KR20170041337A - Composition for Preventing, Improving or Treating of Th1-mediated Immune Disease or Th2-mediated Immune Disease Comprising Extracts from Bacillus amyloliquefaciens subsp. plantarum as an Active Ingredients - Google Patents
Composition for Preventing, Improving or Treating of Th1-mediated Immune Disease or Th2-mediated Immune Disease Comprising Extracts from Bacillus amyloliquefaciens subsp. plantarum as an Active Ingredients Download PDFInfo
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- KR20170041337A KR20170041337A KR1020150140588A KR20150140588A KR20170041337A KR 20170041337 A KR20170041337 A KR 20170041337A KR 1020150140588 A KR1020150140588 A KR 1020150140588A KR 20150140588 A KR20150140588 A KR 20150140588A KR 20170041337 A KR20170041337 A KR 20170041337A
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Abstract
본 발명은 바실러스 아밀로리퀴파시엔스 플란타럼 아종(Bacillus amyloliquefaciens subsp. plantarum) 균주를 유효성분으로 포함하는 Th1-매개 면역 질환 또는 Th2-매개 면역 질환의 예방, 개선 또는 치료용 조성물에 관한 것이다. 본 발명의 바실러스 아밀로리퀴파시엔스 플란타럼 아종 균주는 조절 T 세포를 활성화시키고, 항염증 사이토카인인 IL-10 생성을 증가시키며, 면역활성 사이토카인인 IL-12생성을 억제시키고, IgE 항체의 생성양을 감소시킴으로써 Th1-매개 면역 질환 또는 Th2-매개 면역 질환을 효과적으로 제어하는바 항알레르기성 조성물 및 항염증성 조성물로 사용이 가능한 이점이 있다.The present invention relates to a composition for preventing, ameliorating or treating a Th1-mediated immune disease or a Th2-mediated immune disease, which comprises a Bacillus amyloliquefaciens subsp. Plantarum strain as an active ingredient. The Bacillus amyloliquefaciens plutelum subspecies strain of the present invention activates regulatory T cells, increases IL-10 production, which is an anti-inflammatory cytokine, inhibits the production of IL-12, an immunologically active cytokine, Lt; RTI ID = 0.0 > Th1-mediated < / RTI > immune disease or Th2-mediated immune disease by decreasing the amount of the anti-allergic < RTI ID =
Description
본 발명은 바실러스 아밀로리퀴파시엔스 플란타럼 아종(Bacillus amyloliquefaciens subsp. plantarum) 균주를 유효성분으로 포함하는 Th1-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 or a Th2-mediated immune disease, which comprises a Bacillus amyloliquefaciens subsp. Plantarum strain as an active ingredient.
우리나라에서 천식의 발생이 계속해서 증가되고 있으며 2007년 통계에 의하면 천식으로 사망한 환자수가 2,023명으로 보고되었다. 또한, 우리나라 소아 알레르기 천식의 유병률은 80년대 초에 비해 2배 이상 증가했고 소아 100명 중 10명이 천식을 앓고 있으며 이중 50%가 평생 천식을 앓는다. 따라서 알레르기 질환의 발병 예방 및 효과적인 제어 기술이 절실히 필요한 상태이다. The incidence of asthma continues to increase in Korea. According to 2007 statistics, 2,023 patients were reported to die from asthma. In addition, the prevalence of pediatric allergic asthma in Korea has more than doubled from the early 1980s, and 10 out of 100 children have asthma, of which 50% have lifelong asthma. Therefore, the prevention of the onset of allergic diseases and effective control technology are urgently needed.
기존 알레르기 천식 치료방법은 근본치료가 되지 않고 있으며, 여러 약제 중 2 가지 이상을 병용하여 질환의 완화 내지 감소시키는 것에 지나지 않으며 이러한 약들은 대부분 심각한 부작용을 나타내어 문제점을 가지고 있다. 또한, 오말리주맙(Omalizumab)과 같은 항체제제들은 개발 및 치료 시 아주 많은 비용이 들어가는 문제를 안고 있다.Existing allergic asthma treatment is not a fundamental treatment, and it is merely to alleviate or reduce the disease by using two or more of several medicines, and most of these medicines have serious side effects and have problems. In addition, antibody preparations such as omalizumab are costly in development and treatment.
최근 미국을 중심으로 장내 세균의 균총을 규명하는 메타지놈 프로젝트 진행결과 장내 균총의 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 세계 시장 규모는 2013년 기준 약 29조원이며, 7.6%의 성장률을 보이고 있어 2018년에는 43.4조원 규모로 성장할 것으로 예측된다. 아시아 시장은 2013년 기준 3,500억원 규모로 시장 내 50% 이상은 일본 시장이 차지하고 있다. 국내 프로바이오틱스 시장 규모는 2013년 기준 583억원이며, 2018년까지 연평균 성장률 15%를 보여 2018년에는 1,395억원으로 증가할 것이라 예측되고 있다.The world market for probiotics is expected to grow to W43.4trn in 2018 with a growth rate of 7.6% in 2013, about 29 trillion won. The Asian market is worth W350bn in 2013, with the Japanese market accounting for more than 50% of the market. The domestic probiotic market is expected to grow to W139.5bn by 2018, with annual average growth of 15% until 2018, reaching W58.3bn by 2013.
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 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. 따라서 프로바이오틱스의 경우 인 비보 시스템에서의 연구가 요구되는 실정이다.Studies of fundamental mechanisms are poor, and most of the work is done in vitro . In other words, despite the oral intake of probiotics, most of the previous studies have focused mainly on in vitro experiments using cell lines, and these experimental methods have been replaced by studies on the ability of humans to ingest probiotics There is a big drawback that can not be. 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. Therefore, it is necessary to study in the case of probiotics.
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 질병의 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 type 1 diabetes, rheumatoid arthritis, degenerative arthritis, and ulcerative colitis Research is also actively underway. In addition, the role of probiotics and their functions are attracting much attention for the treatment of diseases such as allergy, asthma, and atopy.
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. In addition, recently, the therapeutic effect of probiotics as an immunomodulatory agent 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 메주로부터 항알레르기 및 항염증 활성을 갖는 신규한 바실러스 아밀로리퀴파시엔스 플란타럼 아종(Bacillus amyloliquefaciens subsp. plantarum) 균주를 선별하고, 생쥐에서 직접 분리한 면역세포에 상기 균주를 처리한 경우 조절 T 세포의 유도, 면역 활성 사이토카인인 IL-12 생성 억제, 항염증 활성을 갖는 사이토카인인 IL-10 생성 증가 및 면역글로불린 E(IgE) 생성이 억제되는 인 비보 시스템에 가까운 결과를 도출하여 본 발명의 바실러스 아밀로리퀴파시엔스 플란타럼 아종 균주가 알레르기 및 염증을 효과적으로 제어할 수 있음을 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. Wherein a result, the novel Bacillus amyl Lowry quinolyl Pacific Enschede Planta column subspecies (Bacillus amyloliquefaciens subsp. Plantarum) immune cells by selecting the strains and isolated directly from the mice with the traditional fermentation antiallergic and anti-inflammatory activity from products of Meju when treated with strain induction of regulatory T cells, the immune active cytokine is IL-12 generation inhibition, the IL-10 produced increased cytokine with anti-inflammatory activity, and the immunoglobulin E (IgE) in vivo systems that are generated is suppressed The present inventors have completed the present invention by confirming that the Bacillus amyloliquefaciens plutalum subspecies of the present invention can effectively control allergy and inflammation.
따라서, 본 발명의 목적은 바실러스 아밀로리퀴파시엔스 플란타럼 아종 균주를 유효성분으로 포함하는 Th1-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 or a Th2-mediated immune disease, which comprises Bacillus amyloliquefaciens plutelum subspecies as an active ingredient.
본 발명의 다른 목적은 Th1-매개 면역 질환 또는 Th2-매개 면역 질환의 예방, 개선 또는 치료 활성을 갖는 신규한 바실러스 아밀로리퀴파시엔스 플란타럼 아종 균주를 제공하는데 있다. It is another object of the present invention to provide a novel Bacillus amyloliquefaciens placterium subsp. Strain having a preventive, ameliorative or therapeutic activity against a Th1-mediated immune disease or a 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 바실러스 아밀로리퀴파시엔스 플란타럼 아종(Bacillus amyloliquefaciens subsp. plantarum) 균주를 유효성분으로 포함하는 Th1-매개 면역 질환 또는 Th2-매개 면역 질환의 예방, 개선 또는 치료용 조성물을 제공한다.According to one aspect of the present invention, there is provided a method for preventing, ameliorating, or ameliorating a Th1-mediated immune disease or a Th2-mediated immune disease comprising an active ingredient of Bacillus amyloliquefaciens subsp. Plantarum strain Or a therapeutic composition.
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 메주로부터 항알레르기 및 항염증 활성을 갖는 신규한 바실러스 아밀로리퀴파시엔스 플란타럼 아종 균주를 선별하고, 생쥐에서 직접 분리한 면역세포에 상기 균주를 처리한 경우 조절 T 세포의 유도, 면역 활성 사이토카인인 IL-12 생성 억제, 항염증 활성을 갖는 사이토카인인 IL-10 생성 증가 및 면역글로불린 E(IgE) 생성을 억제하는 인 비보 시스템에 가까운 결과를 도출하여 본 발명의 바실러스 아밀로리퀴파시엔스 플란타럼 아종 균주가 알레르기 및 염증을 효과적으로 제어할 수 있음을 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 new strain of Bacillus amyloliquefaciens plastarum having antiallergic and anti-inflammatory activity was selected from a fermented food, Meju, and when the strain was directly treated with the above-mentioned strain, The results are close to those of an in vivo system that inhibits the induction of cells, suppression of IL-12 production as an immunologically active cytokine, increase of IL-10 production as a cytokine having antiinflammatory activity, and production of immunoglobulin E (IgE) Of the Bacillus amyloliquefaciens plastarium subsp. Strains of the present invention can effectively control allergy and inflammation.
따라서 본 발명은 바실러스 아밀로리퀴파시엔스 플란타럼 아종 균주를 유효성분으로 포함하는 Th1-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 or a Th2-mediated immune disease, which comprises Bacillus amyloliquefaciens plutelum subspecies as an active ingredient.
본 명세서에서 용어 “유효성분으로 포함하는”이란 하기의 바실러스 아밀로리퀴파시엔스 플란타럼 아종 균주의 효능 또는 활성을 달성하는 데 충분한 양을 포함하는 것을 의미한다. 본 발명의 바실러스 아밀로리퀴파시엔스 플란타럼 아종 균주는 식품(예컨대, 메주)으로부터 분리한 미생물 균주인바 과량 투여하여도 인체에 부작용이 없으므로 상기 바실러스 아밀로리퀴파시엔스 플란타럼 아종 균주가 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 the subspecies Bacillus amyloliquefaciens plutelum subsp. The Bacillus amyloliquefaciens plutelum subspecies strain of the present invention is a microorganism strain isolated from a food (for example, meju). Since the Bacillus amyloliquefaciens plutelum subsp. Strain has no adverse effect on the human body even when administered in an excessive amount, The quantitative upper limits included in the composition of the present invention can be selected by a person skilled in the art within a suitable range.
본 발명의 일 구현예에 따르면, 본 발명의 조성물은 조절 T 세포를 유도한다. 상기 조절 T 세포의 유도는 조절 T 세포의 활성을 조절하는 인자인 Foxp3 발현 증가에 의하여 확인할 수 있다(도 1).According to one embodiment of the invention, the composition of the invention induces regulatory T cells. Induction of the regulatory T cells can be confirmed by an increase in expression of Foxp3, a factor that regulates the activity of regulatory T cells (Fig. 1).
본 발명의 다른 구현예에 따르면, 본 발명의 조성물은 조절 T 세포를 음성 대조군과 비교하여 3-30배, 3-20배, 3-15배, 5-30배, 5-20배, 5-15배, 7-30배, 7-20배, 7-15배, 10-30배, 10-20배, 10-15배 또는 12배 유도한다.According to another embodiment of the present invention, the composition of the present invention is administered at a dose of 3-30 times, 3-20 times, 3-15 times, 5-30 times, 5-20 times, 5- 7-fold, 7-fold, 7-fold, 10-fold, 10-fold, 10-fold or 12-fold induction.
본 발명의 일 구현예에 따르면, 본 발명의 조성물은 IL-10 생성을 증가시킨다. IL-10은 대식세포와 모노사이트 및 T-세포 림프구 복제와 염증성 사이토카인 (IL-1, TNF-α, TGF-β, IL-6, IL-8 및 IL-12)의 분비를 억제하는 림프계 세포에 의해 생성되는 강력한 항염증성 사이토카인으로서 IL-10이 증가되면 염증반응이 억제된다.According to one embodiment of the invention, the composition of the present invention increases IL-10 production. IL-10 inhibits the secretion of macrophages and monocytes and T-cell lymphocyte replication and the secretion of inflammatory cytokines (IL-1, TNF-α, TGF-β, IL-6, IL-8 and IL-12) Increased IL-10 as a potent anti-inflammatory cytokine produced by cells inhibits the inflammatory response.
본 발명의 일 구현예에 따르면, 본 발명의 조성물은 IL-12 생성을 억제시킨다.According to one embodiment of the present invention, the composition of the present invention inhibits IL-12 production.
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 아나필락시스 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. That is, IgE is an antibody that causes anaphylactic reaction or inflammatory reaction due to allergy. When the above IgE production is inhibited, allergic reaction or inflammatory reaction is suppressed.
본 발명의 다른 구현예에 따르면, 본 발명의 조성물은 IgE 생성을 음성 대조군과 비교하여 30-90%, 30-80%, 30-70%, 30-60%, 40-90%, 40-80%, 40-70%, 40-60%, 50-90%, 50-80%, 50-70%, 50-60% 또는 55-60% 억제시킨다.According to another embodiment of the present invention, the composition of the present invention comprises 30-90%, 30-80%, 30-70%, 30-60%, 40-90%, 40-80% %, 40-70%, 40-60%, 50-90%, 50-80%, 50-70%, 50-60%, or 55-60%.
본 발명의 일 구현예에 따르면, 본 발명의 조성물은 IL-12 생성양에 대한 IL-10 생성양의 비율을 50-200이 되도록 한다. 본 발명의 다른 구현예에 따르면, 본 발명의 조성물은 IL-12 생성양에 대한 IL-10 생성양의 비율을 100-200, 130-200, 150-200, 100-170, 130-170, 150-170 또는 160-170이 되도록 한다.According to one embodiment of the present invention, the composition of the present invention is such that the ratio of the amount of IL-10 production to the amount of IL-12 production is 50-200. According to another embodiment of the present invention, the composition of the present invention has a ratio of the amount of IL-10 produced to the amount of produced IL-12 by 100-200, 130-200, 150-200, 100-170, 130-170, 150 -170 or 160-170.
본 발명의 조성물은 다양한 Th1-매개 면역 질환, 질병 또는 상태의 예방, 개선 또는 치료에 이용될 수 있다.The compositions of the present invention can be used for the prevention, amelioration or treatment of various ThI-mediated immune diseases, diseases or conditions.
본 명세서에서, 용어 "Th1-매개 면역 질환"은 Th1 세포의 생성 및/또는 활성에 의해 생성되는 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 disease" refers to a cytokine, such as IL-l [beta], IL-2, IL-12, IFN-y or TNF-alpha produced by the production and / And the like.
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, 크론씨병, 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.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, type 1 diabetes, type 2 diabetes, rheumatoid arthritis, Reactive Arthritis, osteoarthritis, psoriasis, scleroderma, osteoporosis, The present invention relates to the use of a compound of formula (I) or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for the treatment and / or prophylaxis of inflammation, myocarditis, endocarditis, pericarditis, cystic fibrosis, Hashimoto's thyroiditis, Graves' disease, leprosy, syphilis, Lyme disease, Borreliosis, Chronic inflammatory bowel syndrome, chronic fatigue syndrome, chronic fatigue syndrome, chronic fatigue immunodeficiency syndrome, muscular pain syndrome, amyotrophic lateral sclerosis, amyotrophic lateral sclerosis, amyotrophic lateral sclerosis, amyotrophic lateral sclerosis, amyotrophic lateral sclerosis Socio-sclerosis, Parkinson's disease, multiple sclerosis, autism spectrum disorders, attention deficit disorder, and attention deficit hyperactivity disorder It is not fixed. According to one embodiment of the present invention, it is applied to graft rejection, autoimmune disease or inflammatory diseases.
본 발명의 일 구현예에 따르면, 본 발명의 조성물이 적용되는 Th1-매개 면역 질환은 염증 질환이고, 본 발명의 다른 구현예에 따르면, 대장염, 염증성 장질환, 타입 1 당뇨병, 타입 2 당뇨병 및 류마티스 관절염이다.According to one embodiment of the present invention, the Th1-mediated immune disease to which the composition of the present invention is applied is an inflammatory disease, and according to another embodiment of the present invention, is selected from the group consisting of colitis, inflammatory bowel disease, type 1 diabetes, It is arthritis.
본 발명의 조성물은 다양한 Th2-매개 면역 질환, 질병 또는 상태의 예방 또는 치료에 이용될 수 있다.The compositions of the present invention may be used for the prevention or treatment of various Th2-mediated immune diseases, diseases or conditions.
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 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 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 아나필라시스 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 구현 예에 의하면, 상기 알레르기는 천식, 알레르기성 비염, 알레르기성 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 asthma, allergic rhinitis, allergic dermatitis, allergic atopic dermatitis or food allergy.
본 발명의 일 구현예에 따르면, 본 발명의 균주는 메주로부터 분리된 균주이다.According to one embodiment of the present invention, the strain of the present invention is a strain isolated from Meju.
본 발명의 일 구현예에 따르면, 본 발명의 균주는 바실러스 아밀로리퀴파시엔스 플란타럼 아종 F2189(기탁번호 KCCM 11282P) 균주이다.According to one embodiment of the present invention, the strain of the present invention is a strain of Bacillus amyloliquefaciens < RTI ID = 0.0 > Flutarum subsp. F2189 (Accession No. KCCM 11282P).
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 구현 예에 따르면, 본 발명의 조성물은 (a) 상술한 본 발명의 바실러스 아밀로리퀴파시엔스 플란타럼 아종 균주의 약제학적 유효량; 및 (b) 약제학적으로 허용되는 담체를 포함하는 약제학적 조성물이다. 본 명세서에서 용어 “약제학적 유효량”은 상술한 바실러스 아밀로리퀴파시엔스 플란타럼 아종 균주의 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-described Bacillus amyloliquefaciens plutelum subspecies 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 Bacillus amyloliquefaciens plastorum subsp. Strain 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 바실러스 아밀로리퀴파시엔스 플란타럼 아종 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 dose of the Bacillus amyloliquefaciens platelum subsp. Coli, 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 기능성 식품 조성물 또는 식품 조성물로 제공될 수 있다.The composition of the present invention may be provided as a functional food composition or a food composition.
본 발명의 조성물이 기능성 식품 조성물 또는 식품 조성물로 제조되는 경우, 유효성분으로서 바실러스 아밀로리퀴파시엔스 플란타럼 아종 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 from a functional food composition or a food composition, it includes not only Bacillus amyloliquefaciens plastorum subsp. Strain as an active ingredient, but also ingredients normally added in food production, Proteins, carbohydrates, fats, nutrients, flavoring agents 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 균주 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 strain 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 바실러스 아밀로리퀴파시엔스 플란타럼 아종 균주를 유효성분 포함하는 항알레르기용 조성물이 화장료 조성물로 제조되는 경우, 유효 성분으로서의 바실러스 아밀로리퀴파시엔스 플란타럼 균주 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 the subspecies Bacillus amyloliquefaciens placterium subsp. Strain of the present invention is prepared from a cosmetic composition, it is usually added to the cosmetic composition in addition to the Bacillus amyloliquefaciensplanterum strain as an active ingredient And include conventional adjuvants such as stabilizers, 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 바실러스 아밀로리퀴파시엔스 플란타럼 아종 균주를 유효성분 포함하는 항알레르기용 조성물이 사료 조성물로 제조되는 경우, 바실러스 아밀로리퀴파시엔스 플란타럼 균주를 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 anti-allergic composition comprising the active ingredient of the subspecies Bacillus amyloliquefaciens plutalum subsp. Strain of the present invention is prepared from the feed composition, the strain of Bacillus amyloliquefaciens plastarum is used as it is, An additive to be added, and the like. 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 또는 Th2-매개 면역 질환의 예방, 개선 또는 치료 활성을 갖는 바실러스 아밀로리퀴파시엔스 플란타럼 아종 F2189 균주(기탁번호 KCCM 11282P)를 제공한다.According to another aspect of the present invention, the present invention provides a Bacillus amyloliquefaciens subtilant subsp. F2189 strain (Accession No. KCCM 11282P) having a preventive, ameliorative or therapeutic activity of a Th1-mediated immune disease or a Th2- to provide.
본 발명의 Th1-매개 면역 질환 또는 Th2-매개 면역 질환의 예방, 개선 또는 치료 활성을 갖는 상술한 Th1-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.The composition for preventing, ameliorating or treating the aforementioned Th1-mediated immune disease or Th2-mediated immune disease having the preventive, ameliorating or curative activity of the Th1-mediated immune disease or Th2-mediated immune disease of the present invention and the target disease Therefore, in order to avoid the excessive complexity of the present specification, the description thereof will be omitted.
본 발명의 특징 및 이점을 요약하면 다음과 같다: The features and advantages of the present invention are summarized as follows:
(a) 본 발명은 바실러스 아밀로리퀴파시엔스 플란타럼 아종(Bacillus amyloliquefaciens subsp. plantarum) 균주를 유효성분으로 포함하는 Th1-매개 면역 질환 또는 Th2-매개 면역 질환의 예방, 개선 또는 치료용 조성물을 제공한다.(a) The present invention relates to a composition for preventing, ameliorating or treating a Th1-mediated immune disease or a Th2-mediated immune disease comprising an active ingredient of a strain of Bacillus amyloliquefaciens subsp. plantarum to provide.
(b) 본 발명은 Th1-매개 면역 질환 또는 Th2-매개 면역 질환의 예방, 개선 또는 치료 활성을 갖는 신규한 바실러스 아밀로리퀴파시엔스 플란타럼 아종 F2189(기탁번호 KCCM 11282P) 균주를 제공한다. (b) The present invention provides a novel strain of Bacillus amyloliquefaciens plastarum subsp. F2189 (Accession No. KCCM 11282P) having an activity of preventing, ameliorating or treating a Th1-mediated immune disease or a Th2-mediated immune disease.
(c) 본 발명의 바실러스 아밀로리퀴파시엔스 플란타럼 아종 균주는 조절 T 세포를 유도하고, 항염증 사이토카인인 IL-10 생성을 증가시키며, 면역활성 사이토카인인 IL-12 생성을 억제시키며, IgE 항체의 생성양을 감소시킴으로써 Th1-매개 면역 질환 또는 Th2-매개 면역 질환을 효과적으로 제어하는바 항알레르기성 조성물 및 항염증성 조성물로 사용이 가능한 이점이 있다.(c) The Bacillus amyloliquefaciens plutelum subspecies strain of the present invention induces regulatory T cells, increases IL-10 production, an anti-inflammatory cytokine, inhibits the production of IL-12, an immunologically active cytokine , Can be used as anti-allergic and anti-inflammatory compositions that effectively control Thl-mediated immune disease or Th2-mediated immune disease by decreasing the amount of IgE antibody produced.
도 1은 바실러스 아밀로리퀴파시엔스 플란타럼 아종 F2189 균주 및 양성대조군인 IRT5의 공동배양에 따른 Foxp3의 발현 정도를 측정한 결과이다.FIG. 1 shows the results of measurement of the expression level of Foxp3 according to co-culture of Bacillus amyloliquefaciens plu- tantum subsp. F2189 strain and IRT5 as a positive control.
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
실험 방법 및 실험 재료Experimental Methods and Materials
균주의 분리 및 동정Isolation and Identification of Strain
균주는 트립티케이스 대두 한천 배지(TSB 배지, BD236950, 디프코社, 미국)를 이용하여 전통식으로 제조된 메주((주)뚝배기식품)로부터 분리하였으며, 16S rDNA 시퀀싱을 통해 상기 분리된 균주를 동정하였다. 동정 결과, 상기 균주의 16s rDNA 염기서열(서열목록 제1서열)은 기존의 바실러스 아밀로리퀴파시엔스 플란타럼 아종 CP000560 균주와 100%의 상동성을 보였다. The strains were isolated from a traditional soybean agar medium (TSB medium, BD236950, Difco Co., USA) and were isolated from a traditional soybean agar medium (Ttukbaegi). The isolates were identified by 16S rDNA sequencing Respectively. As a result of the identification, the 16s rDNA sequence (the first sequence of the sequence listing) of the above strain showed 100% homology with the conventional Bacillus amyloliquefaciens plutelum subsp. CP000560 strain.
본 균주의 배양을 위한 배지 조성은 TSB 배지이며, 배양조건은 pH 7.3 ± 0.2, 온도 37℃ 및 24시간 진탕배양이며, 산소요구성은 통성혐기성이고 동결건조보존 또는 세포현탁액 동결을 통해 균주 보존이 가능하다. 이 균주를 바실러스 아밀로리퀴파시엔스 플란타럼 아종(Bacillus amyloliquefaciens subsp. plantarum) F2189로 명명하고, 국제미생물기탁기관인 한국미생물보존센터(KCCM)에 2012년 6월 14일자로 기탁하였으며, 기탁번호 KCCM 11282P를 부여받았다.The culture medium for the cultivation of this strain is TSB medium, and the culture conditions are pH 7.3 ± 0.2, shaking culture at 37 ° C. for 24 hours. Oxygen requirement is aseptic anaerobic and can be preserved by freeze-drying preservation or cell suspension freezing Do. Named the strain as Bacillus amyl Lori rake Pacifico Enschede Planta Rum subspecies (Bacillus amyloliquefaciens subsp. Plantarum) F2189, and was deposited on June 14, 2012 in the International microbiological deposit institutions Korea Culture Center of Microorganisms (KCCM), Accession No. KCCM 11282P.
실험동물Experimental animal
본 연구를 위해 유전적으로 어떠한 변형도 일어나지 않은 야생형의 생쥐(계통 번호-C57BL/6, 스탁 번호-000664, the Jackson laboratory)를 사용하였다. 또한, Foxp3의 발현 정도를 비교적 쉽게 확인하기 위해 유전적으로 변형된 생쥐(Foxp3-GFP 넉 인 마우스, 계통 이름-B6.Cg-Foxp3 tm2Tch /J, 스탁 번호-006772, the Jackson laboratory)를 이용하였다. 상기 Foxp3-GFP 넉 인 마우스의 경우 야생형의 종을 기반으로 만들어졌기 때문에 전반적인 유전 정보는 동일하나, Foxp3가 발현할 때 형광 신호를 낼 수 있는 분자인 EGFP(enhanced green fluorescence protein)가 함께 발현하여 이러한 형광 신호가 Foxp3 발현 정도를 대변해 주기 때문에 이 생쥐를 통해 감지가 어려운 Foxp3의 발현 정도를 항체의 사용 없이도 비교적 용이하게 확인할 수 있다.For this study, wild-type mice (strain No. -C57BL / 6, STOCK No. -000664, the Jackson laboratory), which had no genetic modification, were used. In addition, genetically modified mice (Foxp3-GFP knockin mouse, strain name-B6.Cg-Foxp3 tm2Tch / J, STACK No. -006772, the Jackson laboratory) were used to comparatively easily detect the expression level of Foxp3. Foxp3-GFP knock-in mice were constructed based on wild-type species, so their overall genetic information is the same, but EGFP (enhanced green fluorescence protein), a molecule capable of generating a fluorescent signal when Foxp3 is expressed, Since the fluorescence signal represents the degree of Foxp3 expression, the degree of expression of Foxp3, which is difficult to detect through this mouse, can be relatively easily detected without the use of antibodies.
면역 세포 분리Immune cell isolation
생쥐의 장간막 림프절(mesenteric lymph node)을 적출한 후, 림프절에 존재하는 면역 세포(대부분 림프구)를 단일 세포 부유하여 실험에 이용하였다. 장내에 존재하는 프로바이오틱스는 장 내 면역계에 존재하는 면역 세포들에 의해 인지되기 때문에 프로바이오틱스의 특성을 분석하기 위해 적절한 면역 세포는 장간막 림프절에 존재하는 면역 세포이다. 따라서, 이 림프절에서 분리한 면역 세포로 바실러스 아밀로리퀴파시엔스 플란타럼 아종 F2189의 특성을 분석하였다.After the mesenteric lymph node of the mouse was removed, the immune cells (mostly lymphocytes) present in the lymph nodes were suspended in a single cell and used for the experiment. Because the probiotics present in the intestine are recognized by immune cells present in the intestinal immune system, appropriate immune cells are immune cells present in the mesenteric lymph nodes to characterize the probiotics. Therefore, we analyzed the characteristics of Bacillus amyloliquefaciens subtilante subsp. F2189 as immunocytes isolated from the lymph nodes.
공동 배양(co-culture) Co-culture
분리한 면역 세포와 바실러스 아밀로리퀴파시엔스 플란타럼 아종 F2189는 1:10 비율 즉, 면역 세포 3x106과 균주 3x107 cfu를 72시간 동안 37℃ 배양기에서 배양하였다. 이 때 항생제인 젠타마이신(11811-031, 15 μg/mL, GIBCO社)을 함께 처리하여 시험균주의 과잉성장을 방지하였다.Separated immune cells and Bacillus amyloliquefaciens supratantrum subsp. F2189 were cultured in a 1:10 ratio, that is, 3x10 6 of the immune cells and 3x10 7 cfu of the strain for 72 hours in a 37 ° C incubator. At that time, the antibiotic gentamycin (11811-031, 15 μg / mL, GIBCO) was treated together to prevent the overgrowth of the test strain.
효소면역측정법(Enzyme-linked immunosorbent assay, ELISA) Enzyme-linked immunosorbent assay (ELISA)
ELISA는 효소를 표식자로 하여 항원항체반응을 이용한 항원 또는 항체의 양을 측정하는 방법 중 하나이다. 면역 세포와 균주를 공동 배양 후 상등액에 존재하는 사이토카인의 양을 측정하기 위해 IL-10(Mouse IL-10 ELISA Ready-SET-Go, eBioscience社) 및 IL-12p70(Mouse IL-12p70 ELISA Ready-SET-Go, eBioscience社) ELISA를 실시하였다. 각각의 사이토카인을 감지하는 코팅용 항체를 96웰에 처리한 후, 상층액을 넣고 일정 시간 동안 반응이 진행되도록 놓아둔 후, 각각의 사이토카인을 감지하는 또 다른 검출용 항체를 처리하였다. 이 때 처리하는 검출용 항체는 효소(HRP)와 결합하고 있는데, 이 때 효소의 기질(Tetramethylbenzidine Substrate Solution, eBioscience)을 첨가하여 효소-기질 반응에 의한 결과물로 색의 변화가 일어난다. 이러한 간접적인 방법을 통해 사이토카인의 절대량을 측정할 수 있다.ELISA is a method of measuring the amount of an antigen or an antibody using an antigen-antibody reaction using an enzyme as a marker. (Mouse IL-10 ELISA Ready-SET-Go, eBioscience) and IL-12p70 (Mouse IL-12p70 ELISA Ready- SET-Go, eBioscience) ELISA. The coating antibody for detecting each cytokine was treated in 96 wells, and the supernatant was added thereto. After allowing the reaction to proceed for a predetermined period of time, another detection antibody for detecting each cytokine was treated. At this time, the antibody for detection is bound to the enzyme (HRP), and a color change occurs as a result of an enzyme-substrate reaction by adding an enzyme substrate (Tetramethylbenzidine Substrate Solution, eBioscience). The absolute amount of cytokine can be measured by this indirect method.
IL-10(interleukin 10)은 대표적인 면역관용 사이토카인이며, IL-12(interleukin 12)는 대표적인 면역활성 사이토카인으로 알려져 있으므로 두 사이토카인의 절대적/상대적 양을 파악하여 항알레르기 특성을 갖은 균주를 선별할 수 있다. 이에 본 실험에서는 Foxp3 넉 인 실험용 생쥐의 장간막 림프절 세포를 분리하여 시험균주와 1:10 비율로 혼합한 후 배양하였다. 3일간 배양 후 배양 상등액을 취하여 면역 활성 사이토카인인 IL-12p70과 항염증 사이토카인인 IL-10의 절대량을 ELISA(Enzyme linked immunosorbent assay)를 통해 측정하였으며, 이 두 분자의 양을 상대적으로 수치화하여 비교하였다.IL-10 (interleukin 10) is a representative immune tolerance cytokine. Since IL-12 (interleukin 12) is known as a representative immunologically active cytokine, the absolute / relative amount of two cytokines is determined and a strain having anti- can do. In this experiment, mesenteric lymph node cells of Foxp3 knock-in mice were isolated and mixed with test strain at a ratio of 1:10. After culturing for 3 days, the culture supernatant was taken and the absolute amount of IL-12p70, an immunologically active cytokine, and IL-10, an anti-inflammatory cytokine, were measured by ELISA (enzyme linked immunosorbent assay) Respectively.
유세포 분석기(Flow cytometry)를 통한 표면 분자(surface molecule) 발현 측정 Measurement of Surface Molecule Expression by Flow Cytometry
유세포 분석기는 레이저를 기반으로 하여 세포의 특정 신호를 감지해 내는 기술로, 분석기에 내재되어 있는 전기 장치에 의해 이러한 신호가 감지되며 이를 통해 살아있는 세포의 생체 분자 발현 정도를 확인할 수 있다. 세포의 표면 분자 발현 정도를 비교하기 위해 바실러스 아밀로리퀴파시엔스 플란타럼 아종 F2189과 공동 배양한 면역 세포들을 이 유세포 분석기(COULTER Epics XL, BECKMAN社)를 통해 Foxp3가 발현할 때 함께 발현하는 GFP 시그널을 측정함으로써 Foxp3의 발현양을 측정ㆍ비교하였다.A flow cytometer is a laser-based technology that detects specific signals of cells. Such signals are detected by an electrical device embedded in the analyzer, and thus the degree of biomolecular expression of living cells can be checked. In order to compare the degree of surface expression of the cells, immune cells co-cultured with Bacillus amyloliquefaciens subsp. Subtilis subsp. F2189 were transfected with Foxp3 expressing GFP (COULTER Epics XL, BECKMAN) The amount of Foxp3 expression was measured and compared by measuring the signal.
조절 T 세포는 T 세포의 부분 집합 중 하나로 다른 T 세포와 다르게 과도한 면역 반응을 억제하는 역할을 수행한다. 이러한 조절 T 세포가 알레르기 질환을 억제한다는 것이 다양한 연구 결과를 통해 뒷받침되고 있다. 시험균주와 장간막 림프절 세포를 공동배양 시, 조절 T 세포의 분포를 늘릴 수 있는 균주가 항 알레르기 효능을 띠는 프로바이오틱스가 될 가능성이 높다. Foxp3는 과도한 면역을 억제하는 T 세포의 서브셋(subset)인 조절 T 세포의 전사인자로, Foxp3 발현 정도를 통해 조절 T 세포의 분포를 확인할 수 있으며 Foxp3 넉 인(Knock-in) 실험용 생쥐를 이용하면, 효율적으로 조절 T 세포(regulatory T cell)의 분포를 평가할 수 있다. 따라서, 시험균주들과 조절 T 세포 간의 상호작용을 알아보기 위해 Foxp3 넉 인 실험용 생쥐의 장간막 림프절 세포를 분리하여 각각의 시험균주와 1:10 비율 혼합한 후 3일간 공동 배양을 진행하였다. 3일 후, 시험균주와 공동 배양한 세포를 걷어 낸 후, Foxp3와 함께 발현하는 GFP의 발현 정도를 유세포 분석기를 통해 확인하였다.Regulatory T cells are one of a subset of T cells that, unlike other T cells, play a role in suppressing excessive immune responses. Various studies have shown that these regulatory T cells inhibit allergic diseases. When the test strain and mesenteric lymph node cells are co-cultured, a strain capable of increasing the distribution of regulatory T cells is likely to be a probiotic with antiallergic efficacy. Foxp3 is a transcription factor of regulatory T cells, a subset of T cells that inhibit excessive immunity. Foxp3 expression can be used to determine the distribution of regulatory T cells. Foxp3 knock-in mice , And the distribution of regulatory T cells can be evaluated efficiently. Therefore, mesenteric lymph node cells of Foxp3 knock-in mice were separated and tested for 1: 10 ratio with each test strain and then co-cultured for 3 days. After 3 days, the cell co-cultured with the test strain was removed and the expression level of GFP expressed with Foxp3 was confirmed by flow cytometry.
IgE 생성 감소 효능 측정Measuring efficacy of reducing IgE production
면역글로불린 E(IgE: immunoglobulin E)는 B 세포가 분비하는 면역 글로불린(항체) 중의 하나로 정상적인 상황에서는 발현 정도가 매우 낮으나 알레르기 상황에서는 IgE가 높아짐으로써 다양한 알레르기 반응이 증폭된다. 이 때문에 IgE의 발현 정도는 천식 아토피 피부염 등 다양한 알레르기 질환에서 진단 인자로 간주된다. 따라서 본 균주가 지속적으로 IgE가 생성되는 상태인 알러지 모델의 생쥐로부터 얻은 면역세포에서의 IgE 생성에 어떤 영향을 주는지 알아봄으로써, 본 발명의 균주의 항알레르기 능력을 확인하였다. Immunoglobulin E (IgE) is one of immunoglobulins (antibodies) secreted by B cells. Its expression level is very low under normal conditions. However, allergic reactions are amplified by increasing IgE in allergic situations. Therefore, the degree of IgE expression is regarded as a diagnostic factor in various allergic diseases such as asthma and atopic dermatitis. Therefore, the anti-allergic ability of the strain of the present invention was confirmed by examining the effect of the strain on the IgE production in immune cells obtained from an allergic model mouse in which IgE was continuously produced.
BALB/C 마우스에 집먼지진드기(mite)와 DNCB로 아토피 피부염을 유도한 후 병변 지역과 가까이에 존재하는 림프절(Draining lymph node)에서 면역 세포를 획득하였다. 상기 면역 세포(3x106 cfu)와 바실러스 아밀로리퀴파시엔스 플란타럼 아종 F2189(3x107 cfu)를 1:10 비율로 72시간 동안 37℃ 배양기에서 배양 한 뒤 샌드위치 ELISA 키트(sandwich ELISA kit, BD Biosciences, 미국)를 이용하여 IgE의 발현량을 확인하였다.After inducing atopic dermatitis with house dust mite and DNCB in BALB / C mice, immune cells were obtained from the lymph node located near the lesion area (Draining lymph node). The immune cells (3x10 6 cfu) and Bacillus amyloliquefaciens plastarum subsp. Subsp. F2189 (3x10 7 cfu) were cultured in a 1:10 ratio for 72 hours in a 37 ° C incubator, and then subjected to a sandwich ELISA kit (sandwich ELISA kit, BD Biosciences, USA) was used to confirm the expression level of IgE.
실험 결과Experiment result
항알레르기 활성 측정 - Foxp3 발현량 증가Measuring antiallergic activity - Increasing the expression of Foxp3
바실러스 아밀로리퀴파시엔스 플란타럼 아종 F2189를 장간막 세포와 공동배양 시 Foxp3의 발현 정도가 각각 17.76%으로 각 실험배치의 양성대조군인 IRT5(HK Kwon, CG Lee, JS So, CS Chae, JS Hwang, A Sahoo, JH Nam, JH Rhee, KC Hwang, SH Im. 2010. Generation of regulatory dendritic cells and CD4+Foxp3+ T cells by probiotics administration suppresses immune disorders. PANS. 107;5. 2159-2164)에 비해 높은 발현량을 보인바, 조절 T 세포의 분포 증진을 통해 알레르기 질환을 억제할 수 있을 것으로 사료된다. Expression of Foxp3 was 17.76% when co-cultured with mesenteric cells, and the positive control group IRT5 (HK Kwon, CG Lee, JS So, CS Chae, JS Hwang , a Sahoo, Nam JH, JH Rhee, Hwang KC, SH Im 2010. Generation of regulatory dendritic cells and CD4 + Foxp3 + T cells by administration probiotics suppresses immune disorders PANS 107;... high expression compared to 5 2159-2164). , It may be possible to inhibit allergic diseases by improving the distribution of regulatory T cells.
IL-10 및 IL-12 분비능 확인Confirm IL-10 and IL-12 secretion
바실러스 아밀로리퀴파시엔스 플란타럼 아종 F2189 균주와 공동배양 시 lL-10 및 IL-12의 상대적인 비율(lL-10/IL-12)이 166.95으로, 음성대조군 및 양성대조군인 IRT5에 비해 높게 나타나 바실러스 아밀로리퀴파시엔스 플란타럼 아종 F2189 균주는 항염증활성을 가질 것으로 판단된다.The relative proportion of IL-10 and IL-12 (lL-10 / IL-12) was 166.95 when co-incubated with the Bacillus amyloliquefaciens platelum subsp. Subsp. F2189 strain and was higher than the negative control and the positive control group IRT5 The Bacillus amyloliquefaciensplanterum subsp. F2189 strain is thought to have anti-inflammatory activity.
*미검출(not detect), 검출 영역에서 벗어날 정도도 소량이 분비되므로 항염증활성을 기대할 수 없음.* It is not detectable, and anti-inflammatory activity can not be expected because it secretes a small amount to escape from the detection area.
*IRT5: 5개 균주로 게재된 논문과 특허를 고려할 때 항알레르기 활성이 있는 양성대조군으로 활용할 수 있음.* IRT5: Can be used as a positive control with antiallergic activity considering 5 articles and patents published in 5 strains.
IgE 생성 감소 효능 확인Identification of reduced IgE production
알레르기 모델 생쥐를 이용한 IgE 감소 효능을 확인한 결과 바실러스 아밀로리퀴파시엔스 플란타럼 아종 F2189 균주와 전체 면역 세포를 공동 배양 하였을 경우 IgE 생성을 억제시키는 경향성을 보였다.The IgE reduction effect of allergic model mice was shown to suppress IgE production when co-cultured with Bacillus amyloliquefaciens subsp. Subsp. Subsp. F2189 and whole immune cells.
요약summary
Foxp3+ 세포 분포와 IL-10 및 IL-12 두 사이토카인의 상대적 비율을 조사한 결과, 바실러스 아밀로리퀴파시엔스 플란타럼 아종 F2189 균주는 조절 T 세포 유도와 항염증성 사이토카인 분비를 통해 항알레르기 및 항염증 활성을 가지며, IgE 생성을 억제하는 프로바이오틱스 균주임을 확인하였다.The relative proportion of Foxp3 + cell distribution and IL-10 and IL-12 cytokines were examined. As a result, Bacillus amyloliquefaciens subsp. Subsp. Subsp. F2189 induced anti-allergic and anti-allergic effects through regulatory T cell induction and anti-inflammatory cytokine secretion Inflammatory activity, and proved to be a probiotic strain inhibiting IgE production.
<110> KOREA FOOD RESEARCH INSTITUTE <120> Composition for Preventing, Improving or Treating of Th1-mediated Immune Disease or Th2-mediated Immune Disease Comprising Extracts from Bacillus amyloliquefaciens subsp. plantarum as an Active Ingredients <130> PN150426 <160> 1 <170> KopatentIn 2.0 <210> 1 <211> 1474 <212> DNA <213> 16S rDNA of Bacillus amyloliquefaciens supsp. plantarum F2189 <400> 1 aggacgaacg ctggcggcgt gcctaataca tgcaagtcga gcggacagat gggagcttgc 60 tccctgatgt tagcggcgga cgggtgagta acacgtgggt aacctgcctg taagactggg 120 ataactccgg gaaaccgggg ctaataccgg atggttgtct gaaccgcatg gttcagacat 180 aaaaggtggc ttcggctacc acttacagat ggacccgcgg cgcattagct agttggtgag 240 gtaacggctc accaaggcga cgatgcgtag ccgacctgag agggtgatcg gccacactgg 300 gactgagaca cggcccagac tcctacggga ggcagcagta gggaatcttc cgcaatggac 360 gaaagtctga cggagcaacg ccgcgtgagt gatgaaggtt ttcggatcgt aaagctctgt 420 tgttagggaa gaacaagtgc cgttcaaata gggcggcacc ttgacggtac ctaaccagaa 480 agccacggct aactacgtgc cagcagccgc ggtaatacgt aggtggcaag cgttgtccgg 540 aattattggg cgtaaagggc tcgcaggcgg tttcttaagt ctgatgtgaa agcccccggc 600 tcaaccgggg agggtcattg gaaactgggg aacttgagtg cagaagagga gagtggaatt 660 ccacgtgtag cggtgaaatg cgtagagatg tggaggaaca ccagtggcga aggcgactct 720 ctggtctgta actgacgctg aggagcgaaa gcgtggggag cgaacaggat tagataccct 780 ggtagtccac gccgtaaacg atgagtgcta agtgttaggg ggtttccgcc ccttagtgct 840 gcagctaacg cattaagcac tccgcctggg gagtacggtc gcaagactga aactcaaagg 900 aattgacggg ggcccgcaca agcggtggag catgtggttt aattcgaagc aacgcgaaga 960 accttaccag gtcttgacat cctctgacaa tcctagagat aggacgtccc cttcgggggc 1020 agagtgacag gtggtgcatg gttgtcgtca gctcgtgtcg tgagatgttg ggttaagtcc 1080 cgcaacgagc gcaacccttg atcttagttg ccagcattca gttgggcact ctaaggtgac 1140 tgccggtgac aaaccggagg aaggtgggga tgacgtcaaa tcatcatgcc ccttatgacc 1200 tgggctacac acgtgctaca atggacagaa caaagggcag cgaaaccgcg aggttaagcc 1260 aatcccacaa atctgttctc agttcggatc gcagtctgca actcgactgc gtgaagctgg 1320 aatcgctagt aatcgcggat cagcatgccg cggtgaatac gttcccgggc cttgtacaca 1380 ccgcccgtca caccacgaga gtttgtaaca cccgaagtcg gtgaggtaac cttttaggag 1440 ccagccgccg aagtgggaca gatgattggg gtga 1474 <110> KOREA FOOD RESEARCH INSTITUTE <120> Composition for Preventing, Improving or Treating of Th1-mediated Immune Disease or Th2-mediated Immune Disease Comprising Extracts from Bacillus amyloliquefaciens subsp. plantarum as an Active Ingredients <130> PN150426 <160> 1 <170> Kopatentin 2.0 <210> 1 <211> 1474 <212> DNA ≪ 213 > 16S rDNA of Bacillus amyloliquefaciens supsp. plantarum F2189 <400> 1 aggacgaacg ctggcggcgt gcctaataca tgcaagtcga gcggacagat gggagcttgc 60 tccctgatgt tagcggcgga cgggtgagta acacgtgggt aacctgcctg taagactggg 120 ataactccgg gaaaccgggg ctaataccgg atggttgtct gaaccgcatg gttcagacat 180 aaaaggtggc ttcggctacc acttacagat ggacccgcgg cgcattagct agttggtgag 240 gtaacggctc accaaggcga cgatgcgtag ccgacctgag agggtgatcg gccacactgg 300 gactgagaca cggcccagac tcctacggga ggcagcagta gggaatcttc cgcaatggac 360 gaaagtctga cggagcaacg ccgcgtgagt gatgaaggtt ttcggatcgt aaagctctgt 420 tgttagggaa gaacaagtgc cgttcaaata gggcggcacc ttgacggtac ctaaccagaa 480 agccacggct aactacgtgc cagcagccgc ggtaatacgt aggtggcaag cgttgtccgg 540 aattattggg cgtaaagggc tcgcaggcgg tttcttaagt ctgatgtgaa agcccccggc 600 tcaaccgggg agggtcattg gaaactgggg aacttgagtg cagaagagga gagtggaatt 660 ccacgtgtag cggtgaaatg cgtagagatg tggaggaaca ccagtggcga aggcgactct 720 ctggtctgta actgacgctg aggagcgaaa gcgtggggag cgaacaggat tagataccct 780 ggtagtccac gccgtaaacg atgagtgcta agtgttaggg ggtttccgcc ccttagtgct 840 gcagctaacg cattaagcac tccgcctggg gagtacggtc gcaagactga aactcaaagg 900 aattgacggg ggcccgcaca agcggtggag catgtggttt aattcgaagc aacgcgaaga 960 accttaccag gtcttgacat cctctgacaa tcctagagat aggacgtccc cttcgggggc 1020 agagtgacag gtggtgcatg gttgtcgtca gctcgtgtcg tgagatgttg ggttaagtcc 1080 cgcaacgagc gcaacccttg atcttagttg ccagcattca gttgggcact ctaaggtgac 1140 tgccggtgac aaaccggagg aaggtgggga tgacgtcaaa tcatcatgcc ccttatgacc 1200 tgggctacac acgtgctaca atggacagaa caaagggcag cgaaaccgcg aggttaagcc 1260 aatcccacaa atctgttctc agttcggatc gcagtctgca actcgactgc gtgaagctgg 1320 aatcgctagt aatcgcggat cagcatgccg cggtgaatac gttcccgggc cttgtacaca 1380 ccgcccgtca caccacgaga gtttgtaaca cccgaagtcg gtgaggtaac cttttaggag 1440 ccagccgccg aagtgggaca gatgattggg gtga 1474
Claims (12)
Bacillus amyl quinone Lowry Pacific Enschede Planta column subspecies (Bacillus amyloliquefaciens subsp. Plantarum) Th1- or Th2- mediated immune diseases mediated prevention of immune diseases, improvement or therapeutic composition comprising the strain, as an active ingredient.
2. The composition of claim 1, wherein said composition activates regulatory T cells.
2. The composition of claim 1, wherein the composition increases IL-10 production.
2. The composition of claim 1, wherein said composition inhibits IL-12 production.
2. The composition of claim 1, wherein the composition inhibits IgE production.
The composition of claim 1, wherein the composition is such that the ratio of the amount of IL-10 production to the amount of IL-12 production is from 50-200.
2. The composition of claim 1, wherein said ThI-mediated immune disorder is an 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 strain is a strain isolated from Meju.
2. The composition according to claim 1, wherein the strain is a strain of Bacillus amyloliquefaciens < RTI ID = 0.0 > Flutarum subsp. ≪ / RTI > F2189 (Accession No. KCCM 11282P).
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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| KR20190068110A (en) * | 2017-12-08 | 2019-06-18 | 광주여자대학교 산학협력단 | Cosmetic composition comprising antibacterial extract from Bacillus sp. culture broth |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| KR20190068110A (en) * | 2017-12-08 | 2019-06-18 | 광주여자대학교 산학협력단 | Cosmetic composition comprising antibacterial extract from Bacillus sp. culture broth |
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