KR20220128545A - A pharmaceutical composition for preventing or treating liver fibrosis containing Lactobacillus delbrueckii subsp. lactis CKDB001 - Google Patents
A pharmaceutical composition for preventing or treating liver fibrosis containing Lactobacillus delbrueckii subsp. lactis CKDB001 Download PDFInfo
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- KR20220128545A KR20220128545A KR1020210032544A KR20210032544A KR20220128545A KR 20220128545 A KR20220128545 A KR 20220128545A KR 1020210032544 A KR1020210032544 A KR 1020210032544A KR 20210032544 A KR20210032544 A KR 20210032544A KR 20220128545 A KR20220128545 A KR 20220128545A
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Abstract
Description
본 발명은 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주를 포함하는 간섬유증 예방 또는 치료용 약제학적 조성물, 간섬유증 예방 또는 개선용 건강기능식품 조성물 및 간섬유증 예방 또는 개선용 건강식품 조성물에 관한 것이다. The present invention is Lactobacillus delbrooki subsp. It relates to a pharmaceutical composition for preventing or treating liver fibrosis, a health functional food composition for preventing or improving liver fibrosis, and a health food composition for preventing or improving liver fibrosis, comprising the lactis CKDB001 strain.
인체면역세포의 약 60%가 장애 존재하기 때문에 장이 건강해야 신체가 건강하다. 현대인들의 불규칙한 생활습관과 스트레스 등으로 장내세균의 불균형이 발생하여 장 건강에 영향을 준다. 이때 유산균은 장내 유익균 증가와 유해균 감소에 도움을 주어 장내 미생물총을 조절한다. 장내 미생물은 건강과 질병에 중요한 역할을 한다. 장내 미생물총의 조절을 통하여 유익균의 비율을 높여서 면역 조절 활성효과, 공복 혈당 감소, 병원성 박테리아 부착 및 침입방지 등 다양한 질환들의 개선을 위해 사용될 수 있다[Hallajzadeh J, Eslami RD, Tanomand A. Effect of Lactobacillus delbrueckii Subsp. lactis PTCC1057 on Serum Glucose, Fetuin-A, and Sestrin 3 Levels in Streptozotocin-Induced Diabetic Mice. Probiotics Antimicrob Proteins 2020, Yu Q, Zhu L, Wang Z, Li P, Yang Q. Lactobacillus delbrueckii ssp. lactis R4 prevents Salmonella typhimurium SL1344-induced damage to tight junctions and adherens junctions. J Microbiol 2012; 50:613-7].Because about 60% of the immune cells of the human body are impaired, the body must be healthy when the intestine is healthy. Irregular lifestyle and stress of modern people cause an imbalance of intestinal bacteria, which affects gut health. At this time, lactic acid bacteria help to increase the beneficial bacteria in the intestine and reduce the harmful bacteria, thereby regulating the intestinal microflora. The gut microbiome plays an important role in health and disease. By increasing the ratio of beneficial bacteria through the regulation of the intestinal microflora, it can be used to improve various diseases such as immunomodulatory activity effect, reduction of fasting blood sugar, and prevention of pathogenic bacteria adhesion and invasion [Hallajzadeh J, Eslami RD, Tanomand A. Effect of Lactobacillus delbrueckii Subsp. lactis PTCC1057 on Serum Glucose, Fetuin-A, and Sestrin 3 Levels in Streptozotocin-Induced Diabetic Mice. Probiotics Antimicrob Proteins 2020, Yu Q, Zhu L, Wang Z, Li P, Yang Q. Lactobacillus delbrueckii ssp. lactis R4 prevents Salmonella typhimurium SL1344-induced damage to tight junctions and adherens junctions. J Microbiol 2012; 50:613-7].
유산균은 위와 장에서 다양한 메커니즘을 통해 장내에 군집을 형성하여 살 수 있다. 장-간 축에 의해 유산균의 유익한 효과는 간경화, 비알코올성 지방간 질환 및 알코올성 간질환의 간 기능 개선으로 확장될 수 있기 때문에 유산균 투여를 통해 장내 환경 및 간질환을 개선할 수 있다[Sharma V, Garg S, Aggarwal S. Probiotics and liver disease. Perm J 2013; 17:62-7].Lactobacilli can live by forming colonies in the intestine through various mechanisms in the stomach and intestines. Because the beneficial effect of lactic acid bacteria by the intestinal-liver axis can be extended to improvement of liver function in cirrhosis, nonalcoholic fatty liver disease and alcoholic liver disease, it is possible to improve the intestinal environment and liver disease through lactic acid bacteria administration [Sharma V, Garg S, Aggarwal S. Probiotics and liver disease. Perm J 2013; 17:62-7].
간섬유증은 간에 섬유가 증가한 상태로 대부분 만성간질환에서 발생하는 콜라겐을 포함한 세포 외 기질 단백질의 과도한 축적으로 일어난다. 진행성 간섬유증은 간경변, 간부전 및 문맥 고혈압을 유발하며 간이식이 필요할 수도 있다[Bataller R, Brenner DA. Liver fibrosis. J Clin Invest 2005; 115:209-18].Liver fibrosis is a condition in which liver fibers are increased, and it is caused by excessive accumulation of extracellular matrix proteins including collagen, which occurs mostly in chronic liver disease. Progressive liver fibrosis causes cirrhosis, liver failure and portal hypertension and may require liver transplantation [Bataller R, Brenner DA. Liver fibrosis. J Clin Invest 2005; 115:209-18].
간 담즙 정체성 질환은 심각한 사망률과 관련된 만성 간질환의 관련 원인을 나타낸다. 이에 대한 치료 전략을 이해하고 해결하는 것이 병리학적 특징을 요약하는 생체 내 모델을 개발하는데 필수적이다. DDC로 명명된 3,5-디에톡시카르보닐-1,4-디하이드로콜리딘의 공급은 담즙정체성 질환의 생체모델로 섬유화와 염증성 침윤과 같은 인간 담즙 정체성 질환의 주요 병리학적 특징이 재현된다[Pose E, Sancho-Bru P, Coll M. 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine Diet: A Rodent Model in Cholestasis Research. Methods Mol Biol 2019; 1981:249-57].Hepatic cholestatic disease represents an associated cause of chronic liver disease associated with severe mortality. Understanding and addressing therapeutic strategies for this is essential for developing in vivo models that recapitulate pathological features. The supply of 3,5-diethoxycarbonyl-1,4-dihydrocollidine, named DDC, is a biomodel of cholestatic disease, reproducing the major pathological features of human cholestatic disease, such as fibrosis and inflammatory infiltration [ Pose E, Sancho-Bru P, Coll M. 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine Diet: A Rodent Model in Cholestasis Research. Methods Mol Biol 2019; 1981:249-57].
CCl4로 명명된 사염화탄소의 전형적인 독성은 간경변과 간섬유증을 유발하는 대표적인 물질이다. 이로 유발된 간섬유증은 만성 간병변의 결과로 간암종으로 진행될 수 있다. 사염화탄소는 흡입, 구강 또는 위내 투여, 피하주사 및 복강내 주사가 가능하고 음용수에 타서 복합 투여하면 더 빨리 유도할 수 있다[Dong S, Chen QL, Song YN, Sun Y, Wei B, Li XY, et al. Mechanisms of CCl4-induced liver fibrosis with combined transcriptomic and proteomic analysis. J Toxicol Sci 2016; 41:561-72].The typical toxicity of carbon tetrachloride, named CCl 4 , is a representative substance that causes cirrhosis and liver fibrosis. This induced hepatic fibrosis can progress to hepatocarcinoma as a result of chronic liver lesions. Carbon tetrachloride can be induced by inhalation, oral or intragastric administration, subcutaneous injection and intraperitoneal injection, and can be induced faster by mixing it with drinking water and administering it [Dong S, Chen QL, Song YN, Sun Y, Wei B, Li XY, et al. al. Mechanisms of CCl4-induced liver fibrosis with combined transcriptomic and proteomic analysis. J Toxicol Sci 2016; 41:561-72].
항생제는 우리 몸에서 유해균을 없애는 일을 한다. 그러나 항생제의 과용과 남용은 알레르기 반응, 발진, 설사 등의 부작용과 지속적으로 낮은 농도의 항생제에 노출되면 약효가 저하하는 내성이 생긴다. 동물 사육에서 유해균 감염을 막기 위해 항생제를 사용하면 우유, 계란, 육류와 같은 항생제 잔여물이 남을 수 있다. 이러한 잔여물은 항생제 내성 박테리아의 면역 병리학적으로 다양한 부작용을 일으킬 수 있다[Bacanli M, Basaran N. Importance of antibiotic residues in animal food. Food Chem Toxicol 2019; 125:462-6].Antibiotics work to eliminate harmful bacteria from our body. However, overuse and abuse of antibiotics causes side effects such as allergic reactions, rashes, and diarrhea, and resistance that decreases the efficacy of antibiotics when continuously exposed to low concentrations of antibiotics. If antibiotics are used in animal breeding to prevent harmful bacterial infections, antibiotic residues such as milk, eggs and meat can remain. These residues can cause various immunopathological side effects of antibiotic-resistant bacteria [Bacanli M, Basaran N. Importance of antibiotic residues in animal food. Food Chem Toxicol 2019; 125:462-6].
생균제는 유해균에 대한 저항성 증진을 통한 가축의 생산성 증진을 위해 가축에 급여하기 위한 살아있는 젖산균으로서 항생제의 대체제로 사용될 수 있으며, 사람의 체내에서도 유해균을 조절하는 역할을 할 수 있다. 하지만 이러한 생균제의 이로운 특성을 이용하기 위해서는 인간 및 동물의 소화관에서 미생물의 효과를 확인하는 것이 중요하다. 이와 같이 장내 미생물총을 복원하거나 개선하는 생균제를 활용하여 현대 질병의 치료제 개발을 기대해 볼 수 있다. Probiotics can be used as a substitute for antibiotics as live lactic acid bacteria for feeding livestock to improve the productivity of livestock by enhancing resistance to harmful bacteria, and can also play a role in controlling harmful bacteria in the human body. However, in order to exploit the beneficial properties of these probiotics, it is important to determine the effects of microorganisms in the digestive tract of humans and animals. As such, it can be expected to develop therapeutic agents for modern diseases by using probiotics that restore or improve the intestinal microflora.
본 발명은 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주가 간섬유화을 개선하고 장내 미생물총 조절로 인한 면역 증진효과가 있어 후보 생균제를 간섬유증 치료제로 제안하고자 하는 것을 목적으로 한다. The present invention is Lactobacillus delbrooki subsp. The purpose of this study is to propose a candidate probiotic as a treatment for hepatic fibrosis as the lactis CKDB001 strain improves liver fibrosis and has an immune-enhancing effect by regulating the intestinal microflora.
또한, 본 발명이 해결하고자 하는 과제들은 이상에서 언급된 과제로 제한되지 않으며, 언급되지 않은 또 다른 과제들은 아래의 기재로부터 통상의 기술자에게 명확하게 이해될 수 있을 것이다.In addition, the problems to be solved by the present invention are not limited to the problems mentioned above, and other problems not mentioned will be clearly understood by those skilled in the art from the following description.
상기와 같은 목적을 달성하기 위하여 본 발명의 일 실시예에 따르면, 수탁번호 KCTC 14149BP 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주를 유효성분으로 포함하는 간섬유증 예방 또는 치료용 약제학적 조성물이 제공된다. According to one embodiment of the present invention in order to achieve the above object, accession number KCTC 14149BP Lactobacillus delbrooki subsp. There is provided a pharmaceutical composition for preventing or treating liver fibrosis comprising the lactis CKDB001 strain as an active ingredient.
본 발명의 일 실시예에 따라, 상기 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주는 발효된 원유로부터 분리된 것일 수 있다. According to an embodiment of the present invention, the Lactobacillus delbrooki subsp. The lactis CKDB001 strain may be isolated from fermented milk.
본 발명의 일 실시예에 따라, 상기 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주는 분말의 생균제 형태로 포함된 것일 수 있다. According to an embodiment of the present invention, the Lactobacillus delbrooki subsp. The lactis CKDB001 strain may be included in the form of a powdered probiotic.
본 발명의 다른 일 실시예에 따라, 수탁번호 KCTC 14149BP 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주를 포함하는 간섬유증 예방 또는 개선용 건강기능식품 조성물이 제공된다. According to another embodiment of the present invention, accession number KCTC 14149BP Lactobacillus delbrooki subsp. There is provided a health functional food composition for preventing or improving liver fibrosis comprising the lactis CKDB001 strain.
본 발명의 일 실시예에 따라, 상기 건강기능식품은 정제, 캡슐제, 환제 또는 액제 형태의 식품일 수 있다. According to an embodiment of the present invention, the health functional food may be food in the form of tablets, capsules, pills, or liquids.
한편, 본 발명의 다른 일 실시예에 따라, 수탁번호 KCTC 14149BP 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주를 포함하는 간섬유증 예방 또는 개선용 건강식품 조성물이 제공된다. On the other hand, according to another embodiment of the present invention, accession number KCTC 14149BP Lactobacillus delbrooki subsp. There is provided a health food composition for preventing or improving liver fibrosis comprising the lactis CKDB001 strain.
본 발명의 일 실시예에 따라, 상기 건강식품은 드링크제, 육류, 소세지, 빵, 캔디류, 스넥류, 면류, 아이스크림류, 유제품, 스프, 이온음료, 음료수, 알코올 음료, 껌, 차 및 비타민 복합제로 이루어진 군에서 선택되는 적어도 어느 하나일 수 있다.According to an embodiment of the present invention, the health food is a drink, meat, sausage, bread, candy, snack, noodles, ice cream, dairy product, soup, ionic beverage, beverage, alcoholic beverage, gum, tea and vitamin complex consisting of It may be at least one selected from the group.
본 발명에 따른 락토바실러스 델브루키 subsp. 락티스 CKDB001 (Lactobacillus delbrueckii subsp. lactis CKDB001) 균주를 간섬유증 유도 마우스에 투여하였을 경우 간 조직에서 섬유화 유전자 발현을 저하시키고 병리학적으로 간섬유화로부터 보호 및 억제시키는 효과를 가지므로 간섬유증에 대한 예방과 치료에 이용될 수 있다. Lactobacillus delbrooki subsp according to the present invention. When lactis CKDB001 ( Lactobacillus delbrueckii subsp . lactis CKDB001 ) strain is administered to hepatic fibrosis-induced mice, it reduces the expression of fibrosis genes in liver tissue and has the effect of protecting and inhibiting pathologically from hepatic fibrosis. can be used for treatment.
도 1은 DDC 식이 섭취로 유도한 간섬유증 마우스 모델 모식도이다.
도 2는 DDC 모델에서 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주의 체중 및 간 무게 보호효과 비교도이다.
도 3은 DDC 모델에서 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주의 섬유화 유전자 발현 억제 측정도이다.
도 4는 DDC 식이 모델에서 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주의 섬유화 진행 억제 병리학적 비교도이다.
도 5는 CCl4 주사로 유도한 간섬유증 마우스 모델 모식도이다.
도 6은 CCl4 모델에서 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주의 체중 및 간 무게 보호효과 비교도이다.
도 7은 CCl4 모델에서 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주의 섬유화 유전자 발현 억제 측정도이다.
도 8은 CCl4 모델에서 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주의 섬유화 진행 억제 병리학적 비교도이다. 1 is a schematic diagram of a mouse model of liver fibrosis induced by DDC dietary intake.
Figure 2 is Lactobacillus delbrooki subsp in the DDC model. It is a comparison diagram of the protective effect on body weight and liver weight of the lactis CKDB001 strain.
3 is a Lactobacillus delbrooki subsp in the DDC model. It is a measure of inhibition of fibrosis gene expression of lactis CKDB001 strain.
Figure 4 is Lactobacillus delbrooki subsp in the DDC diet model. It is a pathological comparison diagram of inhibition of fibrosis progression of lactis CKDB001 strain.
5 is a schematic diagram of a mouse model of liver fibrosis induced by CCl 4 injection.
Figure 6 is CCl 4 Lactobacillus delbrooki subsp in the model. It is a comparison diagram of the protective effect on body weight and liver weight of the lactis CKDB001 strain.
7 is a Lactobacillus delbrooki subsp in the CCl 4 model. It is a measure of the inhibition of fibrosis gene expression of the lactis CKDB001 strain.
Figure 8 is Lactobacillus delbrooki subsp in the CCl 4 model. It is a pathological comparison diagram of inhibition of fibrosis progression of the lactis CKDB001 strain.
이하, 본 발명에 대하여 상세히 설명하기로 한다. 이에 앞서, 본 명세서 및 특허청구범위에 사용된 용어 또는 단어는 통상적이거나 사전적인 의미로 한정해서 해석되어서는 아니되며, 발명자는 그 자신의 발명을 가장 최선의 방법으로 설명하기 위해 용어의 개념을 적절하게 정의할 수 있다는 원칙에 입각하여 본 발명의 기술적 사상에 부합하는 의미와 개념으로 해석되어야만 한다. 따라서, 본 명세서에 기재된 실시예에 기재된 구성은 본 발명의 가장 바람직한 일 실시예에 불과할 뿐이고 본 발명의 기술적 사상을 모두 대변하는 것은 아니므로, 본 출원시점에 있어서 이들을 대체할 수 있는 다양한 균등물과 변형예들이 있을 수 있음을 이해하여야 한다.Hereinafter, the present invention will be described in detail. Prior to this, the terms or words used in the present specification and claims should not be construed as being limited to their ordinary or dictionary meanings, and the inventor should properly understand the concept of the term in order to best describe his invention. It should be interpreted as meaning and concept consistent with the technical idea of the present invention based on the principle that it can be defined in Therefore, the configuration described in the embodiment described in this specification is only the most preferred embodiment of the present invention and does not represent all of the technical idea of the present invention, so various equivalents and It should be understood that there may be variations.
본 발명의 일 실시예에 따라, 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주를 유효성분으로 포함하는 간섬유증 예방 또는 치료용 약제학적 조성물이 제공된다. 본 발명에 있어서, 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주 균주는 "한국생명공학연구원 미생물자원센터(Korean Collection for Type Culture, KCTC)"에 수탁번호 "KCTC 14149BP"로 기탁된 것이다. 이하에서 상기 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주 (Lactobacillus delbrueckii subsp. lactis CKDB001)는 L. lactis CKDB001과 혼용하여 사용될 수 있다. According to an embodiment of the present invention, Lactobacillus delbrooki subsp. There is provided a pharmaceutical composition for preventing or treating liver fibrosis comprising the lactis CKDB001 strain as an active ingredient. In the present invention, Lactobacillus delbrooki subsp. The lactis CKDB001 strain was deposited with the "Korean Collection for Type Culture (KCTC)" with accession number "KCTC 14149BP". Hereinafter, the Lactobacillus delbrooki subsp. Lactis CKDB001 strain ( Lactobacillus delbrueckii subsp . lactis CKDB001 ) can be used in combination with L. lactis CKDB001.
한편, 본 발명의 일 실시예에 따라, 상기 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주는 발효된 원유로부터 분리된 것일 수 있다. On the other hand, according to an embodiment of the present invention, the Lactobacillus delbrooki subsp. The lactis CKDB001 strain may be isolated from fermented milk.
또한, 상기 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주는 분말의 생균제 형태로 포함된 것일 수 있으며, 보다 구체적으로 1그람(g) 당 1.10E+11 집락형성단위(CFU)의 상기 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주 분말의 생균제를 제공할 수 있다. In addition, the Lactobacillus delbrooki subsp. The Lactis CKDB001 strain may be contained in the form of a probiotic powder, and more specifically, 1.10E+11 colony forming units (CFU) per 1 gram (g) of the Lactobacillus delbrooki subsp. A probiotic of lactis CKDB001 strain powder can be provided.
본 발명의 일 실시예에 따라, 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주를 포함하는 간섬유증 예방 또는 개선용 건강기능식품 조성물이 제공된다. According to an embodiment of the present invention, Lactobacillus delbrooki subsp. There is provided a health functional food composition for preventing or improving liver fibrosis comprising the lactis CKDB001 strain.
이때, 상기 건강기능식품은 정제, 캡슐제, 환제 또는 액제 형태의 식품일 수 있다. In this case, the health functional food may be food in the form of tablets, capsules, pills, or liquids.
본 발명의 일 실시예에 따라, 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주를 포함하는 간섬유증 예방 또는 개선용 건강식품 조성물이 제공된다. According to an embodiment of the present invention, Lactobacillus delbrooki subsp. There is provided a health food composition for preventing or improving liver fibrosis comprising the lactis CKDB001 strain.
본 발명의 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주를 건강기능식품 및 건강식품 조성물로 사용하는 경우 식품의 종류에는 특별한 제한은 없다. 본 발명의 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주를 첨가할 수 있는 식품의 예로는 드링크제, 육류, 소시지, 빵, 비스킷, 떡, 초콜릿, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 알코올 음료 및 비타민 복합제, 유제품 및 유가공 제품 등이 있으며, 통상적인 의미에서의 건강기능식품 및 건강식품 조성물을 모두 포함한다.Lactobacillus delbrooki subsp of the present invention. When the lactis CKDB001 strain is used as a health functional food and health food composition, there is no particular limitation on the type of food. Lactobacillus delbrooki subsp of the present invention. Examples of foods to which the lactis CKDB001 strain can be added include drinks, meat, sausage, bread, biscuits, rice cakes, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, and various There are soups, beverages, alcoholic beverages and vitamin complexes, dairy products, and dairy products, and includes all health functional foods and health food compositions in the ordinary sense.
본 발명에 따른 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주를 포함하는 건강기능식품 및 건강식품 조성물은 식품 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주의 혼합량은 그의 사용 목적(예방 또는 개선용)에 따라 적합하게 결정될 수 있다. 일반적으로 건강기능식품 및 건강식품 조성물 중의 상기 조성물의 양은 전체 식품 중량의 0.1 내지 90 중량부로 가할 수 있다. 그러나 건강 유지를 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양의 범위 이하일 수 있다. Lactobacillus delbrooki subsp according to the present invention. The health functional food and health food composition containing the lactis CKDB001 strain may be added to food as it is or used together with other food or food ingredients, and may be appropriately used according to a conventional method. Lactobacillus delbrooki subsp. The mixing amount of the lactis CKDB001 strain may be appropriately determined depending on the purpose of its use (for prevention or improvement). In general, the amount of the composition in the health functional food and health food composition may be added in an amount of 0.1 to 90 parts by weight based on the total weight of the food. However, in the case of long-term ingestion for the purpose of maintaining health or for health control, the amount may be less than the above range.
본 발명의 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주를 함유하는 외에는 다른 성분에는 특별한 제한이 없으며 통상의 음료와 같이 여러 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트라이톨 등의 당알코올이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 건강기능식품 및 건강식품 조성물 100 g 당 일반적으로 약 1 내지 20 g, 바람직하게는 약 5 내지 12 g이다.Lactobacillus delbrooki subsp of the present invention. There is no particular limitation on other ingredients other than containing the lactis CKDB001 strain, and it may contain various flavoring agents or natural carbohydrates as additional ingredients like a conventional beverage. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; disaccharides such as maltose, sucrose and the like; and polysaccharides such as conventional sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those described above, natural flavoring agents (taumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 g of the health functional food and health food composition of the present invention.
상기 외에는 본 발명의 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주를 함유하는 건강기능식품 및 건강식품 조성물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 건강기능식품 및 건강식품 조성물은 천연 과일쥬스 및 과일쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다.In addition to the above, Lactobacillus delbrooki subsp. The health functional food and health food composition containing the lactis CKDB001 strain contains various nutrients, vitamins, minerals (electrolytes), synthetic flavoring agents and flavoring agents such as natural flavoring agents, coloring agents and thickening agents (cheese, chocolate, etc.), pect acids and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. In addition, the health functional food and health food composition of the present invention may contain natural fruit juice, fruit juice, and fruit for the production of a vegetable drink.
이하 본 발명을 실시예에 의하여 더욱 상세하게 설명한다. 이들 실시예는 단지 본 발명을 보다 구체적으로 설명하기 위한 것으로, 본 발명의 범위가 이들 실시예에 국한되지 않는다는 것은 당업계에서 통상의 지식을 가진 자에게 있어서 자명할 것이다.Hereinafter, the present invention will be described in more detail by way of Examples. These examples are merely for illustrating the present invention in more detail, and it will be apparent to those of ordinary skill in the art that the scope of the present invention is not limited to these examples.
실시예 1. 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주의 분리Example 1. Lactobacillus delbrooki subsp. Isolation of Lactis CKDB001 strain
1. 생균제 미생물 후보의 특성 확인 및 동정1. Characterization and Identification of Probiotic Microbial Candidates
본 발명의 생균제 미생물은 발효된 원유에서 분리되었고 ㈜종근당 바이오에서 제공받았다. 생균제 유산균은 그람 양성이다. 다음 기준에 따라 특성이 확인되었다.The probiotic microorganism of the present invention was isolated from fermented crude oil and was provided by Chong Kun Dang Bio. Probiotics Lactobacilli are Gram-positive. Characteristics were confirmed according to the following criteria.
1) In vitro 안전성 측정1) In vitro safety measurement
2) 구강에서 위를 거쳐 장까지 이동하는 동안의 안정성2) Stability during movement from the oral cavity through the stomach to the intestine
3) 항생제 감수성3) Antibiotic susceptibility
이러한 특성을 측정한 결과는 아래 표 1과 같이 정리되었다.The results of measuring these characteristics are summarized in Table 1 below.
2. 선택된 균주의 동정2. Identification of selected strains
가) 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주의 동정go) Lactobacillus delbrooki subsp. Identification of Lactis CKDB001 strain
이 균주는 전장유전체분석을 통해 Lactobacillus delbrueckii subsp. lactis로 식별되었다. 분리된 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주는 생균제로 만들어지기 위해, 생물학적으로 순수한 배양으로 유지되었다. This strain was identified as Lactobacillus delbrueckii subsp. lactis was identified. Isolated Lactobacillus delbrooki subsp. The lactis CKDB001 strain was maintained as a biologically pure culture to make it a probiotic.
나) 동정된 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주에 대한 생화학적 테스트 B) Identified Lactobacillus delbrooki subsp. Biochemical test against lactis CKDB001 strain
락토바실러스 델브루키 subsp. 락티스 CKDB001 균주는 그람 염색 및 현미경 관찰로 동정되었다.Lactobacillus delbrooki subsp. Lactis CKDB001 strain was identified by Gram staining and microscopic observation.
실시예 2. 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주 조성물의 준비Example 2. Lactobacillus delbrooki subsp. Preparation of Lactis CKDB001 strain composition
락토바실러스 델브루키 subsp. 락티스 CKDB001 균주는 ㈜종근당바이오에서 공급받았다. 정제된 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주는 동결건조 시킨 미세분말 형태로 전달받았다.Lactobacillus delbrooki subsp. Lactis CKDB001 strain was supplied by Chong Kun Dang Bio. Purified Lactobacillus delbrooki subsp. Lactis CKDB001 strain was delivered in the form of lyophilized fine powder.
1. 동결건조 시킨 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주를 미세분말 형태로 준비1. Lyophilized Lactobacillus delbrooki subsp. Lactis CKDB001 strain prepared in fine powder form
2. 위산에 약한 생존율을 높이기 위한 ㈜종근당바이오에서 특수 코팅처리로 준비2. Prepared with special coating treatment by Chong Kun Dang Bio to increase the survival rate weak to gastric acid
3. 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주는 109 CFU/g의 농도로 증류수에 현탁 하여 주 2회 공급하였다.3. Lactobacillus delbrooki subsp. Lactis CKDB001 strain was suspended in distilled water at a concentration of 10 9 CFU/g and supplied twice a week.
실시예 3. 간섬유증 유도 마우스 모델 유도 및 분석방법Example 3. Hepatic fibrosis induction mouse model induction and analysis method
동물모델 평가를 위해 특정 병원체가 없는 5주령의 C57BL/6J 수컷 마우스를 두열바이오텍(서울, 한국)에서 구매하였다. 모든 마우스들은 12/12시간 명/암 주기로 22±2℃ 온도에서 전용 케이지에 개별적으로 수용하였다. 실험 진행 동안 모든 마우스들은 물과 음식에 자유롭게 접근할 수 있도록 하였고 매일 관찰하였다. 실험은 모든 그룹에 대한 적응기간을 포함하였고 이 기간 동안에는 1주일 동안 정상적인 사료를 제공하였다. 실험동물들은 인도주의적 치료를 받았으며 모든 절차는 실험실 동물의 관리 및 사용을 위한 국립보건원 지침을 따랐으며 한림대학교 의과대학 동물실험 및 사용위원회(2019-4)의 승인을 받았다.For animal model evaluation, 5-week-old C57BL/6J male mice without specific pathogens were purchased from Dooyeol Biotech (Seoul, Korea). All mice were individually housed in dedicated cages at a temperature of 22±2° C. with a 12/12 h light/dark cycle. During the experiment, all mice had free access to water and food and were observed daily. The experiment included an adaptation period for all groups, and normal feed was provided for 1 week during this period. The laboratory animals received humanitarian treatment, and all procedures followed the guidelines of the National Institutes of Health for the Care and Use of Laboratory Animals, and were approved by the Animal Experiment and Use Committee (2019-4) of Hallym University College of Medicine.
1. 3,5-디에톡시카르보닐-1,4-디하이드로콜리딘 모델1. 3,5-diethoxycarbonyl-1,4-dihydrocollidine model
식이 섭취로 간섬유증 모델을 유도하기 위해 0.1%의 3,5-디에톡시카르보닐-1,4-디하이드로콜리딘(이하 줄여서 DDC) 혼합사료를 두열바이오텍에서 제조하여 3주간 자유롭게 섭취하도록 하였다. 간섬유증 모델 마우스는 3개의 그룹으로 분류하였다(도 1): 정상(n=6), 질병유도식이(n=6), 그리고 질병유도식이와 함께 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주 섭취(n=6).In order to induce a liver fibrosis model through dietary intake, a 0.1% 3,5-diethoxycarbonyl-1,4-dihydrocollidine (hereinafter abbreviated DDC) mixed feed was prepared by Dooyeol Biotech and allowed to be freely consumed for 3 weeks. Hepatic fibrosis model mice were classified into three groups ( FIG. 1 ): normal (n=6), disease-inducing diet (n=6), and Lactobacillus delbrooki subsp with disease-inducing diet. Lactis CKDB001 strain intake (n=6).
2. 사염화탄소 모델2. Carbon tetrachloride model
복강주사로 간섬유증 모델을 유도하기 위해 옥수수기름(시그마, 미국)과 사염화탄소(이하 줄여서 CCl4)(쇼와, 일본) 4:1 희석하여 10주 동안 주 2회씩 복강 주입하여 간섬유증 모델을 확립하였다. 간섬유증 모델 마우스는 3개의 그룹으로 분류하였다(도 5): 정상(n=6), 질병유도주사(n=6), 그리고 질병유도주사와 함께 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주 섭취(n=6).To induce a liver fibrosis model by intraperitoneal injection, corn oil (Sigma, USA) and carbon tetrachloride (hereinafter abbreviated CCl 4 ) (Showa, Japan) were diluted 4:1 and intraperitoneally injected twice a week for 10 weeks to establish a liver fibrosis model did. Hepatic fibrosis model mice were classified into three groups ( FIG. 5 ): normal (n=6), disease-inducing injection (n=6), and Lactobacillus delbrooki subsp with disease-inducing injection. Lactis CKDB001 strain intake (n=6).
3. 처리방법3. Treatment method
각 동물모델에 따라 4주 및 11주 후 흡입 마취제 투여(에어래인액, 미국)를 통해 동물을 희생시켰다. 체중과 간 무게를 측정하고 혈액 및 간조직을 분리했다. 전혈(800μL) 샘플을 원심 분리 (19,000 g, 5분)하여 혈청을 분리하였다. 간 조직은 빠르게 분리하여 80℃에 보관했다.After 4 weeks and 11 weeks according to each animal model, animals were sacrificed by administration of an inhaled anesthetic (Airlane solution, USA). Body weight and liver weight were measured, and blood and liver tissues were isolated. A sample of whole blood (800 μL) was centrifuged (19,000 g, 5 min) to separate serum. Liver tissue was quickly isolated and stored at 80 °C.
4. 병리학분석4. Pathological analysis
분리된 간 조직을 10% 포르말린으로 고정시키고 파라핀에 매립시키고, 조직 섹션을 헤마톡실린에오신(H&E), 마손트라이크롬(MT), 및 시리우스레드(SR) 염색을 하였다. 간경화의 분석을 위해 사용되는 병리학적 분석인 그레이딩(염증정도, 단편적 또는 가교 괴사[등급0: 없음, 1: 괴사 없는 문맥염증 또는 소엽 염증, 2: 경미한 문맥 주위 염증 및 단편 괴사 또는 국소 간세포 괴사, 3: 중등도 문맥 주의 염증 및 단편 괴사 또는 심한 초점 세포손상, 4: 심한 문맥 주위 염증 및 단편 괴사 또는 가교 괴사])과 스테이징(섬유증정도[등급0: 섬유증 없음, 1: 확장된 섬유성 문맥관, 2: 문맥 주위 섬유증 또는 문맥에서 문맥 중격까지, 구조적 왜곡 없음, 3: 구조적 왜곡이 있는 섬유증 연결, 명백한 간경변 없음, 4: 간경변 가능성 있음 또는 확정])를 평가하였다.The isolated liver tissue was fixed with 10% formalin and embedded in paraffin, and tissue sections were stained with hematoxylineosin (H&E), mason trichrome (MT), and Sirius Red (SR). Grading pathological analysis used for the analysis of liver cirrhosis (inflammation, fractional or bridging necrosis [grade 0: none, 1: portal inflammation or lobular inflammation without necrosis, 2: mild periportal inflammation and fragmentary necrosis or focal hepatocellular necrosis, 3: moderate portal vein inflammation and fragment necrosis or severe focal cell injury, 4: severe periportal inflammation and fragment necrosis or bridge necrosis]) and staging (grade 0: no fibrosis, 1: dilated fibrotic portal vein, 2: periportal fibrosis or portal vein to portal septum, no structural distortion, 3: fibrotic linkage with structural distortion, no apparent cirrhosis, 4: possible or confirmed cirrhosis]).
5. 섬유화인자에 대한 간 조직 분석5. Analysis of liver tissue for fibrosis factor
조직으로부터의 mRNA의 분리는 제조사의 지시에 따라 트리졸 시약 키트(인비트로젠, 미국)를 사용하여 수행했다. cDNA 합성 키트(어플라이드 바이오시스템즈, 미국)를 사용하여 mRNA (2 μg)를 cDNA로 합성했다. cDNA는 루나 유니버셜 마스터 믹스(뉴잉글랜드바이오랩, 미국) 및 각 표적-특이적 프로브-프라이머를 사용하여 정량적 PCR (qPCR)을 수행하였다.Isolation of mRNA from tissues was performed using the Trizol reagent kit (Invitrogen, USA) according to the manufacturer's instructions. mRNA (2 μg) was synthesized into cDNA using a cDNA synthesis kit (Applied Biosystems, USA). Quantitative PCR (qPCR) was performed for cDNA using Luna Universal Master Mix (New England Biolab, USA) and each target-specific probe-primer.
6. 데이터 분석6. Data Analysis
연속 변수는 평균 및 표준편차로 분석하였다. 체중, 섬유화인자 및 조직학 분석을 위해 One-way ANOVA, the Kruskal-Wallis test, 그리고 independent sample T-test를 수행했다. 추가 통계 분석을 위해 데이터를 NOREVA (http://idrb.zju.edu.cn/noreva)의 MSTUS55를 기반으로 하였다. 계층 적 군집 분석(HCA)을 수행하고 사후 테스트를 통한 분산분석(ANOVA)을 다중 실험 뷰어(MeV)를 사용하여 수행하였다. 유의확률 P값 <0.05는 통계적 유의성을 나타내는 것으로 간주된다. 모든 통계 분석은 SPSS 소프트웨어(ver. 19, SPSS Inc., Chicago, IL, USA)를 사용하여 수행하였다.Continuous variables were analyzed as mean and standard deviation. One-way ANOVA, the Kruskal-Wallis test, and independent sample T-test were performed for body weight, fibrosis factor and histological analysis. Data were based on MSTUS55 from NOREVA (http://idrb.zju.edu.cn/noreva) for further statistical analysis. Hierarchical cluster analysis (HCA) was performed and analysis of variance (ANOVA) with post-test was performed using a multiple experiment viewer (MeV). A significance probability P value <0.05 is considered to indicate statistical significance. All statistical analyzes were performed using SPSS software (ver. 19, SPSS Inc., Chicago, IL, USA).
실시예 4. 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주의 간섬유증 유도 마우스 모델에서 간섬유화 억제능력 측정Example 4. Lactobacillus delbrooki subsp. Measurement of liver fibrosis inhibition ability in a mouse model of hepatic fibrosis induction of lactis CKDB001 strain
1. 간섬유증 유도 마우스 모델에서의 간섬유화 인자 억제효과1. Inhibitory effect of hepatic fibrosis factor in hepatic fibrosis-induced mouse model
간섬유증 질환은 섬유화의 진행이 가장 큰 특징이다. 섬유화의 원인으로는 TGF-β의 과발현과 간성상 세포의 비정상적인 활성 등 다양하다. 아직 정확한 원인에 대해 밝혀지지 않았지만, 간섬유화에서 대표적인 섬유화 인자(Timp1, Col1a, 및 TGF-β)들은 질환의 평가에서 유용하게 사용될 수 있다. 따라서 qPCR을 통해 간섬유증 유도 모델에서 각 섬유화 인자들의 발현을 비교 분석하였다. 간섬유증의 유도로 인하여 크게 증가된 Timp1, Col1a, 및 TGF-β의 발현이 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주를 섭취함에 따라 유의적으로 감소되는 것을 확인했다. The most characteristic feature of liver fibrosis disease is the progression of fibrosis. There are various causes of fibrosis, such as overexpression of TGF-β and abnormal activity of hepatic stellate cells. Although the exact cause has not yet been elucidated, representative fibrosis factors (Timp1, Col1a, and TGF-β) in liver fibrosis can be usefully used in the evaluation of diseases. Therefore, the expression of each fibrosis factor in the liver fibrosis induction model was comparatively analyzed through qPCR. The greatly increased expression of Timp1, Col1a, and TGF-β due to the induction of hepatic fibrosis was found in Lactobacillus delbrooki subsp. It was confirmed that the lactis CKDB001 strain was significantly reduced by ingestion.
가) DDC모델A) DDC model
간섬유증 유도 식이를 3주동안 공급하면서 정상 식이군, 간섬유증 유도군, 그리고 간섬유증 유도군에 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주를 투여하였다. 간섬유증을 유도하면서 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주를 투여했을 때 간경화에서 대표적인 섬유화인자인 Col1a, Timp1 및 TGF-β의 발현이 현저하게 감소하였다. Col1a의 경우 간섬유증을 유도한 대조군 22.2±4.8에서 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주 투여 시 12±2.4(p <0.05)로, Timp1의 경우 53.1±7.6에서 32.8±1.9(p <0.05), 그리고 TGF-β의 경우 8.1±1.7에서 5.1±0.7(p <0.05)로 감소시켰다(도 3 참조). Lactobacillus delbrooki subsp. Lactis CKDB001 strain was administered. While inducing liver fibrosis, Lactobacillus delbrooki subsp. When the lactis CKDB001 strain was administered, the expression of Col1a, Timp1 and TGF-β, which are representative fibrotic factors in cirrhosis, was significantly reduced. In the case of Col1a, Lactobacillus delbrooki subsp. When administered with lactis CKDB001 strain, 12±2.4 ( p <0.05), for Timp1, from 53.1±7.6 to 32.8±1.9 ( p <0.05), and for TGF-β, 8.1±1.7 to 5.1±0.7 ( p <0.05) was reduced to (see FIG. 3).
나) CCl4 모델B) CCl 4 model
간섬유증 유도 주사를 10주 동안 복강 주사하면서 정상 식이군, 간섬유증 유도군, 그리고 간섬유증 유도군에 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주를 투여하였다. Col1a의 경우 간섬유증을 유도한 대조군 29.3±5.9에서 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주 투여 시 16.9±5.5(p <0.05)로, Timp1의 경우 5.2±1.4에서 2.2±1.2(p <0.05), 그리고 TGF-β의 경우 2.2±0.5에서 1.6±0.6(p <0.05)로 감소시켰다(도 7 참조).Hepatic fibrosis induction injection was administered intraperitoneally for 10 weeks, and Lactobacillus delbrooki subsp. Lactis CKDB001 strain was administered. In the case of Col1a, Lactobacillus delbrooki subsp. Lactis CKDB001 strain administered 16.9±5.5 ( p <0.05), Timp1 5.2±1.4 to 2.2±1.2 ( p <0.05), and TGF-β 2.2±0.5 to 1.6±0.6 ( p <0.05) was reduced to (see FIG. 7).
3. 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주의 간섬유화 유도 마우스 모델에서의 간경화 보호효과3. Lactobacillus delbrooki subsp. The protective effect of liver cirrhosis in a mouse model of hepatic fibrosis induction of lactis CKDB001 strain
간경화의 간섬유화를 보다 확실하게 확인하기 위하여 병리학적 분석을 수행하였다. 간 조직은 헤마톡실린에오신, 마손트라이크롬, 및 시리우스레드 염색을 통해 수행했다. 간섬유증 유도 모델에서 섬유화가 증가되어 그레에딩, 스테이징 그리고 시리우스레드 측정면적이 정상 대조군에 비해 크게 증가하였다. 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주섭취를 통해 증가된 그레이딩, 스테이징, 그리고 시리우스레드 측정면적을 모두 감소시켜 보호효과를 확인했다. Pathological analysis was performed to more reliably confirm liver fibrosis of cirrhosis. Liver tissue was performed by staining with hematoxylineosin, mason trichrome, and Sirius Red. In the hepatic fibrosis induction model, fibrosis was increased, and the grading, staging, and Sirius red measurement areas were significantly increased compared to the normal control group. Lactobacillus delbrooki subsp. The protective effect was confirmed by reducing all of the increased grading, staging, and Sirius Red measurement area through ingestion of the Lactis CKDB001 strain.
가) DDC 모델A) DDC model
간섬유증 모델 유도 시 시리우스레드 염색 측정면적이 43.1±5.5에서 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주 섭취 시 22.7±11.4(p <0.01)로 감소하였다. When the liver fibrosis model was induced, the Sirius red staining area was 43.1±5.5 and Lactobacillus delbrooki subsp. When the lactis CKDB001 strain was ingested, it decreased to 22.7±11.4 ( p <0.01).
나) CCl4 모델B) CCl 4 model
간섬유증 모델 유도 시 그레이딩 3에서 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주 섭취 시 2.8±0.2로, 스테이징 3에서 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주 섭취 시 2.8±0.4로 감소하였다. 시리우스레드 염색 측정면적이 29.8±6에서 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주 섭취 시 24±3.8로 감소하였다. Lactobacillus delbrooki subsp. in grade 3 upon induction of hepatic fibrosis model. When the Lactis CKDB001 strain was ingested, it was 2.8±0.2, and in stage 3, Lactobacillus delbrooki subsp. When the lactis CKDB001 strain was ingested, it was reduced to 2.8±0.4. Sirius red staining area was 29.8±6 and Lactobacillus delbrooki subsp. When the lactis CKDB001 strain was ingested, it was reduced to 24±3.8.
이상으로 본 발명의 특정한 부분을 상세히 기술하였는 바, 당업계의 통상의 지식을 가진 자에게 있어서, 이러한 구체적 기술은 단지 바람직한 실시예일 뿐이며, 이에 의해 본 발명의 범위가 제한되는 것이 아닌 점은 명백할 것이다. 따라서, 본 발명의 실질적인 범위는 첨부된 청구항들과 그것들의 등가물에 의하여 정의된다고 할 것이다.As the specific parts of the present invention have been described in detail above, for those of ordinary skill in the art, it is clear that these specific descriptions are only preferred embodiments, and the scope of the present invention is not limited thereby. will be. Accordingly, it is intended that the substantial scope of the present invention be defined by the appended claims and their equivalents.
Claims (9)
상기 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주는 발효된 원유로부터 분리된 것인, 간섬유증 예방 또는 치료용 약제학적 조성물. According to claim 1,
The Lactobacillus delbrooki subsp. Lactis CKDB001 strain is a pharmaceutical composition for preventing or treating liver fibrosis, which is isolated from fermented raw milk.
상기 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주는 분말의 생균제 형태로 포함된 것인, 간섬유증 예방 또는 치료용 약제학적 조성물. According to claim 1,
The Lactobacillus delbrooki subsp. Lactis CKDB001 strain is a pharmaceutical composition for preventing or treating liver fibrosis, which is contained in the form of a probiotic powder.
상기 건강기능식품은 정제, 캡슐제, 환제 또는 액제 형태의 식품인 간섬유증 예방 또는 개선용 건강기능식품 조성물. 5. The method of claim 4,
The health functional food is a health functional food composition for preventing or improving liver fibrosis, which is a food in the form of a tablet, capsule, pill or liquid.
상기 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주는 발효된 원유로부터 분리된 것인, 간섬유증 예방 또는 개선용 건강기능식품 조성물. 5. The method of claim 4,
The Lactobacillus delbrooki subsp. Lactis CKDB001 strain is a health functional food composition for preventing or improving liver fibrosis, which is isolated from fermented raw milk.
상기 락토바실러스 델브루키 subsp. 락티스 CKDB001 균주는 분말의 생균제 형태로 포함된 것인, 간섬유증 예방 또는 개선용 건강기능식품 조성물. 5. The method of claim 4,
The Lactobacillus delbrooki subsp. Lactis CKDB001 strain is a health functional food composition for preventing or improving liver fibrosis, which is contained in the form of a probiotic powder.
상기 건강식품은 드링크제, 육류, 소세지, 빵, 캔디류, 스넥류, 면류, 아이스크림류, 유제품, 스프, 이온음료, 음료수, 알코올 음료, 껌, 차 및 비타민 복합제로 이루어진 군에서 선택되는 적어도 어느 하나인, 간섬유증 예방 또는 개선용 건강식품 조성물.
9. The method of claim 8,
The health food is at least one selected from the group consisting of drinks, meat, sausage, bread, candy, snacks, noodles, ice cream, dairy products, soups, ionic drinks, beverages, alcoholic beverages, gum, tea and vitamin complexes, A health food composition for preventing or improving liver fibrosis.
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