KR101240192B1 - Lactobacillus acidophilus K-59, extracts from ginseng-fermented products using K-59 for improving insulin secretion and manufacturing method thereof - Google Patents
Lactobacillus acidophilus K-59, extracts from ginseng-fermented products using K-59 for improving insulin secretion and manufacturing method thereof Download PDFInfo
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- KR101240192B1 KR101240192B1 KR1020100117241A KR20100117241A KR101240192B1 KR 101240192 B1 KR101240192 B1 KR 101240192B1 KR 1020100117241 A KR1020100117241 A KR 1020100117241A KR 20100117241 A KR20100117241 A KR 20100117241A KR 101240192 B1 KR101240192 B1 KR 101240192B1
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- ginseng
- extract
- fermentation
- ginsenosides
- strain
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Abstract
본 발명은 신규 락토바실러스 아시도필러스(Lactobacillus acidophilus) K-59 (KFCC11467P) 균주; 상기 균주로부터 얻어진 알파-람노시다제; 상기 균주 또는 이로부터 얻어진 알파-람노시다제를 이용한 인슐린 분비 개선용 인삼 발효물 또는 발효물의 추출물; 및 그의 제조방법에 관한 것으로서 보다 상세하게는 인삼을 발효시킬 수 있는 신규한 K-59 및 상기 균주로 인삼을 발효시켜 인슐린 분비 개선에 적용할 수 있는 인삼 발효 추출물 및 이의 제조방법에 관한 것이다. 본 발명의 인삼을 K-59 균주로 발효시켜 얻은 발효 추출물은 인슐린 분비 촉진 효과가 우수하여 공복혈당장애자, 내당능장애자, 당뇨병 전단계로 진단받은 자 및 당뇨병 환자의 치료 또는 예방에 효과가 있다.The present invention is a novel Lactobacillus acidophilus K-59 (KFCC11467P) strain; Alpha-lamnosidase obtained from the strain; Extract of ginseng fermentation product or fermentation product for improving insulin secretion using the strain or alpha-lamnosidase obtained therefrom; And it relates to a manufacturing method thereof in more detail relates to a ginseng fermented extract and fermented ginseng that can be applied to improve the secretion of insulin by fermenting ginseng with the novel K-59 capable of fermenting ginseng and the strain. The fermented extract obtained by fermenting ginseng of the present invention with K-59 strain has an excellent effect of promoting insulin secretion and is effective in treating or preventing fasting glucose disorders, impaired glucose tolerance, prediabetes, and diabetic patients.
Description
본 발명은 인삼을 발효할 수 있는 새로운 균주, 이러한 균주 또는 이러한 균주로부터 생산된 특정 효소를 이용하는 방법, 균주를 이용하여 얻은 산물, 이러한 산물의 용도 등에 관한 것이다. The present invention relates to new strains capable of fermenting ginseng, methods using such strains or specific enzymes produced from such strains, products obtained using strains, uses of these products, and the like.
인삼은 식물 분류학상 오가과(Araliaceae) 인삼속(Panax)에 속하는 다년생 숙근초로서 지구상에 약 11종이 알려져 있으며, 대표적인 종으로 고려인삼(Panax ginseng C.A. Meyer)은 아시아 극동 지역(한국, 북만주, 러시아 일부)에 자생한다.Panax ginseng is a perennial root of the genus Panax in the genus Araliaceae. About 11 species of ginseng are known on the earth.Panax ginseng CA Meyer is a representative species of Panax ginseng (Panax ginseng CA Meyer). Grow wild)
인삼의 성분으로는 사포닌(saponin), 페놀성 성분, 폴리아세칠렌 성분, 알칼로이드 성분, 다당체 등이 알려져 있다. 특히 사포닌 성분은 인삼 특이 성분으로 진세노사이드(ginsenosides)라 칭하며 30종 이상이 알려져 있으며, 인삼 약효에 있어서 가장 중요한 역할을 하는 것으로 알려져 있다.As the components of ginseng, saponin, phenolic component, polyacexylene component, alkaloid component, polysaccharide and the like are known. In particular, saponin components are called ginsenosides (ginsenosides) as a ginseng specific component, and more than 30 kinds are known, and are known to play the most important role in ginseng drug efficacy.
인삼에 있는 사포닌을 의미하는 진세노사이드(Ginsenoside)는 인삼 건조량의 약 5％를 차지하며, 트리터페노이드(triterpenoid) 계열의 다마란(dammarane) 골격에 포도당(glucose), 아라비노즈(arabinose), 자일로즈(xylose), 람노즈(rhamnose) 등이 결합되어 있는 중성 배당체이다. 비당부분에 붙어있는 -OH의 수에 따라 2개인 (3, 12번 위치) 경우 프로토파낙사디올(protopanaxadiol; PPD) 계열 사포닌, 3개인 (3, 6, 12번 위치) 경우 프로토파낙사트리올(protopanaxatriol; PPT) 계열 사포닌이라 한다. PPD과 PPT의 R1, R2, R3 위치의 -OH에 글루코오스(glucose), 아라비노오스(arabinose), 자일로오스(xylose), 람노오스(rhamnose) 등이 결합된다. 30종 이상의 진세노사이드가 인삼으로부터 분리 보고되었으나 실제 인삼을 추출하여 분석할 때 상당한 양이 검출되는 것은 Rb1, Rb2, Rc, Rd, Re, Rg1의 6종이 전체 사포닌의 90％ 이상을 차지하고 있으며 나머지 사포닌 성분들은 그 함량이 낮다.Ginsenoside, which means saponin in ginseng, accounts for about 5% of ginseng dry weight. Glucose, arabinose, and triterpenoid-based dammarane skeletons It is a neutral glycoside with xylose and rhamnose. Protopanaxadiol (PPD) family saponins for two (3, 12) depending on the number of -OH attached to the non-sugar moiety, protopanaxatriol for three (3, 6, 12) (protopanaxatriol; PPT) family is called saponin. Glucose, arabinose, xylose, rhamnose, and the like are combined with -OH at the positions R1, R2 and R3 of the PPD and PPT. More than 30 species of ginsenosides have been reported from ginseng, but a significant amount of ginseng was detected when extracting and analyzing ginseng. Six species of Rb1, Rb2, Rc, Rd, Re, and Rg1 accounted for more than 90% of the total saponin. Saponin components are low in content.
진세노사이드는 인체 내에서 그대로 흡수되는 것이 아니라 인체 장내 Bacteriodes, Fusobactrium, Eubacterium, Provetella 종 등의 미생물에 의하여 분해되어 그 대사체가 흡수된다. 진세노사이드 Rb1의 경우, 장내 미생물에 의해 진세노사이드 Rd, 컴파운드 케이(compound K, 이하 C-K라로 약칭함)와 프로토파낙사디올로 순차적으로 전환된다. PPD계 진세노사이드인 Rb1, Rb2, Rc, Rd는 장내에서 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol(C-K)로 대사되어 흡수된다. PPT계 진세노사이드인 진세노사이드 Re, Rf, Rg1은 장내에서 Rh1, F1, 프로토파낙사트리올(protopanaxatriol)로 대사된다. Rb1, Rb2, Rc, Rd 등은 장내 미생물에 의하여 20(R)-/20(S)-ginsenoside Rg3로 전환되며, Rg3는 장내 미생물에 의하여 Rh2로 전환된다.Ginsenosides are not absorbed as they are in the human body, but are degraded by microorganisms such as Bacteriodes, Fusobactrium, Eubacterium, and Provetella species in the human intestine to absorb their metabolites. In the case of ginsenoside Rb1, it is sequentially converted to ginsenoside Rd, compound K (hereinafter abbreviated as C-K) and protopanaxadiol by intestinal microorganisms. PPD ginsenosides Rb1, Rb2, Rc, Rd are metabolized and absorbed by 20-O-β-D-glucopyranosyl-20 (S) -protopanaxadiol (C-K) in the intestine. PPT ginsenosides ginsenosides Re, Rf, Rg1 are metabolized in the intestine into Rh1, F1, protopanaxatriol. Rb1, Rb2, Rc, Rd and the like are converted to 20 (R)-/ 20 (S) -ginsenoside Rg3 by intestinal microorganisms, and Rg3 is converted to Rh2 by intestinal microorganisms.
진세노사이드를 분해하는 장내 미생물은 사람의 체질, 식습관에 따라 그 존재의 유무와 보유하고 있는 정도가 다르며, 대사산물로 전환하는 전환율에 차이가 있어서 인삼을 섭취한 후 저마다 효능의 차이가 나타날 수 있다. 장내 미생물 균총이 다르기 때문에 진세노사이드의 전환율과 생체이용률은 다를 수밖에 없다(J. Pharm. Pharmacol., 50, pp.1155-1160, 1998). 따라서 장내 미생물의 차이로 인한 효능과 흡수율의 차이를 없애기 위해, 진세노사이드를 대사하는 미생물을 발굴하는 것이 필요하다.The intestinal microorganisms that break down ginsenosides differ in their presence and retention according to human constitution and dietary habits, and there is a difference in the conversion rate to metabolites. have. Due to different intestinal microflora, ginsenoside conversion and bioavailability are different (J. Pharm. Pharmacol., 50, pp. 1155-1160, 1998). Therefore, in order to eliminate the difference in efficacy and absorption rate due to the difference between the intestinal microorganisms, it is necessary to find a microorganism that metabolizes ginsenosides.
한편 인체가 항상 필요로 하는 포도당은 몸속에서 혈당으로 존재하는 데 공복 시에는 간, 근육 및 지방에 저장된 포도당이 다시 혈액으로 방출되고 식사를 하면 약 2~3시간 동안 위장관에서 흡수된 다량의 포도당이 혈액을 거쳐 간, 근육 및 지방에 저장된다. 이러한 체내 에너지 대사가 자동으로 조절되는 것은 바로 췌장 베타세포에서 분비되는 인슐린의 양을 조절함으로써 이루어지게 된다. On the other hand, glucose, which is always needed by the human body, exists as blood sugar in the body. When fasting, glucose stored in the liver, muscles and fats is released into the blood again, and when eaten, a large amount of glucose absorbed from the gastrointestinal tract for about 2 to 3 hours It is stored in the liver, muscles and fats via the blood. The automatic regulation of energy metabolism in the body is achieved by controlling the amount of insulin secreted from pancreatic beta cells.
체내에서 혈당(blood glucose)은 80~120mg/dL으로 항상 일정하게 유지되는데, 이 현상을 포도당 항상성(glucose homeostasis; 이하 당항상성이라 약칭함)이라고 한다. 인체가 당항상성을 유지하는 과정에는 췌장의 베타(β)세포와 알파(α)세포에서 각각 분비되는 인슐린(insulin)과 글루카곤(glucagon)이 관여한다. 식사 직후에는 혈당이 상승하고 이때 분비된 인슐린은 간, 근육, 지방세포 등의 말초조직에 포도당을 에너지원으로 사용할 수 있게 공급하고, 또한 간 및 근육에 포도당을 글리코겐 (glycogen)으로 저장시켜 혈당을 정상화시킨다. 공복에는 혈당이 저하되고 이때 글루카곤이 분비되어 간에서 글리코겐이 포도당으로 분해되어 혈당을 정상화시킨다 . 공복 기간이 길어지면 간의 글리코겐이 고갈되고, 아미노산 등의 당신생합성(gluconeogenesis) 전구체가 간에서 포도당으로 전환되어 혈당을 정상으로 유지시킨다.Blood glucose in the body is always maintained at 80-120 mg / dL, which is called glucose homeostasis (abbreviated as glucose homeostasis). In the process of maintaining the human body glycemic insulin (insulin) and glucagon (glucagon) secreted from the beta (β) cells and alpha (α) cells of the pancreas, respectively. Immediately after a meal, blood sugar rises, and insulin secreted at this time supplies glucose to the peripheral tissues such as liver, muscle, and fat cells to be used as an energy source, and glucose is stored in the liver and muscle as glycogen (glycogen). Normalize Fasting lowers blood sugar and glucagon is secreted, which breaks down glycogen into glucose in the liver to normalize blood sugar. When the fasting period is longer, glycogen is depleted in the liver, and gluconeogenesis precursors such as amino acids are converted to glucose in the liver to keep blood sugar normal.
당항상성을 유지하는 기능이 저하되면 공복 혈당(fasting glucose)이나 식후 혈당(postprandial glucose)이 조금씩 오르거나 오른 상태가 되어 있는 내당능장애(耐糖能障碍; glucose intolerance)의 단계로 넘어간다. 내당능장애는 사람에 따라서 수개월간 지속되거나 수년에서 10년 이상 지속되기도 한다. 내당능장애 상태가 모두 당뇨병 단계로 진행되지는 않는다. 그러나 내당능장애 상태에서 당항상성을 유지하는 기능 저하가 계속되면 제2형 당뇨병이 발병한다.When the function of maintaining the glycemic state is reduced, fasting glucose or postprandial glucose rises or rises to a state of glucose intolerance (耐 糖 能 障碍; glucose intolerance) is a step up. Impaired glucose tolerance lasts for months or even for years to 10 years, depending on the person. Not all glucose tolerance states progress to the diabetic stage. However, type 2 diabetes develops if the hypoglycemic function continues to be impaired in glucose tolerance.
당뇨병을 예방하거나 치료하기 위해서는 당뇨병의 발병 원인인 균형 잃은 당항상성 조절 기전을 개선시키는 방법이 효과적이다. 이 방법에 약물 치료가 있을 수 있는데, 당뇨병이 이미 진전된 경우에는 약물 치료가 불가피하지만 당뇨병을 예방하기 위한 목적으로는 약물에 대한 부작용을 감안할 때 바람직한 방법이 아니다. 당뇨 예방을 위해서는 약물보다 효과는 약하지만 부작용 없는 건강기능식품이 효과적이다. 그러나 현재 국내에 시판되는 혈당강하용 건강기능식품은 탄수화물 소화 효소 저해 등 식후 혈당의 일시적 저하만을 목표로 하기 때문에 그 제품의 섭취에 의한 혈당강하효과는 일시적이며 근본적인 당뇨병의 병인 해소와는 거리가 있다. 또한 당항상성을 유지하는 상호보완적인 여러 기작을 동시에 만족시키는 복합 기능의 건강기능식품이 단일 기작에 근거한 단일 성분인 의약품에 비하여 당뇨 예방 및 치료에 가장 이상적이지만 이러한 소재는 아직 개발되지 못하고 있는 실정이다.
In order to prevent or treat diabetes, it is effective to improve the unbalanced glycemic control mechanism that causes diabetes. There may be drug treatment in this method, which is inevitable if diabetes is already advanced, but it is not a desirable method in view of the side effects of the drug for the purpose of preventing diabetes. To prevent diabetes, health functional foods are less effective than drugs, but have no side effects. However, the current hypoglycemic functional foods in Korea target only a temporary decrease in post-prandial blood sugar, such as inhibition of carbohydrate digestive enzymes, so the hypoglycemic effect of ingesting the product is temporary and far from eliminating the underlying etiology of diabetes. . In addition, multi-functional dietary supplements that simultaneously satisfy several complementary mechanisms, which are always ideal, are ideal for the prevention and treatment of diabetes compared to single-component drugs based on a single mechanism, but these materials have not yet been developed. .
따라서 본 발명이 이루고자 하는 기술적 과제는 인삼에서 생체이용률이 낮은 진세노사이드 Rg1, Rb1, Re 등을 진세노사이드 Rh1, Rg3, Rh2, C-K 등으로 생성 및/또는 전환시킬 수 있는 방법을 제공하는 것이다.Accordingly, the present invention is to provide a method for generating and / or converting ginsenosides Rg1, Rb1, Re, and the like to ginsenosides Rh1, Rg3, Rh2, CK and the like having low bioavailability in ginseng. .
본 발명이 이루고자 하는 다른 기술적 과제는 상기 Rh1, Rg3, Rh2, C-K 등의 생성 및/또는 전환이 가능한 신규 균주 및 이러한 균주로부터 얻은 동일 용도의 효소를 제공하는 것이다.Another technical problem to be achieved by the present invention is to provide a novel strain capable of producing and / or converting the Rh1, Rg3, Rh2, C-K and the like and enzymes of the same use obtained from these strains.
본 발명이 이루고자 하는 또 다른 기술적 과제는 상기 균주 및 이러한 균주로부터 얻은 특정 효소를 이용한 인삼 발효물 또는 이러한 발효물의 추출물; 이러한 발효물 또는 추출물을 제조하는 방법; 및 이들의 유용한 용도를 제공하는 것이다.Another technical problem to be achieved by the present invention is a ginseng fermentation or extract of such a fermentation using the strain and a specific enzyme obtained from such a strain; A method of making such fermentation or extract; And their useful uses.
상기 기술적 과제를 달성하기 위하여, 본 발명은 새롭게 분리 동정된 락토바실러스 아시도필러스(Lactobacillus acidophilus) K-59 (KFCC11467P) 균주(K-59로 약칭함)를 제공한다.In order to achieve the above technical problem, the present invention provides a newly isolated and identified Lactobacillus acidophilus K-59 (KFCC11467P) strain (abbreviated as K-59).
본 발명의 신규한 K-59는 김치에서 BL 평판배지 계수 희석법을 이용하여 단일 콜로니(colony)를 분리한 후 유산균에 해당하는 특징 및 성상을 보이는 단일 콜로니를 재차 취하여 MRS broth의 액체배지에 접종한 후 배양하여 얻었다. 이 균주로부터 DNA를 추출하여 16S rRNA를 실시하고 BLAST 프로그램을 사용하여 균주의 상동성을 검색한바, 상기 균주가 락토바실러스 아시도필러스 CTSPL1 균주의 16S rRNA 유전자와 96％ 상동성을 가짐을 알게되어 K-59 균주로 명명하고 이를 미생물보존센터에 2009년 10월 22일 기탁하여 KFCC11467P의 기탁번호를 부여 받았다.The novel K-59 of the present invention was isolated from a single colony (colony) by using a BL plate medium dilution method in kimchi, and then recaptured a single colony showing characteristics and properties corresponding to lactic acid bacteria and inoculated into a liquid medium of MRS broth. After culturing was obtained. DNA was extracted from the strain, 16S rRNA was performed, and the homology of the strain was searched using the BLAST program. The strain was found to have 96% homology with the 16S rRNA gene of the Lactobacillus asidophilus CTSPL1 strain. It was named K-59 strain and it was deposited with the microbial preservation center on October 22, 2009 and was given the accession number of KFCC11467P.
본 발명에 따른 유산균 균주는 통상적인 락토바실러스 속 미생물의 배양법에 의해 대량으로 배양할 수 있다. 배양배지로는 탄소원, 질소원, 비타민 및 미네랄로 구성된 배지를 사용할 수 있다. 예를 들어, MRS 액체 배지 및 우유가 첨가된 액체 배지를 사용할 수 있다. 배양은 통상의 유산균 배양 조건으로 수행할 수 있으며, 예를 들어 약 15-45℃에서 약 10-72시간 동안 배양할 수 있다. 배양액 중의 배양배지를 제거하고 농축된 균체만을 회수하기 위해 원심분리 또는 여과과정을 거칠 수 있으며 이러한 단계는 당업자의 필요에 따라 수행할 수 있다. 농축된 균체는 통상적인 방법에 따라 냉동하거나 냉동건조하여 그 활성을 잃지 않도록 보존할 수 있다. 또한, 본 발명에 따른 미생물은 당업계에 공지된 통상적인 물리화학적 돌연변이 방법 등에 의해 이와 동등한 활성을 가지거나 또는 이보다 우수한 활성을 가지도록 개선 또는 개량될 수 있다.The lactic acid bacteria strain according to the present invention can be cultured in large quantities by a conventional method of culturing Lactobacillus sp. The culture medium may be a medium consisting of a carbon source, nitrogen source, vitamins and minerals. For example, MRS liquid medium and liquid medium with milk added can be used. The culture can be carried out under conventional lactic acid culture conditions, for example, can be incubated for about 10-72 hours at about 15-45 ℃. Centrifugation or filtration may be performed to remove the culture medium in the culture and recover only concentrated cells, and this step may be performed according to the needs of those skilled in the art. The concentrated cells can be preserved so as not to lose their activity by freezing or lyophilizing according to a conventional method. In addition, the microorganism according to the present invention may be improved or improved to have equivalent activity or better activity by conventional physicochemical mutation methods and the like known in the art.
본 발명에 따른 K-59 균주 또는 이러한 균주로부터 생성된 알파-람노시다제(rhamnosidase)는 인삼을 발효시켜 유용한 성분의 함량을 증가시킬 수 있다. 따라서, 본 발명은 또한 락토바실러스 아시도필러스(Lactobacillus acidophilus) K-59 (KFCC11467P)에 의해 발효된 것을 특징으로 하는 인삼 발효물을 제공한다.The K-59 strain according to the present invention or alpha-rhamnosidase produced from such strains can increase the content of useful ingredients by fermenting ginseng. Accordingly, the present invention also provides Lactobacillus acidophilus ) to provide a ginseng fermentation, characterized in that fermented by K-59 (KFCC11467P).
본 발명에 따른 K-59 균주로 발효된 인삼 발효물 또는 이러한 발효물의 추출물은 인슐린 분리 활성을 개선함으로써 포도당 항상성을 유지 또는 개선할 수 있으며, 베타세포 이상, 공복혈당 장애, 내당능 장애(glucose intolerance), 당뇨병 전단계 (prediabetes), 당뇨병, 인슐린 분비저하 등을 예방, 치료 또는 개선할 수 있다.Ginseng fermentation or extract of such fermentation fermented with K-59 strain according to the present invention can maintain or improve glucose homeostasis by improving insulin separation activity, beta cell abnormality, impaired fasting glucose, impaired glucose tolerance (glucose intolerance) , Diabetes, prediabetes, diabetes, insulin secretion, etc. can be prevented, treated or improved.
따라서 본 발명은 치료학적으로 또는 예방학적으로 유효한 양의 K-59 균주로 발효된 인삼 발효물 또는 이러한 발효물의 추출물을 치료 또는 예방이 필요한 개체에게 투여하는 것을 포함하는 포도당 항상성을 유지 또는 개선하는 방법을 제공한다.Accordingly, the present invention provides a method for maintaining or improving glucose homeostasis, comprising administering to a subject in need thereof a ginseng fermentation product or a extract of such fermentation fermented with a therapeutically or prophylactically effective amount of K-59 strain. To provide.
본 발명의 신규한 K-59는 고농도의 인삼 배지에서도 생장이 가능한 한편, 극성이 높은 진세노사이드인 Rg1, Rb1, Re 등을 극성이 낮은 진세노사이드인 Rh1, Rg3, C-K 및 Rh2로 대사시킬 수 있다. 따라서 본 발명은 락토바실러스 아시도필러스(Lactobacillus acidophilus) K-59 (KFCC11467P)로 발효시키는 것을 특징으로 하는 인삼의 생체이용률이 낮은 성분인 진세노사이드 Rg1, Rb1, Rg1 또는 Re을 진세노사이드 Rh1, Rg3, Rh2 또는 C-K로 전환시키는 방법을 제공한다.The novel K-59 of the present invention is capable of growing in high concentration ginseng medium, while metabolizing the highly polar ginsenosides Rg1, Rb1, Re, etc. into the less polar ginsenosides Rh1, Rg3, CK and Rh2. Can be. Therefore, the present invention is Lactobacillus Lactobacillus acidophilus ) A method of converting ginsenoside Rg1, Rb1, Rg1 or Re, which is a low bioavailability component of ginseng, fermented with K-59 (KFCC11467P) to ginsenoside Rh1, Rg3, Rh2 or CK do.
본 발명은 또한 상기 K-59 균주의 알파-람노시다제의 기능을 이용하여 인삼의 성분인 특정 진세노사이드들을 생체이용률이 더 높은 진세노사이드들로 전환시키는 방법을 제공한다.The present invention also provides a method for converting certain ginsenosides of ginseng into ginsenosides with higher bioavailability using the function of alpha-lamnosidase of the K-59 strain.
본 발명에서는 단순히 Rh1, Rg3, C-K 및 Rh2의 함량 증가만을 목표로 인삼을 발효시킨 것은 아니며, K-59에 의한 발효에 의해 인슐린 분비 활성이 증진되도록 K-59 발효과정 모니터링의 지표 성분들로서 Rh1, Rg3, C-K 및 Rh2를 설정하였다.In the present invention, the ginseng was not fermented with the aim of merely increasing the contents of Rh1, Rg3, CK and Rh2, and Rh1, as indicator components of K-59 fermentation monitoring to enhance insulin secretion activity by fermentation by K-59. Rg3, CK and Rh2 were set.
본 발명의 인슐린 분비 개선용 추출물은 기존의 인삼 발효물에 비하여 진세노사이드 Rh1(프로토파나사트리올; protopanaxatriol)과 Rh2(프로토파나사다이올; protopanaxadiol)를 동시에 많이 함유한다는 특징이 있으며, 이는 기존의 인삼 발효물보다 진일보한 것으로 생각된다.The extract for improving insulin secretion of the present invention is characterized by containing a lot of ginsenoside Rh1 (protopanaxatriol) and Rh2 (protopanaxadiol) at the same time compared to the conventional ginseng fermentation, which It is thought that it is more advanced than ginseng fermentation.
본 발명에 따른 K-59 균주의 인삼 발효물은 통상의 기술자에게 알려진 다양한 방법을 사용하여 제조될 수 있다.Ginseng fermentation of K-59 strain according to the present invention can be prepared using a variety of methods known to those skilled in the art.
본 발명에 따른 인삼으로 본 발명의 후술하는 실시예에서는 인삼의 일종인 수삼을 건조하여 백삼을 제조한 후 주근(main roots; MR)과 미삼(hairy roots; HR)으로 분리하여 발효시켰다. 그러나 주근과 미삼으로 분리하지 않고 백삼 자체를 발효시키는 방법도 본 발명의 범위에 포함되며, 인삼 자체를 발효시켜 사용할 수도 있고, 또한 백삼을 증숙하여 홍삼, 선삼 등으로 가공한 후 발효시키는 방법도 본 발명의 범위에 들어갈 수 있다. In the following examples of the present invention as a ginseng according to the present invention dried ginseng, a kind of ginseng to produce white ginseng and then fermented by separating into main roots (MR) and hairy roots (HR). However, the method of fermenting white ginseng itself without separating it into freckles and ginseng is also included in the scope of the present invention, and may also be used by fermenting ginseng itself, and also the method of fermenting white ginseng by processing it with red ginseng, sun ginseng and the like. It may fall within the scope of the invention.
또한 인삼은 소정의 크기로 절단한 고상의 인삼 절편; 인삼 분말; 인삼 분쇄물; 다양한 유기용매, 정제수 또는 이들의 혼합물을 사용한 인삼 추출물; 이러한 인삼 유래 물질들의 정제수 현탁액 등을 이용하여 발효될 수 있으나, 본 발명이 이러한 구체적인 방법에 한정되는 것은 아니다. 예를 들어 인삼 추출물을 이용하는 경우 본 발명에 따른 인삼 발효 추출물(인삼 발효물의 추출물)은 상기 인삼 추출물을 사용한 액체 배지에 K-59를 접종하여 발효시켜 얻은 인삼 발효물을 에탄올 또는 주정의 용매로 추출한 후 얻어진 추출물을 여과하여 얻을 수 있다.In addition, ginseng is a solid ginseng slice cut into a predetermined size; Ginseng powder; Ginseng grind; Ginseng extract using various organic solvents, purified water or mixtures thereof; It may be fermented using purified water suspension of such ginseng derived materials, but the present invention is not limited to this specific method. For example, in case of using ginseng extract, the ginseng fermented extract (extract of ginseng fermented product) according to the present invention is obtained by inoculating the ginseng fermented product obtained by inoculating the liquid medium using the ginseng extract by fermentation with ethanol or alcohol solvent. The obtained extract can then be obtained by filtration.
상기 발효물은 본 발명에 따른 균주를 인삼 성분을 함유한 적합한 액체 배지에서 배양한 배양액 자체, 상기 배양액을 여과 또는 원심분리하여 균주를 제거한 여액(여과액 또는 원심분리한 상등액), 상기 배양액을 초음파 처리하거나 상기 배양액에 용해효소(lysozyme)를 처리하여 수득한 세포 파쇄액 등을 포함하나, 이에 한정되는 것은 아니다.The fermentation product is cultured by culturing the strain according to the present invention in a suitable liquid medium containing ginseng components, the filtrate (filtered or centrifuged supernatant) from which the strain was removed by filtration or centrifugation of the culture medium, and the culture solution by ultrasonic Cell lysates obtained by treating or treating lysozyme in the culture, but are not limited thereto.
인삼의 발효에 사용되는 단순한 인삼 추출물 또는 K-59 균주의 인삼 발효물의 추출물을 제조하는데 있어, 추출용매로는 정제수; 메탄올, 에탄올, 프로필알코올, 부틸알코올 등의 탄소수 1 내지 4의 저급 알코올; 글리세린, 부틸렌글라이콜, 프로필렌글라이콜 등의 다가 알코올; 메틸아세테이트, 에틸아세테이트, 아세톤, 벤젠, 헥산, 디에틸에테르, 디클로로메탄 등의 탄화수소계 용매; 또는 이들은 혼합 용매를 이용할 수 있으나, 정제수, 에탄올 또는 농도 50~95％의 주정이 본 발명의 목적상 더 바람직하다.In preparing a simple ginseng extract or K-59 strain of ginseng fermentation product used for fermentation of ginseng, the extraction solvent is purified water; Lower alcohols having 1 to 4 carbon atoms such as methanol, ethanol, propyl alcohol and butyl alcohol; Polyhydric alcohols such as glycerin, butylene glycol and propylene glycol; Hydrocarbon solvents such as methyl acetate, ethyl acetate, acetone, benzene, hexane, diethyl ether and dichloromethane; Or they may use a mixed solvent, but purified water, ethanol or a spirit having a concentration of 50 to 95% is more preferable for the purposes of the present invention.
또 본 발명에 따른 추출물은 본 발명이 속한 분야에서 통상의 지식을 가진 자에게 잘 알려진 추출방법을 이용하여 제조될 수 있다. 즉, 인삼을 음건하여 분쇄한 후, 추출용매를 인삼의 1 내지 20배 부피량 만큼 가하여 추출하고 나서, 선택적으로 (감압)농축, 건조 또는 정제 과정을 거쳐 제조할 수 있다. 보다 구체적으로, 전술한 방법과 같이 추출용매를 가하여 추출하되 (a) 냉각 콘덴서가 장치되어 용매가 증발되는 것을 방지한 상태에서 50 내지 100℃의 온도 조건에서 1 내지 20시간 가열하여 추출하거나, (b) 5 내지 37℃의 온도 조건에서 1 내지 15일간 침적시켜 유효성분을 추출할 수 있다. 즉, 교반 추출, 환류 냉각 추출, 냉침 추출, 초음파 추출 또는 초임계 추출 등의 추출방법을 사용하여 제조할 수 있다.In addition, the extract according to the present invention can be prepared using an extraction method well known to those skilled in the art. That is, after ginseng is dried and pulverized, the extraction solvent may be extracted by adding 1 to 20 times the volume of ginseng, followed by selective (decompression) concentration, drying or purification. More specifically, extraction by adding an extraction solvent as in the above-described method (a) extraction by heating for 1 to 20 hours at a temperature condition of 50 to 100 ℃ in the cooling condenser is installed to prevent the solvent from evaporating, or ( b) The active ingredient may be extracted by immersion for 1 to 15 days at a temperature of 5 to 37 ℃. That is, it can be produced by an extraction method such as stirring extraction, reflux cooling extraction, cold extraction, ultrasonic extraction or supercritical extraction.
따라서, 본 발명은 또한 (S1) 인삼을 락토바실러스 아시도필러스(Lactobacillus acidophilus) K-59 (KFCC11467P)로 발효시켜 발효물을 얻는 단계; 및 (S2) 상기 발효물의 추출물을 제조하는 단계를 포함하는 것을 특징으로 하는 당항상성을 유지하거나 개선시킬 수 있는 인삼 발효 추출물의 제조방법 또는 인삼 추출물의 당항상성 효능을 향상시키는 방법을 제공하며, 이러한 제조방법에 있어 상기 발효는 35~37℃에서 3~10일 동안 이루어지고, 상기 추출물은 에탄올 또는 에탄올 수용액 추출물이며, 추출온도 및 추출시간은 약 60℃~80℃ 및 약 2~4시간인 것이 더 바람직하다. 선택적으로 추출 후 여과하는 단계를 포함할 수 있다.Accordingly, the present invention also comprises the step of fermenting (S1) ginseng with Lactobacillus acidophilus K-59 (KFCC11467P) to obtain a fermentation product; And (S2) provides a method of producing a ginseng fermentation extract that can maintain or improve the sugar always characterized in that it comprises the step of preparing the extract of the fermentation, or a method for improving the sugar efficacy of the ginseng extract, In the production method, the fermentation is made for 3 to 10 days at 35 ~ 37 ℃, the extract is ethanol or ethanol aqueous solution extract, extraction temperature and extraction time is about 60 ℃ ~ 80 ℃ and about 2 to 4 hours More preferred. Optionally, after extraction, filtering may be included.
보다 바람직하게, 본 발명은 (S1) 인삼을 건조하여 백삼을 제조한 후 백삼 분말을 얻는 단계; (S2) 백삼 분말에 정제수, 에탄올 또는 이들의 혼합물을 가하여 추출하여 동결건조하여 백삼 추출물 분말을 제조하는 단계; (3) 상기 추출물 분말에 증류수를 가하고 멸균한 후 K-59로 발효시키는 단계(더욱 바람직하게는, 35~37℃에서 3~10일 동안); (4) 상기 발효물을 에탄올 또는 주정으로 추출(더욱 바람직하게는, 60℃~80℃에서 2~4시간 동안)하고 여과하여 발효 추출물을 제조하는 단계를 거쳐 제조되는 인삼 발효 추출물의 제조방법을 제공한다.More preferably, the present invention comprises the steps of obtaining white ginseng powder after drying (S1) ginseng to produce white ginseng; (S2) extracting by adding purified water, ethanol or a mixture thereof to the white ginseng powder to freeze-dried to prepare a white ginseng extract powder; (3) adding distilled water to the extract powder and sterilizing it and then fermenting with K-59 (more preferably, for 3 to 10 days at 35 to 37 ° C.); (4) extracting the fermented product with ethanol or alcohol (more preferably, for 2-4 hours at 60 ℃ ~ 80 ℃) and filtered to prepare a ginseng fermented extract prepared by the step of preparing a fermentation extract to provide.
본 발명에 따른 포도당 항상성 유지, 개선 또는 치료용 조성물은 본 발명에 따른 인삼 발효물 또는 이러한 발효물의 추출물을 유효성분으로 포함하며 의약품 및 건강기능식품의 형태로 제조될 수 있다. 이러한 의약품 및 건강기능식품은 약제학적으로 허용되는 부형제 또는 첨가제를 포함할 수 있다. 본 발명의 조성물은 단독으로 혹은 어떤 편리한 운반체, 부형제 등과 함께 혼합하여 투여될 수 있고, 그러한 투여 제형은 단회투여 또는 반복투여 제형일 수 있다. The composition for maintaining, improving or treating glucose homeostasis according to the present invention includes the ginseng fermentation product according to the present invention or an extract of such fermentation as an active ingredient and may be prepared in the form of medicines and health functional foods. Such medicines and nutraceuticals may include pharmaceutically acceptable excipients or additives. The compositions of the present invention may be administered alone or in admixture with any convenient vehicle, excipient, or the like, and such dosage forms may be single-dose or multiple-dose formulations.
본 발명의 조성물을 포함하는 의약품 또는 건강기능식품은 고형 제제 또는 액상 제제일 수 있다. 고형 제제는 산제, 과립제, 정제, 캅셀제, 좌제 등이 있으나, 이에 한정되는 것은 아니다. 고형 제제에는 부형제, 착향제, 결합제, 방부제, 붕해제, 활택제, 충진제 등이 포함될 수 있으나 이에 한정되는 것은 아니다. 액상 제제로는 물, 프로필렌 글리콜 용액 같은 용액제, 현탁액제, 유제 등이 있으나, 이에 한정되는 것은 아니며, 적당한 착색제, 착향제, 안정화제, 점성화제 등을 첨가하여 제조할 수 있다.The pharmaceutical or nutraceutical containing the composition of the present invention may be a solid preparation or a liquid preparation. Solid preparations include, but are not limited to, powders, granules, tablets, capsules, suppositories, and the like. Solid form preparations may include, but are not limited to, excipients, flavors, binders, preservatives, disintegrants, lubricants, fillers and the like. Liquid formulations include, but are not limited to, solutions such as water, propylene glycol solutions, suspensions, emulsions, and the like, and may be prepared by adding suitable colorants, flavors, stabilizers, viscosity agents, and the like.
예를 들어, 산제는 본 발명의 추출물 또는 발효물과 유당, 전분, 미결정셀룰로오스 등 약제학적으로 허용되는 적당한 부형제를 단순 혼합함으로써 제조될 수 있다. 과립제는 본 발명의 추출물 또는 발효물; 약제학적으로 허용되는 적당한 부형제; 및 폴리비닐피롤리돈, 히드록시프로필셀룰로오스 등의 약제학적으로 허용되는 적당한 결합제를 혼합한 후, 물, 에탄올, 이소프로판올 등의 용매를 이용한 습식과립법 또는 압축력을 이용한 건식과립법을 이용하여 제조될 수 있다. 또한 정제는 상기 과립제를 마그네슘스테아레이트 등의 약제학적으로 허용되는 적당한 활택제화 혼합한 후, 타정기를 이용하여 타정함으로써 제조될 수 있다.For example, powders may be prepared by simply mixing the extract or fermentation product of the present invention with a suitable pharmaceutically acceptable excipient such as lactose, starch, microcrystalline cellulose. Granules are extracts or fermented products of the present invention; Pharmaceutically acceptable excipients; And a pharmaceutically acceptable binder such as polyvinylpyrrolidone and hydroxypropyl cellulose, and then prepared by using a wet granulation method using a solvent such as water, ethanol, isopropanol, or a dry granulation method using a compressive force. Can be. Tablets may also be prepared by mixing the granules with a suitable pharmaceutically acceptable glidant such as magnesium stearate and then tableting using a tableting machine.
본 발명의 조성물은 치료해야할 질환 및 개체의 상태에 따라 경구제, 주사제(예를 들어, 근육주사, 복강주사, 정맥주사, 주입(infusion), 피하주사, 임플란트), 흡입제, 비강투여제, 질제, 직장투여제, 설하제, 트랜스더말제, 토피칼제 등으로 투여될 수 있으나, 이에 한정되는 것은 아니다. 투여경로에 따라 통상적으로 사용되고 비독성인, 약제학적으로 허용되는 운반체, 첨가제, 비히클을 포함하는 적당한 투여 유닛 제형으로 제제화될 수 있다. 일정 시간 동안 약물을 지속적으로 방출할 수 있는 데포(depot) 제형 또한 본 발명의 범위에 포함된다.The composition of the present invention may be administered orally or parenterally (for example, intramuscular injection, intraperitoneal injection, intravenous injection, infusion, subcutaneous injection, implant), inhalant, nasal administration agent, , Rectal, sublingual, transdermal, topical, and the like, but is not limited thereto. It may be formulated into a suitable dosage unit dosage form comprising a pharmaceutically acceptable carrier, excipient, vehicle, conventionally used and nontoxic, depending on the route of administration. Depot formulations capable of continually releasing the drug for a period of time are also within the scope of the present invention.
포도당 항상성 유지, 개선 또는 치료라는 목적을 달성하기 위하여 본 발명의 추출물 또는 발효물은 매일 약 0.001 mg/kg 내지 약 10 g/kg이 투여될 수 있으며, 약 0.01 mg/kg 내지 약 1 g/kg의 1일 투여 용량이 바람직하다. 그러나 상기 투여량은 추출물 또는 발효물의 정제 정도, 환자의 상태(연령, 성별, 체중 등), 치료하고 있는 상태의 심각성 등에 따라 다양할 수 있다. 필요에 따라 편리성을 위하여 1일 총 투여량이 나누어지고 하루 동안 여러 번 나누어 투여될 수 있다.
To achieve the purpose of maintaining, improving or treating glucose homeostasis, the extract or fermentation product of the present invention may be administered from about 0.001 mg / kg to about 10 g / kg daily, and from about 0.01 mg / kg to about 1 g / kg Daily doses of are preferred. However, the dosage may vary depending on the degree of purification of the extract or fermentation, the condition of the patient (age, sex, weight, etc.), the severity of the condition being treated, and the like. If desired, the total daily dose may be divided for convenience and divided several times throughout the day.
본 발명은 신규한 유산균 K-59를 제공한다. 이러한 K-59는 인삼 및 인삼 성분을 발효시킬 수 있다.The present invention provides a novel lactic acid bacteria K-59. Such K-59 can ferment ginseng and ginseng components.
본 발명은 상기 신규한 K-59 또는 이로부터 얻어진 알파-람노시다제를 이용하여 인삼에서 생체 이용률이 낮은 진세노사이드인 Re를 생체이용률이 높은 진세노사이드 Rh1, Rg3, Rh2, C-K 등으로 전환시킬 수 있다.The present invention converts Re, a low bioavailability ginsenoside in ginseng, to ginsenosides Rh1, Rg3, Rh2, CK and the like using g-59 or the alpha-lamnosidase obtained therefrom. You can.
본 발명은 상기 신규한 K-59 또는 이로부터 얻어진 알파-람노시다제를 이용하여 인삼에서 생체 이용률이 낮은 진세노사이드 Rg1, Rb1 등을 진세노사이드 Rh1, Rg3, Rh2, C-K 등으로 전환시킬 수 있는 인삼 발효 추출물의 제조방법을 제공할 수 있다.The present invention can convert ginsenosides Rg1, Rb1 and the like having low bioavailability in ginseng into ginsenosides Rh1, Rg3, Rh2, CK, etc. using the novel K-59 or alpha-lamnosidase obtained therefrom. It can provide a method for producing a ginseng fermented extract.
본 발명에 의한 당항상성 개선용 인삼 발효 추출물은 췌장 소도에서의 인슐린 분비를 증가시키며, 인삼 자체가 나타내는 효과보다 더욱 증가된 효과를 나타낸다.Ginseng fermentation extract for improving the glycemic state according to the present invention increases the insulin secretion in pancreatic islets, it shows an effect that is further increased than the effect exhibited by ginseng itself.
도 1은 K-59 균주의 게놈(genomic) DNA를 이용한 PCT 산물의 아가로스 겔 전기영동 결과이다.
도 2는 본 발명에서 이용한 클로닝 pGEM-T easy vector의 개열지도이다.1 shows agarose gel electrophoresis of PCT products using genomic DNA of K-59 strain.
2 is a cleavage map of the cloning pGEM-T easy vector used in the present invention.
이하, 본 발명의 이해를 돕기 위하여 실시예 등을 들어 상세하게 설명하기로 한다. 그러나, 본 발명에 따른 실시예들은 여러 가지 다른 형태로 변형될 수 있으며, 본 발명의 범위가 하기 실시예들에 한정되는 것으로 해석되어서는 안 된다. 본 발명의 실시예들은 당업계에서 평균적인 지식을 가진 자에게 본 발명을 보다 완전하게 설명하기 위해 제공되는 것이다.
Hereinafter, embodiments of the present invention will be described in detail to facilitate understanding of the present invention. However, the embodiments according to the present invention can be modified into various other forms, and the scope of the present invention should not be construed as being limited to the following embodiments. Embodiments of the invention are provided to more fully describe the present invention to those skilled in the art.
<실시예 1> 락토바실러스 아시도필러스(Lactobacillus acidophilus) K-59 균주(KFCC11467P)의 분리 및 동정Example 1 Isolation and Identification of Lactobacillus acidophilus K-59 Strain (KFCC11467P)
상기 균주는 김치 유래 유산균으로서, 김치 조성물을 멸균된 생리식염수에 희석하여 그 상등액을 십진법으로 희석해가며 5 % 말피를 포함하는 BL 평판배지에 도말하였다. 유산균 구별배지인 BL 평판배지에서 유산간균 특유의 환을 포함하는 집락을 취하여 단일균주를 분리하였고, 본 균주를 계대하여 실험에 사용하였다.The strain is lactic acid bacteria derived from kimchi, the kimchi composition was diluted in sterile physiological saline, and the supernatant was diluted in a decimal method and plated on a BL plate medium containing 5% malt. A colony containing lactic acid bacterium-specific rings was isolated from the BL plate medium, which is a lactic acid bacteria discriminating medium, and a single strain was isolated, and this strain was passaged and used for experiments.
상기 균주는 MRS 액체 배지, 평판배지, 사면배지에 접종한 것을 37℃ 항온 배양기에서 배양하여 사용하였다.The strain was inoculated in MRS liquid medium, plate medium, slope medium was used by culturing in a 37 ℃ constant temperature incubator.
상기 균주는 그람염색 후, 광학현미경에서 400배 확대하여 관찰한 결과, 그람 양성의 간균형태로 확인되었으며, 3 % 과산화수소수를 균주의 군집에 떨어뜨려 기포발생 유무를 관찰하여 카탈라아제 활성이 음성임을 확인하였다. After gram staining, the strain was magnified 400 times on an optical microscope, and it was confirmed that it was a gram-positive bacillus form, and 3% hydrogen peroxide solution was dropped into a population of strains to observe whether bubbles were generated and confirmed that catalase activity was negative. It was.
상기 균주로부터 DNA를 추출하여 16S rRNA를 제작하여 BLAST 프로그램을 사용하여 상동성을 검색하였다. DNA 정제 키트(purification kit)를 이용하여 상기 균주로부터 DNA를 추출하고 이를 16S rRNA 분자의 양끝에 존재하는 보존성이 높은 염기서열 영역을 표적으로 삼아 PCR 프라이머 [27f (5'-agagtttgatcctggctcag-3')(서열번호 2)와 1492r (5'-ggctaccttgttacgactt-3')(서열번호 3)]를 제작하여 사이즈 1,400 bp의 DNA 조각을 제작하였다. 이 조각으로부터 PCR 프라이머를 제거하고, 518F (5'-ccagcagccgcggtaatacg-3')(서열번호 4)와 800R (5'-taccagggtatctaatcc-3')(서열번호 5)를 이용하여 염기서열을 시퀀싱하였고, 그 결과를 온라인상에서 서열 데이터를 분석하는 프로그램인 BLAST 프로그램을 사용하여 상동성을 검색하였다.DNA was extracted from the strain, 16S rRNA was produced, and homology was searched using the BLAST program. DNA primers were extracted from the strain using a DNA purification kit, and the PCR primers [27f (5'-agagtttgatcctggctcag-3 ') (a target of the highly conserved sequence region at both ends of the 16S rRNA molecule were used). SEQ ID NO: 2) and 1492r (5'-ggctaccttgttacgactt-3 ') (SEQ ID NO: 3)] were used to prepare a DNA fragment of 1,400 bp. PCR primers were removed from this fragment, and sequencing was performed using 518F (5'-ccagcagccgcggtaatacg-3 ') (SEQ ID NO: 4) and 800R (5'-taccagggtatctaatcc-3') (SEQ ID NO: 5). The results were searched for homology using the BLAST program, a program that analyzes sequence data online.
균주의 생성물(product)을 블라스트 조사(blast search)한 결과 Lactobacilus acidophillus strain CECT 4179의 16S rRNA gene과 96%의 상동성을 갖는 것을 알 수 있어 상기 균주를 락토바실러스 애시도필러스(Lactobacilus acidophillus) K-59로 명명하고 이를 한국미생물보존센터(Korean Culture Center of Microorganisms; KCCM)에 2009년 10월 22일자로 기탁번호 KFCC11467P로 기탁하였다. A blast search of the product of the strain revealed a 96% homology with the 16S rRNA gene of Lactobacilus acidophillus strain CECT 4179. The strain was identified as Lactobacilus acidophillus K. It was named -59 and deposited with the Korean Culture Center of Microorganisms (KCCM) under the accession number KFCC11467P dated October 22, 2009.
본 발명에 따른 신규 K-59 균주의 16s DNA 염기서열 분석결과는 서열번호 1에 나타내었다.
16s DNA sequence analysis of the novel K-59 strain according to the present invention is shown in SEQ ID NO: 1.
<실시예 2> 인삼 분말 및 추출물 분말의 제조Example 2 Preparation of Ginseng Powder and Extract Powder
인삼 분말의 제조Preparation of Ginseng Powder
인삼 추출물 제조에 사용한 인삼 분말은 다음과 같이 제조하였다. 인삼은 안성산 5년근을 건조하여 백삼 주근, 백삼 미근(미삼)으로 분리하여 통상적인 방법으로 분말을 만들었다.Ginseng powder used to prepare the ginseng extract was prepared as follows. Ginseng was dried 5 years old root of Anseong and separated into white ginseng root and white ginseng root (misam) to make powder in the usual way.
인삼 증류수 추출물의 제조Preparation of Ginseng Distilled Water Extract
얻어진 백삼 분말을 각각 백삼 분말 1kg당 증류수 10리터를 가하여 60℃~100℃에서 약 3~7시간 추출하여 동결건조하여 분말로 제조하였다.10 liters of distilled water was added per 1 kg of white ginseng powder, and the white ginseng powder was extracted for about 3 to 7 hours at 60 ° C to 100 ° C, and lyophilized to prepare a powder.
인삼 에탄올 추출물의 제조Preparation of Ginseng Ethanol Extract
얻어진 백삼 주근 분말을 각각 분말 1kg당 에탄올 10리터를 가하여 60℃~80℃에서 약 3~7시간 추출하고 감압건조후 동결건조하여 분말로 제조하였다.
10 g of ethanol per 1 kg of powder was added to extract the white ginseng root powder.
<실시예 3> 백삼 발효물의 제조Example 3 Preparation of Fermented White Ginseng
백삼 주근 발효물의 제조 (실시예 3-1)Preparation of White Ginseng Root Ferment (Example 3-1)
상기 실시예 2에서 얻은 백삼 주근 추출물 분말 20g에 증류수 2,000㎖를 가하고 멸균한 다음 K-59 2g을 넣고 37℃에서 7일간 발효시켜 발효물을 얻었다. 이 발효물을 에탄올 2,000㎖로 70℃에서 3시간 동안 추출하고 여과하여 백삼 주근 발효 추출물을 제조하였다. 2,000 g of distilled water was added to 20 g of white ginseng fructus extract powder obtained in Example 2, followed by sterilization. Then, 2 g of K-59 was added and fermented at 37 ° C. for 7 days to obtain a fermented product. This fermented product was extracted with 2,000 ml of ethanol at 70 ° C. for 3 hours and filtered to prepare white ginseng root fermented extract.
백삼 미근(미삼) 발효물의 제조 (실시예 3-2)Preparation of White Ginseng Root (Missam) Fermented Product (Example 3-2)
상기 제조예에서 얻은 백삼 미근(미삼) 추출물 분말 20g에 증류수 2,000㎖를 가하고 멸균한 다음 K-59 2g을 넣고 37℃에서 7일간 발효시켜 발효물을 얻었다. 이 발효물을 에탄올 2,000㎖로 70℃에서 3시간 동안 추출하고 여과하여 백삼 미근(미삼) 발효 추출물을 제조하였다. 2,000 g of distilled water was added to 20 g of the white ginseng root (misam) extract powder obtained in the preparation example, followed by sterilization, and 2 g of K-59 was added thereto, followed by fermentation at 37 ° C. for 7 days to obtain a fermented product. This fermented product was extracted with 2,000 ml of ethanol at 70 ° C. for 3 hours, and filtered to prepare a white ginseng root (misam) fermented extract.
<비교예 1> 통상적인 백삼 추출물의 제조Comparative Example 1 Preparation of Common White Ginseng Extract
백삼 주근 추출물의 제조 (비교예 1-1)Preparation of White Ginseng Root Extract (Comparative Example 1-1)
백삼 주근 분말 20g에 증류수 2,000㎖를 가하여 멸균한 후 에탄올 2,000㎖로 70℃에서 3시간 추출하고 여과하여 백삼 주근 추출물을 제조하였다.2,000 g of distilled water was added to 20 g of white ginseng root powder and sterilized, followed by extraction with 2,000 ml of ethanol at 70 ° C. for 3 hours, followed by filtration to prepare white ginseng root extract.
백삼 미삼 추출물의 제조 (비교예 1-2)Preparation of White Ginseng Misam Extract (Comparative Example 1-2)
백삼 미삼 분말 20g에 증류수 2,000㎖를 가하여 멸균한 후 에탄올 2,000㎖로 70℃에서 3시간 추출하고 여과하여 백삼 미삼 추출물을 제조하였다.
2,000 g of distilled water was added to 20 g of white ginseng rice ginseng powder and sterilized, followed by extraction with 2,000 ml of ethanol at 70 ° C. for 3 hours, followed by filtration.
<시험예 1> 함량분석 실험Test Example 1 Content Analysis Experiment
K-59에 의한 인삼의 발효가 진세노사이드 함량에 미치는 영향을 평가하였다. 상기 실시예 3-1, 실시예 3-2, 비교예 1-1, 및 비교예 1-2에서 얻은 각각의 추출물에 각각의 추출물과 동량의 메탄올(methanol)을 넣고 원심분리하여 상등액을 얻었다. 얻은 상등액 중에서 100 ml을 감압농축하고 각각의 추출물을 0.2g씩 취하여 메탄올 100ml씩 3회 추출하였다. 이 추출물을 감압 농축시킨 후 물 100ml를 넣어 현탁시키고, 에테르 100ml씩으로 3회 추출하고 나머지 물분획을 다시 100ml씩으로 3회 추출하고 감압 농축시켰다. 이어서 메탄올 1ml에 용해시켜 HPLC(칼럼: Develosil ODS-UG-5 Batch #10054 (NOMURA CHEMICAL, Japan); 용매: 증류수-아세토나이트릴 [0-35 min (90:10), 35-30min(5:95)])로 분석하여 하기 표 1과 같은 사포닌 함량 분석결과를 얻었다. The effect of fermentation of ginseng by K-59 on ginsenoside content was evaluated. In each extract obtained in Example 3-1, Example 3-2, Comparative Example 1-1, and Comparative Example 1-2, each extract and the same amount of methanol (methanol) was added to the supernatant by centrifugation. 100 ml of the obtained supernatant was concentrated under reduced pressure, 0.2 g of each extract was extracted, and 100 ml of methanol were extracted three times. The extract was concentrated under reduced pressure, suspended in 100 ml of water, extracted three times with 100 ml of ether, and the remaining water fraction was extracted three times with 100 ml each and concentrated under reduced pressure. Then dissolved in 1 ml of methanol, HPLC (column: Develosil ODS-UG-5 Batch # 10054 (NOMURA CHEMICAL, Japan); solvent: distilled water-acetonitrile [0-35 min (90:10), 35-30 min (5: 95)]) to obtain the saponin content analysis results as shown in Table 1 below.
(비교예 1-1)Ginseng root
(Comparative Example 1-1)
(실시예 3-1)K-59 Fermented Ginseng Root
(Example 3-1)
(비교예 1-2)Misam
(Comparative Example 1-2)
(실시예 3-2)K-59 Fermented Misam
(Example 3-2)
(N.D.: Not Detected)(N.D .: Not Detected)
상기 표 1에 나타나는 바와 같이, 실시예 3-1 및 실시예 3-2에서 K-59 발효에 의하여 백삼 주근에는 함유되어 있지 않은 Rh1, Rg3, C-K, Rh2가 발효 백삼 주근에는 각각 5.6, 1.6, 1.1, 6.5％ 함유되었으며, 미삼에는 함유되어 있지 않은 Rh1, Rg3, C-K, Rh2가 발효 미삼에는 각각 1.6, 4.8, 2.0, 4.6％ 함유되었다. 즉 K-59 발효에 의하여 백삼에는 함유되지 않은 성분들이 발효 백삼에 생성되었다. 이는 K-59 균주를 이용하여 발효시킨 인삼 발효물에는 단순한 인삼에 함유되지 않은 성분들이 생성되어, 상기 K-59는 인삼에서 진세노사이드 Rh1, Rg3, C-K, Rh2를 생성 및/또는 전환시킬 수 있음을 알 수 있었다.
As shown in Table 1, in Examples 3-1 and 3-2, Rh1, Rg3, CK, Rh2, which are not contained in white ginseng roots by K-59 fermentation, were 5.6, 1.6, 1.1, 6.5% of Rh1, Rg3, CK, and Rh2, which were not contained in rice ginseng, contained 1.6, 4.8, 2.0, and 4.6%, respectively. In other words, K-59 fermentation produced ingredients not contained in white ginseng fermented white ginseng. This means that the ginseng fermentation product fermented with the K-59 strain produces components not contained in simple ginseng, and the K-59 can generate and / or convert ginsenosides Rh1, Rg3, CK, and Rh2 in ginseng. I could see that.
<시험예 2> 췌장 소도에서의 인슐린 분비에 미치는 영향Test Example 2 Effect on Insulin Secretion in Pancreatic Islets
포도당에 반응하는 실험계인 흰쥐 췌장 소도의 일차 배양으로 인슐린 분비 효과를 검증하였다.Insulin secretion was verified by primary culture of rat pancreatic islets, an experimental system that responds to glucose.
췌장 소도의 분리 및 배양은 다음과 같이 실시하였다. 스프래그 돌리 흰쥐 (Sprague-Dawley rats)로부터 췌장 소도의 분리는 콜라게나제(collagenase)를 총담관에 직접 주입하는 방법을 이용하였다. 떼어낸 췌장은 피콜(ficoll) 경사를 이용하여 소도를 분리하였다. 소도를 크렙스 링거 이탄화 버퍼(KRB; Krebs-Ringer bicarbonate buffer, pH 7.2)에 담아 37℃, 5％ CO2 배양기에서 1일간 배양 후 사용하였다.Pancreatic islets were isolated and cultured as follows. Isolation of pancreatic islets from Sprague-Dawley rats was performed by injecting collagenase directly into the bile duct. The detached pancreas was isolated by using a ficoll gradient. Sodium was contained in Krebs-Ringer bicarbonate buffer (KRB, pH 7.2) and used after incubation in 37 ° C., 5% CO 2 incubator for 1 day.
인슐린 분비의 검사는 다음과 같이 실시하였다. 24시간 배양한 췌장 소도를 KRB로 2회 수세 후 각 웰 당 일정 크기의 것들로 3개씩 옮긴 다음 포도당 농도에 따른 분비능과 배양 시간에 따른 분비능 그리고 생물전환물에 의한 인슐린 분비능을 측정하였다. 인슐린 농도의 측정은 효소면역방법(EIA; enzyme immunoassay) 이용한 키트를 사용하였다. 그 결과를 표 2에 나타내었다.Insulin secretion was examined as follows. The pancreatic islets incubated for 24 hours were washed twice with KRB, and then three of them were fixed in size per well, and the secretion ability according to the glucose concentration, the secretion ability according to the culture time, and the insulin secretion ability by the bioconversion were measured. Insulin concentration was measured using a kit using enzyme immunoassay (EIA). The results are shown in Table 2.
(비교예 1-1)White ginseng root
(Comparative Example 1-1)
(실시예 3-1)K-59 Fermentation
(Example 3-1)
(비교예 1-2)White ginseng root
(Comparative Example 1-2)
(실시예 3-2)K-59 Fermentation
(Example 3-2)
상기 표 2에 나타나는 바와 같이, 본 발명의 미삼의 K-59 발효물의 에탄올 추출물은 미삼 추출물을 단독으로 사용한 것에 비하여 배지 농도 3.3mM에서의 (기저) 인슐린 분비는 증가하였으나, 배지 농도 16.7mM에서의 인슐린 분비(포도당 자극)는 미삼 추출물을 단독으로 사용한 것과 동일하였다. 이는 그 자체가 인슐린 분비 효과가 있는 것으로서 당항상성 조절이 안 되는 사람들에게는 효과적일 수 있음을 의미한다.As shown in Table 2, the ethanol extract of the K-59 fermentation of the ginseng of the present invention was increased (base) insulin secretion at 3.3 mM medium, but at a medium concentration of 16.7 mM compared to that of the ginseng extract alone Insulin secretion (glucose stimulation) was the same as that of the rice extract alone. This, in itself, has the effect of secreting insulin, which means that it can be effective for those who do not always have control.
한편, 본 발명의 백삼 주근의 K-59 발효물의 에탄올 추출물은 인삼 추출물을 단독으로 사용한 것에 비하여 배지 농도 3.3mM에서의(기저) 인슐린 분비를 증진시켰으며, 배지 농도 16.7mM에서의 인슐린 분비(포도당 자극)도 주근 추출물을 단독으로 사용한 것에 비하여 증가시켰다. 이는 자체적으로도 인슐린 분비 효과를 보이며, 포도당에 의한 인슐린 분비도 증강시켜주는 효과로서 당항상성 조절이 안 되는 사람들에게는 이상적인 효과이다.
Meanwhile, the ethanol extract of K-59 fermentation of white ginseng root of the present invention enhanced (base) insulin secretion at a medium concentration of 3.3 mM and glucose secretion (glucose) at a medium concentration of 16.7 mM compared with the ginseng extract alone. Irritation) was also increased compared to the use of the root extract. This is an insulin secretion effect on its own, it is also an effect that enhances insulin secretion by glucose is ideal for those who do not always control glucose.
<시험예 3> K-59에 의한 진세노사이드 Re의 생물전환Test Example 3 Bioconversion of Ginsenoside Re by K-59
1) 진세노사이드 Re의 제조1) Preparation of Ginsenoside Re
인삼 추출물로부터 ginsenoside Re를 기존의 방법(Shin YW, Bae EA, Kim SS, Lee YC, Lee BY, Kim DH. The effects of ginsenoside Re and its metabolite, ginsenoside Rh1, on 12-O-tetradecanoylphorbol 13-acetate- and oxazolone-induced mouse dermatitis models. Planta Med. 2006;72::376-8)에 따라 분리하였다. The ginsenoside Re from ginseng extract was prepared by conventional methods (Shin YW, Bae EA, Kim SS, Lee YC, Lee BY, Kim DH.The effects of ginsenoside Re and its metabolite, ginsenoside Rh1, on 12-O-tetradecanoylphorbol 13-acetate and oxazolone-induced mouse dermatitis models.Planta Med. 2006; 72 :: 376-8).
2) K-59 균주의 ginsenoside Re의 대사활성 측정2) Determination of the metabolic activity of ginsenoside Re of K-59 strain
50 mM 인산완충액과 200 μM의 ginsenoside Re을 함유한 반응액 5 ml에 인산완충액에 현탁된 균체 100 mg을 넣고 흔들면서 37℃에서 24시간 배양하고 1-부탄올 5 ml로 추출하고 TLC로 반응생성물을 측정하였다. 상기 균체는 미리 GAM broth에서 혐기적으로 배양하였다.100 mg of the cells suspended in phosphate buffer was added to 5 ml of the reaction solution containing 50 mM phosphate buffer and 200 μM ginsenoside Re, incubated at 37 ° C. for 24 hours, extracted with 5 ml of 1-butanol, and the reaction product was extracted with TLC. Measured. The cells were previously anaerobicly cultured in GAM broth.
3) K-59 균주의 알파-람노시다제(rhamnosidase) 유전자의 클로닝3) Cloning of alpha-rhamnosidase gene of K-59 strain
GenBank에 등록되어 있는 L. acidophilus NCFM의 α-람노시다제 유전자의 염기서열을 이용하여 프라이머를 제작하였으며, 이 프라이머는 클로닝(cloning)을 위해 5’ 과 3’ 말단에 각각 제한효소인 BamHI과 XhoI을 영역(site)을 갖도록 하였다.A primer was prepared using the nucleotide sequence of the α-lamnosidase gene of L. acidophilus NCFM registered in GenBank, and this primer was used for the cloning of Bam HI and restriction enzymes at the 5 'and 3' ends, respectively. Xho I was allowed to have a site.
K-59 균주를 GAM broth에서 24시간 키운 후 게놈(genomic) DNA를 분리 정제하였다. 이 게놈 DNA를 주형으로 하고 앞에서 제작한 프라이머를 이용하여 어닐링(annealing) 온도를 48℃로 하여 PCR을 한 결과 약 2700 bp 크기의 PCR 절편(fragment)을 얻을 수 있었다. 이 PCR 절편을 겔 용리(gel elution)한 후 정제하여 T easy vector 에 클로닝하여 시퀀싱을 하였으며, BLAST를 이용하여 기존의 L. acidophilus NCFM의 α-람노시다제와 상동성을 조사하였을 때 99% 상동성을 나타내었다.K-59 strain was grown for 24 hours in GAM broth and genomic DNA was isolated and purified. PCR fragments of about 2700 bp in size were obtained by PCR using the genomic DNA as a template and annealing at 48 ° C. using the primers prepared above. The PCR fragment was purified by gel elution, cloned into T easy vectors, and sequenced. The homology with α-lamnosidase of L. acidophilus NCFM was examined using 99% phase. Same sex.
PCT 산물의 아가로스 겔 전기영동 결과를 도 1에 나타내었으며, 클로닝 pGEM-T easy vector의 개열지도를 도 2에 나타내었다. K-59의 알파-람노시다제의 염기서열 분석 결과를 서열목록 서열번호 6에 나타내었다.Agarose gel electrophoresis results of the PCT product are shown in FIG. 1, and a cleavage map of the cloning pGEM-T easy vector is shown in FIG. 2. The results of nucleotide sequence analysis of alpha-lamnosidase of K-59 are shown in SEQ ID NO: 6.
4) K-59 균주의 진세노사이드 Re의 생물전환능4) Bioconversion Capacity of Ginsenoside Re of K-59 Strain
진세노사이드 Re (200 μM) 함유한 배양액(20 ml)에 K-59 (100mg)을 넣어 24시간 배양하고 1-부탄올 20 ml로 추출하여 감압농축하고 시험예 1에 따라 사포닌을 분석하였다. 그 결과를 하기 표 3에 나타내었다.K-59 (100 mg) was added to a culture solution (20 ml) containing ginsenoside Re (200 μM), incubated for 24 hours, extracted with 20 ml of 1-butanol, and concentrated under reduced pressure, and saponin was analyzed according to Test Example 1. The results are shown in Table 3 below.
표 3에 나타나는 바와 같이, 기질로 진세노사이드 Re만을 이용할 경우 Rg1과 Rh1이 증가하였으며, 상기 표 1의 결과에 기초할 때 발효가 계속 진행됨에 따라 생성된 Rg1은 다시 기질로 이용되어 Rh1 등의 진세노사이드 함량이 증가할 것으로 추측된다. 다만, 본 발명은 이러한 예측에 한정되는 것은 아니다.As shown in Table 3, Rg1 and Rh1 were increased when only ginsenoside Re was used as a substrate, and based on the results of Table 1, as the fermentation was continued, the produced Rg1 was again used as a substrate, such as Rh1. It is assumed that the ginsenoside content will increase. However, the present invention is not limited to this prediction.
상기 결과를 종합하면, 본 발명에 따른 백삼의 K-59 발효물 및 이의 추출물은 흰쥐 췌장소도에서의 기저 및 포도당 자극에 의한 인슐린 분비를 증가시켰다. 이러한 결과를 토대로, 본 발명의 당항상성 개선용 조성물은 약학 조성물로 사용되는 경우 당항상성 유지을 유지하는 기능을 회복시킬 수 있어서, 공복혈당 장애자, 내당능 장애자, 당뇨병 전단계로 진단받은 자, 인슐린 분비 촉진제 등으로 유용하게 사용될 수 있음을 확인하였다.Taken together, the K-59 fermentation extract of white ginseng and its extract increased insulin secretion by basal and glucose stimulation in rat pancreatic islets. Based on these results, the composition for improving glycemic resistance of the present invention can restore the function of maintaining glycemic stability when used as a pharmaceutical composition, such as impaired fasting glucose, impaired glucose tolerance, a person diagnosed with prediabetes, an insulin secretagogue, etc. It was confirmed that it can be usefully used.
상술한 바와 같이, 본 발명의 바람직한 실시예를 참조하여 설명하였지만 해당 기술 분야의 숙련된 당업자라면 하기의 특허청구범위에 기재된 본 발명의 사상 및 영역으로부터 벗어나지 않는 범위 내에서 본 발명을 다양하게 수정 및 변경시킬 수 있음을 이해할 수 있을 것이다.
Although the preferred embodiments of the present invention have been disclosed for illustrative purposes, those skilled in the art will appreciate that various modifications, additions and substitutions are possible, without departing from the scope and spirit of the invention as disclosed in the accompanying claims. It will be understood that the present invention can be changed.
본 발명의 신규한 K-59 균주 또는 이로부터 얻어진 알파-람노시다제는 천연 성분의 발효에 사용될 수 있다.The novel K-59 strain of the present invention or alpha-rhamnosidase obtained therefrom can be used for fermentation of natural ingredients.
본 발명의 신규한 K-59 균주 또는 이로부터 얻어진 알파-람노시다제는 인삼 추출물 또는 인삼 성분을 발효시킬 수 있어 이로부터 인삼 발효 추출물 또는 인삼 성분 발효물을 얻을 수 있다.The novel K-59 strain of the present invention or the alpha-rhamnosidase obtained therefrom can ferment ginseng extract or ginseng component, thereby obtaining ginseng fermented extract or ginseng component fermented product.
본 발명의 K-59 균주 또는 이로부터 얻어진 알파-람노시다제는 인삼에서 생체 이용률이 낮은 진세노사이드 Rg1, Rb1, Re 등을 진세노사이드 Rh1, Rg3, Rh2, C-K 등으로 전환 및/또는 생성시킬 수 있어 본 발명에 의한 인삼 발효 추출물이 함유된 약제학적 제제, 건강기능식품에 적용할 수 있다.K-59 strain of the present invention or an alpha-lamnosidase obtained therefrom converts and / or produces ginsenosides Rg1, Rb1, Re and the like with low bioavailability in ginseng to ginsenosides Rh1, Rg3, Rh2, CK and the like Can be applied to pharmaceutical preparations, health functional foods containing the ginseng fermented extract according to the present invention.
본 발명의 당항상성 개선용 인삼 발효물 또는 이의 추출물은 약학 조성물로 사용되는 경우 당항상성을 유지하는 기능을 회복시킬 수 있어서, 공복혈당 장애자, 내당능 장애자, 당뇨병 전단계로 진단받은 자, 당뇨병 환자의 인슐린 분비 개선제로 유용하게 사용될 수 있다.Ginseng fermentation extract or its extract for improving the glycemic state of the present invention can restore the function to maintain the glycemic state when used as a pharmaceutical composition, fasting glucose impaired, impaired glucose tolerance, those diagnosed with prediabetes, insulin of diabetic patients It can be usefully used as a secretion improving agent.
<110> Korea Food Research Institute <120> Lactobacillus adidophilus K-59, extracts from ginseng-fermented products using K-59 for improving insulin secretion and manufacturing method thereof <130> P10-259 <160> 6 <170> KopatentIn 1.71 <210> 1 <211> 1491 <212> DNA <213> 16s DNA of Lactobacilus acidophillus K-59 (KFCC11467P) <400> 1 ctcagacgaa cgcggcggcg tgcntaatac atgcaagtcg agcgagctga accaacagat 60 tcacttcggt gatgacgttg ggaacgcgag cggcggatgg gtgagtaaca tgtggggaac 120 tgccccatag tctgggatac cacttggaaa caggtgctaa taccggataa gaaagcagat 180 cgcatgatca gcttataaaa ggcggcgtaa gctgtcgcta tgggatggcc ccgcggtgca 240 ttagctagtt ggtagggtaa cggcctacca aggcaatgat gcatagccga gttgagagac 300 tgatcggcca catcgggact gagacacggc ccaaactcct acgggaggca gcagtaggga 360 atcttccaca atggacgaaa gtctgatgga gcaacgccgc gtgagtgaag aaggttttcg 420 gatcgtaaag ctctgttgtt ggtgaagaag gatagaggta gtaactggcc tttatttgac 480 ggtaatcaac cagaaagtca cggctaacta cgtgccagca gccgcggtaa tacgtaggtg 540 gccagcgttg tccggattta ttgggcgtaa agcgagcgca ggcggaagaa taagtctgat 600 gtgaaagccc tcggcttaac cgaggaactg catcggaaac tgtttttctt gagtgcagaa 660 gaggagagtg gaactccatg tgtagcggtg gaatgcgtag atatatggaa gaacaccagt 720 ggcgaaggcg gctctctggt ctgcaactga cgctgaggct cgaaagcatg ggtagcgaac 780 aggattagat accctggtag tccatgccgt aaacgatgag tgctaagtgt tgggaggttt 840 ccgcctctca gtgctgcagc taacgcatta agcactccgc ctggggagta cgaccgcaag 900 gttgaaactc aaaggaattg acgggggccc gcacaagcgg tggagcatgt ggtttaattc 960 gaagcaacgc gaagaacctt accaggtctt gacatctagt gcaatccgta gagatacgga 1020 gttcccttcg gggacactaa gacaggtggt gcatggctgt cgtcagctcg tgtcgtgaga 1080 tgttggggtt aagtcccgca acgagcgcaa acccttgtca tttagtttgc cagcatttaa 1140 gtttgggcca ctctaatgag actgcccggg tgacaaaccc gaaggagggt ggggggatga 1200 ccgtcaagtc attcaatgcc cctttattga cctgggctac cacacgttgc taacaatgga 1260 cagtaacaac gagggagcaa gcctgcgaaa ggcaagcgaa tctctaaaag ctgttctcag 1320 ttcggactgc agtctgcaac tcgactgcac gaagctggaa tcgctagtaa tcgcggatca 1380 gcacgcgcgc gtggtaatac actttcccgg gcccttgtan acacccgccc gtcacaccat 1440 gggagtctgc atgcccaagc cngtnnctac ctttcggann ncgtctangc a 1491 <210> 2 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> PCR Primer (27f) <400> 2 agagtttgat cctggctcag 20 <210> 3 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> PCR Primer (1492r) <400> 3 ggctaccttg ttacgactt 19 <210> 4 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> 518F for DNA Sequencing <400> 4 ccagcagccg cggtaatacg 20 <210> 5 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> 800R for DNA Sequencing <400> 5 taccagggta tctaatcc 18 <210> 6 <211> 1254 <212> DNA <213> Alpha-Rhamnosidase of K-59 <400> 6 acttatcgat tttttgacga tttaggagtt ttgaagcaaa attattctca aatgaaaaat 60 tgggttgatt ggattaccca aaatactaaa accaaatact tatggattgg acaaatgcaa 120 ttaggagatt ggctttcctt ggataatggg gctaatcctc agggcaaaac taacgaagat 180 tatattgcat ctatttatta ttttgtttct gcaagcatag tatctaaagc agctagattg 240 cttcattacg atatggagtc agactattac gaaaatttgg ctagaaatat aaagacaaat 300 attttaaatg aatttgttac tgaaaaaggt aggatagcca ttgatactca gacagcattg 360 gtttcagcgt tacatttcgg attagtgcat gattatcaaa agtcacaggt tgtagctgat 420 ttagtgaaaa aagtaaaaga tgacaataag catttacaga ctggatttgt tgggacacca 480 tttttattgt cggtattatc aaataataat cagcatcatt tggctatgga tatttttatg 540 caagaagatt gcccaagttg gctttatgaa gtaaatatgg gagcaaccac aatatgggaa 600 cgttggaatt cggtattacc tgatggtaag atgaatcctg aagggatgaa ttcattaaat 660 cattatagtt ttggcgctgt gatgatgtgg atgtatcaat gtgtagtagg tttaaatcaa 720 tttgatgctg gatttaaaga aatttacttt gcacctaaat ttgattgtcg attaaaagat 780 atatattcag agtttgattc aacatatggg aagattaaag tggaatatca tttggagacc 840 aatgaaaagc atttgataag aatgaattta gtcataccat ttggagtgaa aatgaaggtt 900 aagttgccta gatctgctaa atatttgatt aacggaaaag aaaagatagg tattgttaaa 960 ttagaatatg ggaaatacga tattagttat attccaacta agagctactt aaattattat 1020 gatttaaata gtaagcttgt tgatatttta gataataacg atcttgtgaa aagaattgat 1080 caaattgatg aaaagatctt gcagaaagta aaaagaatgg gaaataccag aagtatattt 1140 attaatttaa aaatagatga attgcttgat ttcgaagaaa tttcacagga agaaaaaaat 1200 cagcttgttg atatttttcc taaaacaatt tttataaagt tgaatctctt ttaa 1254 <110> Korea Food Research Institute <120> Lactobacillus adidophilus K-59, extracts from ginseng-fermented products using K-59 for improving insulin secretion and manufacturing method <130> P10-259 <160> 6 <170> Kopatentin 1.71 <210> 1 <211> 1491 <212> DNA <213> 16s DNA of Lactobacilus acidophillus K-59 (KFCC11467P) <400> 1 ctcagacgaa cgcggcggcg tgcntaatac atgcaagtcg agcgagctga accaacagat 60 tcacttcggt gatgacgttg ggaacgcgag cggcggatgg gtgagtaaca tgtggggaac 120 tgccccatag tctgggatac cacttggaaa caggtgctaa taccggataa gaaagcagat 180 cgcatgatca gcttataaaa ggcggcgtaa gctgtcgcta tgggatggcc ccgcggtgca 240 ttagctagtt ggtagggtaa cggcctacca aggcaatgat gcatagccga gttgagagac 300 tgatcggcca catcgggact gagacacggc ccaaactcct acgggaggca gcagtaggga 360 atcttccaca atggacgaaa gtctgatgga gcaacgccgc gtgagtgaag aaggttttcg 420 gatcgtaaag ctctgttgtt ggtgaagaag gatagaggta gtaactggcc tttatttgac 480 ggtaatcaac cagaaagtca cggctaacta cgtgccagca gccgcggtaa tacgtaggtg 540 gccagcgttg tccggattta ttgggcgtaa agcgagcgca ggcggaagaa taagtctgat 600 gtgaaagccc tcggcttaac cgaggaactg catcggaaac tgtttttctt gagtgcagaa 660 gaggagagtg gaactccatg tgtagcggtg gaatgcgtag atatatggaa gaacaccagt 720 ggcgaaggcg gctctctggt ctgcaactga cgctgaggct cgaaagcatg ggtagcgaac 780 aggattagat accctggtag tccatgccgt aaacgatgag tgctaagtgt tgggaggttt 840 ccgcctctca gtgctgcagc taacgcatta agcactccgc ctggggagta cgaccgcaag 900 gttgaaactc aaaggaattg acgggggccc gcacaagcgg tggagcatgt ggtttaattc 960 gaagcaacgc gaagaacctt accaggtctt gacatctagt gcaatccgta gagatacgga 1020 gttcccttcg gggacactaa gacaggtggt gcatggctgt cgtcagctcg tgtcgtgaga 1080 tgttggggtt aagtcccgca acgagcgcaa acccttgtca tttagtttgc cagcatttaa 1140 gtttgggcca ctctaatgag actgcccggg tgacaaaccc gaaggagggt ggggggatga 1200 ccgtcaagtc attcaatgcc cctttattga cctgggctac cacacgttgc taacaatgga 1260 cagtaacaac gagggagcaa gcctgcgaaa ggcaagcgaa tctctaaaag ctgttctcag 1320 ttcggactgc agtctgcaac tcgactgcac gaagctggaa tcgctagtaa tcgcggatca 1380 gcacgcgcgc gtggtaatac actttcccgg gcccttgtan acacccgccc gtcacaccat 1440 gggagtctgc atgcccaagc cngtnnctac ctttcggann ncgtctangc a 1491 <210> 2 <211> 20 <212> DNA <213> Artificial Sequence <220> PCR Primer (27f) <400> 2 agagtttgat cctggctcag 20 <210> 3 <211> 19 <212> DNA <213> Artificial Sequence <220> PCR Primer (1492r) <400> 3 ggctaccttg ttacgactt 19 <210> 4 <211> 20 <212> DNA <213> Artificial Sequence <220> <223> 518F for DNA Sequencing <400> 4 ccagcagccg cggtaatacg 20 <210> 5 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> 800R for DNA Sequencing <400> 5 taccagggta tctaatcc 18 <210> 6 <211> 1254 <212> DNA <213> Alpha-Rhamnosidase of K-59 <400> 6 acttatcgat tttttgacga tttaggagtt ttgaagcaaa attattctca aatgaaaaat 60 tgggttgatt ggattaccca aaatactaaa accaaatact tatggattgg acaaatgcaa 120 ttaggagatt ggctttcctt ggataatggg gctaatcctc agggcaaaac taacgaagat 180 tatattgcat ctatttatta ttttgtttct gcaagcatag tatctaaagc agctagattg 240 cttcattacg atatggagtc agactattac gaaaatttgg ctagaaatat aaagacaaat 300 attttaaatg aatttgttac tgaaaaaggt aggatagcca ttgatactca gacagcattg 360 gtttcagcgt tacatttcgg attagtgcat gattatcaaa agtcacaggt tgtagctgat 420 ttagtgaaaa aagtaaaaga tgacaataag catttacaga ctggatttgt tgggacacca 480 tttttattgt cggtattatc aaataataat cagcatcatt tggctatgga tatttttatg 540 caagaagatt gcccaagttg gctttatgaa gtaaatatgg gagcaaccac aatatgggaa 600 cgttggaatt cggtattacc tgatggtaag atgaatcctg aagggatgaa ttcattaaat 660 cattatagtt ttggcgctgt gatgatgtgg atgtatcaat gtgtagtagg tttaaatcaa 720 tttgatgctg gatttaaaga aatttacttt gcacctaaat ttgattgtcg attaaaagat 780 atatattcag agtttgattc aacatatggg aagattaaag tggaatatca tttggagacc 840 aatgaaaagc atttgataag aatgaattta gtcataccat ttggagtgaa aatgaaggtt 900 aagttgccta gatctgctaa atatttgatt aacggaaaag aaaagatagg tattgttaaa 960 ttagaatatg ggaaatacga tattagttat attccaacta agagctactt aaattattat 1020 gatttaaata gtaagcttgt tgatatttta gataataacg atcttgtgaa aagaattgat 1080 caaattgatg aaaagatctt gcagaaagta aaaagaatgg gaaataccag aagtatattt 1140 attaatttaa aaatagatga attgcttgat ttcgaagaaa tttcacagga agaaaaaaat 1200 cagcttgttg atatttttcc taaaacaatt tttataaagt tgaatctctt ttaa 1254
Claims (8)
ⅰ. 인삼의 진세노사이드 Rb1, Rg1 또는 Re가 진세노사이드 Rh1, Rg3, Rh2 또는 C-K로 전환되거나; 또는 ⅱ. 당항상성이 향상된 인삼 발효물.It is characterized in that it is fermented by Lactobacillus acidophilus K-59 (KFCC11467P) or alpha-rhamnosidase obtained therefrom,
I. Ginsenosides Rb1, Rg1 or Re of ginseng are converted to ginsenosides Rh1, Rg3, Rh2 or CK; Or ii. Ginseng fermentation with improved sugar content.
(S2) 상기 발효물의 추출물을 제조하는 단계를 포함하는 것을 특징으로 하는,
ⅰ. 인삼의 진세노사이드 Rb1, Rg1 또는 Re가 진세노사이드 Rh1, Rg3, Rh2 또는 C-K로 전환되거나, 또는 ⅱ. 당항상성이 향상된 인삼 발효 추출물의 제조방법.(S1) fermenting ginseng with Lactobacillus acidophilus K-59 (KFCC11467P) or alpha-lamnosidase obtained therefrom to obtain a fermentation product; And
(S2) characterized in that it comprises the step of preparing an extract of the fermentation product,
I. Ginsenosides Rb1, Rg1 or Re of ginseng are converted to ginsenosides Rh1, Rg3, Rh2 or CK, or ii. Method of producing ginseng fermented extract with improved sugar compatibility.
ⅰ. 인삼의 진세노사이드 Rb1, Rg1 또는 Re가 진세노사이드 Rh1, Rg3, Rh2 또는 C-K로 전환되거나, 또는 ⅱ. 당항상성이 향상된 인삼 발효 추출물의 제조방법.According to claim 3, wherein the fermentation is made for 3 to 10 days at 35 ~ 37 ℃, the extract is characterized in that the ethanol or ethanol aqueous solution extract
I. Ginsenosides Rb1, Rg1 or Re of ginseng are converted to ginsenosides Rh1, Rg3, Rh2 or CK, or ii. Method of producing ginseng fermented extract with improved sugar compatibility.
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| CN104127566A (en) * | 2014-07-01 | 2014-11-05 | 第五永长 | Traditional Chinese medicine composition capable of improving peripheral and central tissue insulin sensitivity |
| KR20160013641A (en) | 2014-07-28 | 2016-02-05 | 홍소영 | Novel Lactobacillus pentosus NEO 1 and extracts from ginseng-fermented products using Lactobacillus pentosus NEO 1 and manufacturing method thereof |
| KR20160065245A (en) | 2014-11-28 | 2016-06-09 | (주)지에프씨 | Composition of culture medium for cultivation of Lactobacillus, ginseng berry-fermented extracts comprising thereof and cosmetic composition for improving skin conditions |
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| CN104127566A (en) * | 2014-07-01 | 2014-11-05 | 第五永长 | Traditional Chinese medicine composition capable of improving peripheral and central tissue insulin sensitivity |
| KR20160013641A (en) | 2014-07-28 | 2016-02-05 | 홍소영 | Novel Lactobacillus pentosus NEO 1 and extracts from ginseng-fermented products using Lactobacillus pentosus NEO 1 and manufacturing method thereof |
| KR20160065245A (en) | 2014-11-28 | 2016-06-09 | (주)지에프씨 | Composition of culture medium for cultivation of Lactobacillus, ginseng berry-fermented extracts comprising thereof and cosmetic composition for improving skin conditions |
| KR101718465B1 (en) | 2016-01-08 | 2017-03-21 | 강희철 | Novel Lactobacillus Casei GFC 1 and Extracts from Ginseng-fermented Products Using Lactobacillus Casei GFC 1 and Manufacturing Method Thereof |
| KR101980684B1 (en) | 2018-12-14 | 2019-05-22 | (주)해피바이오 | Method For Producing Ginseng Flower Extract With Enhanced Ginsenoside F4 Content and The Cosmetic Composition Including The Sam |
| KR102106018B1 (en) | 2019-08-09 | 2020-05-15 | (주)지에프씨생명과학 | Method For Producing Steaming Ginseng Berry Fermented Extracts Having Preventive and Improving Effects of Liver Damage |
| KR102310898B1 (en) | 2021-02-16 | 2021-10-08 | 주식회사 메디오젠 | Composition for anti-oxidant comprising dried powder of culture of Lactobacillus acidophilus |
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