KR20170020679A - Composition for Preventing, Improving or Treating of Th1-mediated Immune Disease, Th17-mediated Immune Disease or Th2-mediated Immune Disease Comprising Extracts from Lactococcus lactis as an Active Ingredients - Google Patents
Composition for Preventing, Improving or Treating of Th1-mediated Immune Disease, Th17-mediated Immune Disease or Th2-mediated Immune Disease Comprising Extracts from Lactococcus lactis as an Active Ingredients Download PDFInfo
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- KR20170020679A KR20170020679A KR1020150114937A KR20150114937A KR20170020679A KR 20170020679 A KR20170020679 A KR 20170020679A KR 1020150114937 A KR1020150114937 A KR 1020150114937A KR 20150114937 A KR20150114937 A KR 20150114937A KR 20170020679 A KR20170020679 A KR 20170020679A
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- mediated immune
- immune disease
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- lactococcus lactis
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Abstract
Description
본 발명은 락토코쿠스 락티스(Lactococcus lactis)를 유효성분으로 포함하는 Th1-매개 면역 질환, Th17-매개 면역 질환 또는 Th2-매개 면역 질환의 예방, 개선 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for preventing, ameliorating or treating a Th1-mediated immune disease, a Th17-mediated immune disease or a Th2-mediated immune disease, which comprises Lactococcus lactis as an active ingredient.
최근 미국을 중심으로 장내 세균의 균총을 규명하는 메타지놈 프로젝트 진행결과 장내균총의 분포와 알레르기를 포함하는 다양한 면역계 질환과 상관관계가 밝혀지고 있다. 따라서, 장내 세균의 분포와 다양성 그리고 장 면역과 면역계가 밀접히 연관되어 지고 있음이 규명되고 있는 단계이다. Recently, Metagenome project to identify intestinal microflora in the US has been linked to various immune system diseases including distribution of intestinal microflora and allergy. Therefore, the distribution and diversity of intestinal bacteria and intestinal immunity are closely related to each other.
프로바이오틱스 관련 시장은 2003년을 기준으로 미국의 시장규모는 1억 4430만불로 시장규모액의 증가는 11.2%이었으며 2010년까지 연평균 성장률은 13.0%로 예상되었으며 2010년 시장 규모는 약 3억 9400만 달러였다. 유럽의 시장 규모는 2003년 기준 4천만 30만불로 15.8% 증가하였으며, 2010년까지의 연평균 성장률은 16.7%로 예상되고 있다. 예상되는 2010년 예상 시장 규모는 1억 3790만 달러이며 국내 프로바이오틱스 시장 규모는 1000억원을 넘는 것으로 추정되고 있다. The market size of the probiotics market was US $ 144.3 million as of 2003. The market size was 11.2%, and the annual average growth rate was estimated at 13.0% by 2010. The market size in 2010 was about 394 million dollars Respectively. The European market grew 15.8% to $ 40.3 million in 2003, and the average annual growth rate until 2010 is expected to be 16.7%. The expected 2010 market size is estimated at $ 137.9 million, and the domestic probiotic market is estimated to exceed 100 billion won.
알레르기억제와 같은 면역제어용 프로바이오틱스 발굴 및 평가 기술은 아직 확립되지 않은 상태임으로, 체계적인 인 비트로 또는 인 비보 모방 스크리닝 시스템을 개발하고 그 기술을 잘 활용한다면 경제적인 효용가치도 막대할 것으로 예상된다. The technology for detecting and evaluating immunity control probiotics such as allergy suppression has not yet been established. Therefore, it is expected that if the systematic in-vitro or in-vivo mimic screening system is developed and utilized well, the economic utility value will also be enormous.
근본적 작용기작에 대한 연구는 미비한 상태이며 및 대부분의 연구가 인 비트로에서 행해지고 있다. 즉 프로바이오틱스의 섭취는 구강을 통해 이루어짐에도 불구하고 지금까지의 연구는 대부분 세포주를 이용한 인 비트로 실험이 주를 이루었으며 이러한 실험 방법은 사람이 프로바이오틱스의 섭취 시 나타낼 수 있는 기능에 대한 연구를 대체할 수 없는 큰 단점이 있다. 또한, 프로바이오틱스에 노출되는 장내 면역계(GALT)는 다양한 면역세포가 동시에 존재하여 상호작용을 일으켜 프로바이오틱스의 면역작용을 나타내나 인 비트로 실험은 생체 내 환경과는 차이가 많다.Research on the fundamental mechanism is lacking, and most of the research is done in vitro . Although the ingestion of probiotics is carried out through the oral cavity, most of the research to date has been focused on in vitro experiments using cell lines, and these experimental methods can be replaced by studies on the functions that people may experience when ingesting probiotics There is a major drawback. In addition, the intestinal immune system (GALT) exposed to probiotics exhibits immune functions of probiotics due to the presence of various immune cells at the same time, and the in vitro experiment is different from the in vivo environment.
이에 본 발명에서는 한국형 전통식품에서 분리한 균주의 항알레르기 활성을 평가하기 위해 다양한 면역세포를 생쥐에서 직접 분리한 후 이들에 대한 락토코쿠스 락티스(Lactococcus lactis)의 영향을 평가함으로써 인 비보 시스템에 가까운 연구결과를 도출하였다.In this invention, in order to evaluate the antiallergic activity of strains isolated from Korean traditional foods, various immune cells were directly isolated from mice, and then the effect of Lactococcus lactis was evaluated on them , A close study result was derived.
현재 해외의 프로바이오틱스에 대한 면역조절 능력의 평가는 다양한 질환 동물모델에 적용되고 있으며, 그 성과 역시 해마다 가파른 속도로 증가하고 있는 단계이다. 1형 당뇨병, 류마티스 관절염, 퇴행성 관절염, 궤양성 대장염과 같은 염증성 질환들의 염증 반응 억제를 타겟팅하는 분야만이 아니라 독감 바이러스나 암과 같은 질병에 대항할 수 있도록 면역 반응을 증대시킬 수 있는 프로바이오틱스의 기능에 대해서도 연구가 활발히 진행 중이다. 이외에도 알레르기, 천식, 아토피와 같은 예방 및 치료 목적으로도 프로바이오틱스의 역할 및 그 기능이 많은 주목을 받고 있다.Currently, the evaluation of immunity control for overseas probiotics is applied to various disease animal models, and the results are also increasing at a rapid pace every year. The ability of probiotics to increase the immune response to fight against diseases such as influenza virus or cancer, as well as areas that target inflammatory responses to inflammatory diseases such as
대부분의 프로바이오틱스는 유래가 인간의 장 또는 식품이기 때문에 동물모델을 이용한 효능이 입증되면 다른 화학적 약제와 안정성의 입증에 큰 문제가 없다는 장점이 있다. 또한 최근 들어 면역조절제로서 프로바이오틱스의 질병 치료 효능이 다양한 임상실험을 통해 검증되고 있다. 천식, 궤양성 대장염, 관절염 등의 질병이 많이 시도되어지고 있으며 최근 들어 아토피에 대한 임상시도 및 연구가 가속화 되고 있는 실정이다.Because most probiotics are derived from human intestines or foods, there is an advantage in that there is no major problem in proving the stability of other chemical agents when proven efficacy using animal models. Recently, the efficacy of probiotics as an immunomodulator has been verified through various clinical trials. Asthma, ulcerative colitis, and arthritis. Recently, clinical trials and studies on atopy have been accelerated.
산업화 동향 분석에 따르면 전통적으로 강세인 유럽에서 프로바이오틱스 개발을 주도하고 있으며 미국, 일본 등지에서도 최근에 기능성 프로바이오틱스 개발 및 사업화가 활발히 진행되고 있는 상태이다. 대표적인 상품으로 VSL3#는 캐나다의 VSL Phamaceutical company에 의해서 개발되었으며, 현재 전세계 시장을 대상으로 활발한 판매활동을 벌이고 있으며 최근에 국내시장에도 면역조절 개별인정형으로 판매되고 있다.According to industrialization trend analysis, it is leading the development of probiotics in Europe, which is traditionally strong, and the development and commercialization of functional probiotics is being actively carried out in the US and Japan recently. VSL3 # was developed by the VSL Phamaceutical company in Canada. It is currently active in the global market, and recently it has been marketed as an immunity regulator in the domestic market.
본 명세서 전체에 걸쳐 다수의 논문 및 특허문헌이 참조되고 그 인용이 표시되어 있다. 인용된 논문 및 특허문헌의 개시 내용은 그 전체로서 본 명세서에 참조로 삽입되어 본 발명이 속하는 기술 분야의 수준 및 본 발명의 내용이 보다 명확하게 설명된다.Numerous papers and patent documents are referenced and cited throughout this specification. The disclosures of the cited papers and patent documents are incorporated herein by reference in their entirety to better understand the state of the art to which the present invention pertains and the content of the present invention.
본 발명자들은 Th1 또는 Th2 면역 반응에 의해 유발되는 알레르기 및 염증 질환, 질병 또는 상태를 예방 또는 치료하기 위한 프로바이오틱스를 개발하고자 예의 연구 노력하였다. 그 결과, 전통발효식품인 김치로부터 항알레르기 및 항염증 활성을 갖는 신규한 락토코쿠스 락티스(Lactococcus lactis) 균주를 선별하고, 상기 균주를 처리한 경우 면역과민반응 유도동물모델에서의 면역글로불린 E(IgE) 생성 감소 및 Th1-관련 사이토카인, Th17-관련 사이토카인 및 Th2-관련 사이토카인의 감소에 의하여 알레르기 및 염증이 효과적으로 제어됨을 확인함으로써 본 발명을 완성하였다.The present inventors have made extensive efforts to develop probiotics for the prevention or treatment of allergy and inflammatory diseases, diseases or conditions induced by Th1 or Th2 immune responses. As a result, a novel fermented food, Lactococcus lactis , having antiallergic and anti - inflammatory activity, lactis strains were selected, and when the strains were treated, reduction of immunoglobulin E (IgE) production and reduction of Th1-associated cytokine, Th17-related cytokine and Th2-related cytokine in an immunosuppressive induction animal model Thereby confirming that allergy and inflammation are effectively controlled, thereby completing the present invention.
따라서, 본 발명의 목적은 락토코쿠스 락티스(Lactococcus lactis)를 유효성분으로 포함하는 Th1-매개 면역 질환, Th17-매개 면역 질환 또는 Th2-매개 면역 질환의 예방, 개선 또는 치료용 조성물을 제공하는 데 있다.Accordingly, an object of the present invention is to provide a composition for preventing, ameliorating or treating a Th1-mediated immune disease, a Th17-mediated immune disease or a Th2-mediated immune disease comprising Lactococcus lactis as an active ingredient There is.
본 발명의 다른 목적은 Th1-매개 면역 질환, Th17-매개 면역 질환 또는 Th2-매개 면역 질환의 예방, 개선 또는 치료 활성을 갖는 신규한 락토코쿠스 락티스 균주를 제공하는데 있다. It is another object of the present invention to provide a novel Lactococcus lactis strain having a preventive, ameliorative or therapeutic activity of ThI-mediated immune disease, Th17-mediated immune disease or Th2-mediated immune disease.
본 발명의 다른 목적 및 이점은 하기의 발명의 상세한 설명, 청구범위 및 도면에 의해 보다 명확하게 된다.Other objects and advantages of the present invention will become more apparent from the following detailed description of the invention, claims and drawings.
본 발명의 일 양태에 따르면, 본 발명은 락토코쿠스 락티스(Lactococcus lactis)를 유효성분으로 포함하는 Th1-매개 면역 질환, Th17-매개 면역 질환 또는 Th2-매개 면역 질환의 예방, 개선 또는 치료용 조성물을 제공한다.According to one aspect of the present invention, the present invention provides a method for preventing, ameliorating or treating a Th1-mediated immune disease, a Th17-mediated immune disease, or a Th2-mediated immune disease comprising Lactococcus lactis as an active ingredient Lt; / RTI >
본 발명자들은 Th1, Th17 또는 Th2 면역 반응에 의해 유발되는 알레르기 및 염증 질환, 질병 또는 상태를 예방 또는 치료하기 위한 프로바이오틱스를 개발하고자 예의 연구 노력하였다. 그 결과, 전통발효식품인 김치로부터 항알레르기 및 항염증 활성을 갖는 신규한 락토코쿠스 락티스(Lactococcus lactis) 균주를 선별하고, 상기 균주를 처리한 경우 면역과민반응 유도동물모델에서의 면역글로불린 E(IgE) 생성 감소 및 Th1-관련 사이토카인, Th17-관련 사이토카인 및 Th2-관련 사이토카인의 감소에 의하여 알레르기 및 염증이 효과적으로 제어됨을 확인하였다.The present inventors have made extensive efforts to develop probiotics for the prevention or treatment of allergic and inflammatory diseases, diseases or conditions induced by Th1, Th17 or Th2 immune responses. As a result, a novel fermented food, Lactococcus lactis , having antiallergic and anti - inflammatory activity, lactis strains were selected, and when the strains were treated, reduction of immunoglobulin E (IgE) production and reduction of Th1-associated cytokine, Th17-related cytokine and Th2-related cytokine in an immunosuppressive induction animal model It was confirmed that allergy and inflammation were effectively controlled.
따라서 본 발명은 락토코쿠스 락티스를 유효성분으로 포함하는 Th1-매개 면역 질환, Th17-매개 면역 질환 또는 Th2-매개 면역 질환의 예방, 개선 또는 치료용 조성물에 관한 것이다.Accordingly, the present invention relates to a composition for preventing, ameliorating or treating a Th1-mediated immune disease, a Th17-mediated immune disease or a Th2-mediated immune disease, which comprises lactococcus lactis as an active ingredient.
본 명세서에서 용어 “유효성분으로 포함하는”이란 하기의 락토코쿠스 락티스(Lactococcus lactis)의 효능 또는 활성을 달성하는 데 충분한 양을 포함하는 것을 의미한다. 본 발명의 락토코쿠스 락티스는 식품으로부터 분리한 미생물 균주인바 과량 투여하여도 인체에 부작용이 없으므로 상기 락토코쿠스 락티스가 본 발명의 조성물에 포함된 양적 상한은 당업자가 적절한 범위 내에서 선택하여 실시할 수 있다.As used herein, the term " comprising as an active ingredient " is meant to include an amount sufficient to achieve the efficacy or activity of Lactococcus lactis described below. Since the lactococcus lactis of the present invention is a microorganism strain isolated from food and does not adversely affect the human body even when administered in an excessive amount, the quantitative upper limit of the lactococcus lactis contained in the composition of the present invention can be selected by a person skilled in the art .
본 발명의 일 구현예에 따르면, 본 발명의 조성물은 IL-4 생성을 감소시킨다. IL-4는 비만세포의 탈과립화를 유도하여 염증성 매개물을 방출함으로써 알레르기 반응을 유도하는 IgE의 분비를 촉진시키는 대표적인 Th2-관련 사이토카인이다. 따라서 IL-4의 생성이 억제되는 경우 알레르기 증상이 완화된다. 본 발명의 다른 구현예에 따르면, 본 발명의 조성물은 음성 대조군에 비하여 IL-4 생성을 20-90%, 30-90%, 40-90%, 50-80% 또는 60-70% 감소시킨다.According to one embodiment of the present invention, the composition of the present invention reduces IL-4 production. IL-4 is a typical Th2-related cytokine that promotes the secretion of IgE, which induces allergic reactions by inducing degranulation of mast cells and releasing inflammatory mediators. Therefore, if the production of IL-4 is inhibited, allergic symptoms are alleviated. According to another embodiment of the invention, the composition of the invention reduces IL-4 production by 20-90%, 30-90%, 40-90%, 50-80% or 60-70% compared to the negative control.
본 발명의 일 구현예에 따르면, 본 발명의 조성물은 IgE 생성을 억제시킨다. IgE는 면역 글로불린 E(immunoglobulin E)로 비만세포 또는 혈중의 호염기구 등에 친화성을 가져 이들에 부착된 IgE 항체와 이에 대응하는 항원(알레르겐)이 반응하면 염증반응을 일으키게 된다. 즉, IgE는 알레르기에 의한 아나필락시 또는 염증반응을 일으키는 항체인바 상기 IgE 생성이 억제되면 알레르기 반응 또는 염증반응이 억제된다.According to one embodiment of the present invention, the composition of the present invention inhibits IgE production. IgE is an immunoglobulin E, which has an affinity for mucous cells or basophils in the blood, and causes an inflammatory reaction when IgE antibodies attached thereto and the corresponding antigens (allergens) react with each other. In other words, IgE is an antibody that causes anaphylactic or inflammatory reaction due to allergy. When the above IgE production is inhibited, allergic reaction or inflammatory reaction is suppressed.
본 발명의 일 구현예에 따르면, 본 발명의 조성물은 Th1-관련 사이토카인 생성을 억제시킨다. 따라서 본 발명의 조성물은 다양한 Th1-매개 면역 질환, 질병 또는 상태의 예방, 개선 또는 치료에 이용될 수 있다. 본 발명의 다른 구현예에 따르면, 본 발명의 조성물은 IFN-γ 생성을 억제시킨다.According to one embodiment of the present invention, the composition of the present invention inhibits Th1-associated cytokine production. Thus, the compositions of the present invention can be used for the prevention, amelioration or treatment of various Th1-mediated immune diseases, diseases or conditions. According to another embodiment of the present invention, the composition of the present invention inhibits IFN-y production.
본 명세서에서, 용어 "Th1-매개 면역 질환"은 Th1 세포의 생성 및/또는 활성에 의해 생성되는 사이토카인(Th1-관련 사이토카인), 예컨대, IL-1β, IL-2, IL-12, IFN-γ 또는 TNF-α 등이 관여하는 질환을 의미한다.As used herein, the term "Th1-mediated immune disorder" refers to a cytokine (Th1-associated cytokine) produced by the production and / or activity of Th1 cells such as IL-1β, IL-2, IL- -γ or TNF-α.
본 명세서에서 용어 "Th1 세포"는 유전자 발현, 단백질 분비 및 기능적 활성 측면에서 특정되는 헬퍼 T 세포 림포사이트의 서브세트를 의미한다. 예를 들어, Th1 세포는 IL-2 및 IFN-γ를 합성하지만 IL-4, IL-5, IL-10 및 IL-13는 합성하지 않는 사이토카인 발현 패턴을 나타낸다. Th1 세포는 다양한 세포내 병원균에 대한 세포-매개 면역반응, 기관-특이적 자가면역 질환 및 지연성 과민반응에 관여한다. As used herein, the term "Th1 cell" refers to a subset of helper T cell lymphocytes that are specified in terms of gene expression, protein secretion, and functional activity. For example, Th1 cells synthesize IL-2 and IFN-y, but IL-4, IL-5, IL-10 and IL-13 do not synthesize cytokine expression patterns. Th1 cells are involved in cell-mediated immune responses, organ-specific autoimmune diseases and delayed hypersensitivity reactions to a variety of intracellular pathogens.
본 발명의 조성물이 적용되는 Th1-매개 면역 질환은 특별하게 제한되지 않는다. 예컨대, 본 발명의 조성물이 적용되는 Th1-매개 면역 질환은 대장염, 염증성 장질환, 타입 1 당뇨병, 타입 2 당뇨병, 류마티스 관절염, 반응성 관절염(Reactive Arthritis), 골관절염, 건선, 공피증, 골다공증, 아테롬성 동맥경화증, 심근염, 심내막염, 심낭염, 낭성 섬유증, 하시모토 갑상선염, 그레이브스병, 나병, 매독, 라임 질환(Lyme), 보렐리아증(Borreliosis), 신경성-보렐리아증, 결핵, 사르코이드증(Sarcoidosis), 낭창, 원판성 낭창, 동창성 루프스, 루프스 신염, 전신성 홍반성 루프스, 천식, 황반변성, 포도막염, 과민대장 증후군, 크로씨병, 쇼그랜 증후군, 섬유근통, 만성피로 증후군, 만성피로 면역부전 증후군, 근육통성 뇌척수염, 근위축성 측삭경화증, 파킨스병, 다발경화증, 자폐스펙트럼 장애, 주의력결핍 장애 및 주의력 결핍 과잉행동장애를 포함하나, 이에 한정되는 것은 아니다. 본 발명의 일 구현예에 따르면, 이식 거부, 자가면역질환 또는 염증 질환에 적용된다. 본 발명의 다른 구현예에 따르면, 본 발명의 조성물이 적용되는 Th1-매개 면역 질환은 염증 질환이다.Th1-mediated immune diseases to which the composition of the present invention is applied are not particularly limited. For example, a Th1-mediated immune disorder to which the composition of the present invention is applied is selected from the group consisting of colitis, inflammatory bowel disease,
본 발명의 일 구현예에 따르면, 본 발명의 조성물은 Th17-관련 사이토카인 생성을 억제시킨다. 따라서 본 발명의 조성물은 다양한 Th17-매개 면역 질환, 질병 또는 상태의 예방, 개선 또는 치료에 이용될 수 있다. 본 발명의 다른 구현예에 따르면, 본 발명의 조성물은 IL-17 생성을 억제시킨다.According to one embodiment of the present invention, the composition of the present invention inhibits Th17-associated cytokine production. Thus, the compositions of the present invention can be used for the prevention, amelioration or treatment of various Th17-mediated immune diseases, diseases or conditions. According to another embodiment of the present invention, the composition of the present invention inhibits IL-17 production.
본 명세서에서, 용어 "Th17-매개 면역 질환"은 Th17 세포의 생성 및/또는 활성에 의해 생성되는 사이토카인(Th17-관련 사이토카인), 예컨대, IL-17이 관여하는 질환을 의미한다.As used herein, the term "Th17-mediated immune disease" means a disease involving a cytokine (Th17-related cytokine) such as IL-17 produced by the production and / or activity of Th17 cells.
본 명세서에서 용어 "Th17 세포"는 유전자 발현, 단백질 분비 및 기능적 활성 측면에서 특정되는 헬퍼 T 세포 림포사이트의 서브세트를 의미한다. 예를 들어, Th17 세포는 TGF-β, IL-6 또는 IL-21에 의해 유도되어 IL-17, IL-22 및 IL-21 등을 합성하지만 IL-2, IL-4, IL-5 및 IL-13는 합성하지 않는 사이토카인 발현 패턴을 나타낸다. Th17 세포는 염증 및 자가면역 병인에 직접적인 역할을 하며 병원체에 대한 숙주방어 또는 이상 면역반응을 유도한다고 보고되어 있다.As used herein, the term "Th17 cell" refers to a subset of helper T cell lymphocytes that are specified in terms of gene expression, protein secretion and functional activity. For example, Th17 cells are induced by TGF- [beta], IL-6 or IL-21 to synthesize IL-17, IL-22 and IL-21 but not IL-2, IL-4, -13 indicates a cytokine expression pattern not synthesized. Th17 cells have been reported to play a direct role in inflammation and autoimmune pathogenesis and to induce host defense or an abnormal immune response to the pathogen.
본 발명의 조성물이 적용되는 Th17-매개 면역 질환은 특별하게 제한되지 않는다. 예컨대, 본 발명의 조성물이 적용되는 Th17-매개 면역 질환은 류마티스관절염, 건선, 다발성 경화증, 대장염, 염증성 장질환, 전신홍반루프스 등과 같은 염증성 자가면역질환을 포함하나, 이에 한정되는 것은 아니다. 본 발명의 일 구현예에 따르면, 이식 거부, 자가면역질환 또는 염증 질환에 적용된다. 본 발명의 다른 구현예에 따르면, 본 발명의 조성물이 적용되는 Th17-매개 면역 질환은 염증 질환이다.The Th17-mediated immune diseases to which the composition of the present invention is applied are not particularly limited. For example, a Th17-mediated immune disorder to which the composition of the present invention is applied includes, but is not limited to, inflammatory autoimmune diseases such as rheumatoid arthritis, psoriasis, multiple sclerosis, colitis, inflammatory bowel disease, systemic erythema lupus and the like. According to one embodiment of the present invention, it is applied to graft rejection, autoimmune disease or inflammatory diseases. According to another embodiment of the present invention, the Th17-mediated immune disease to which the composition of the present invention is applied is an inflammatory disease.
본 발명의 일 구현예에 따르면, 본 발명의 조성물은 Th2-관련 사이토카인 생성을 억제시킨다. 따라서 본 발명의 조성물은 다양한 Th2-매개 면역 질환, 질병 또는 상태의 예방, 개선 또는 치료에 이용될 수 있다. 본 발명의 다른 구현예에 따르면, 본 발명의 조성물은 IL-4 및 IL-13 사이토카인 생성을 억제시킨다.According to one embodiment of the invention, the composition of the present invention inhibits Th2-associated cytokine production. Thus, the compositions of the present invention can be used for the prevention, amelioration or treatment of various Th2-mediated immune diseases, diseases or conditions. According to another embodiment of the present invention, the composition of the present invention inhibits IL-4 and IL-13 cytokine production.
본 명세서에서, 용어 “Th2-매개 면역 질환”은 알레르겐-특이 Th2 세포의 생성 및 활성에 의한 IgE 및 비만세포가 관여하는 질환을 의미한다.As used herein, the term " Th2-mediated immune disease " refers to diseases in which IgE and mast cells are involved by the production and activity of allergen-specific Th2 cells.
본 명세서에서 용어 “Th2 세포”는 유전자 발현, 단백질 분비 및 기능적 활성 측면에서 특정되는 헬퍼 T 세포 림포사이트의 서브세트를 의미한다. 예를 들어, Th2 세포는 IL-4, IL-5 및 IL-13 사이토카인(Th2-관련 사이토카인) 발현 패턴을 나타낸다. Th2 세포는 체액성 면역반응에 관여한다. As used herein, the term " Th2 cell " refers to a subset of helper T cell lymphocytes that are specified in terms of gene expression, protein secretion, and functional activity. For example, Th2 cells exhibit IL-4, IL-5 and IL-13 cytokine (Th2-related cytokine) expression patterns. Th2 cells are involved in the humoral immune response.
본 발명의 조성물이 적용되는 Th2-매개 면역 질환은 특별하게 제한되지 않으며, 본 발명의 일 구현예에 따르면, 상기 Th2-매개 면역 질환은 알레르기 질환이다.The Th2-mediated immune disease to which the composition of the present invention is applied is not particularly limited, and according to one embodiment of the present invention, the Th2-mediated immune disease is an allergic disease.
본 명세서에서, 용어 “알레르기”는 인체의 어떤 물질에 대한 과민증, 즉 외부로부터 들어온 물질에 대한 신체 면역계의 과도한 반응으로 유발되는 다양한 질환, 질병 또는 이상 상태를 의미한다. 본 발명의 조성물에 적용되는 알레르기 질환으로는, 바람직하게는, 제 Ⅰ 형 즉시형 과민반응 및 제 Ⅳ 형 지연형 과민반응이다. 제 Ⅰ 형 즉시형 과민반응은 기관지 천식, 알레르기성 비염, 아토피성 피부염, 알레르기성 결막염, 알레르기성 중이염, 두드러기 및 아나필라틱 쇼크(anaphylatic shock)이고, 제 Ⅳ 형 지연형 과민반응은 접촉성 과민증, 알레르기성 접촉성 피부염, 세균 알레르기, 진균 알레르기, 바이러스 알레르기, 약물 알레르기, 갑상선염 및 알레르기성 뇌염이다. 제 Ⅰ 형 즉시형 과민반응은 2 단계로 나뉘는데 제 1 단계는 알레르겐의 체내 침입에 의하여 IgE 및 IgG1의 분비를 억제하고, IgG2a의 분비를 증가시키는 IL-12 및 IFN-γ를 생산하는 Th1 세포반응과 IL-4, IL-5 및 IL-13 등을 생산하는 Th2 세포반응의 균형이 Th2 쪽으로 기울어지게 되면 Th2의 과도한 면역반응으로 IL-4 및 IL-13 등이 분비되고 그 영향으로 B 세포가 생산한 IgE 특이항체들이 비만세포(mast cell) 및 호염기구(basophil)의 표면에 부착됨으로써 알레르기 발증이 준비된 단계이다. 이를 알레르겐에 감작되었다고 한다. 알레르기 발증의 제 2 단계는 초기반응과 후기반응으로 나뉘며, 초기반응은 알레르겐이 체내에 재침입하여 비만세포를 자극하고 탈과립 반응을 유발하여 이때 방출된, 히스타민, 지질대사물, 사이토카인 등에 의한 혈관확장 등이 일어나는 것이고, 후기반응은 해당 조직에 호중구, 호산구, 대식세포, Th2 세포, 호염기구 등이 침윤하여 활성화됨으로써 염증이 유발되어 아토피피부염, 비염, 천식 등을 일으키는 것이다. 본 발명의 어떠한 구현예에 의하면, 상기 알레르기는 알레르기성 접촉성 피부염, 알레르기성 아토피 피부염 또는 식품 알레르기이다.As used herein, the term " allergy " refers to a variety of diseases, conditions, or abnormal conditions caused by hypersensitivity to certain substances in the body, i.e., excessive response of the body's immune system to substances introduced from the outside. The allergic diseases to be applied to the composition of the present invention are preferably Type I immediate hypersensitivity reaction and Type IV delayed hypersensitivity reaction. Type I immediate hypersensitivity reactions are bronchial asthma, allergic rhinitis, atopic dermatitis, allergic conjunctivitis, allergic otitis media, urticaria and anaphylatic shock, Type IV delayed hypersensitivity is contact hypersensitivity , Allergic contact dermatitis, bacterial allergies, fungal allergies, viral allergies, drug allergies, thyroiditis and allergic encephalitis. The type I immediate-type hypersensitivity reaction is divided into two stages. The first step is to suppress the secretion of IgE and IgG1 by the invasion of the allergen and the Th1 cell reaction to produce IL-12 and IFN-γ which increase secretion of IgG2a And IL-4, IL-5, and IL-13, the IL-4 and IL-13 are secreted by the excessive immune response of Th2, The IgE-specific antibodies produced are attached to the surface of mast cells and basophils, so that allergic inflammation is prepared. It has been sensitized to allergens. The second stage of the allergic manifestation is divided into an initial reaction and a late reaction. Allergens re-enter the body to stimulate mast cells and induce a degranulation reaction, which causes release of histamine, lipid metabolites, cytokines, And eosinophil, eosinophil, macrophage, Th2 cell, and basophil are infiltrated into the affected tissue to induce inflammation, resulting in atopic dermatitis, rhinitis, asthma, and the like. According to some embodiments of the present invention, the allergy is allergic contact dermatitis, allergic atopic dermatitis or food allergy.
본 발명의 일 구현예에 따르면, 본 발명의 락토코쿠스 락티스는 김치로부터 분리된 균주이다.According to one embodiment of the present invention, the lactococcus lactis of the present invention is a strain isolated from kimchi.
본 발명의 일 구현예에 따르면, 본 발명의 락토코쿠스 락티스는 락토코쿠스 락티스 KF140 균주(기탁번호 KCCM 11673P)이다.According to one embodiment of the present invention, the lactococcus lactis of the present invention is a lactococcus lactis strain KF140 (Deposit No. KCCM 11673P).
본 발명의 조성물은 약제학적 조성물, 식품 조성물, 기능성 식품 조성물, 화장료 조성물 또는 사료 조성물이다.The composition of the present invention is a pharmaceutical composition, a food composition, a functional food composition, a cosmetic composition or a feed composition.
본 발명의 조성물은 약제학적 조성물로 제조될 수 있다.The compositions of the present invention may be prepared with pharmaceutical compositions.
본 발명의 바람직한 구현예에 따르면, 본 발명의 조성물은 (a) 상술한 본 발명의 락토코쿠스 락티스의 약제학적 유효량; 및 (b) 약제학적으로 허용되는 담체를 포함하는 약제학적 조성물이다. 본 명세서에서 용어 “약제학적 유효량”은 상술한 락토코쿠스 락티스의 효능 또는 활성을 달성하는 데 충분한 양을 의미한다.According to a preferred embodiment of the present invention, the composition of the present invention comprises (a) a pharmaceutically effective amount of the above-mentioned lactococcus lactis of the present invention; And (b) a pharmaceutically acceptable carrier. As used herein, the term "pharmaceutically effective amount" means an amount sufficient to achieve efficacy or activity of the lactococcus lactis described above.
본 발명의 조성물이 약제학적 조성물로 제조되는 경우, 본 발명의 약제학적 조성물은 약제학적으로 허용되는 담체를 포함한다. 본 발명의 약제학적 조성물에 포함되는 약제학적으로 허용되는 담체는 제제시에 통상적으로 이용되는 것으로서, 락토스, 덱스트로스, 수크로스, 솔비톨, 만니톨, 전분, 아카시아 고무, 인산 칼슘, 알기네이트, 젤라틴, 규산 칼슘, 미세결정성 셀룰로스, 폴리비닐피롤리돈, 셀룰로스, 물, 시럽, 메틸 셀룰로스, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 활석, 스테아르산 마그네슘 및 미네랄 오일 등을 포함하나, 이에 한정되는 것은 아니다. 본 발명의 약제학적 조성물은 상기 성분들 이외에 윤활제, 습윤제, 감미제, 향미제, 유화제, 현탁제, 보존제 등을 추가로 포함할 수 있다. 적합한 약제학적으로 허용되는 담체 및 제제는 Remington's Pharmaceutical Sciences (19th ed., 1995)에 상세히 기재되어 있다.When the composition of the present invention is manufactured from a pharmaceutical composition, the pharmaceutical composition of the present invention includes a pharmaceutically acceptable carrier. The pharmaceutically acceptable carriers to be contained in the pharmaceutical composition of the present invention are those conventionally used in the present invention and include lactose, dextrose, sucrose, sorbitol, mannitol, starch, acacia rubber, calcium phosphate, alginate, gelatin, But are not limited to, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrups, methylcellulose, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. It is not. The pharmaceutical composition of the present invention may further contain a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, etc. in addition to the above components. Suitable pharmaceutically acceptable carriers and formulations are described in detail in Remington ' s Pharmaceutical Sciences (19th ed., 1995).
본 발명의 약제학적 조성물은 경구 또는 비경구 투여할 수 있으며, 본 발명의 일 구현예에 따르면 경구 투여 방식으로 적용된다.The pharmaceutical composition of the present invention may be administered orally or parenterally, and may be administered orally in accordance with an embodiment of the present invention.
본 발명의 약제학적 조성물의 적합한 투여량은 제제화 방법, 투여 방식, 환자의 연령, 체중, 성, 병적 상태, 음식, 투여 시간, 투여 경로, 배설 속도 및 반응 감응성과 같은 요인들에 의해 다양하게 처방될 수 있다. 본 발명의 약제학적 조성물에 포함된 생리활성물질인 락토코쿠스 락티스 KF140 균주의 투여량은 성인 기준으로 0.0001-1000 ㎎/kg 범위 내이다.The appropriate dosage of the pharmaceutical composition of the present invention may vary depending on factors such as the formulation method, administration method, age, body weight, sex, pathological condition, food, administration time, administration route, excretion rate, . The dosage of Lactococcus lactis KF140, which is a physiologically active substance contained in the pharmaceutical composition of the present invention, is within the range of 0.0001-1000 mg / kg on an adult basis.
본 발명의 약제학적 조성물은 당해 발명이 속하는 기술분야에서 통상의 지식을 가진 자가 용이하게 실시할 수 있는 방법에 따라, 약제학적으로 허용되는 담체 및/또는 부형제를 이용하여 제제화함으로써 단위 용량 형태로 제조되거나 또는 다용량 용기 내에 내입시켜 제조될 수 있다. 이때 제형은 오일 또는 수성 매질중의 용액, 현탁액, 시럽제 또는 유화액 형태이거나 엑스제, 산제, 분말제, 과립제, 정제 또는 캅셀제 형태일 수도 있으며, 분산제 또는 안정화제를 추가적으로 포함할 수 있다.The pharmaceutical composition of the present invention may be formulated into a unit dose form by formulating it using a pharmaceutically acceptable carrier and / or excipient according to a method which can be easily carried out by a person having ordinary skill in the art to which the present invention belongs. Or by intrusion into a multi-dose container. The formulations may be in the form of solutions, suspensions, syrups or emulsions in oils or aqueous media, or in the form of excipients, powders, powders, granules, tablets or capsules, and may additionally contain dispersing or stabilizing agents.
본 발명의 조성물은 식품 조성물로 제공될 수 있다.The composition of the present invention can be provided as a food composition.
본 발명의 조성물이 식품 조성물로 제조되는 경우, 유효성분으로서 락토코쿠스 락티스 KF140 균주 뿐만 아니라, 식품 제조 시에 통상적으로 첨가되는 성분을 포함하며, 예를 들어, 단백질, 탄수화물, 지방, 영양소, 조미제 및 향미제를 포함한다. 상술한 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스, 올리고당 등; 및 폴리사카라이드, 예를 들어 덱스트린, 사이클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 향미제로서 천연 향미제 [타우마틴, 스테비아 추출물 (예를 들어 레바우디오시드 A, 글리시르히진 등]) 및 합성 향미제(사카린, 아스파르탐 등)를 사용할 수 있다.When the composition of the present invention is prepared as a food composition, it contains not only Lactococcus lactis strain KF140 as an active ingredient but also a component ordinarily added at the time of food production. For example, protein, carbohydrate, fat, Seasoning and flavoring agents. Examples of the above-mentioned carbohydrates are monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, oligosaccharides and the like; And polysaccharides such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. Natural flavorings such as tau martin and stevia extract (e.g., rebaudioside A and glycyrrhizin) and synthetic flavorings (saccharine, aspartame, etc.) can be used as flavorings.
예컨대, 본 발명의 식품 조성물이 드링크제로 제조되는 경우에는 본 발명의 조성물 이외에 구연산, 액상과당, 설탕, 포도당, 초산, 사과산, 과즙, 두충 추출액, 대추 추출액, 감초 추출액 등을 추가로 포함시킬 수 있다. For example, when the food composition of the present invention is prepared as a drink, citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, juice, mulberry extract, jujube extract and licorice extract may be further added in addition to the composition of the present invention .
본 발명의 조성물은 화장료 조성물로 제조될 수 있다.The composition of the present invention can be prepared with a cosmetic composition.
본 발명의 락토코쿠스 락티스를 유효성분 포함하는 항알레르기용 조성물이 화장료 조성물로 제조되는 경우, 유효 성분으로서의 락토코쿠스 락티스 이외에 화장료 조성물에 통상적으로 이용되는 성분들을 포함하며, 예컨대 안정화제, 용해화제, 비타민, 안료 및 향료와 같은 통상적인 보조제, 그리고 담체를 포함한다.When the antiallergic composition comprising the active ingredient of lactococusa lactis according to the present invention is prepared from a cosmetic composition, it includes the components conventionally used in cosmetic compositions in addition to lactococlu lactis as an active ingredient, and examples thereof include stabilizers, Customary adjuvants such as solubilizers, vitamins, pigments and flavoring agents, and carriers.
본 발명의 화장료 조성물은 당업계에서 통상적으로 제조되는 어떠한 제형으로도 제조될 수 있으며, 예를 들어, 용액, 현탁액, 유탁액, 페이스트, 겔, 크림, 로션, 파우더, 비누, 계면활성제-함유 클린싱, 오일, 분말 파운데이션, 유탁액 파운데이션, 왁스 파운데이션 및 스프레이 등으로 제형화될 수 있으나, 이에 한정되는 것은 아니다. 보다 상세하게는, 유연 화장수, 영양 화장수, 영양 크림, 마사지 크림, 에센스, 아이 크림, 클렌징 크림, 클렌징 포옴, 클렌징 워터, 팩, 스프레이 또는 파우더의 제형으로 제조될 수 있다.The cosmetic composition of the present invention can be prepared into any of the formulations conventionally produced in the art and can be used as a solution, a suspension, an emulsion, a paste, a gel, a cream, a lotion, a powder, a soap, , Oil, powder foundation, emulsion foundation, wax foundation and spray, but is not limited thereto. More specifically, it can be manufactured in the form of a soft lotion, a nutritional lotion, a nutritional cream, a massage cream, an essence, an eye cream, a cleansing cream, a cleansing foam, a cleansing water, a pack, a spray or a powder.
본 발명의 제형이 페이스트, 크림 또는 겔인 경우에는 담체 성분으로서 동물성유, 식물성유, 왁스, 파라핀, 전분, 트라칸트, 셀룰로오스 유도체, 폴리에틸렌 글리콜, 실리콘, 벤토나이트, 실리카, 탈크 또는 산화아연 등이 이용될 수 있다.When the formulation of the present invention is a paste, cream or gel, an animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as the carrier component .
본 발명의 제형이 페이스트, 크림 또는 겔인 경우에는 담체 성분으로서 동물성유, 식물성유, 왁스, 파라핀, 전분, 트라칸트, 셀룰로오스 유도체, 폴리에틸렌 글리콜, 실리콘, 벤토나이트, 실리카, 탈크 또는 산화아연 등이 이용될수 있다.When the formulation of the present invention is a paste, cream or gel, an animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as the carrier component have.
본 발명의 제형이 파우더 또는 스프레이인 경우에는 담체 성분으로서 락토스, 탈크, 실리카, 알루미늄 히드록시드, 칼슘 실리케이트 또는 폴리아미드 파우더가 이용될 수 있고, 특히 스프레이인 경우에는 추가적으로 클로로플루오로히드로카본, 프로판/부탄 또는 디메틸 에테르와 같은 추진체를 포함할 수 있다.When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component. In the case of a spray, in particular, / Propane or dimethyl ether.
본 발명의 제형이 용액 또는 유탁액인 경우에는 담체 성분으로서 용매, 용해화제 또는 유탁화제가 이용되고, 예컨대 물, 에탄올, 이소프로판올, 에틸카보네이트, 에틸 아세테이트, 벤질 알코올, 벤질 벤조에이트, 프로필렌 글리콜, 1,3-부틸글리콜 오일, 글리세롤 지방족 에스테르, 폴리에틸렌 글리콜 또는 소르비탄의 지방산 에스테르가 있다.When the formulation of the present invention is a solution or an emulsion, a solvent, a dissolving agent or an emulsifying agent is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, , 3-butyl glycol oil, glycerol aliphatic ester, polyethylene glycol or sorbitan fatty acid esters.
본 발명의 제형이 현탁액인 경우에는 담체 성분으로서 물, 에탄올 또는 프로필렌 글리콜과 같은 액상의 희석제, 에톡실화 이소스테아릴 알코올, 폴리옥시에틸렌 소르비톨 에스테르 및 폴리옥시에틸렌 소르비탄 에스테르와 같은 현탁제, 미소결정성 셀룰로오스, 알루미늄 메타히드록시드, 벤토나이트, 아가 또는 트라칸트 등이 이용될 수 있다.In the case where the formulation of the present invention is a suspension, a carrier such as water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Cellulose, aluminum metahydroxide, bentonite, agar or tracant, etc. may be used.
본 발명의 제형이 계면-활성제 함유 클린징인 경우에는 담체 성분으로서 지방족 알코올 설페이트, 지방족 알코올 에테르 설페이트, 설포숙신산 모노에스테르, 이세티오네이트, 이미다졸리늄 유도체, 메틸타우레이트, 사르코시네이트, 지방산 아미드 에테르 설페이트, 알킬아미도베타인, 지방족 알코올, 지방산 글리세리드, 지방산 디에탄올아미드, 식물성 유, 라놀린 유도체 또는 에톡실화 글리세롤 지방산 에스테르 등이 이용될 수 있다.When the formulation of the present invention is an interfacial active agent-containing cleansing, the carrier component may include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyltaurate, sarcosinate, fatty acid amide Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives, or ethoxylated glycerol fatty acid esters.
본 발명의 조성물은 사료 조성물로 제조될 수 있다.The composition of the present invention may be prepared from a feed composition.
본 발명의 락토코쿠스 락티스를 유효성분 포함하는 항알레르기용 조성물이 사료 조성물로 제조되는 경우, 락토코쿠스 락티스를 그대로, 또는 사료 제조시 통상적으로 첨가되는 첨가제 등을 가하여 제조할 수 있다. 예컨대, 비타민, 아미노산류, 미네랄 등의 각종 양분, 항산화제, 항생물질, 항균제 및 기타의 첨가제이다. 그 형상에는 분체, 과립, 펠릿 또는 현탁액 등이 포함된다.When the composition for anti-allergy comprising the active ingredient of lactococus lactis of the present invention is prepared from a feed composition, lactococcus lactis may be prepared as it is or by adding an additive usually added in the production of feed. For example, various nutrients such as vitamins, amino acids and minerals, antioxidants, antibiotics, antibacterial agents and other additives. The shape includes powders, granules, pellets or suspensions, and the like.
본 발명의 조성물이 사료 조성물로 제조되는 경우, 육상 또는 수상 동물에 대하여 단독으로 또는 사료에 혼합하여 공급할 수 있다. 본 발명의 사료에는 분말사료, 고형사료, 모이스트 펠릿사료, 드라이 펠릿사료, EP(Extruder Pellet) 사료, 날먹이 등이 포함되며, 이에 한정되는 것은 아니다.When the composition of the present invention is prepared from a feed composition, it may be supplied to the land or aquatic animals singly or in a feed mixture. The feed of the present invention includes, but is not limited to, powdered feed, solid feed, moist pellet feed, dry pellet feed, extruder pellet (EP) feed,
본 발명의 다른 양태에 따르면, 본 발명은 Th1-매개 면역 질환, Th17-매개 면역 질환 또는 Th2-매개 면역 질환의 예방, 개선 또는 치료 활성을 갖는 락토코쿠스 락티스 KF140 균주(기탁번호 KCCM 11673P)를 제공한다.According to another aspect of the present invention, the present invention provides a lactococcus lactis strain KF140 (accession number KCCM 11673P) having a preventive, ameliorative or therapeutic activity of a Th1-mediated immune disease, a Th17-mediated immune disease or a Th2- Lt; / RTI >
본 발명의 Th1-매개 면역 질환, Th17-매개 면역 질환 또는 Th2-매개 면역 질환의 예방, 개선 또는 치료 활성을 갖는 균주는 상술한 Th1-매개 면역 질환, Th17-매개 면역 질환 또는 Th2-매개 면역 질환의 예방, 개선 또는 치료용 조성물과 대상 질환을 공통으로 하기 때문에, 상기 조성물과의 관계에서 공통된 내용은 본 명세서의 과도한 복잡성을 피하기 위하여, 그 기재를 생략한다.A strain having the preventive, ameliorating, or therapeutic activity of the Th1-mediated immune disease, Th17-mediated disease or Th2-mediated immune disease of the present invention is a Th1-mediated immune disease, a Th17-mediated immune disease or a Th2- The present invention is not limited to the composition for preventing, ameliorating, or treating the disease, and the subject disease is common, so that the common content in relation to the composition is omitted in order to avoid the excessive complexity of the present specification.
본 발명의 특징 및 이점을 요약하면 다음과 같다: The features and advantages of the present invention are summarized as follows:
(a) 본 발명은 락토코쿠스 락티스(Lactococcus lactis)를 유효성분으로 포함하는 Th1-매개 면역 질환, Th17-매개 면역 질환 또는 Th2-매개 면역 질환의 예방, 개선 또는 치료용 조성물을 제공한다.(a) The present invention provides a composition for preventing, ameliorating or treating a Th1-mediated immune disease, a Th17-mediated immune disease or a Th2-mediated immune disease comprising Lactococcus lactis as an active ingredient.
(b) 본 발명은 Th1-매개 면역 질환, Th17-매개 면역 질환 또는 Th2-매개 면역 질환의 예방, 개선 또는 치료 활성을 갖는 신규한 락토코쿠스 락티스 KF140 균주(기탁번호 KCCM 11673P)를 제공한다. (b) The present invention provides a novel Lactococcus lactis KF140 strain (Accession No. KCCM 11673P) having a preventive, ameliorative or therapeutic activity of a Th1-mediated immune disease, a Th17-mediated immune disease or a Th2-mediated immune disease .
(c) 본 발명의 락토코쿠스 락티스는 면역과민반응 시 면역글로불린 E(IgE)의 생성 및 Th1-관련 사이토카인, Th17-관련 사이토카인 및 Th2-관련 사이토카인 생성을 감소시킴으로써 Th1-매개 면역 질환, Th17-매개 면역 질환 또는 Th2-매개 면역 질환을 효과적으로 제어하는바 항알레르기성 조성물 및 항염증성 조성물로 사용이 가능한 이점이 있다.(c) Lactococcus lactis of the present invention inhibits the production of immunoglobulin E (IgE) and the production of Th1-mediated immunity There is an advantage that it can be used as an anti-allergic composition and an anti-inflammatory composition that effectively control diseases, Th17-mediated immune diseases or Th2-mediated immune diseases.
도 1은 락토코쿠스 락티스 KF140 균주의 경구 투여에 따른 귀두께 변화를 나타낸다.
도 2는 락토코쿠스 락티스 KF140 균주의 경구 투여에 따른 병변지역의 증상을 나타낸다.
도 3은 식품 알레르기 모델 제작을 위한 스케쥴을 나타낸다.
도 4는 락토코쿠스 락티스 KF140 균주의 식품 알레르기에 대한 영향을 직장온도 변화(도 4a), 설사 반응(도 4b) 및 아나필락시스(도 4c)로 측정한 결과를 나타낸다.
도 5는 락토코쿠스 락티스 KF140 균주의 경구 투여에 따른 접촉성 피부염 모델에서의 귀두께 변화를 나타낸다.Figure 1 shows changes in the glans according to oral administration of Lactococcus lactis strain KF140.
FIG. 2 shows symptoms of a lesion area following oral administration of Lactococcus lactis strain KF140.
Figure 3 shows a schedule for producing a food allergy model.
Fig. 4 shows the results of measuring the effect of lactococcus lactis strain KF140 on the food allergy by rectal temperature change (Fig. 4A), diarrhea reaction (Fig. 4B) and anaphylactic (Fig.
Figure 5 shows changes in glans in contact dermatitis models following oral administration of Lactococcus lactis strain KF140.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로, 본 발명의 요지에 따라 본 발명의 범위가 이들 실시예에 의해 제한되지 않는다는 것은 당업계에서 통상의 지식을 가진 자에 있어서 자명할 것이다.Hereinafter, the present invention will be described in more detail with reference to Examples. It is to be understood by those skilled in the art that these embodiments are only for describing the present invention in more detail and that the scope of the present invention is not limited by these embodiments in accordance with the gist of the present invention .
실시예Example
실시예 1: 균주의 분리 및 동정Example 1: Isolation and Identification of Strain
균주는 락토바실러스 MRS 한천 배지(MRS 배지, BD288130, 디프코社, 미국)를 이용하여 전통식으로 제조된 김치로부터 두 균주를 분리하였으며, 16S rDNA 시퀀싱을 통해 상기 분리된 균주들을 동정하였다. 동정 결과, 상기 균주의 16s rDNA 염기서열(서열목록 제1서열)은 기존의 락토코쿠스 락티스 NCDO604(T) 균주와 99.8%의 상동성을 보였다. The strains were isolated from Kimchi which was prepared by conventional methods using Lactobacillus MRS agar medium (MRS medium, BD288130, Difco, USA), and the isolated strains were identified by 16S rDNA sequencing. As a result of the identification, the 16s rDNA sequence (the first sequence of the sequence listing) of the strain showed 99.8% homology with the conventional Lactococcus lactis NCDO604 (T) strain.
본 균주들의 배양을 위한 배지 조성은 MRS 배지이며, 배양조건은 pH 6.5 ± 0.2, 온도 37℃ 및 48시간 정치배양이며, 산소요구성은 통성혐기성이고 동결건조보존 또는 세포현탁액 동결을 통해 균주 보존이 가능하다. 이 균주들을 락토코쿠스 락티스(Lactococcus lactis) KF140로 명명하고, 국제미생물기탁기관인 한국미생물보존센터(KCCM)에 2015년 3월 6일자로 기탁하였으며, 기탁번호 KCCM 11673P를 부여받았다.The culture medium for the cultivation of these strains is MRS medium, the culture conditions are pH 6.5 ± 0.2, temperature incubation at 37 ° C. for 48 hours, and the oxygen requirement is uniform anaerobic and can be preserved by lyophilization preservation or cell suspension freezing Do. These strains were transformed into Lactococcus lactis ) KF140, deposited at the Korean Microorganism Conservation Center (KCCM), an international microorganism depository, on March 6, 2015, and assigned the deposit number KCCM 11673P.
실시예 2: Th2 사이토카인 억제에 의한 항알레르기 활성Example 2: Antiallergic activity by Th2 cytokine inhibition
5주령된 암컷 Balb/c 생쥐에 1주 간격으로 2차례 알레르겐(OVA)을 복강면역하여 알레르기를 유발하였다. OVA(20 μg)와 알럼(aluminum hydroxide gel, 2 mg)의 혼합액을 30분간 섞어준 다음 한 마리당 100 μL씩 복강 주사하였다. 면역 1주 후 생쥐 비장을 적출하여 단세포화 및 용혈한 비장세포를 96-웰 플레이트에 5×106 세포/웰로 분주하였다. 이때 항원(OVA, 100 μg/mL) 및 락토코쿠스 락티스 KF140(5×107 CFU/웰을 첨가하고 37℃ CO2 인큐베이터에서 72 시간 배양 후 상징액을 회수하고 대표적인 Th2-관련 사이토카인인 IL-4의 분비량을 측정하였다.Five - week - old female Balb / c mice were immunized twice per week with an allergen (OVA) to induce allergy. A mixture of OVA (20 μg) and aluminum hydroxide gel (2 mg) was mixed for 30 minutes, and then 100 μL per well was intraperitoneally injected. The mouse spleen after
그 결과, 락토코쿠스 락티스 KF140 균주가 IL-4의 생성을 억제함으로써 알레르기 반응을 억제할 수 있음을 확인하였다.As a result, it was confirmed that the Lactococcus lactis KF140 strain inhibits allergic reaction by inhibiting the production of IL-4.
실시예 3: 항아토피 활성Example 3: Anti-atopic activity
아토피 유도 Induction of atopy
BALB/C 마우스에 락토코쿠스 락티스 KF140을 5×108 CFU/일로 주 5회 이상 경구투여를 진행하였다. 경구투여 3주 후, 마우스의 귀를 외과용 테이프(surgical tape)를 이용하여 벗긴 후 2% DNCB(2,4-디나이트로클로로벤젠, 2,4-dinitrochlorobenzene)를 양쪽 귀에 20 μL 씩 도포하였다. 일주일 후 2% DNCB 및 150 μg의 진드기를 주 1회씩 번갈아 처리하는 방법으로 4주 반복하여 아토피 피부염을 유발시켰다.Lactococcus lactis KF140 was orally administered to BALB / C mice at 5 × 10 8 CFU / day for 5 times or more per week. Three weeks after the oral administration, the ear of the mouse was peeled off with a surgical tape, and 20 μL of 2% DNCB (2,4-dinitrochlorobenzene) was applied to both ears . One week later, atopic dermatitis was induced by repeating 4 weeks of treatment with 2% DNCB and 150 μg of mite each once a week.
귀 두께 및 조직학적 변화Ear thickness and histological changes
실험기간 동안 마우스의 귀 두께 변화를 1주일 단위로 측정하였다. 그 결과, PBS 투여군(음성 대조군)과는 달리, 락토코쿠스 락티스 KF140 균주 경구 투여시 귀 두께 증가가 감소하였다(도 1).During the experimental period, changes in the ear thickness of the mice were measured on a weekly basis. As a result, unlike the PBS-treated group (negative control group), the ear thickness increase was decreased upon oral administration of Lactococcus lactis KF140 strain (Fig. 1).
또한, 귀부분에 염증, 각질이 일어난 음성 대조군과는 달리, 락토코쿠스 락티스 KF140 균주 경구 투여시 상기 증상이 경미하게 나타나 항아토피 활성을 보였다(도 2).In addition, unlike the negative control in which inflammation and keratinization occurred in the ear portion, the above symptoms were slightly observed upon oral administration of Lactococcus lactis KF140 strain (Fig. 2).
사이토카인 변화Cytokine change
세포학적 분석을 위하여 마우스의 림프절[드레이닝 림프절: 표면 림프절, 액와부 림프절, 기관지 림프절)]에서 드레이닝 림프구를 분리한 후, 항원인 진드기로 세포를 자극시킨 다음 발현되는 사이토카인을 e-Bioscience사의 사이토카인 정량 키트를 이용하여 ELISA 방법을 통해 확인하였다.For cytologic analysis, draining lymphocytes were isolated from mouse lymph nodes (draining lymph node: surface lymph node, axillary lymph node, bronchial lymph node)], and then the cells were stimulated with an antigen, mite, and the expressed cytokine was analyzed by e-Bioscience ELISA method using a cytokine quantitative kit.
그 결과, 하기 표 2에서 볼 수 있는 바와 같이 락토코쿠스 락티스 KF140을 각각 지속적으로 투여한 실험군에서는 아토피 피부염 발병 및 악화를 촉진하는 염증성 사이토카인인 IFN-γ와 IL-17A의 양이 감소하는 양상을 보였으며, Th2-관련 사이토카인인 IL-4 및 IL-13의 분비량도 감소하여 락토코쿠스 락티스 KF140가 아토피 피부염 억제 활성이 있음을 확인하였다.As a result, as shown in the following Table 2, in the experiment group in which Lactococcus lactis KF140 was continuously administered, the amount of IFN-γ and IL-17A, which are inflammatory cytokines promoting the onset and aggravation of atopic dermatitis, And the secretion of IL-4 and IL-13, which are Th2-related cytokines, was also decreased, confirming that Lactococcus lactis KF140 has atopic dermatitis inhibitory activity.
실시예 4: 식품 알레르기 억제 활성Example 4: Food allergy inhibitory activity
식품알레르기 유도 및 락토코쿠스 락티스 KF140 투여Food allergy induction and administration of Lactococcus lactis KF140
실험동물은 5주령의 자성 BALB/c 마우스를 (주)오리엔트바이오로부터 공급받아 실험동물실에서 일주일간 사육, 순화시킨 후 사용하였다. OVA(20 μg) 및 알럼(2 mg) 혼합 용액을 마리당 100 uL씩 복강 주사하여 1차 면역하고, 14일 뒤 동일한 방법으로 2차 면역을 실시하였다. 2차 면역 14일 후 락토코쿠스 락티스 KF140 균주를 마리당 5×108 CFU/일 농도로 매일 투여하였고, 3일 간격으로 50 mg/마리/일 농도의 OVA를 경구투여하여 알레르기를 유발시켰다(도 3). OVA와 균주 경구투여 후 3분 간격으로 식품알레르기 유발 지표인 아낙필락시스 반응과 설사반응을 확인하였으며, 직장온도의 변화를 20분 간격으로 60분 동안 측정하였다. 이 때 정상 대조군(Naive)은 1, 2 차 면역 및 OVA를 투여를 진행하지 않은 정상 마우스이며, 샴(sham) 군은 음성 대조군으로 락토코구스 락티스 KF140 균주 투여군과 동일하게 1, 2차 면역을 실시하고 3일 간격으로 OVA로 식품알레르기를 유발하였으나, 락토코쿠스 락티스 KF140 균주 대신 PBS만을 투여하였다. The experimental animals were fed with 5-week-old magnetic BALB / c mice from Orient Bio Inc., and were used for breeding and refining for one week in an experimental animal room. A mixture of OVA (20 μg) and Alum (2 mg) was injected intraperitoneally in a dose of 100 μL per mouse, followed by primary immunization and 14 days later for secondary immunization. 14 days after the second immunization, Lactococcus lactis strain KF140 was administered daily at a concentration of 5 × 10 8 CFU / day, and allergic reactions were induced by oral administration of OVA at a concentration of 50 mg / mouse / day every 3 days 3). At 3 - minute intervals after oral administration of OVA and strain, anaphylactic reaction and diarrhea reaction were observed, and changes in rectal temperature were measured at intervals of 20 minutes for 60 minutes. The normal control group (Naive) was a normal mouse in which the first and second immunization and OVA were not administered, and the sham group was negative control group, and same as the Lactococcus lactis KF140 strain, , And caused food allergy by OVA at intervals of 3 days, but only PBS was administered instead of Lactococcus lactis KF140 strain.
그 결과, 락토코쿠스 락티스 KF140 균주를 투여한 경우, 직장온도가 샴(sham)군에 비해 높게 유지되었으며(도 4a), 설사반응이나 아나필락시스 반응도 역시 샴군에 비해 적게 일어나 락토코쿠스 락티스 KF140 균주가 식품알레르기 증상완화 활성이 있음을 확인하였다(도 4b 및 4c). As a result, when the Lactococcus lactis strain KF140 was administered, the rectal temperature remained higher than that of the sham group (Fig. 4A), and the diarrhea reaction and the anaphylactic reaction were also lower than those of the sham group, and Lactococcus lactis KF140 It was confirmed that the strain had activity of alleviating the symptoms of food allergy (Figs. 4B and 4C).
혈청 IgE 변화Changes in serum IgE
실험종료 후 마우스 안와정맥을 통해 채혈한 후, 3500 rpm에서 10분간 원심분리하여 혈청을 분리하였다. 분리한 혈청 내 IgE 함량은 BD사의 마우스 IgE 정량 키트를 사용하여 측정하였다.After the end of the experiment, blood was drawn through the mouse orbit, and the serum was separated by centrifugation at 3500 rpm for 10 minutes. The IgE content in the separated serum was measured using a mouse IgE quantitative kit from BD.
그 결과, 하기 표 3에서 볼 수 있는 바와 같이 락토코쿠스 락티스 KF140 균주 투여시 알레르기 증상과 밀접한 관련이 있는 IgE가 감소하였다.As a result, IgE, which is closely related to the allergic symptoms, was decreased when Lactococcus lactis strain KF140 was administered, as shown in Table 3 below.
사이토카인 변화Cytokine change
각 그룹의 마우스에서 MLN 및 비장을 적출한 후, 단세포 현탁 과정 후 5x106 세포를 72시간 동안 배양하였다. 72시간 배양 후, 상층액에 존재하는 사이토크인을 BD사의 사이토카인 정량 키트를 이용하여 ELISA 방법을 통해 확인하였다.After the MLN and spleen were removed from each group of mice, 5x10 < 6 > cells were cultured for 72 hours after single cell suspension. After culturing for 72 hours, cytokine present in the supernatant was confirmed by an ELISA method using a cytokine quantitation kit from BD.
그 결과, 표 3에서 볼 수 있는 바와 같이 락토코쿠스 락티스 KF140 균주 투여시 MLN 배양상등액에서 IgE 생산을 유도하는 IL-4 및 IL-13 분비가 감소한바, 락토코쿠스 락티스 KF140 균주의 식품 알레르기 억제 활성을 확인할 수 있었다.As a result, as shown in Table 3, when the Lactococcus lactis KF140 strain was administered, the secretion of IL-4 and IL-13 inducing IgE production in the MLN culture supernatant was decreased, and the Lactococcus lactis strain KF140 Allergy inhibitory activity could be confirmed.
* 덱사메타손 : 덱사메타손은 항염증작용이 있는 스테로이드 호르몬의 당질코르티코이드 계열의 약물로서 류머니즘성관절염, 알레르기성 질환, 피부질환, 알레르기성 및 염증성 안질환 등의 치료에 사용되므로, 본 실시예의 양성대조군으로 사용됨.* Dexamethasone: dexamethasone is a glucocorticoid-based drug of steroid hormone with antiinflammatory action and is used for the treatment of rheumatoid arthritis, allergic diseases, skin diseases, allergic and inflammatory eye diseases, Used.
실시예 5: 접촉성 피부염 억제 활성Example 5: Contact dermatitis inhibitory activity
접촉성 피부염 유도 및 락토코쿠스 락티스 KF140 투여Induction of contact dermatitis and administration of Lactococcus lactis KF140
5주령의 암컷 BALB/c를 1주일간 적응시킨 후 일 0(Day 0)에 정상대조군(Naive)를 제외한 모든 실험군의 옆구리 털을 제모한 후 5% TMA용액[아세톤과 이소프로필미리스테이트(isopropylmyristate)의 4:1(v/v) 혼합액을 용매로 사용] 50 μL를 도포하여 첫 감작을 실시하였다. 감작 5일 후 정상대조군(Naive)를 제외한 모든 실험군을 대상으로 5% TMA 10 μL를 양쪽 귀에 2차 감작시키고, 이후 3일에 한번 2% TMA 10 μL를 양쪽 귀에 도포하였다. 락토코쿠스 락티스 KF140는 1차 감작 후 매일 5×108 CFU/마리 농도로 투여하였고, 샴군은 락토코쿠스 락티스 KF140를 현탁하는데 사용한 PBS만을 동량 투여하였다. Five week old female BALB / c was applied for 1 week, and hair follicles of all experimental groups except for Naive were epilated at
TMA는 피부외피를 통과하여 피부내부로 침입 후 피부조직의 단백질과 결합하여 면역세포의 알레르기성 과민반응을 유도하는 화학적 합텐(hapten)의 일종으로 Th2 반응을 강하게 유도하며, TMA의 반복 처리는 유발부위의 염증발생 및 조직의 두께 증가를 유도한다. 락토코쿠스 락티스 KF140을 투여시 TMA를 처리한 귀 두께가 대조군에 비해 감소하였다(도 5).TMA is a type of chemical hapten that induces allergic hypersensitivity of immune cells by binding to protein of skin tissue after penetrating into the skin through skin envelope and inducing Th2 reaction strongly and inducing repeated treatment of TMA Site inflammation and tissue thickness increase. When Lactococcus lactis KF140 was administered, the thickness of the ear treated with TMA decreased compared to the control (Fig. 5).
혈청 IgE 변화Changes in serum IgE
실험종료 후 마우스 안와정맥을 통해 채혈한 후, 3500 rpm에서 10분간 원심분리하여 혈청을 분리하였다. 분리한 혈청 내 IgE 함량은 BD사의 마우스 IgE 정량 키트를 사용하여 측정하였다.After the end of the experiment, blood was drawn through the mouse orbit, and the serum was separated by centrifugation at 3500 rpm for 10 minutes. The IgE content in the separated serum was measured using a mouse IgE quantitative kit from BD.
그 결과, 하기 표 4에서 볼 수 있는 바와 같이 알레르기성 접촉성 피부염 환자에서 높은 발현을 보이는 IgE 함량이 샴군에 비해 감소하였다.As a result, as shown in Table 4 below, IgE content, which is highly expressed in allergic contact dermatitis patients, was decreased as compared with the sham group.
사이토카인 변화Cytokine change
각 그룹의 마우스에서 DLN 및 비장을 적출한 후, 단세포 현탁 과정 후 3x106 세포 96시간 동안 배양하였다. 이 때 항원 특이적 반응을 확인하기 위해 세포만 배양하는 경우 및 진드기를 10 μg 처리한 두 경우로 나눠 진행하였으며, 96시간 배양후 상층액에 존재하는 사이토카인을 BD사의 사이토카인 정량 키트를 이용하여 ELISA 방법을 통해 확인하였다.DLN and spleen were removed from each group of mice, and then cultured for 96 hours at 3 × 10 6 cells after single cell suspension. In order to confirm the antigen-specific reaction, the cells were divided into two groups, ie, culturing only the cells and 10 μg of the mite. After culturing for 96 hours, the cytokine in the supernatant was assayed using a BD cytokine quantitation kit ELISA method.
그 결과, 하기 표 4에서 볼 수 있는 바와 같이 DLN에서 Th2-관련 사이토카인인 IL-4와 IL-13의 분비량이 감소하는 것으로 나타나 락토코쿠스 락티스 KF140이 알레르기성 접촉성 피부염 억제 활성이 있음을 확인하였다. As a result, as shown in the following Table 4, the secretion amount of IL-4 and IL-13, which are Th2-related cytokines in DLN, decreased, and Lactococcus lactis KF140 showed allergic contact dermatitis inhibitory activity Respectively.
* 프레드니솔론 : 면역억제제로 사용되는 의약품으로실험의 양성 대조군으로 사용* Prednisolone: a drug used as an immunosuppressive agent and used as a positive control for the experiment
이상으로 본 발명의 특정한 부분을 상세히 기술하였는바, 당업계의 통상의 지식을 가진 자에게 있어서 이러한 구체적인 기술은 단지 바람직한 구현 예일 뿐이며, 이에 본 발명의 범위가 제한되는 것이 아닌 점은 명백하다. 따라서 본 발명의 실질적인 범위는 첨부된 청구항과 그의 등가물에 의하여 정의된다고 할 것이다.While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the same is by way of illustration and example only and is not to be construed as limiting the scope of the present invention. It is therefore intended that the scope of the invention be defined by the claims appended hereto and their equivalents.
<110> KOREA FOOD RESEARCH INSTITUTE <120> Composition for Preventing, Improving or Treating of Th1-mediated Immune Disease, Th17-mediated Immune Disease or Th2-mediated Immune Disease Comprising Extracts from Lactococcus lactis as an Active Ingredients <130> PN150262 <160> 1 <170> KopatentIn 2.0 <210> 1 <211> 1490 <212> DNA <213> Lactococcus lactis KF140 16S rDNA <400> 1 tgatcatggc tcaggacgaa cgctggcggc gtgcctaata catgcaagtt gagcgctgaa 60 ggttggtact tgtaccgact ggatgagcag cgaacgggtg agtaacgcgt ggggaatctg 120 cctttgagcg ggggacaaca tttggaaacg aatgctaata ccgcataaaa actttaaaca 180 caagttttaa gtttgaaaga tgcaattgca tcactcaaag atgatcccgc gttgtattag 240 ctagttggtg aggtaaaggc tcaccaaggc gatgatacat agccgacctg agagggtgat 300 cggccacatt gggactgaga cacggcccaa actcctacgg gaggcagcag tagggaatct 360 tcggcaatgg acgaaagtct gaccgagcaa cgccgcgtga gtgaagaagg ttttcggatc 420 gtaaaactct gttggtagag aagaacgttg gtgagagtgg aaagctcatc aagtgacggt 480 aactacccag aaagggacgg ctaactacgt gccagcagcc gcggtaatac gtaggtcccg 540 agcgttgtcg ggatttattg ggcgtaaagc gagcgcaggt ggtttattaa gtctggtgta 600 aaaggcagtg gctcaaccat tgtatgcatt ggaaactggt agacttgagt gcaggagagg 660 agagtggaat tccatgtgta gcggtgaaat gcgtagatat atggaggaac accggtggcg 720 aaagcggctc tctggcctgt aactgacact gaggctcgaa agcgtgggga gcaaacagga 780 ttagataccc tggtagtcca cgccgtaaac gatgagtgct agatgtaggg agctataagt 840 tctctgtatc gcagctaacg caataagcac tccgcctggg gagtacgacc gcaaggttga 900 aactcaaagg aattgacggg ggcccgcaca agcggtggag catgtggttt aattcgaagc 960 aacgcgaaga accttaccag gtcttgacat actcgtgcta ttcctagaga taggaagttc 1020 cttcgggaca cgggatacag gtggtgcatg gttgtcgtca gctcgtgtcg tgagatgttg 1080 ggttaagtcc cgcaacgagc gcaaccccta ttgttagttg ccatcattaa gttgggcact 1140 ctaacgagac tgccggtgat aaaccggagg aaggtgggga tgacgtcaaa tcatcatgcc 1200 ccttatgacc tgggctacac acgtgctaca atggatggta caacgagtcg cgagacagtg 1260 atgtttagct aatctcttaa aaccattctc agttcggatt gtaggctgca actcgcctac 1320 atgaagtcgg aatcgctagt aatcgcggat cacacgccgc ggggttgaat acgttcccgg 1380 gccttgtaca caccgcccgt cacaccacgg gagttgggag tacccgaagt atgttgccta 1440 accgcaaagg agggcgcttc ctaaagtaag accgatgact gggggtgaag 1490 <110> KOREA FOOD RESEARCH INSTITUTE <120> Composition for Preventing, Improving or Treating of Th1-mediated Immune Disease, Th17-mediated Immune Disease or Th2-mediated Immune Disease Comprising Extracts from Lactococcus lactis as an Active Ingredients <130> PN150262 <160> 1 <170> Kopatentin 2.0 <210> 1 <211> 1490 <212> DNA <213> Lactococcus lactis KF140 16S rDNA <400> 1 tgatcatggc tcaggacgaa cgctggcggc gtgcctaata catgcaagtt gagcgctgaa 60 ggttggtact tgtaccgact ggatgagcag cgaacgggtg agtaacgcgt ggggaatctg 120 cctttgagcg ggggacaaca tttggaaacg aatgctaata ccgcataaaa actttaaaca 180 caagttttaa gtttgaaaga tgcaattgca tcactcaaag atgatcccgc gttgtattag 240 ctagttggtg aggtaaaggc tcaccaaggc gatgatacat agccgacctg agagggtgat 300 cggccacatt gggactgaga cacggcccaa actcctacgg gaggcagcag tagggaatct 360 tcggcaatgg acgaaagtct gaccgagcaa cgccgcgtga gtgaagaagg ttttcggatc 420 gtaaaactct gttggtagag aagaacgttg gtgagagtgg aaagctcatc aagtgacggt 480 aactacccag aaagggacgg ctaactacgt gccagcagcc gcggtaatac gtaggtcccg 540 agcgttgtcg ggatttattg ggcgtaaagc gagcgcaggt ggtttattaa gtctggtgta 600 aaaggcagtg gctcaaccat tgtatgcatt ggaaactggt agacttgagt gcaggagagg 660 agagtggaat tccatgtgta gcggtgaaat gcgtagatat atggaggaac accggtggcg 720 aaagcggctc tctggcctgt aactgacact gaggctcgaa agcgtgggga gcaaacagga 780 ttagataccc tggtagtcca cgccgtaaac gatgagtgct agatgtaggg agctataagt 840 tctctgtatc gcagctaacg caataagcac tccgcctggg gagtacgacc gcaaggttga 900 aactcaaagg aattgacggg ggcccgcaca agcggtggag catgtggttt aattcgaagc 960 aacgcgaaga accttaccag gtcttgacat actcgtgcta ttcctagaga taggaagttc 1020 cttcgggaca cgggatacag gtggtgcatg gttgtcgtca gctcgtgtcg tgagatgttg 1080 ggttaagtcc cgcaacgagc gcaaccccta ttgttagttg ccatcattaa gttgggcact 1140 ctaacgagac tgccggtgat aaaccggagg aaggtgggga tgacgtcaaa tcatcatgcc 1200 ccttatgacc tgggctacac acgtgctaca atggatggta caacgagtcg cgagacagtg 1260 atgtttagct aatctcttaa aaccattctc agttcggatt gtaggctgca actcgcctac 1320 atgaagtcgg aatcgctagt aatcgcggat cacacgccgc ggggttgaat acgttcccgg 1380 gccttgtaca caccgcccgt cacaccacgg gagttgggag tacccgaagt atgttgccta 1440 accgcaaagg agggcgcttc ctaaagtaag accgatgact gggggtgaag 1490
Claims (11)
A composition for preventing, ameliorating or treating a Th1-mediated immune disease, a Th17-mediated immune disease or a Th2-mediated immune disease, comprising Lactococcus lactis as an active ingredient.
2. The composition of claim 1, wherein the composition inhibits IgE production.
2. The composition of claim 1, wherein the composition inhibits Th1-associated cytokine production.
2. The composition of claim 1, wherein the composition inhibits Th17-associated cytokine production.
2. The composition of claim 1, wherein said composition inhibits Th2-associated cytokine production.
The composition of claim 1, wherein said Th1-mediated immune disorder or Th17-mediated immune disorder is a transplant rejection, autoimmune disease or inflammatory disease.
2. The composition of claim 1, wherein the Th2-mediated immune disorder is an allergic disease.
2. The composition of claim 1, wherein the lactococusa lactis is a strain isolated from kimchi.
The composition according to claim 1, wherein the lactococus lactis is a lactococcus lactis KF140 strain (Accession No. KCCM 11673P).
The composition of claim 1, wherein the composition is a pharmaceutical composition, a food composition, a functional food composition, a cosmetic composition or a feed composition.
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Cited By (5)
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| KR20190061836A (en) * | 2017-11-28 | 2019-06-05 | (주)아모레퍼시픽 | Composition comprising lactic acid bacteria derived from camellia japonica for caring damages of skin cells by microdust |
| CN110506106A (en) * | 2017-04-06 | 2019-11-26 | 韩国食品研究院 | With the active novel strain and application thereof for reducing advanced glycation end products |
| KR102154254B1 (en) * | 2020-04-29 | 2020-09-09 | (주)녹십자웰빙 | Novel Lactic Acid Bacteria with Excellent Immune function enhancing effect and Food Composition Containing the Same and Health Functional Food Composition Containing the Same and Probiotics comprising the Same |
| KR20220076301A (en) * | 2020-11-30 | 2022-06-08 | 주식회사 엠디헬스케어 | Composition for preventing, treating, or alleviating eosinophilic inflammatory diseases or Th2 hypersensitivity immune diseases comprising vesicle derived from lactococcus lactis |
| KR102538644B1 (en) * | 2022-11-14 | 2023-06-01 | 주식회사 유니베라 | Novel lactococcus lactis subsp. hordniae uab10 strain derived from aloe having anti-inflammatory activity, antibacterial activity, acid resistance, bile tolerance and intestinal adhesion ability and uses thereof |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110506106A (en) * | 2017-04-06 | 2019-11-26 | 韩国食品研究院 | With the active novel strain and application thereof for reducing advanced glycation end products |
| US20200270709A1 (en) * | 2017-04-06 | 2020-08-27 | Korea Food Research Institute | Novel Strain Having Activity Of Reducing Advanced Glycation End Products And Use Thereof |
| KR20190061836A (en) * | 2017-11-28 | 2019-06-05 | (주)아모레퍼시픽 | Composition comprising lactic acid bacteria derived from camellia japonica for caring damages of skin cells by microdust |
| KR102154254B1 (en) * | 2020-04-29 | 2020-09-09 | (주)녹십자웰빙 | Novel Lactic Acid Bacteria with Excellent Immune function enhancing effect and Food Composition Containing the Same and Health Functional Food Composition Containing the Same and Probiotics comprising the Same |
| KR20220076301A (en) * | 2020-11-30 | 2022-06-08 | 주식회사 엠디헬스케어 | Composition for preventing, treating, or alleviating eosinophilic inflammatory diseases or Th2 hypersensitivity immune diseases comprising vesicle derived from lactococcus lactis |
| KR102538644B1 (en) * | 2022-11-14 | 2023-06-01 | 주식회사 유니베라 | Novel lactococcus lactis subsp. hordniae uab10 strain derived from aloe having anti-inflammatory activity, antibacterial activity, acid resistance, bile tolerance and intestinal adhesion ability and uses thereof |
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