KR102470116B1 - Pharmaceutical Composition for Prevention or Treatment of Non-alcoholic Fatty Liver Disease Comprising Butyricimonas Strain as an Active Ingredient - Google Patents
Pharmaceutical Composition for Prevention or Treatment of Non-alcoholic Fatty Liver Disease Comprising Butyricimonas Strain as an Active Ingredient Download PDFInfo
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- KR102470116B1 KR102470116B1 KR1020200176461A KR20200176461A KR102470116B1 KR 102470116 B1 KR102470116 B1 KR 102470116B1 KR 1020200176461 A KR1020200176461 A KR 1020200176461A KR 20200176461 A KR20200176461 A KR 20200176461A KR 102470116 B1 KR102470116 B1 KR 102470116B1
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- butyricimonas
- fatty liver
- liver disease
- strain
- genus
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Abstract
본 발명은 부티리시모나스 속(Butyricimonas sp.) 균주, 이의 배양액, 이의 농축액, 이의 건조물, 또는 이들의 조합을 유효성분으로 포함하는 지방간 질환의 예방 또는 치료용 약학적 조성물; 부티리시모나스 속(Butyricimonas sp.) 균주, 이의 배양액, 이의 농축액, 이의 건조물, 또는 이들의 조합을 유효성분으로 포함하는 지방간 질환의 예방 또는 개선, 간 보호 또는 간 기능 개선용 식품 조성물; 상기 식품 조성물을 포함하는 건강기능식품; 및 부티리시모나스 속(Butyricimonas sp.) 균주, 이의 배양액, 이의 농축액, 이의 건조물, 또는 이들의 조합을 유효성분으로 포함하는 지방간 질환의 예방 또는 개선, 간 보호 또는 간 기능 개선용 사료 조성물에 관한 것이다.
본 발명에 따른 조성물은 고지방식이로 인한 혈액 내 지방 및 간 내 지방의 축적을 억제하고, 간을 보호하는 효과를 나타내어, 지방간 질환의 예방 또는 치료용으로 유용하게 사용될 수 있다.The present invention Butyricimonas genus ( Butyricimonas sp. ) Strains, a culture thereof, a concentrate thereof, a dried product thereof, or a pharmaceutical composition for preventing or treating fatty liver disease comprising a combination thereof as an active ingredient; Butyricimonas genus ( Butyricimonas sp. ) strain, its culture medium, its concentrate, its dried form, or a food composition for preventing or improving fatty liver disease, liver protection or liver function improvement comprising a combination thereof as an active ingredient; Health functional food containing the food composition; And Butyricimonas genus ( Butyricimonas sp. ) Relates to a feed composition for preventing or improving fatty liver disease, protecting the liver or improving liver function, comprising a strain thereof, a culture medium thereof, a concentrate thereof, a dried product thereof, or a combination thereof as an active ingredient. .
The composition according to the present invention inhibits the accumulation of fat in the blood and liver due to a high-fat diet and exhibits liver-protecting effects, so it can be usefully used for preventing or treating fatty liver disease.
Description
본 발명은 부티리시모나스 속(Butyricimonas sp.) 균주, 이의 배양액, 이의 농축액, 이의 건조물, 또는 이들의 조합을 유효성분으로 포함하는 지방간 질환의 예방 또는 치료용 약학적 조성물; 부티리시모나스 속(Butyricimonas sp.) 균주, 이의 배양액, 이의 농축액, 이의 건조물, 또는 이들의 조합을 유효성분으로 포함하는 지방간 질환의 예방 또는 개선, 간 보호 또는 간 기능 개선용 식품 조성물; 상기 식품 조성물을 포함하는 건강기능식품; 및 부티리시모나스 속(Butyricimonas sp.) 균주, 이의 배양액, 이의 농축액, 이의 건조물, 또는 이들의 조합을 유효성분으로 포함하는 지방간 질환의 예방 또는 개선, 간 보호 또는 간 기능 개선용 사료 조성물에 관한 것이다. The present invention Butyricimonas genus ( Butyricimonas sp. ) Strains, a culture thereof, a concentrate thereof, a dried product thereof, or a pharmaceutical composition for preventing or treating fatty liver disease comprising a combination thereof as an active ingredient; Butyricimonas genus ( Butyricimonas sp. ) strain, its culture medium, its concentrate, its dried form, or a food composition for preventing or improving fatty liver disease, liver protection or liver function improvement comprising a combination thereof as an active ingredient; Health functional food containing the food composition; And Butyricimonas genus ( Butyricimonas sp. ) Relates to a feed composition for preventing or improving fatty liver disease, protecting the liver or improving liver function, comprising a strain thereof, a culture medium thereof, a concentrate thereof, a dried product thereof, or a combination thereof as an active ingredient. .
간은 우리 몸에서 각종 대사 작용, 해독, 분해, 합성 및 분비를 담당하는 중요한 장기로, (i) 에너지 대사 관리 기능, (ii) 효소, 알부민, 인지질 등의 합성, 저장 및 분배 기능, (iii) 각종 대사산물을 담관을 통해 십이지장으로 배설하는 기능 및 (iv) 해독 및 분해 기능 등을 갖는다. 이러한 역할을 하는 간의 기능에 이상이 발생하면 생체의 영양소 대사에 문제를 유발하게 되며, 간 기능 이상을 일으키는 간 질환에는 지방간, 간염, 간경변증, 간암 등이 있다. The liver is an important organ responsible for various metabolic processes, detoxification, decomposition, synthesis, and secretion in our body. ) It has the function of excreting various metabolites into the duodenum through the bile duct and (iv) the function of detoxification and decomposition. Abnormalities in the function of the liver, which plays this role, cause problems with nutrient metabolism in the body, and liver diseases that cause abnormal liver function include fatty liver, hepatitis, cirrhosis, and liver cancer.
그 중, 지방간은 정상 간에서 지방이 차지하는 비율(5%)보다 많은 양의 지방이 간에 축적된 증상을 의미한다. 지방간은 크게 과음으로 인한 알콜성 지방간과 비만, 당뇨병, 고지혈증, 약물 등으로 인한 비알콜성 지방간으로 나눌 수 있는데, 알콜성 지방간은 알콜을 많이 섭취하게 되면 간에서 지방 합성이 촉진되고 정상적인 에너지 대사가 이루어지지 않아 발생하고, 비알콜성 지방간은 알콜 이외의 원인으로 인하여 발생한다. 상기 비알콜성 지방간은 지방 대사의 이상을 초래하는 성인병에 동반되는 경우가 빈번한 것으로 알려져 있으며, 특히 비알콜성 지방간 질환(non-alcoholic fatty liver disease, NAFLD)은 가장 흔한 간질환의 하나로서 간에 지방이 축적되어 발생하며, 이 질환은 염증에 더 민감하게 반응하게 하여 간의 기능을 저하시키게 된다. Among them, fatty liver refers to a symptom in which a larger amount of fat is accumulated in the liver than the proportion (5%) of fat in the normal liver. Fatty liver can be largely divided into alcoholic fatty liver caused by excessive drinking and non-alcoholic fatty liver caused by obesity, diabetes, hyperlipidemia, drugs, etc. Non-alcoholic fatty liver occurs due to causes other than alcohol. It is known that the non-alcoholic fatty liver is frequently accompanied by adult diseases that cause abnormal fat metabolism, and in particular, non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases, This accumulation occurs, and this disease makes the liver more sensitive to inflammation and deteriorates liver function.
그 중, 비알콜성 지방간 질환은 과량의 알콜을 섭취하지 않은 환자에서 염증 반응을 동반하지 않는 단순 지방간, 및 이에 의해 진전되어 간세포의 염증반응, 간섬유화 및 간경화를 포함하는 넓은 범위의 질환을 의미한다. 비알콜성 지방간 질환은 원인에 따라 원발성과 속발성으로 나뉜다. 원발성은 대사증후군의 특징인 고지혈증, 당뇨, 또는 비만 등에 의해 발생되며, 속발성은 급격한 체중 감소, 기아 등과 같은 영양적 원인, 다양한 약물, 대사성 원인 및 기타 요인에 의해 발생하는 것으로 알려져 있다. Among them, non-alcoholic fatty liver disease refers to a wide range of diseases, including simple fatty liver without inflammatory reactions in patients who have not consumed excessive alcohol, and inflammatory reactions of hepatocytes, liver fibrosis, and cirrhosis caused by it. do. Non-alcoholic fatty liver disease is divided into primary and secondary depending on the cause. It is known that primary is caused by hyperlipidemia, diabetes, or obesity, which are characteristics of metabolic syndrome, and secondary is caused by nutritional causes such as rapid weight loss and starvation, various drugs, metabolic causes, and other factors.
알콜성 지방간의 경우에는, 알콜의 섭취를 억제함으로써, 증상의 완화 또는 호전을 기대할 수 있는 반면, 비알콜성 지방간의 경우에는 뚜렷한 발병원인이 밝혀져 있지 않아, 상대적으로 치료에 어려움을 겪고 있다. 비알콜성 지방간 질환의 치료와 관련하여, 몇 가지 당뇨 또는 비만 치료 약제 투여의 지방간 질환에 대한 효과가 보고된 바 있다. 경구용 비만치료제로 사용되고 있는 올리스탓(Orlistat)의 경우 지방간염 환자에서 간의 조직학적 향상을 유도했다는 보고(Hussein et al., 2007)가 있으며, PPAR(peroxisome proliferator-activated receptor)의 작용물질(agonist)인 티아졸리딘디온(Thiazolidinedione, TZD) 계열의 약물은 간과 근육에서의 지방 축척을 억제하고, 비알콜성 지방간 질환의 동물 모델에서 간에 대해 직접적인 항 섬유화 작용을 나타내는 것으로 보고된 바 있다(Galli A et al., 2002). 현재 운동이나 금주, 식이요법 등과 약물 치료를 병행해서 간 질환을 치료하고는 있지만, 근본적으로 완전히 치유가 되기는 어렵기 때문에 효과적이고 개선된 간 질환 치료제 또는 간 보호제의 개발이 계속적으로 필요하다.In the case of alcoholic fatty liver, by suppressing the intake of alcohol, relief or improvement of symptoms can be expected, whereas in the case of non-alcoholic fatty liver, a clear cause is not identified, so treatment is relatively difficult. Regarding the treatment of non-alcoholic fatty liver disease, the effect of administration of several drugs for treating diabetes or obesity has been reported. In the case of Orlistat, which is used as an oral obesity treatment, there is a report that it induces histological improvement of the liver in patients with steatohepatitis (Hussein et al. , 2007), and it is also known as an agonist of PPAR (peroxisome proliferator-activated receptor). ), Thiazolidinedione (TZD) drugs have been reported to inhibit fat accumulation in the liver and muscle, and to show a direct anti-fibrotic action on the liver in an animal model of non-alcoholic fatty liver disease (Galli A et al. , 2002). Currently, although liver disease is treated with exercise, abstinence, diet, and drug therapy, it is fundamentally difficult to completely cure liver disease, so the development of effective and improved liver disease treatment or liver protection agents is continuously needed.
한편, 천연물을 사용하여 간 기능 개선 효과를 살펴본 연구로는, 간 기능 유지 및 개선에 유용한 발효유 및 그 제조방법(한국특허등록 제10-0461580호), 헛개나무 열매 추출물을 유효성분으로 함유하는 간 기능 개선 효과와 숙취개선 효능을 가진 기능성 식품조성물(한국특허공개 제2003-0027615호), 진주초 식물의 추출물을 포함하는 B형 간염 치료제 및 그 제조방법(한국특허공개 제2003-0063308호) 등이 개발된 바 있다. 그러나 여전히 상업적으로 성공할 만큼 지방간 질환 예방 또는 치료 효과가 우수하고 부작용이 적은 천연물 유래 기술에 대한 필요성이 있다.On the other hand, studies examining the effect of improving liver function using natural products include fermented milk useful for maintaining and improving liver function and its manufacturing method (Korean Patent Registration No. 10-0461580), and liver containing extracts of the fruit of Hovenia japonica as an active ingredient. Functional food composition with function improvement effect and hangover improvement effect (Korean Patent Publication No. 2003-0027615), hepatitis B treatment containing pearl plant extract and manufacturing method thereof (Korean Patent Publication No. 2003-0063308), etc. this has been developed. However, there is still a need for a natural product-derived technology that is commercially successful enough to be effective in preventing or treating fatty liver disease and has fewer side effects.
이러한 배경 하에서, 본 발명자들은 천연물 유래 성분을 이용한 지방간 질환 치료제를 개발하기 위하여 예의 연구 노력한 결과, 부티리시모나스 속 균주가 고지방식이로 인한 혈액 내 지방 및 간 내 지방의 축적을 억제하고, 간을 보호하는 효과를 나타내어, 지방간 질환의 예방 및 치료에 유용하게 사용될 수 있음을 확인하여 본 발명을 완성하였다.Under this background, the present inventors have made intensive research efforts to develop a therapeutic agent for fatty liver disease using natural product-derived ingredients. The present invention was completed by confirming that it exhibits a protective effect and can be usefully used for the prevention and treatment of fatty liver disease.
본 발명은 전술한 문제 및 이와 연관된 다른 문제를 해결하는 것을 목적으로 한다.The present invention aims to solve the above problems and other problems related thereto.
본 발명의 일 예시적 목적은 부티리시모나스 속(Butyricimonas sp.) 균주, 이의 배양액, 이의 농축액, 이의 건조물, 또는 이들의 조합을 유효성분으로 포함하는 지방간 질환의 예방 또는 치료용 약학적 조성물을 제공하는 것이다.An exemplary object of the present invention is to provide a pharmaceutical composition for preventing or treating fatty liver disease comprising a Butyricimonas sp. strain, a culture thereof, a concentrate thereof, a dried product thereof, or a combination thereof as an active ingredient. is to do
본 발명의 다른 예시적 목적은 부티리시모나스 속(Butyricimonas sp.) 균주, 이의 배양액, 이의 농축액, 이의 건조물, 또는 이들의 조합을 유효성분으로 포함하는 지방간 질환의 예방 또는 개선, 간 보호 또는 간 기능 개선용 식품 조성물; 및 상기 조성물을 포함하는 건강기능식품을 제공하는 것이다.Another exemplary object of the present invention is Butyricimonas genus ( Butyricimonas sp. ) strain, its culture, its concentrate, its dried, or prevention or improvement of fatty liver disease comprising a combination thereof as an active ingredient, liver protection or liver function food compositions for improvement; And to provide a health functional food containing the composition.
본 발명의 또 다른 예시적 목적은 부티리시모나스 속(Butyricimonas sp.) 균주, 이의 배양액, 이의 농축액, 이의 건조물, 또는 이들의 조합을 유효성분으로 포함하는 지방간 질환의 예방 또는 개선, 간 보호 또는 간 기능 개선용 사료 조성물을 제공하는 것이다.Another exemplary object of the present invention is Butyricimonas genus ( Butyricimonas sp. ) strain, its culture, its concentrate, its dried, or prevention or improvement of fatty liver disease comprising a combination thereof as an active ingredient, liver protection or liver It is to provide a feed composition for functional improvement.
이를 구체적으로 설명하면 다음과 같다. 한편, 본 출원에서 개시된 각각의 설명 및 실시형태는 각각의 다른 설명 및 실시 형태에도 적용될 수 있다. 즉, 본 출원에서 개시된 다양한 요소들의 모든 조합이 본 출원의 범주에 속한다. 또한, 하기 기술된 구체적인 서술에 의하여 본 출원의 범주가 제한된다고 볼 수 없다.A detailed description of this is as follows. Meanwhile, each description and embodiment disclosed in this application may also be applied to each other description and embodiment. That is, all combinations of various elements disclosed in this application fall within the scope of this application. In addition, the scope of the present application is not to be construed as being limited by the specific descriptions described below.
상기 목적을 달성하기 위한 본 발명의 일 양태는 부티리시모나스 속(Butyricimonas sp.) 균주, 이의 배양액, 이의 농축액, 이의 건조물, 또는 이들의 조합을 유효성분으로 포함하는 지방간 질환의 예방 또는 치료용 약학적 조성물을 제공한다. One aspect of the present invention for achieving the above object is Butyricimonas genus ( Butyricimonas sp. ) Strains, a culture thereof, a concentrate thereof, a dried product thereof, or a pharmaceutical for preventing or treating fatty liver disease comprising a combination thereof as an active ingredient It provides an enemy composition.
본 발명의 용어 "부티리시모나스 속(Butyricimonas sp.)" 균주는 쥐 및 인간과 같은 다양한 포유류의 위장관에 존재하는 미생물을 의미하는 것으로, 이는 그람 음성 및 혐기성 속에 해당한다. The term " Butyricimonas genus" of the present invention refers to microorganisms present in the gastrointestinal tract of various mammals such as mice and humans, which correspond to Gram-negative and anaerobic genus.
본 발명의 상기 부티리시모나스 속 균주는 생균, 사균 또는 이들의 조합일 수 있다. 구체적으로, 상기 사균은 열처리에 의한 사균일 수 있으나, 이에 제한되는 것은 아니다.The strain of the genus Butyricsimonas of the present invention may be live bacteria, dead bacteria, or a combination thereof. Specifically, the dead cells may be cells killed by heat treatment, but are not limited thereto.
본 발명의 상기 부티리시모나스 속 균주는 구체적으로 부티리시모나스 비로사(Butyricimonas virosa), 부티리시모나스 패시호미니스(Butyricimonas faecihominis), 부티리시모나스 파라비로사(Butyricimonas paravirosa), 부티리시모나스 시너지스티카(Butyricimonas synergistica), 또는 부티리시모나스 패칼리스(Butyricimonas faecalis)일 수 있고, 보다 더 구체적으로는 부티리시모나스 비로사(Butyricimonas virosa) 또는 부티리시모나스 시너지스티카(Butyricimonas synergistica)일 수 있으나, 이에 제한되는 것은 아니다.The Butyricimonas genus strains of the present invention are specifically Butyricimonas virosa ( Butyricimonas virosa ), Butyricimonas paecihominis ( Butyricimonas faecihominis ), Butyricimonas paravirosa ( Butyricimonas paravirosa ), Butyricimonas synergistica ( Butyricimonas synergistica ), or Butyricimonas faecalis , and more specifically, Butyricimonas virosa or Butyricimonas synergistica , but not limited thereto.
본 발명의 용어 "배양액" 또는 "배양물"은 균주를 배지에 배양하여 균주가 영양분을 섭취하고 물질대사를 통해 생겨난 부산물과 균주 등이 포함된 배지를 의미하는 것으로, 구체적으로 부티리시모나스 속 균주의 배양액 또는 배양물을 의미할 수 있고, 더욱 구체적으로는 부티리시모나스 비로사 또는 부티리시모나스 시너지스티카의 배양액 또는 배양물을 의미할 수 있다. 또한, 상기 배양액의 농축액 또는 희석액, 상기 배양액 건조하여 얻은 건조물 또는 동결건조물, 상기 배양액의 조정제물이나 정제물, 또는 이들의 혼합물 또한 본 발명의 조성물 내 유효성분으로 포함될 수 있다.The term "culture medium" or "culture" of the present invention refers to a medium containing by-products and strains generated through ingestion of nutrients and metabolism by culturing a strain in a medium, specifically, a strain of the genus Butyricimonas. It may mean a culture medium or culture of, and more specifically, it may mean a culture medium or culture of Butyricimonas virosa or Butyricimonas synergistica. In addition, a concentrate or dilution of the culture solution, a dried product or lyophilized product obtained by drying the culture solution, a crude or purified product of the culture solution, or a mixture thereof may also be included as an active ingredient in the composition of the present invention.
본 발명의 용어 "유효성분"이란 단독으로 목적하는 활성을 나타내거나, 또는 그 자체는 활성이 없는 담체와 함께 활성을 나타낼 수 있는 성분을 의미한다.The term "active ingredient" of the present invention refers to a component that exhibits the desired activity alone or that can exhibit activity together with a carrier that has no activity itself.
본 발명의 조성물에서 유효성분은 지방간 질환의 예방 또는 치료 활성, 간 보호 활성 또는 간 기능 개선 활성을 나타낼 수 있는 한 그 구체적 용도, 제형, 배합 목적 등에 따라 임의의 양(유효량)으로 포함될 수 있는데, 통상적인 유효량은 조성물 전체 중량을 기준으로 할 때 0.01 중량 % 내지 99.9 중량 % 범위 내에서 결정될 수 있다. 상기 "유효량"이란 본 발명 조성물의 적용 대상인 개체에게 당업계의 통상의 기술자의 제언에 의한 투여 기간 동안 본 발명의 조성물이 투여될 때, 지방간 질환의 예방 또는 치료 등 의도한 기능적, 약리학적 효과를 나타낼 수 있는, 본 발명의 조성물에 포함되는 유효성분의 양을 말한다. 이러한 유효량은 당업계의 통상의 기술자가 통상의 능력 범위 내에서 실험적으로 결정될 수 있다.In the composition of the present invention, the active ingredient may be included in any amount (effective amount) according to its specific use, formulation, combination purpose, etc. A typical effective amount can be determined within the range of 0.01% to 99.9% by weight based on the total weight of the composition. The "effective amount" refers to the intended functional and pharmacological effects, such as prevention or treatment of fatty liver disease, when the composition of the present invention is administered to an individual to whom the composition of the present invention is applied during the administration period according to the suggestion of a person skilled in the art. It refers to the amount of the active ingredient contained in the composition of the present invention that can be expressed. Such an effective amount can be empirically determined within the scope of ordinary skill by one of ordinary skill in the art.
본 발명의 약학적 조성물은 유효성분으로 101 내지 1012 CFU 균수, 구체적으로는 106 내지 1010 CFU 균수, 더욱 구체적으로는 108 CFU 균수를 갖는 부티리시모나스 속 균주를 포함할 수 있다.The pharmaceutical composition of the present invention may include, as an active ingredient, a strain of the genus Butyrishimonas having an active ingredient of 10 1 to 10 12 CFU bacteria, specifically 10 6 to 10 10 CFU bacteria, and more specifically 10 8 CFU bacteria.
본 발명의 용어 "지방간 질환"은 정상 간에서 지방이 차지하는 비율(5%)보다 많은 양의 지방이 간에 축적된 증상을 의미한다. 상기 지방간은 과음으로 인한 알콜성 지방간; 또는 비만, 당뇨병, 고지혈증 또는 약물 등으로 인한 비알콜성 지방간을 포함할 수 있다. 알콜성 지방간은 알콜을 많이 섭취하게 되면 간에서 지방 합성이 촉진되고 정상적인 에너지 대사가 이루어지지 않아 발생하고, 비알콜성 지방간은 알콜 이외의 원인으로 인하여 발생하며, 상기 비알콜성 지방간은 지방 대사의 이상을 초래하는 성인병에 동반되는 경우가 빈번한 것으로 알려져 있다.The term "fatty liver disease" of the present invention refers to a symptom in which a greater amount of fat is accumulated in the liver than the proportion (5%) of fat in the normal liver. The fatty liver is alcoholic fatty liver due to excessive drinking; or non-alcoholic fatty liver due to obesity, diabetes, hyperlipidemia, or drugs. Alcoholic fatty liver occurs when a large amount of alcohol is consumed, fat synthesis is promoted in the liver and normal energy metabolism is not achieved, and non-alcoholic fatty liver occurs due to causes other than alcohol. It is known that it is frequently accompanied by adult diseases that cause abnormalities.
본 발명의 상기 지방간 질환은 비알콜성 지방간일 수 있으나, 이에 제한되는 것은 아니다.The fatty liver disease of the present invention may be non-alcoholic fatty liver, but is not limited thereto.
본 발명의 용어 "비알콜성 지방간 질환 (Non-alcoholic fatty liver disease, NAFLD)"은 알콜이 아닌 다른 발생 원인에 기인하여 간에 지방이 축적되는 질환을 의미한다. 비알콜성 지방간 질환은 원발성과 속발성에 따른 비알콜성 지방간 질환을 모두 포함하나, 바람직하게는 원발성 고지혈증, 당뇨 또는 비만으로부터 발생되는 비알콜성 지방간 질환을 의미한다. 예를 들어, 비알콜성 지방간 질환은 단순 지방간(Simple steatosis) 질환, 영양성 지방간 질환, 기아성 지방간 질환, 비만성 지방간 질환, 당뇨병성 지방간 질환, 지방간염 및 이러한 질환의 전진에 의해 발생되는 간섬유화 (Liver fibrosis)와 간경화 (Liver cirrhosis)를 포함한다. The term "Non-alcoholic fatty liver disease (NAFLD)" of the present invention refers to a disease in which fat is accumulated in the liver due to causes other than alcohol. Non-alcoholic fatty liver disease includes both primary and secondary non-alcoholic fatty liver disease, but preferably refers to non-alcoholic fatty liver disease caused by primary hyperlipidemia, diabetes or obesity. For example, non-alcoholic fatty liver disease includes simple steatosis disease, nutritional fatty liver disease, starvation fatty liver disease, obese fatty liver disease, diabetic fatty liver disease, steatohepatitis, and liver fibrosis caused by the progression of these diseases. (Liver fibrosis) and liver cirrhosis (Liver cirrhosis).
본 발명의 용어 "예방"은 본 발명의 약학적 조성물의 투여를 통해 지방간 질환의 발명을 억제 또는 지연시키는 모든 행위를 의미하며, 본 발명의 용어 "치료"는 본 발명의 약학 조성물을 투여함으로써 지방간 질환이 호전 또는 완화되거나 이롭게 변경되는 모든 행위를 의미한다.The term "prevention" of the present invention refers to any action that inhibits or delays the onset of fatty liver disease through administration of the pharmaceutical composition of the present invention, and the term "treatment" of the present invention refers to fatty liver disease by administering the pharmaceutical composition of the present invention. It means any action that ameliorates, alleviates, or beneficially alters a disease.
상기 지방간 질환의 예방 또는 치료는 간 조직에서 지방 생성을 억제하거나, 간 내 지방 축적을 억제하여 달성되는 것일 수 있다.The prevention or treatment of fatty liver disease may be achieved by inhibiting fat production in liver tissue or inhibiting fat accumulation in the liver.
본 발명의 용어 "약학적 조성물"은 질병의 예방 또는 치료를 목적으로 제조된 것을 의미하며, 각각 통상의 방법에 따라 다양한 형태로 제형화하여 사용될 수 있다. 예컨대, 투여 경로에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽 등의 경구형 제형으로 제형화할 수 있고, 외용제, 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다. 구체적으로, 상기 투여 경로는 국소 경로, 경구 경로, 정맥 내 경로, 근육 내 경로, 및 점막 조직을 통한 직접 흡수를 포함하는 임의의 적절한 경로일 수 있으며, 두 가지 이상의 경로를 조합하여 사용할 수도 있다. 두 가지 이상 경로의 조합의 예는 투여 경로에 따른 두 가지 이상의 제형의 약물이 조합된 경우로서 예컨대 1차로 어느 한 약물은 정맥 내 경로로 투여하고 2차로 다른 약물은 국소 경로로 투여하는 경우이다.The term "pharmaceutical composition" of the present invention means prepared for the purpose of preventing or treating a disease, and may be formulated and used in various forms according to conventional methods, respectively. For example, depending on the route of administration, it can be formulated into oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, etc., and can be formulated and used in the form of external preparations and sterile injection solutions. Specifically, the route of administration may be any appropriate route including topical route, oral route, intravenous route, intramuscular route, and direct absorption through mucosal tissue, and two or more routes may be used in combination. An example of a combination of two or more routes is a case in which two or more formulations of drugs are combined according to the route of administration, for example, one drug is firstly administered intravenously and the other drug is secondly administered through a topical route.
약학적으로 허용되는 담체는 투여 경로나 제형에 따라 당업계에 주지되어 있으며, 구체적으로는 '대한민국약전'을 포함한 각국의 약전을 참조할 수 있다.Pharmaceutically acceptable carriers are well known in the art depending on the route of administration or dosage form, and specific reference may be made to the pharmacopoeia of each country including the 'Korean Pharmacopoeia'.
본 발명의 약학적 조성물은, 약학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 또는 희석제를 추가로 포함하는 지방간 질환의 예방 또는 치료용 약학적 조성물의 형태로 제조될 수 있는데, 상기 담체는 비자연적 담체(non-naturally occuring carrier)를 포함할 수 있다. 구체적으로, 상기 약학적 조성물은, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다. 본 발명에서, 상기 약학적 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(calcium carbonate), 수크로스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스티레이트, 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는 데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.The pharmaceutical composition of the present invention may be prepared in the form of a pharmaceutical composition for preventing or treating fatty liver disease, further comprising an appropriate carrier, excipient or diluent commonly used in the manufacture of pharmaceutical compositions, the carrier Non-naturally occurring carriers may be included. Specifically, the pharmaceutical composition is formulated in the form of oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories and sterile injection solutions according to conventional methods, respectively. can be used In the present invention, carriers, excipients, and diluents that may be included in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, and calcium phosphate. , calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. When formulated, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations contain at least one excipient such as starch, calcium carbonate, sucrose or lactose. It is prepared by mixing lactose and gelatin. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid formulations for oral use include suspensions, solutions for internal use, emulsions, syrups, etc., and various excipients such as wetting agents, sweeteners, aromatics, preservatives, etc. may be included in addition to water and liquid paraffin, which are commonly used simple diluents. have. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried formulations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents. As a base for the suppository, witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerogeratin and the like may be used.
약학적 조성물의 구체적인 제제화와 관련하여서는 당업계에 공지되어 있으며, 예컨대 문헌[Remington's Pharmaceutical Sciences(19th ed., 1995)] 등을 참조할 수 있다. 상기 문헌은 본 명세서의 일부로서 간주 된다.The specific formulation of the pharmaceutical composition is known in the art, and reference may be made to, for example, Remington's Pharmaceutical Sciences (19th ed., 1995). These documents are considered as part of this specification.
본 발명에 따른 약학적 조성물의 구체적인 투여량은 제제화 방법, 환자의 상태 및 체중, 환자의 성별, 연령, 질병의 정도, 약물형태, 투여경로 및 기간, 배설 속도, 반응 감응성 등과 같은 요인들에 따라 당업자에 의해 다양하게 선택될 수 있으며, 투여량 및 횟수는 어떠한 면에서든 본 발명의 범위를 제한하는 것은 아니다.The specific dosage of the pharmaceutical composition according to the present invention depends on factors such as formulation method, patient's condition and weight, patient's sex, age, disease severity, drug type, administration route and duration, excretion rate, response sensitivity, etc. It can be variously selected by those skilled in the art, and the dosage and frequency do not limit the scope of the present invention in any way.
본 발명의 약학적 조성물은 쥐, 개, 고양이, 소, 말, 돼지, 인간 등의 포유동물에 다양한 경로를 통해 투여될 수 있으며, 인간인 경우가 바람직할 수 있다. 투여의 모든 방식은 예상될 수 있으며, 예를 들어 경구, 정맥, 근육 또는 피하 주사에 의해 투여될 수 있으나, 이에 제한되는 것은 아니다.The pharmaceutical composition of the present invention may be administered to mammals such as mice, dogs, cats, cows, horses, pigs, and humans through various routes, and may be preferably human. Any mode of administration may be expected, and may be administered by, for example, oral, intravenous, intramuscular or subcutaneous injection, but is not limited thereto.
본 발명의 다른 하나의 양태는 부티리시모나스 속(Butyricimonas sp.) 균주, 이의 배양액, 이의 농축액, 이의 건조물, 또는 이들의 조합을 유효성분으로 포함하는 지방간 질환의 예방 또는 개선, 간 보호 또는 간 기능 개선용 식품 조성물; 및 상기 조성물을 포함하는 건강기능식품을 제공한다.Another aspect of the present invention is Butyricimonas genus ( Butyricimonas sp. ) strain, its culture, its concentrate, its dried, or prevention or improvement of fatty liver disease comprising a combination thereof as an active ingredient, liver protection or liver function food compositions for improvement; And it provides a health functional food containing the composition.
상기 지방간 질환은 비알콜성 지방간 질환일 수 있으나, 이에 제한되지 않는다.The fatty liver disease may be non-alcoholic fatty liver disease, but is not limited thereto.
본 발명의 용어 "부티리시모나스 속", "배양액", "유효성분", "지방간 질환", "비알콜성 지방간 질환", 및 "예방" 은 전술한 바와 같다. The terms "butyricimonas genus", "culture medium", "active ingredient", "fatty liver disease", "non-alcoholic fatty liver disease", and "prevention" of the present invention are as described above.
본 발명의 식품 조성물은 유효성분으로 101 내지 1012 CFU 균수, 구체적으로는 106 내지 1010 CFU 균수, 더욱 구체적으로는 108 CFU 균수를 갖는 부티리시모나스 속 균주를 포함할 수 있다.The food composition of the present invention may contain as an active ingredient a strain of the genus Butyrishimonas having an active ingredient of 10 1 to 10 12 CFU bacteria, specifically 10 6 to 10 10 CFU bacteria, more specifically 10 8 CFU bacteria.
본 발명의 식품 조성물은 지방간 질환의 예방 또는 개선, 간 보호 또는 간 기능 개선 효과를 나타낼 수 있다면 다양한 중량%로 부티리시모나스 속 균주를 포함할 수 있으나, 구체적으로 부티리시모나스 속 균주를 식품 조성물의 총중량 대비 0.001 내지 99.9 중량%, 구체적으로는 0.01 내지 99.9 중량%로 포함할 수 있다.If the "food" composition of the present invention can prevent or improve fatty liver disease, protect the liver or exhibit liver function improvement effects, it may contain Butyricimonas strains in various weight percent, but specifically, Butyricimonas strains of the "food" composition It may be included in 0.001 to 99.9% by weight, specifically 0.01 to 99.9% by weight, based on the total weight.
또한, 본 발명의 조성물은 유효성분 이외에, 복용이나 섭취의 편리성을 증진시키기 위하여, 당업계에서 이미 안전성이 검증되고 해당 활성을 갖는 것으로 공지된 임의의 화합물이나 천연 추출물을 추가로 포함할 수 있다.In addition to the active ingredient, the composition of the present invention may further include any compound or natural extract whose safety has already been verified in the art and is known to have a corresponding activity, in order to enhance the convenience of taking or ingesting. .
이러한 화합물 또는 추출물에는 각국 약전(한국에서는 '대한민국약전'), 각국 건강기능식품공전(한국에서는 식약처 고시인 '건강기능식품 기준 및 규격') 등의 공정서에 실려 있는 화합물 또는 추출물, 의약품의 제조·판매를 규율하는 각국의 법률(한국에서는 '약사법')에 따라 품목 허가를 받은 화합물 또는 추출물, 건강기능식품의 제조·판매를 규율하는 각국 법률(한국에서는 '건강기능식품에 관한 법률')에 따라 기능성이 인정된 화합물 또는 추출물이 포함될 수 있다. These compounds or extracts include compounds or extracts listed in compendia such as each country's pharmacopoeia ('Korean Pharmacopoeia' in Korea), each country's Health Functional Food Codex (in Korea, 'Health Functional Food Standards and Specifications', a notification of the Ministry of Food and Drug Safety), etc. Laws of each country regulating the manufacture and sale of compounds, extracts, and health functional foods that have been licensed under each country’s laws (“Pharmaceutical Affairs Act” in Korea) governing manufacturing and sales (“Health Functional Foods Act” in Korea) Accordingly, compounds or extracts whose functionality has been recognized may be included.
본 발명의 용어 "식품"은, 육류, 소시지, 빵, 초콜릿, 캔디류, 스텍류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알코올음료, 비타민 복합제, 영양 보조게(nutritional supplement), 기능성 식품, 식품 첨가제(food additive), 건강 기능 식품 및 건강 식품 등이 있으며, 통상적인 의미의 식품을 모두 포함한다.The term "food" as used herein refers to meat, sausage, bread, chocolate, candy, steaks, confectionery, pizza, ramen, other noodles, chewing gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcohol Beverages, vitamin complexes, nutritional supplements, functional foods, food additives, health functional “foods” and health “foods”, etc., include all “foods” in the usual sense.
상기 건강 식품(health food)은 일반식품에 비해 적극적인 건강유지나 증진 효과를 가지는 식품을 의미하고, 건강보조식품(health supplement food)는 건강보조 목적의 식품을 의미한다. 경우에 따라, 건강 기능 식품, 건강식품, 건강보조식품의 용어는 호용된다.The health food (health food) means a food that has an active health maintenance or promotion effect compared to general food, and health supplement food (health supplement food) means a food for health supplement purposes. In some cases, the terms health functional food, health food, and health supplement food are used interchangeably.
본 발명의 용어 "건강 기능 식품"이란, 특정보건용 식품(food for special health use, FoSHU)와 동일한 용어로, 영양 공급 외에도 생체조절기능이 효율적으로 나타나도록 가공된 의학, 의료효과가 높은 식품을 의미한다. 여기서 "기능(성)"이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건용도에 유용한 효과를 얻는 것을 의미한다. 본 발명의 식품은 당 업계에서 통상적으로 사용되는 방법에 의하여 제조가능하며, 상기 제조시에는 당 업계에서 통상적으로 첨가하는 원료 및 성분을 첨가하여 제조할 수 있다. 또한 상기 식품의 제형 또한 식품으로 인정되는 제형이면 제한 없이 제조될 수 있다. 본 발명의 식품용 조성물은 다양한 형태의 제형으로 제조될 수 있으며, 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용 시 발생할 수 있는 부작용 등이 없는 장점이 있고, 휴대성이 뛰어나, 본 발명의 식품은 지방간 질환의 예방 또는 개선, 간 보호 또는 간 기능 개선 효과를 증진시키기 위한 보조제로 섭취가 가능하다.The term "health functional food" of the present invention is the same term as food for special health use (FoSHU), and refers to medical and high-medical food processed to efficiently display bioregulatory functions in addition to nutritional supply. it means. Here, "function (sex)" means to obtain useful effects for health purposes such as regulating nutrients for the structure and function of the human body or physiological functions. The food of the present invention can be prepared by a method commonly used in the art, and can be prepared by adding raw materials and ingredients commonly added in the art during the manufacture. In addition, the formulation of the food may also be manufactured without limitation as long as it is a formulation recognized as food. The “food” composition of the present invention can be manufactured in various types of dosage forms, and unlike general drugs, has the advantage of using food as a raw material and has no side effects that may occur when taking drugs for a long time, and has excellent portability, so the present invention Medical foods can be consumed as supplements to prevent or improve fatty liver disease, protect the liver, or enhance liver function improvement effects.
구체적으로, 상기 건강 기능 식품은 부티리시모나스 속 균주를 음료, 차류, 향신료, 껌, 과자류 등의 식품소재에 첨가하거나, 캡슐화, 분말화, 현탁액 등으로 제조한 식품으로, 이를 섭취할 경우 건강상 특정한 효과를 가져오는 것을 의미하나, 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용 시 발생할 수 있는 부작용이 없는 장점이 있다.Specifically, the health functional food is a food produced by adding a strain of the genus Butyricimonas to food materials such as beverages, teas, spices, chewing gum, confectionery, etc., or encapsulated, powdered, or suspended, and ingesting it may cause health problems. It means to bring about a specific effect, but unlike general drugs, it has the advantage of not having side effects that can occur when taking a drug for a long time by using food as a raw material.
본 발명의 식품 조성물은, 일상적으로 섭취하는 것이 가능하기 때문에 높은 지방간 질환의 예방 또는 개선, 간 보호 또는 간 기능 개선 효과를 기대할 수 있어 매우 유용하다.Since the "food" composition of the present invention can be ingested on a daily basis, the effect of preventing or improving high fatty liver disease, protecting the liver, or improving liver function can be expected, and is very useful.
본 발명의 식품 조성물은 어떠한 형태로도 제조될 수 있으며, 예컨대 차, 쥬스, 탄산음료, 이온음료 등의 음료류, 우유, 요구루트 등의 가공 유류(乳類), 껌류, 떡, 한과, 빵, 과자, 면 등의 식품류, 정제, 캡슐, 환, 과립, 액상, 분말, 편상, 페이스트상, 시럽, 겔, 젤리, 바 등의 건강기능식품 제제류 등으로 제조될 수 있다. 또한, 본 발명의 식품 조성물은 법률상·기능상의 구분에 있어서 제조·유통 시점의 시행 법규에 부합하는 한 임의의 제품 구분을 띨 수 있다. 예컨대 한국 '건강기능식품에관한법률'에 따른 건강기능식품이거나, 한국 '식품위생법'의 식품공전(식약처 고시 '식품의 기준 및 규격')상 각 식품유형에 따른 과자류, 두류, 다류, 음료류, 특수용도식품 등일 수 있다.The food composition of the present invention can be prepared in any form, for example, beverages such as tea, juice, carbonated beverages, and ionic beverages, processed oils such as milk and yogurt, chewing gum, rice cakes, traditional Korean snacks, bread, It can be manufactured into foods such as confectionery and noodles, health functional food formulations such as tablets, capsules, pills, granules, liquids, powders, flakes, pastes, syrups, gels, jellies, and bars. In addition, the food composition of the present invention may take any product classification as long as it conforms to the enforcement regulations at the time of manufacture and distribution in legal and functional classification. For example, health functional foods according to the 'Health Functional Foods Act' of Korea, or snacks, legumes, teas, and beverages according to each food type in the Food Code of Korea's 'Food Sanitation Act' ("Food Standards and Specifications" notified by the Ministry of Food and Drug Safety). , special purpose foods, etc.
또한, 본 발명의 식품 조성물에는 그 유효성분 이외에 식품첨가물이 포함될 수 있다. 식품첨가물은 일반적으로 식품을 제조, 가공 또는 보존함에 있어 식품에 첨가되어 혼합되거나 침윤되는 물질로서 이해될 수 있는데, 식품과 함께 매일 그리고 장기간 섭취되므로 그 안전성이 보장되어야 한다. 식품의 제조·유통을 규율하는 각국 법률(한국에서는 '식품위생법')에 따른 식품첨가물공전에는 안전성이 보장된 식품첨가물이 성분 면에서 또는 기능 면에서 한정적으로 규정되어 있다. 한국 식품첨가물공전(식약처 고시 '식품첨가물 기준 및 규격')에서는 식품첨가물이 성분 면에서 화학적 합성품, 천연 첨가물 및 혼합 제제류로 구분되어 규정되어 있는데, 이러한 식품첨가물은 기능 면에 있어서는 감미제, 풍미제, 보존제, 유화제, 산미료, 점증제 등으로 구분된다.In addition, the food composition of the present invention may include food additives in addition to the active ingredient. Food additives may generally be understood as substances that are added to, mixed with, or infiltrated into food in manufacturing, processing, or preserving food. Since food is consumed daily and for a long period of time, its safety must be guaranteed. According to the Food Additives Code under each country's laws governing the manufacture and distribution of food (the 'Food Sanitation Act' in Korea), safety-guaranteed food additives are limitedly regulated in terms of ingredients or functions. In the Korean Food Additives Codex (Ministry of Food and Drug Safety notification 'Standards and Specifications for Food Additives'), food additives are classified into chemical synthetic products, natural additives, and mixed formulations in terms of ingredients, and these food additives are classified as sweeteners and flavors in terms of function It is divided into additives, preservatives, emulsifiers, acidulants, and thickeners.
상기 감미제는 식품에 적당한 단맛을 부여하기 위하여 사용되는 것으로, 천연의 것이거나 합성된 것을 사용할 수 있다. 바람직하게는 천연 감미제를 사용하는 경우인데, 천연 감미제로서는 옥수수 시럽 고형물, 꿀, 수크로오스, 프룩토오스, 락토오스, 말토오스 등의 당 감미제를 들 수 있다.The sweetener is used to impart an appropriate sweetness to food, and may be natural or synthetic. Preferably, a natural sweetener is used, and examples of the natural sweetener include sugar sweeteners such as corn syrup solids, honey, sucrose, fructose, lactose, and maltose.
상기 풍미제는 맛이나 향을 좋게 하기 위하여 사용될 수 있는데, 천연의 것과 합성된 것 모두 사용될 수 있다. 바람직하게는 천연의 것을 사용하는 경우이다. 천연의 것을 사용할 경우에 풍미 이외에 영양 강화의 목적도 병행할 수 있다. 천연 풍미제로서는 사과, 레몬, 감귤, 포도, 딸기, 복숭아 등에서 얻어진 것이거나 녹차잎, 둥굴레, 대잎, 계피, 국화 잎, 자스민 등에서 얻어진 것일 수 있다. 또 인삼(홍삼), 죽순, 알로에 베라, 은행 등에서 얻어진 것을 사용할 수 있다. 천연 풍미제는 액상의 농축액이나 고형상의 추출물일 수 있다. 경우에 따라서 합성 풍미제가 사용될 수 있는데, 합성 풍미제로서는 에스테르, 알콜, 알데하이드, 테르펜 등이 이용될 수 있다.The flavoring agent may be used to improve taste or aroma, and both natural and synthetic flavors may be used. Preferably, it is the case of using a natural one. In case of using natural ones, in addition to flavor, the purpose of enhancing nutrition can also be combined. As a natural flavoring agent, it may be obtained from apples, lemons, tangerines, grapes, strawberries, peaches, etc., or obtained from green tea leaves, roundworms, bamboo leaves, cinnamon, chrysanthemum leaves, jasmine, and the like. In addition, those obtained from ginseng (red ginseng), bamboo shoots, aloe vera, ginkgo, etc. can be used. Natural flavors can be liquid concentrates or solid extracts. In some cases, synthetic flavors may be used, and as synthetic flavors, esters, alcohols, aldehydes, terpenes, and the like may be used.
상기 보존제로서는 소르브산칼슘, 소르브산나트륨, 소르브산칼륨, 벤조산칼슘, 벤조산나트륨, 벤조산칼륨, EDTA(에틸렌디아민테트라아세트산) 등이 사용될 수 있고, 또 유화제로서는 아카시아검, 카르복시메틸셀룰로스, 잔탄검, 펙틴 등이 사용될 수 있으며, 산미료로서는 연산, 말산, 푸마르산, 아디프산, 인산, 글루콘산, 타르타르산, 아스코르브산, 아세트산, 인산 등이 사용될 수 있다. 산미료는 맛을 증진시키는 목적 이외에 미생물의 증식을 억제할 목적으로 식품 조성물이 적정 산도로 되도록 첨가될 수 있다.As the preservative, calcium sorbate, sodium sorbate, potassium sorbate, calcium benzoate, sodium benzoate, potassium benzoate, EDTA (ethylenediaminetetraacetic acid), etc. may be used, and as the emulsifier, acacia gum, carboxymethylcellulose, xanthan gum, Pectin and the like may be used, and acidulant, malic acid, fumaric acid, adipic acid, phosphoric acid, gluconic acid, tartaric acid, ascorbic acid, acetic acid, phosphoric acid, and the like may be used as an acidulant. Acidulants may be added to the food composition to have an appropriate acidity for the purpose of inhibiting the growth of microorganisms in addition to improving taste.
상기 점증제로서는 현탁화 구현제, 침강제, 겔형성제, 팽화제 등이 사용될 수 있다.As the thickening agent, a suspending agent, a sedimentation agent, a gel forming agent, a swelling agent, and the like may be used.
본 발명의 식품 조성물은 전술한 바의 식품첨가물 이외에, 기능성과 영양성을 보충, 보강할 목적으로 당업계에 공지되고 식품첨가물로서 안정성이 보장된 생리활성 물질이나 미네랄류를 포함할 수 있다. 상기 생리활성 물질로는 녹차 등에 포함된 카테킨류, 비타민 B1, 비타민 C, 비타민 E, 비타민 B12 등의 비타민류, 토코페롤, 디벤조일티아민 등을 들 수 있으며, 미네랄류로서는 구연산칼슘 등의 칼슘 제제, 스테아린산마그네슘 등의 마그네슘 제제, 구연산철 등의 철 제제, 염화크롬, 요오드칼륨, 셀레늄, 게르마늄, 바나듐, 아연 등을 들 수 있다.In addition to the food additives described above, the food composition of the present invention may include physiologically active substances or minerals known in the art and whose stability is guaranteed as food additives for the purpose of supplementing or reinforcing functionality and nutrition. Examples of the physiologically active substance include catechins contained in green tea, vitamins such as vitamin B1, vitamin C, vitamin E, and vitamin B12, tocopherol, and dibenzoylthiamine. Minerals include calcium preparations such as calcium citrate and stearic acid. Magnesium preparations, such as magnesium, iron preparations, such as iron citrate, chromium chloride, potassium iodine, selenium, germanium, vanadium, zinc, etc. are mentioned.
본 발명의 식품 조성물에는 전술한 바의 식품첨가물이 제품 유형에 따라 그 목적을 달성할 수 있는 적정량으로 포함될 수 있으며, 본 발명의 식품 조성물에 포함될 수 있는 기타의 식품첨가물과 관련하여서는 각국 식품공전이나 식품첨가물 공전을 참조할 수 있다.The food composition of the present invention may contain the above-mentioned food additives in an appropriate amount to achieve the purpose according to the product type, and in relation to other food additives that may be included in the food composition of the present invention, the food code of each country or You can refer to the Food Additives Codex.
본 발명의 다른 하나의 양태는 부티리시모나스 속(Butyricimonas sp.) 균주, 이의 배양액, 이의 농축액, 이의 건조물, 또는 이들의 조합을 유효성분으로 포함하는 지방간 질환의 예방 또는 개선, 간 보호 또는 간 기능 개선용 사료 조성물을 제공한다.Another aspect of the present invention is Butyricimonas genus ( Butyricimonas sp. ) strain, its culture, its concentrate, its dried, or prevention or improvement of fatty liver disease comprising a combination thereof as an active ingredient, liver protection or liver function It provides a feed composition for improvement.
상기 지방간 질환은 비알콜성 지방간 질환일 수 있으나, 이에 제한되는 것은 아니다.The fatty liver disease may be non-alcoholic fatty liver disease, but is not limited thereto.
본 발명의 용어 "부티리시모나스 속", "배양액", "유효성분" "지방간 질환", "비알콜성 지방간 질환" 및 "예방"은 전술한 바와 같다.The terms "butyricimonas genus", "culture medium", "active ingredient", "fatty liver disease", "non-alcoholic fatty liver disease" and "prevention" of the present invention are as described above.
본 발명에서 용어, "사료"는 동물이 먹고, 섭취하며, 소화시키기 위한 임의의 천연 또는 인공 규정식, 한끼식 등 또는 상기 한끼식의 성분으로, 당업계의 공지된 다양한 형태의 사료로 제조가능하며, 구체적으로는 농후 사료, 조사료, 사료 첨가제 또는 특수사료가 포함될 수 있으나 이에 제한되지 않는다.In the present invention, the term "feed" refers to any natural or artificial diet, one meal, etc., or ingredients of the one meal for animals to eat, ingest, and digest, which can be prepared with various types of feed known in the art. And, specifically, concentrated feed, roughage, feed additives or special feed may be included, but is not limited thereto.
농후사료에는 밀, 귀리, 옥수수 등의 곡류를 포함하는 종자열매류, 곡물을 정제하고 얻는 부산물로서 쌀겨, 밀 기울, 보릿겨 등을 포함하는 겨류, 콩, 유체, 깨, 아마인, 코코야자 등을 채유하고 얻는 부산물인 깻묵류와 고구마, 감자 등에서 녹말을 뺀 나머지인 녹말찌꺼기의 주성분인 잔존녹말질류 등의 찌꺼기류, 어분, 물고기찌꺼기, 어류에서 얻은 신선한 액상물(液狀物)을 농축시킨 것인 피시솔루블(fish soluble), 육분(肉粉), 혈분, 우모분, 탈지분유, 우유에서 치즈, 탈지유에서 카제인을 제조할 때의 잔액인 훼이(whey)를 건조한 건조훼이 등의 동물질 사료, 효모, 클로렐라, 해조류가 있으나 이에 제한되지 않는다.Concentrated feed includes seed fruits including grains such as wheat, oats, and corn, bran including rice bran, wheat bran, and barley bran as by-products obtained after refining grains, soybeans, fluids, sesame seeds, linseed, and coco palm. Concentrated fresh liquid obtained from fish meal, fish meal, fish meal, fish meal, fish meal, fish meal, and residual starch, the main component of starch residue, which is the by-product of oil extraction Animal feed, yeast , chlorella, seaweed, but is not limited thereto.
조사료에는 야초, 목초, 풋베기 등의 생초(生草)사료, 사료용 순무, 사료용 비트, 순무의 일종인 루터베어거 등의 뿌리채소류, 생초, 풋베기작물, 곡실(穀實) 등을 사일로에 채워 놓고 젖산발효시킨 저장사료인 사일리지(silage), 야초, 목초를 베어 건조시킨 건초, 종축용(種畜用) 작물의 짚, 콩과 식물의 나뭇잎이 있으며, 이에 제한되지 않는다. 특수사료에는 굴껍테기, 암염 등의 미네랄 사료, 요소나 그 유도체인 디우레이드이소부탄 등의 요소사료, 천연사료원료만을 배합했을 때 부족하기 쉬운 성분을 보충하거나, 사료의 저장성을 높이기 위해서 배합사료에 미량으로 첨가하는 물질인 사료첨가물, 식이보조제가 있으나 이에 제한되지 않는다.Forage, raw grass feed such as wild grass, grass, and green cutting, turnip for feed, beet for feed, root vegetables such as Lutherbearer, a kind of turnip, raw grass, green crops, grain, etc. are put into silos. Silage (silage), which is a stored feed filled and fermented with lactic acid, grass, hay dried by cutting grass, straw of breeding crops, and leaves of leguminous plants, but are not limited thereto. Special feeds include mineral feeds such as oyster shells and rock salt, urea feeds such as urea or its derivative, diureide isobutane, and supplements for ingredients that tend to be insufficient when only natural feed ingredients are mixed, or formulated feeds to improve the storage life of feeds. There are feed additives and dietary supplements, which are substances added in small amounts, but are not limited thereto.
본 발명에 따른 상기 지방간 질환의 예방 또는 개선, 간 보호 또는 간 기능 개선용 사료 조성물은 당업계에 공지된 다양한 사료 제조방법에 따라 적절한 유효 농도 범위에서 부티리시모나스 속(Butyricimonas sp.) 균주, 이의 배양액, 이의 농축액, 이의 건조물, 또는 이들의 조합을 첨가하여 제조 가능하다.The feed composition for preventing or improving fatty liver disease, protecting the liver or improving liver function according to the present invention is a Butyricimonas genus in an appropriate effective concentration range according to various feed manufacturing methods known in the art ( Butyricimonas sp. ) strain, its It can be prepared by adding a culture solution, a concentrate thereof, a dried product thereof, or a combination thereof.
본 발명에 따른 사료 조성물은 지방간 질환의 예방 또는 개선, 간 보호 또는 간 기능 개선을 목적으로 하는 개체이면 특별히 한정되지 않고, 어떠한 것이든 적용가능하다. 예를 들면, 원숭이, 개, 고양이, 토끼, 모르모트, 랫트, 마우스, 소, 양, 돼지, 염소 등과 같은 비인간동물, 조류 및 어류 등 어느 개체에도 적용이 가능하다.The feed composition according to the present invention is not particularly limited as long as it is an individual for the purpose of preventing or improving fatty liver disease, protecting the liver or improving liver function, and any one is applicable. For example, it can be applied to any object such as non-human animals such as monkeys, dogs, cats, rabbits, guinea pigs, rats, mice, cows, sheep, pigs, goats, birds and fish.
본 발명에 따른 부티리시모나스 속(Butyricimonas sp.) 균주를 포함하는 조성물은 고지방식이로 인한 혈액 내 지방 및 간 내 지방의 축적을 억제하고, 간을 보호하는 효과를 나타내어, 지방간 질환의 예방 또는 치료에 유용하게 사용될 수 있다.Butyricimonas genus ( Butyricimonas sp. ) According to the present invention, the composition containing the strain suppresses the accumulation of fat in the blood and liver due to high-fat diet, and exhibits the effect of protecting the liver, preventing or preventing fatty liver disease It can be useful for treatment.
도 1은 마우스에 고지방식이로 비만 마우스 모델을 유도한 후, 부티리시모나스 비로사 또는 부티리시모나스 시너지스티카 균주와 고지방식이를 투여하는 실험 일정을 나타낸 것이다.
도 2a는 마우스에 10주간 고지방식이를 공급한 후, 부티리시모나스 비로사 생균 또는 사균을 고지방식이와 함께 6주 동안 경구 투여한 결과로서 측정된 마우스의 최종 체중을 나타낸 것이다. RD는 정상대조군, HFD는 고지방식이로 인해 비만이 유도된 음성대조군, HFD-LB는 고지방식이로 비만 유도 후 부티리시모나스 비로사 생균을 투여한 실험군, 그리고 HFD-DB는 고지방식이로 비만 유도 후 부티리시모나스 비로사 사균을 투여한 실험군이다. 이때 *P<0.05는 HFD와 비교 시의 통계적 유의성을 나타낸다.
도 2b는 부티리시모나스 비로사 투여 전과 부티리시모나스 비로사 투여 후 마우스의 체중 변화량을 나타낸 것이다. 이때 *P<0.05는 HFD와 비교 시의 통계적 유의성을 나타낸다.
도 3은 마우스에 10주간 고지방식이를 공급한 후, 부티리시모나스 비로사 또는 부티리시모나스 시너지스티카의 생균 또는 사균을 고지방식이와 함께 6주 동안 경구 투여한 결과로서 측정된 마우스의 간 무게를 나타낸 것이다. 이때 *P<0.05는 HFD와 비교 시의 통계적 유의성을 나타낸다.
도 4는 부티리시모나스 비로사 또는 부티리시모나스 시너지스티카의 생균 또는 사균을 투여한 실험군 마우스의 간 조직 내 지방 축적 정도를 H&E 염색법으로 확인한 사진이다.Figure 1 shows an experimental schedule for inducing an obese mouse model with a high-fat diet in mice, and then administering Butyricimonas virosa or Butyricimonas synergistica strains and a high-fat diet.
Figure 2a shows the final body weight of the mice measured as a result of oral administration of live or dead bacteria with a high-fat diet for 6 weeks after feeding the mice with a high-fat diet for 10 weeks. RD is a normal control group, HFD is a negative control group in which obesity is induced by a high-fat diet, HFD-LB is an experimental group in which obesity is induced by a high-fat diet and then Butyricimonas virosa is administered, and HFD-DB is an obese group with a high-fat diet Experimental group administered with killed Butyricimonas virosa bacteria after induction. At this time, *P<0.05 indicates statistical significance when compared with HFD.
Figure 2b shows the change in body weight of mice before and after administration of Butyricimonas virosa and administration of Butyricimonas virosa. At this time, *P<0.05 indicates statistical significance when compared with HFD.
Figure 3 shows the liver weight of mice measured as a result of oral administration of live or dead cells of Butyricimonas virosa or Butyricimonas synergystica together with a high-fat diet for 6 weeks after feeding the mice with a high-fat diet for 10 weeks. it is shown At this time, *P<0.05 indicates statistical significance when compared with HFD.
Figure 4 is a photograph confirming the degree of fat accumulation in the liver tissue of mice in the experimental group administered with live or dead cells of Butyricimonas virosa or Butyricimonas synergystica by H&E staining.
이하, 실시예를 통하여 본 발명의 구성 및 효과를 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 예시하기 위한 것일 뿐, 본 발명의 범위가 이에 의해 한정되는 것은 아니다.Hereinafter, the configuration and effects of the present invention will be described in more detail through examples. These examples are only for illustrating the present invention, and the scope of the present invention is not limited thereto.
실시예 1: 부티리시모나스 비로사(Example 1: Butyricimonas virosa ( Butyricimonas virosaButyricimonas virosa ) 및 부티리시모나스 시너지스티카() and Butyricimonas synergystica ( Butyricimonas synergisticaButyricimonas synergistica ) 균주 확보) strain secured
본 발명에 따른 부티리시모나스 비로사(수탁번호 KCTC 15148) 및 부티리시모나스 시너지스티카는 생물자원센터(Korean Collection for Type Cultures)에서 구입하였다. 5% 말혈청 (Horse serum)이 포함된 Columbia 배양액에 부티리시모나스 비로사를 접종한 후, 약 5일 후 원심분리를 통해 균을 확보하였다. 상기 균을 1108 CFU로 소분한 후, 생균은 투여 전까지 -70 ℃에 보관하였고, 사균은 고압증기멸균기 (121 ℃, 15LB, 15분) 처리 후 보관하였다.Butyricimonas virosa (accession number KCTC 15148) and Butyricimonas synergistica according to the present invention were purchased from the Korean Collection for Type Cultures. After inoculating Butyricimonas virosa in Columbia culture medium containing 5% horse serum, bacteria were obtained through centrifugation after about 5 days. After subdividing the bacteria into 110 8 CFU, live cells were stored at -70 ° C until administration, and dead cells were stored after treatment with a high-pressure steam sterilizer (121 ° C, 15 LB, 15 minutes).
실험예 1: 부티리시모나스 비로사(Experimental Example 1: Butyricimonas Virosa ( Butyricimonas virosaButyricimonas virosa ) 및 부티리시모나스 시너지스티카() and Butyricimonas synergystica ( Butyricimonas synergisticButyricimonas synergistic ) 균주의 동물모델에서의 지방간 질환의 치료 효과) Treatment effect of fatty liver disease in animal models of strains
실험예 1-1: 비만 마우스 모델Experimental Example 1-1: Obese mouse model
실험동물은 수컷 4주령 C57BL/6N 마우스를 샘타코 사(Samtako Co. Ltd.)에서 구입하여 7일간 기본사료 (10 kcal% fat, D12450B)와 물을 자유롭게 공급하면서 실험실 환경에 적응시켰다. 실험군에 대해서는 10주간 고지방식이(60 kcal% fat)를 시작하여 비만을 유도한 후, 추가로 6주간 고지방식이를 섭취하면서 하루 1회 부티리시모나스 비로사 또는 부티리시모나스 시너지스티카를 경구 투여하였다(도 1). 실험 기간 동안 정상식이를 섭취하는 정상대조군, 그리고 고지방식이를 섭취하는 음성대조군을 포함하였다.As experimental animals, 4-week-old male C57BL/6N mice were purchased from Samtako Co. Ltd. and adapted to the laboratory environment while freely supplying basic feed (10 kcal% fat, D12450B) and water for 7 days. For the experimental group, a high-fat diet (60 kcal% fat) was started for 10 weeks to induce obesity, and then Butyricimonas virosa or Butyricimonas synergystica was orally administered once a day while consuming a high-fat diet for an additional 6 weeks. (Fig. 1). During the experiment, a normal control group consuming a normal diet and a negative control group consuming a high-fat diet were included.
실험군은 하기와 같이 분류하였다:Experimental groups were classified as follows:
① 기본 정상식이 (10 kcal% fat)를 섭취하는 정상대조군(Regular diet, RD);① Normal control group consuming a basic normal diet (10 kcal% fat) (Regular diet, RD);
② 16주간 고지방식이 (60 kcal% fat)를 섭취하는 음성대조군(High-fat diet, HFD);② Negative control group consuming a high-fat diet (60 kcal% fat) for 16 weeks (High-fat diet, HFD);
③ 16주간 고지방식이를 섭취하면서, 마지막 6주 동안 본 발명의 부티리시모나스 비로사 또는 부티리시모나스 시너지스티카 생균(1x108 CFU)을 매일 1회 경구 투여한 실험군(HFD-LB);③ While consuming a high-fat diet for 16 weeks, an experimental group (HFD-LB) administered orally once daily with Butyricimonas virosa or Butyricimonas synergistica live bacteria (1x10 8 CFU) of the present invention for the last 6 weeks;
④ 16주간 고지방식이를 섭취하면서, 마지막 6주 동안 본 발명의 부티리시모나스 비로사 또는 부티리시모나스 시너지스티카 사균(1x108 CFU)을 매일 1회 경구 투여한 실험군(HFD-DB).④ While consuming a high-fat diet for 16 weeks, the experimental group (HFD-DB) was orally administered with dead bacteria (1x10 8 CFU) of the present invention butyricimonas virosa or butyricimonas synergystica once daily for the last 6 weeks.
실험 기간 중 마지막 6주 동안 부티리시모나스 비로사 또는 부티리시모나스 시너지스티카 균주와 고지방식이를 투여하면서 지방간 질환의 치료 효능을 관찰하였다.During the last 6 weeks of the experimental period, the treatment efficacy of fatty liver disease was observed while administering Butyricimonas virosa or Butyricimonas synergystica strains and a high-fat diet.
모든 동물 실험은 삼육대학교 동물실험윤리위원회(IACUC)에 승인을 받아 실시하였다(SYUIACUC 2019-004).All animal experiments were conducted with the approval of the Animal Experimentation Ethics Committee (IACUC) of Sahmyook University (SYUIACUC 2019-004).
실험예 1-2: 체중 변화 확인Experimental Example 1-2: Confirmation of weight change
본 발명에 따른 부티리시모나스 속 균주의 체중 감소 효과를 확인하기 위하여, 체중 변화를 측정하였다.In order to confirm the weight loss effect of the Butyricimonas genus strain according to the present invention, the weight change was measured.
구체적으로, 부티리시모나스 비로사 또는 부티리시모나스 시너지스티카 투여 이후, 매주 마우스의 체중을 측정하였으며, 실험 종료 후 대조군 및 실험군의 체중 차이를 비교하였다.Specifically, after administration of Butyricimonas virosa or Butyricimonas synergystica, the weight of the mice was measured every week, and after the end of the experiment, the difference in body weight between the control group and the experimental group was compared.
그 결과, 도 2a 및 도 2b에 나타낸 바와 같이, 고지방식이 섭취 후 6주간 고지방식이와 함께 부티리시모나스 비로사 또는 부티리시모나스 시너지스티카의 생균 및 사균을 투여한 실험군인 HFD-LB 및 HFD-DB의 최종 체중은 고지방식이만 섭취한 대조군(HFD)의 최종 체중보다 낮게 측정된 것을 확인하였으며(도 2a), 부티리시모나스 투여 6주 후에는 부티리시모나스 투여 전과 비교하여 체중이 감소함을 확인하였다(도 2b).As a result, as shown in Figures 2a and 2b, the experimental groups HFD-LB and HFD- were administered with live and dead cells of Butyricimonas virosa or Butyricimonas synergystica together with a high-fat diet for 6 weeks after ingestion of the high-fat diet. It was confirmed that the final weight of the DB was measured lower than the final weight of the control group (HFD) who consumed only the high-fat diet (FIG. 2a), and after 6 weeks of butyricimonas administration, the weight decreased compared to before butyricimonas administration. confirmed (Fig. 2b).
실험예 1-3: 간 무게 변화 확인Experimental Example 1-3: Check liver weight change
본 발명에 따른 부티리시모나스 속 균주의 지방간 형성에 미치는 효과를 확인하기 위하여, 마우스의 간 무게를 측정하였다.In order to confirm the effect of the strain of the genus Butyricimonas according to the present invention on fatty liver formation, the weight of the liver of the mouse was measured.
구체적으로, 실험이 종료된 후 마우스를 희생시켜 마우스의 간 무게를 측정하였다.Specifically, after the experiment was finished, the mouse was sacrificed and the weight of the liver of the mouse was measured.
그 결과, 도 3에 나타낸 바와 같이, 고지방식이를 섭취한 HFD 군에서 간의 무게가 현저히 증가한 반면, 부티리시모나스 비로사 또는 부티리시모나스 시너지스티카의 생균 및 사균을 투여한 HFD-LB 및 HFD-DB 군에서 간의 무게는 정상대조군과 비슷한 정도로 관찰됨을 확인하였다. 이 결과는 고지방식이로 인하여 간 조직에 콜레스테롤 및 중성지질이 축적되었으나, 부티리시모나스 비로사 및 부티리시모나스 시너지스티카가 지방간 형성을 억제할 수 있어 지방간 질환의 예방 또는 치료 효과가 있음을 나타낸다.As a result, as shown in FIG. 3, the weight of the liver significantly increased in the HFD group consuming the high-fat diet, while the HFD-LB and HFD-DB administered with live and dead cells of Butyricimonas virosa or Butyricimonas synergystica. It was confirmed that the weight of the liver in the group was observed at a similar level to that of the normal control group. This result indicates that although cholesterol and triglycerides were accumulated in liver tissue due to the high-fat diet, Butyricimonas virosa and Butyricimonas synergystica can inhibit fatty liver formation, thereby preventing or treating fatty liver disease.
실험예 1-4: 조직학적 변화 확인Experimental Example 1-4: Confirmation of histological changes
본 발명에 따른 부티리시모나스 속 균주가 지질 축적 및 지방간 형성에 미치는 효과를 확인하기 위하여, 간 조직의 H&E (Hematoxylin & eosin) 염색을 통해 지질 축적 상태의 변화를 확인하였다.In order to confirm the effect of the Butyricimonas genus strain according to the present invention on lipid accumulation and fatty liver formation, changes in lipid accumulation state were confirmed through H&E (Hematoxylin & eosin) staining of liver tissue.
구체적으로, 실험이 종료된 후 마우스의 간을 적출하여 조직을 추출하고, 일부분을 10% 포름알데히드에 담근 후, 파라핀 절편을 만들어 H&E 염색을 하여 광학 현미경으로 조직을 관찰하였다. Specifically, after the experiment was completed, the liver of the mouse was extracted, the tissue was extracted, and a portion was immersed in 10% formaldehyde, and then paraffin sections were made and H&E stained, and the tissue was observed under an optical microscope.
그 결과, 도 4에 나타낸 바와 같이, 고지방식이만 섭취한 HFD 군에서는 간 조직 내 지방 소립(lipid droplet)이 많이 축적된 반면, 부티리시모나스 비로사 또는 부티리시모나스 시너지스티카를 투여한 군(HFD+LB 및 HFD+DB)에서는 HFD 군에 비해 간 조직 내 지방 소립의 양이 현저히 감소하였음을 확인하였다. 이상의 결과로부터, 부티리시모나스 비로사 및 부티리시모나스 시너지스티카는 간 내 지방의 축적을 억제할 수 있어, 우수한 지방간 질환의 예방 및 치료 효과가 있음을 확인하였다.As a result, as shown in FIG. 4, in the HFD group consuming only the high-fat diet, a large amount of fat droplets were accumulated in the liver tissue, whereas in the group administered with Butyricimonas virosa or Butyricimonas synergystica (HFD +LB and HFD+DB), it was confirmed that the amount of fat granules in the liver tissue was significantly reduced compared to the HFD group. From the above results, it was confirmed that Butyricimonas virosa and Butyricimonas synergystica can inhibit the accumulation of fat in the liver, and thus have excellent preventive and therapeutic effects of fatty liver disease.
이상의 설명으로부터, 본 발명이 속하는 기술분야의 당업자는 본 발명이 그 기술적 사상이나 필수적 특징을 변경하지 않고서 다른 구체적인 형태로 실시될 수 있다는 것을 이해할 수 있을 것이다. 이와 관련하여, 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적인 것이 아닌 것으로서 이해해야만 한다. 본 발명의 범위는 상기 상세한 설명보다는 후술하는 특허 청구범위의 의미 및 범위 그리고 그 등가 개념으로부터 도출되는 모든 변경 또는 변형된 형태가 본 발명의 범위에 포함되는 것으로 해석되어야 한다.From the above description, those skilled in the art to which the present invention pertains will be able to understand that the present invention may be embodied in other specific forms without changing its technical spirit or essential features. In this regard, the embodiments described above should be understood as illustrative in all respects and not limiting. The scope of the present invention should be construed as including all changes or modifications derived from the meaning and scope of the claims to be described later and equivalent concepts rather than the detailed description above are included in the scope of the present invention.
Claims (14)
상기 부티리시모나스 속(Butyricimonas sp.) 균주는 부티리시모나스 비로사(Butyricimonas virosa) 또는 부티리시모나스 시너지스티카(Butyricimonas synergistica)인, 약학적 조성물.
Butyricimonas genus ( Butyricimonas sp. ) As a pharmaceutical composition for preventing or treating non-alcoholic fatty liver disease, comprising a strain, its culture medium, its concentrate, its dried product, or a combination thereof as an active ingredient,
The Butyricimonas genus (Butyricimonas sp.) strain is Butyricimonas virosa (Butyricimonas virosa) or Butyricimonas Synergistica (Butyricimonas synergistica), a pharmaceutical composition.
상기 부티리시모나스 속(Butyricimonas sp.) 균주는 생균, 사균 또는 이들의 조합 형태로 포함되는 것인, 약학적 조성물.
According to claim 1,
The genus Butyricimonas Butyricimonas ( Butyricimonas sp. ) The strain is a pharmaceutical composition that is included in the form of live bacteria, dead bacteria or a combination thereof.
상기 비알콜성 지방간 질환은 단순 지방간 질환, 영양성 지방간 질환, 기아성 지방간 질환, 비만성 지방간 질환, 당뇨병성 지방간 질환, 지방간염, 간섬유화 및 간경화로 이루어진 군으로부터 선택되는 것인, 약학적 조성물.
According to claim 1,
The non-alcoholic fatty liver disease is selected from the group consisting of uncomplicated fatty liver disease, nutritional fatty liver disease, starvation fatty liver disease, obese fatty liver disease, diabetic fatty liver disease, steatohepatitis, hepatic fibrosis and cirrhosis, pharmaceutical composition.
상기 비알콜성 지방간 질환의 예방 또는 치료는 간 내 지방 축적 억제로 이루어지는 것인, 약학적 조성물.
According to claim 1,
Prevention or treatment of the non-alcoholic fatty liver disease is composed of inhibition of fat accumulation in the liver, a pharmaceutical composition.
상기 부티리시모나스 속(Butyricimonas sp.) 균주는 부티리시모나스 비로사(Butyricimonas virosa) 또는 부티리시모나스 시너지스티카(Butyricimonas synergistica)인, 식품 조성물.
Butyricimonas genus ( Butyricimonas sp. ) A food composition for preventing or improving non-alcoholic fatty liver disease, protecting the liver or improving liver function, comprising a strain thereof, a culture thereof, a concentrate thereof, a dried product thereof, or a combination thereof as an active ingredient. as,
The Butyricimonas genus (Butyricimonas sp.) strain is Butyricimonas virosa (Butyricimonas virosa) or Butyricimonas Synergistica (Butyricimonas synergistica), food composition.
상기 부티리시모나스 속(Butyricimonas sp.) 균주는 생균, 사균 또는 이들의 조합 형태로 포함되는 것인, 식품 조성물.
According to claim 7,
The Butyricimonas genus ( Butyricimonas sp. ) The strain is a food composition that is included in the form of live bacteria, dead bacteria or a combination thereof.
상기 비알콜성 지방간 질환은 단순 지방간 질환, 영양성 지방간 질환, 기아성 지방간 질환, 비만성 지방간 질환, 당뇨병성 지방간 질환, 지방간염, 간섬유화 및 간경화로 이루어진 군으로부터 선택되는 것인, 식품 조성물.
According to claim 7,
The non-alcoholic fatty liver disease is selected from the group consisting of simple fatty liver disease, nutritional fatty liver disease, starvation fatty liver disease, obese fatty liver disease, diabetic fatty liver disease, steatohepatitis, hepatic fibrosis and cirrhosis, food composition.
A health functional food comprising the food composition of any one of claims 7, 8 and 11.
상기 부티리시모나스 속(Butyricimonas sp.) 균주는 부티리시모나스 비로사(Butyricimonas virosa) 또는 부티리시모나스 시너지스티카(Butyricimonas synergistica)인, 사료 조성물.Butyricimonas genus ( Butyricimonas sp. ) strain, its culture medium, its concentrate, its dried product, or a feed composition for preventing or improving non-alcoholic fatty liver disease, protecting the liver or improving liver function, comprising a combination thereof as an active ingredient as,
The Butyricimonas genus (Butyricimonas sp.) strain is Butyricimonas virosa (Butyricimonas virosa) or Butyricimonas Synergistica (Butyricimonas synergistica), feed composition.
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