopyranoside, N-acetylglucosamine, amidaline, arbutin, esculin, salicin, D-cellobiose, D-maltose, D-saccharose, D-trehalose, inulin, D-melezitose, gentibiose, D-to It was confirmed that it exhibits fermentation properties for lanose, D-rixose, and D-tagatose.
실시예 11.Example 11. MG4296와 MG5012 균주의 당뇨 동물 모델에 대한 항 당뇨 효과Anti-diabetic effect on diabetic animal models of MG4296 and MG5012 strains
고지방 식이와 과당에 의해 유도된 제2형 당뇨 동물 모델에서 MG4296 균주와 MG5012 균주의 혈당 저하 효과와 인슐린 저항성 개선 효과를 확인하고자 하는 실험을 실시하였다. In the
11.1 MG4296과 MG5012 균주의 당뇨 동물 모델에 대한 체중 감소 효과11.1 Weight loss effect on diabetic animal models of MG4296 and MG5012 strains
본 실시예를 수행하기 위해 수컷 C57BL/6J 종 마우스를 사용하였다. 일반식이를 섭취한 대조군(ND), 고지방 식이를 섭취하여 당뇨를 유도시킨 대조군(HFD), 고지방 식이를 섭취하여 당뇨를 유발시키고 MG4296을 투여한 실험군 1, 고지방 식이를 섭취하여 당뇨를 유발시키고 MG5012를 투여한 실험군 2를 설정하였다. 대조군과 실험군의 체중을 매주 1회 측정하였다. 동물 모델의 사육조건을 표 11에 나타내었고, 대조군과 실험군의 식이 조건을 표 12에 나타내었다. Male C57BL/6J species mice were used to perform this example. The control group (ND) who consumed the general diet, the control group (HFD) who ingested the high-fat diet to induce diabetes, and the
각 실험군의 주차 별 평균 체중을 그래프로 하여 도 4에 나타내었다.The average weight for each parking group in each experimental group is shown in FIG. 4 as a graph.
[표 11][Table 11]
[표 12]Table 12
도 4에 나타낸 바와 같이, 고지방 식이로 당뇨 유발된 동물모델(HFD)에서는 일반 식이를 섭취한 대조군(ND) 대비 현저한 체중 증가를 나타내나, 고지방 식이로 당뇨 유발된 동물 모델에 본 발명의 유산균 MG4296 또는 MG5012를 섭취시키면 체중 증가율이 현저히 감소되는 것을 확인하였다. 따라서, 본 발명의 MG4296 또는 MG5012 균주는 고지방 식이에 의해 유발되는 인슐린 저항성을 예방 또는 치료하는 효과가 있는 것을 확인하였다. As shown in FIG. 4, in the animal model (HFD) induced by diabetes with a high fat diet, a significant weight gain was observed compared to a control group (ND) ingesting a normal diet, but the lactic acid bacterium MG4296 of the present invention was used in an animal model induced with diabetes with a high fat diet. Or it was confirmed that the intake of MG5012 significantly reduced the rate of weight gain. Therefore, it was confirmed that the MG4296 or MG5012 strain of the present invention has an effect of preventing or treating insulin resistance caused by a high fat diet.
11.2 MG4296과 MG5012 균주의 당뇨 동물 모델에 대한 인슐린 저항성 감소 효과11.2 Effect of reducing insulin resistance on diabetic animal models of MG4296 and MG5012 strains
당뇨 동물 모델에서 MG4296과 MG5012 균주의 인슐린 저항성 감소효과를 확인하기 위한 실험을 실시하였다. 실시예 11.1의 대조군과 실험군에 대하여, 12주차에 DDW(doubled distilled water)에 2g/kg의 농도로 용해시킨 글루코스 용액을 복강 내 주사하고, 0분, 15분, 30분, 60분, 90분 및 120분에 혈당을 측정하였으며, 측정 결과를 도 5에 나타내었다.In the diabetic animal model, an experiment was conducted to confirm the effect of reducing the insulin resistance of the MG4296 and MG5012 strains. For the control group and the experimental group of Example 11.1, a glucose solution dissolved in double distilled water (DDW) at a concentration of 2 g/kg was injected intraperitoneally at
도 5에 나타낸 바와 같이, 복강 내 글루코스 투여 후, 고지방 식이로 당뇨 유발된 동물모델 대조군(HFD)에서는 일반 식이를 섭취한 대조군(ND) 대비 혈당이 급격히 증가하였으나, 본원 발명의 유산균 MG4296 또는 MG5012 균주를 섭취한 당뇨 동물 모델 실험군은 유산균을 섭취하지 않은 당뇨 동물 모델 대조군(HFD)과 비교하여 복강 내 글루코스 투여 후 혈당 상승이 억제되었으며, 일반 식이를 섭취한 대조군(ND)과 비교하여 유사한 정도의 혈당 값을 나타낸 것을 확인하였다. 특히, 본원 발명의 유산균 MG4296 또는 MG5012 균주를 섭취한 당뇨 동물 모델 실험군은 글루코스 투여 90분 경과 후, 혈당 값이 200 이하의 값을 나타내는 것을 확인하였다. 따라서, 본원 발명의 유산균 MG4296 또는 MG5012 균주는 인슐린 저항성 극복에 우수한 효과를 갖는 것을 확인하였다.As shown in FIG. 5, after administration of glucose intraperitoneally, in the animal model control group (HFD) induced by diabetes with a high fat diet, blood glucose rapidly increased compared to the control group (ND) ingesting the normal diet, but the lactic acid bacteria MG4296 or MG5012 strain of the present invention In the diabetic animal model experimental group ingested, blood glucose elevation was suppressed after intraperitoneal glucose administration compared to the diabetic animal model control group (HFD) without lactic acid bacteria, and a similar level of blood sugar compared to the control group (ND) ingesting a normal diet. It confirmed that the value was shown. In particular, the diabetic animal model experimental group ingesting the lactic acid bacteria MG4296 or MG5012 strain of the present invention confirmed that the blood glucose value was less than 200 after 90 minutes of glucose administration. Therefore, it was confirmed that the lactic acid bacteria MG4296 or MG5012 strain of the present invention has an excellent effect on overcoming insulin resistance.
이상, 본 발명내용의 특정한 부분을 상세히 기술하였는 바, 당업계의 통상의 지식을 가진 자에게 있어서, 이러한 구체적인 기술은 단지 바람직한 실시양태일 뿐이며, 이에 의해 본 발명의 범위가 제한되는 것이 아닌 점은 명백할 것이다. 따라서 본 발명의 실질적인 범위는 첨부된 청구항들과 그것들의 등가물에 의해 정의된다고 할 것이다.As described above, specific parts of the present invention have been described in detail. For those skilled in the art, this specific technique is only a preferred embodiment, and it is obvious that the scope of the present invention is not limited thereby. something to do. Therefore, the substantial scope of the present invention will be defined by the appended claims and their equivalents.
Claims (16)
Lactobacillus paracasei MG5012 strain (Accession No. KCTC13831BP) with weight loss effect and hypoglycemic activity.
According to claim 1, wherein the Lactobacillus paracasei MG5012 strain is characterized in that it has α-glucosidase (α-glucosidase) inhibitory activity, Lactobacillus paracasei MG5012 strain.
According to claim 1, wherein the Lactobacillus paracasei MG5012 strain is characterized in that it has an α- amylase (α-amylase) inhibitory activity Lactobacillus paracasei MG5012 strain.
According to claim 1, wherein the Lactobacillus paracasei MG5012 strain is characterized by improving the insulin resistance Lactobacillus paracasei MG5012 strain.
The Lactobacillus paracasei MG5012 strain according to claim 1, wherein the Lactobacillus paracasei MG5012 strain is stable at pH 2 to pH 7.
The Lactobacillus paracasei MG5012 strain according to claim 1, wherein the Lactobacillus paracasei MG5012 strain is stable against bile salts.
According to claim 1, wherein the Lactobacillus paracasei MG5012 strain is characterized in that it exhibits autoaggregation (Autoaggregation) Lactobacillus paracasei MG5012 strain.
According to claim 1, wherein the Lactobacillus paracasei MG5012 strain is characterized in that the cell surface is hydrophobic (hydrophobicity) Lactobacillus paracasei MG5012 strain.
According to claim 1, wherein the Lactobacillus paracasei MG5012 strain is esterase (C4) (Esterase (C4)), esterase lipase (C8) (Esterase Lipase (C8)), leucine arylamidase (Leucine arylamidase), Valine arylamidase, Acid phosphatase, Naphtol-AS-BI-phosphohydrolase, β-glucosidase and α -Lactobacillus paracasei MG5012 strain, characterized in that it exhibits enzymatic activity in glucosidase (α-glucosidase).
According to claim 1, wherein the Lactobacillus paracasei MG5012 strain is D- ribose, D- adonitol, D- galactose, D- glucose, D- fructose, D- mannose, L- sorbose, mannitol, D- Sorbitol, methyl α D-glucopyranoside, N-acetylglucosamine, amygdaline, arbutin, esculin, salicin, D-cellobiose, D-maltose, D-saccharose, D-trehalose, inulin, D- Lactobacillus paracasei MG5012 strain, characterized in that it exhibits fermentation properties to Melezitose, Gentibios, D-Turanos, D-Ryxos and D-Tagatos.
The strain of claim 1, wherein the Lactobacillus paracasei MG5012 strain has antibiotic resistance to vancomycin, kanamycin, and clindamycin.
A health functional food composition for weight loss and lowering blood sugar, comprising at least one selected from the group consisting of the strain of any one of claims 1 to 11, a strain culture medium, and a cell free supernatant of the strain.
Claims 1 to 11 of any one of strains, strain culture medium and cell-free supernatant (cell free supernatant) of the strain comprising at least one selected from the group consisting of, for weight loss; And pharmaceutical compositions for preventing or treating diabetes.
Claims 1 to 11 of any one of strains, strain culture medium and cell-free supernatant (cell free supernatant) of the strain comprising at least one selected from the group consisting of, for weight loss; And health functional food composition for preventing or improving diabetes.
Claims 1 to 11 of any one of strains, strain culture medium and cell-free supernatant (cell free supernatant) of the strain comprising at least one selected from the group consisting of, for weight loss; And quasi-drug composition for preventing or improving diabetes.
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR102294456B1 (en) * | 2021-02-17 | 2021-08-27 | 주식회사 메디오젠 | Infant and child origin lactic acid bacteria Lactobacillus rhamnosus MG4502 and composition comprising the lactic acid bacteria for enhancing intestine activity, anti-oxidant and anti-obesity |
KR102294451B1 (en) * | 2021-02-17 | 2021-08-27 | 주식회사 메디오젠 | Infant and child origin lactic acid bacteria Lactobacillus acidophilus MG4558 and composition comprising the lactic acid bacteria for enhancing intestine activity, anti-oxidant and anti-obesity |
KR102294445B1 (en) * | 2021-02-17 | 2021-08-27 | 주식회사 메디오젠 | Infant and child origin lactic acid bacteria Lactobacillus paracasei MG4592 and composition comprising the lactic acid bacteria for enhancing intestine activity, anti-oxidant and anti-obesity |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100534066B1 (en) | 2001-09-04 | 2005-12-06 | 주식회사 바이오허브 | Mushroom lactic acid fermented solution including effective ingredients for decreasing the value of blood sugar, and method for manufacturing the solution |
KR20120067683A (en) * | 2010-12-16 | 2012-06-26 | 대상에프앤에프 주식회사 | Plant origin lactic acid bacteria lactobacillus plantarum dsr j1-8 having preventing effect of metabolic syndrome and its use |
KR101270599B1 (en) | 2009-05-21 | 2013-06-03 | (주) 엔유씨생활과건강 | Fermented red ginseng composition containing fermented red ginseng and medical plant extracts exhibiting antidiabetic activity |
KR101800608B1 (en) | 2015-11-18 | 2017-12-20 | 강원대학교산학협력단 | Antidiabetic composition containing of cirsium setidens nakai extract method of preparing the same |
KR101892392B1 (en) | 2017-06-12 | 2018-08-27 | 오형근 | Composition for improving hypertension and diabetes |
KR20190090407A (en) * | 2017-12-26 | 2019-08-02 | 주식회사 종근당바이오 | Lactobacillus plantarum K10 having anti-obesity effect and uses thereof |
-
2019
- 2019-12-16 KR KR1020190168222A patent/KR102123838B1/en active IP Right Grant
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR100534066B1 (en) | 2001-09-04 | 2005-12-06 | 주식회사 바이오허브 | Mushroom lactic acid fermented solution including effective ingredients for decreasing the value of blood sugar, and method for manufacturing the solution |
KR101270599B1 (en) | 2009-05-21 | 2013-06-03 | (주) 엔유씨생활과건강 | Fermented red ginseng composition containing fermented red ginseng and medical plant extracts exhibiting antidiabetic activity |
KR20120067683A (en) * | 2010-12-16 | 2012-06-26 | 대상에프앤에프 주식회사 | Plant origin lactic acid bacteria lactobacillus plantarum dsr j1-8 having preventing effect of metabolic syndrome and its use |
KR101800608B1 (en) | 2015-11-18 | 2017-12-20 | 강원대학교산학협력단 | Antidiabetic composition containing of cirsium setidens nakai extract method of preparing the same |
KR101892392B1 (en) | 2017-06-12 | 2018-08-27 | 오형근 | Composition for improving hypertension and diabetes |
KR20190090407A (en) * | 2017-12-26 | 2019-08-02 | 주식회사 종근당바이오 | Lactobacillus plantarum K10 having anti-obesity effect and uses thereof |
Non-Patent Citations (3)
Title |
---|
Eur. J. Nutr.,Vol.53, pp.1465-1474(Epub.2016.01.12.) * |
https://www.ingredientsnetwork.com/47/resourcefile/09/75/81/2019_mediogen_EN.pdf (2019.05.03.)* * |
Mol. Nutr. Food Res., Vol.63, pp.1-9(Epub.2019.09.12.)* * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR102294456B1 (en) * | 2021-02-17 | 2021-08-27 | 주식회사 메디오젠 | Infant and child origin lactic acid bacteria Lactobacillus rhamnosus MG4502 and composition comprising the lactic acid bacteria for enhancing intestine activity, anti-oxidant and anti-obesity |
KR102294451B1 (en) * | 2021-02-17 | 2021-08-27 | 주식회사 메디오젠 | Infant and child origin lactic acid bacteria Lactobacillus acidophilus MG4558 and composition comprising the lactic acid bacteria for enhancing intestine activity, anti-oxidant and anti-obesity |
KR102294445B1 (en) * | 2021-02-17 | 2021-08-27 | 주식회사 메디오젠 | Infant and child origin lactic acid bacteria Lactobacillus paracasei MG4592 and composition comprising the lactic acid bacteria for enhancing intestine activity, anti-oxidant and anti-obesity |
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