KR102502710B1 - Composition containing cinnamic acid for improving intestinal microflora - Google Patents
Composition containing cinnamic acid for improving intestinal microflora Download PDFInfo
- Publication number
- KR102502710B1 KR102502710B1 KR1020200097481A KR20200097481A KR102502710B1 KR 102502710 B1 KR102502710 B1 KR 102502710B1 KR 1020200097481 A KR1020200097481 A KR 1020200097481A KR 20200097481 A KR20200097481 A KR 20200097481A KR 102502710 B1 KR102502710 B1 KR 102502710B1
- Authority
- KR
- South Korea
- Prior art keywords
- cinnamic acid
- intestinal flora
- improving
- microorganisms
- intestinal
- Prior art date
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Classifications
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- A—HUMAN NECESSITIES
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- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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Abstract
본 발명은 신남산을 유효성분으로 포함하는 장내 균총 불균형 개선용 조성물에 관한 것으로, 보다 구체적으로, 신남산을 유효성분으로 포함하는 장내 균총 개선용 약학 조성물; 신남산을 유효성분으로 포함하는 장내 균총 개선용 식품 조성물; 및 신남산을 유효성분으로 포함하는 조성물을 인간을 제외한 개체에 투여하는 단계를 포함하는 장내 균총 개선방법에 관한 것이다.
본 발명의 신남산을 유효성분으로 하는 조성물은 갱년기에 의한 장내 균총 불균형, 장내 균총 다양성 감소, 호기성 장내 미생물 또는 스트레스 내성 미생물의 감소, 또는 장 건강에 도움을 주는 미생물의 감소를 개선하는 효능이 있어, 장내 균총 개선용 조성물로서 유용하게 사용될 수 있다.The present invention relates to a composition for improving intestinal flora imbalance containing cinnamic acid as an active ingredient, and more specifically, to a pharmaceutical composition for improving intestinal flora containing cinnamic acid as an active ingredient; A food composition for improving intestinal flora containing cinnamic acid as an active ingredient; and a method for improving intestinal flora, comprising administering a composition containing cinnamic acid as an active ingredient to a non-human subject.
The composition containing cinnamic acid as an active ingredient of the present invention has the effect of improving intestinal flora imbalance caused by menopause, reduction of intestinal flora diversity, reduction of aerobic intestinal microorganisms or stress-resistant microorganisms, or reduction of microorganisms conducive to intestinal health. , It can be usefully used as a composition for improving intestinal flora.
Description
본 발명은 신남산을 유효성분으로 포함하는 장내 균총 불균형 개선용 조성물에 관한 것으로, 보다 구체적으로, 신남산을 유효성분으로 포함하는 장내 균총 개선용 약학 조성물; 신남산을 유효성분으로 포함하는 장내 균총 개선용 식품 조성물; 및 신남산을 유효성분으로 포함하는 조성물을 인간을 제외한 개체에 투여하는 단계를 포함하는 장내 균총 개선방법에 관한 것이다.The present invention relates to a composition for improving intestinal flora imbalance containing cinnamic acid as an active ingredient, and more specifically, to a pharmaceutical composition for improving intestinal flora containing cinnamic acid as an active ingredient; A food composition for improving intestinal flora containing cinnamic acid as an active ingredient; and a method for improving intestinal flora, comprising administering a composition containing cinnamic acid as an active ingredient to a non-human subject.
사람의 몸에는 사람의 세포 수와 거의 비슷한 숫자의 인체 미생물이 존재한다. 특히 최근에는 인체 미생물의 90% 이상을 차지하는 장내 미생물이 다양한 인체 질환에 관여하고 있음이 밝혀지고 있다. 장내 미생물의 불균형이 비만, 당뇨, 심혈관 질환 등의 만성 대사성 질환과 우울증, 치매와 같은 정신질환을 야기시킬 뿐만 아니라, 뼈 건강에도 영향을 끼치는 것으로 보고되고 있다.There are approximately the same number of human microorganisms as the number of human cells in the human body. In particular, it has recently been revealed that intestinal microbes, which account for more than 90% of human microbes, are involved in various human diseases. It has been reported that the imbalance of intestinal microbes not only causes chronic metabolic diseases such as obesity, diabetes and cardiovascular diseases, and mental diseases such as depression and dementia, but also affects bone health.
갱년기 상태의 여성은 폐경 전과는 다른 장내 미생물 특성을 나타낸다. 미생물 다양성이 감소하게 되고 그람 양성 미생물은 줄어드는 대신 그람 음성 미생물이 증가한다. 특히, 갱년기에 Firmicutes 문(Phylum)이 감소하는 것으로 알려졌는데 장 건강에 중요한 역할을 하는 Lachnospira, Roseburia와 같은 Lachnospiraceae 과(Family)에 속하는 미생물이 줄어들게 된다.Menopausal women show different gut microbiome characteristics than pre-menopausal women. Microbial diversity decreases, and Gram-negative microorganisms increase instead of Gram-positive microorganisms. In particular, it is known that the Firmicutes phylum decreases during menopause, and microorganisms belonging to the Lachnospiraceae family such as Lachnospira and Roseburia, which play an important role in intestinal health, decrease.
이러한 미생물총 불균형은, 세계적인 미생물총 프로파일, 대사 또는 특정 분류군의 수준 면에서, 균형 잡힌 미생물총으로부터 유의하게 벗어난 것으로서 정의될 수 있으며, 질병에 대한 증가된 취약성과 통상 관련된다.This microbiome imbalance can be defined as a significant departure from a balanced microbiome, either in terms of global microbiome profile, metabolism or level of a particular taxa, and is usually associated with increased susceptibility to disease.
한편, 신남산(cinnamic acid)은 화학식 C9H8O2로 표시되는 화합물로, 계피산, 육계산이라고도 한다. 약한 방향을 가진 무색의 바늘 모양 결정이며, 육계유(카시아유), 페루발삼, 소합향유 등에 유리상태로 또는 에스터의 형태로 존재한다. 페닐기와 카복시기가 이중결합에 대하여 반대쪽에 있는 트랜스형과, 같은 쪽에 있는 시스형의 두 이성질체를 생 각할 수 있으나, 천연으로는 안정한 트랜스형이 존재한다. 또한 벤즈알데하이드와 아세트산무수물을 아세트산칼륨의 존재하에 축합시키면 얻을 수 있다.Meanwhile, cinnamic acid is a compound represented by the chemical formula C 9 H 8 O 2 , and is also referred to as cinnamic acid or cinnamic acid. It is a colorless, needle-shaped crystal with a weak direction, and exists in the form of ester or free form in cassia oil, Peru balsam, and fragrant oil. Two isomers can be considered: a trans form in which the phenyl group and the carboxyl group are on opposite sides of the double bond, and a cis form in which the phenyl group and the carboxyl group are on opposite sides of the double bond. However, a stable trans form exists in nature. It can also be obtained by condensing benzaldehyde and acetic anhydride in the presence of potassium acetate.
국내등록특허 10-1754826에서는 상기 신남산으로부터 제조한 미백 기능성 유도체에 관하여 개시하고 있으며, 국내등록특허 10-1181175에서는 신남산 유도체의 항마약 효능에 대하여 개시하고 있으나, 신남산의 장내 미생물 불균형 개선 효능에 대하여는 알려진 바가 없다.Korean Patent No. 10-1754826 discloses a whitening functional derivative prepared from cinnamic acid, and Korean Patent No. 10-1181175 discloses anti-narcotic efficacy of cinnamic acid derivatives. nothing is known about
이러한 배경하에, 본 발명자들은 장내 미생물 불균형을 개선하고자 예의 노력 연구한 결과, 신남산이 갱년기에 의한 장내 미생물 다양성 감소, 호기성 장내 미생물 또는 스트레스 내성 미생물의 감소, 또는 장 건강에 도움을 주는 미생물의 감소를 개선하는 효능이 있음을 확인하여, 본 발명을 완성하였다.Under this background, the present inventors studied diligently to improve intestinal microbial imbalance, and as a result, Sinnamsan reduced intestinal microbial diversity due to menopause, decreased aerobic intestinal microorganisms or stress-resistant microorganisms, or reduced microorganisms conducive to intestinal health. It was confirmed that there is an effect of improving, and the present invention was completed.
본 발명의 하나의 목적은 신남산을 유효성분으로 포함하는 장내 균총 개선용 약학 조성물을 제공하는 것이다.One object of the present invention is to provide a pharmaceutical composition for improving intestinal microflora containing cinnamic acid as an active ingredient.
본 발명의 다른 하나의 목적은 신남산을 유효성분으로 포함하는 장내 균총 개선용 식품 조성물을 제공하는 것이다.Another object of the present invention is to provide a food composition for improving intestinal microflora containing cinnamic acid as an active ingredient.
본 발명의 또 다른 하나의 목적은 신남산을 유효성분으로 포함하는 조성물을 인간을 제외한 개체에 투여하는 단계를 포함하는 장내 균총 개선방법을 제공하는 것이다.Another object of the present invention is to provide a method for improving intestinal flora, comprising administering a composition containing cinnamic acid as an active ingredient to a non-human subject.
상기 목적을 달성하기 위한 본 발명의 하나의 양태는 신남산을 유효성분으로 포함하는 장내 균총 개선용 약학 조성물을 제공한다.One aspect of the present invention for achieving the above object provides a pharmaceutical composition for improving intestinal flora comprising cinnamic acid as an active ingredient.
구체적으로, 상기 개선은 장내 균총 불균형을 회복시킴을 통해 이루어지는 것일 수 있고, 보다 구체적으로, 상기 불균형은 갱년기 증상인 것일 수 있으나, 이에 제한되는 것은 아니다.Specifically, the improvement may be achieved by restoring intestinal flora imbalance, and more specifically, the imbalance may be menopausal symptoms, but is not limited thereto.
또한, 상기 개선은 장내 균총 다양성을 증가시킴을 통해 이루어질 수 있으며, 호기성 장내 미생물 또는 스트레스 내성 미생물의 감소를 통해 이루어지는 것일 수 있고, 장 건강에 도움을 주는 미생물의 증가를 통해 이루어지는 것일 수 있으며, 보다 구체적으로, 상기 장 건강에 도움을 주는 미생물은 라크노스피로세(Lachnospiraceae) 또는 루미노코카새애(Ruminococcaceae)인 것일 수 있으나, 이에 제한되는 것은 아니다.In addition, the improvement may be achieved by increasing the diversity of intestinal flora, by reducing aerobic intestinal microbes or stress-resistant microbes, by increasing microbes conducive to intestinal health, and more Specifically, the microorganism conducive to the intestinal health may be Lachnospiraceae or Ruminococcaae (Ruminococcaceae), but is not limited thereto.
또한, 상기 조성물은 장내 균총 개선에 의해 갱년기 증상을 예방 또는 치료하는 것일 수 있고, 장내 건강을 개선하는 것일 수 있으며, 또한, 추가의 프리바이오틱스(prebiotics)를 포함할 수 있는 것일 수 있다.In addition, the composition may prevent or treat menopausal symptoms by improving intestinal flora, improve intestinal health, and may also include additional prebiotics.
본 발명에서의 용어, “신남산(cinnamic acid)”은 화학식 C9H8O2로 표시되는 화합물로, 계피산, 육계산이라고도 한다. 약한 방향을 가진 무색의 바늘 모양 결정이며, 육계유(카시아유), 페루발삼, 소합향유 등에 유리상태로 또는 에스터의 형태로 존재한다. 페닐기와 카복시기가 이중결합에 대하여 반대쪽에 있는 트랜스형과, 같은 쪽에 있는 시스형의 두 이성질체를 생 각할 수 있으나, 천연으로는 안정한 트랜스형이 존재한다. 또한 벤즈알데하이드와 아세트산무수물을 아세트산칼륨의 존재하에 축합시키면 얻을 수 있다. 상기 신남산의 장내 미생물 불균형 개선 효능에 대하여는 알려진 바 없으며, 본 발명에 의해서 최초로 규명되었다.In the present invention, the term “cinnamic acid” is a compound represented by the chemical formula C 9 H 8 O 2 , and is also referred to as cinnamic acid or cinnamic acid. It is a colorless, needle-shaped crystal with a weak direction, and exists in the form of ester or free form in cassia oil, Peru balsam, and fragrant oil. Two isomers can be considered: a trans form in which the phenyl group and the carboxyl group are on opposite sides of the double bond, and a cis form in which the phenyl group and the carboxyl group are on opposite sides of the double bond. However, a stable trans form exists in nature. It can also be obtained by condensing benzaldehyde and acetic anhydride in the presence of potassium acetate. The efficacy of cinnamic acid for improving intestinal microbial imbalance is unknown, and was first identified by the present invention.
본 발명에서의 용어, "유효성분"은 단독으로 목적으로 하는 활성을 나타내거나 또는 그 자체는 활성이 없는 담체 등과 함께 목적으로 하는 활성을 나타낼 수 있는 성분을 의미한다.As used herein, the term "active ingredient" refers to a component that can exhibit the desired activity alone or together with a carrier having no activity itself.
본 발명에서의 용어, “장내 균총”은 동물의 장내에 특이적으로 분포하여 서식하는 미생물의 집단을 의미한다. 본 발명에 있어서 상기 “장내 균총”은 “장내 미생물”과 혼용되어 사용될 수 있다.As used herein, the term “intestinal flora” refers to a group of microorganisms that are specifically distributed and inhabit the intestines of animals. In the present invention, the "intestinal flora" may be used in combination with "intestinal microorganisms".
본 발명에서의 용어, "개선"은 어떠한 증상이 호전되거나 이롭게 변경되는 모든 행위를 의미한다.As used herein, the term "improvement" refers to any activity that improves or beneficially changes any symptom.
본 발명에서의 용어, “불균형”은 균형이 잡히지 않고 어느 편으로 치우친 상태를 의미한다.The term "imbalance" in the present invention means a state that is not balanced and is biased to one side.
본 발명에서의 용어, “회복”은 원래의 상태로 돌이키거나 원래의 상태를 되찾는 것을 의미하며, 본 발명에 있어서는 장내 균총의 불균형 상태가 본래의 상태로 돌아가는 것을 의미할 수 있다.The term "recovery" in the present invention means to return to the original state or to restore the original state, and in the present invention, it may mean that the imbalanced state of the intestinal flora returns to the original state.
본 발명에서의 용어, “갱년기”는 인체가 성숙기에서 노년기로 접어드는 시기를 의미하며, 여성의 경우 생식 기능이 없어지고 월경이 정지되며, 남성의 경우 성기능이 감퇴되는 현상과 같은 신체 기능 저하 현상이 나타나는 것이 특징이다.As used herein, the term "menopausal" refers to the period when the human body enters old age from maturity, and in the case of women, reproductive function is lost and menstruation stops, and in the case of men, there is a phenomenon of deterioration in body function, such as a phenomenon in which sexual function is reduced. It is characteristic to appear.
본 발명에서의 용어, “다양성”은 모양, 형태, 양식 등이 여러 가지로 많은 특성을 의미하나, 본원 발명에서는 군집 구조의 복잡성을 나타내는 것일 수 있다.The term "diversity" in the present invention means many characteristics in various shapes, forms, patterns, etc., but in the present invention, it may indicate the complexity of the cluster structure.
본 발명에서의 용어, “프리바이오틱스(prebiotics)”는 박테리아의 성장을 자극하여 인체에 유리한 영향을 주는 물질을 의미한다.As used herein, the term “prebiotics” refers to substances that have a beneficial effect on the human body by stimulating the growth of bacteria.
본 발명의 일 실시예에서는, 신남산이 장내 균총 불균형을 개선하는지 알아보기 위하여, 신남산을 동물(쥐) 모델에 투여하여, 장내 균총의 다양성의 변화를 확인하였고(도 1), 호기성 장내 미생물 및 스트레스 내성 미생물 변화를 측정하였으며(도 2), 여성의 갱년기에서 감소하는 것으로 알려진 장내 미생물 라크노스피로세 및 루미노코카새애의 변화를 확인하였다(도 3).In one embodiment of the present invention, in order to determine whether cinnamic acid improves intestinal flora imbalance, cinnamic acid was administered to an animal (rat) model to confirm changes in the diversity of intestinal flora (FIG. 1), and aerobic intestinal microorganisms And changes in stress-resistant microorganisms were measured (FIG. 2), and changes in intestinal microorganisms known to decrease in women's menopause, such as Lachnospirose and Luminococca, were confirmed (FIG. 3).
상기 목적을 달성하기 위한 본 발명의 또 다른 하나의 양태는 신남산을 유효성분으로 포함하는 장내 균총 개선용 식품 조성물을 제공한다.Another aspect of the present invention for achieving the above object provides a food composition for improving intestinal flora comprising cinnamic acid as an active ingredient.
이때, 상기 “신남산”, “유효성분”, “장내 균총”, 및 “개선”에 대한 설명은 상기에서 서술한 바와 같다.At this time, the description of the "cinnamic acid", "active ingredient", "intestinal flora", and "improvement" is as described above.
본 발명의 식품 조성물은 다양한 형태의 식품 첨가제 또는 기능성 식품을 제공한다. 구체적으로, 상기 조성물을 포함하는 침출차, 액상차, 음료, 발효유, 치즈, 요구르트, 주스, 생균제제 또는 건강보조식품 등으로 가공될 수 있으며, 그 외 다양한 식품 첨가제의 형태로 사용될 수 있다.The food composition of the present invention provides food additives or functional foods in various forms. Specifically, it can be processed into leached tea, liquid tea, beverages, fermented milk, cheese, yogurt, juice, probiotics or health supplements containing the composition, and can be used in the form of various other food additives.
본 발명의 식품 조성물은 식품학적으로 허용가능한 담체를 추가로 포함하는 것일 수 있다.The food composition of the present invention may further include a carrier acceptable in food science.
본 발명의 신남산을 첨가할 수 있는 식품의 종류에는 별다른 제한이 없으며, 예를 들어 각종 음료, 껌, 차, 비타민 복합제, 건강보조식품류 등이 있다. 상기 식품 조성물에는 장내 미생물 불균형 개선에 방해가 되지 않는 다른 성분을 추가할 수 있으며, 그 종류는 특별히 제한되지 않는다. 예를 들어, 통상의 식품과 같이 여러 가지 생약 추출물, 식품학적으로 허용가능한 식품보조첨가제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다.There is no particular limitation on the type of food to which the cinnamic acid of the present invention can be added, and examples thereof include various beverages, chewing gum, tea, vitamin complexes, health supplements, and the like. Other ingredients that do not hinder improvement of intestinal microbial imbalance may be added to the food composition, and the type is not particularly limited. For example, it may contain various herbal extracts, food-acceptable food additives, or natural carbohydrates as additional ingredients, like conventional foods.
상기 식품보조첨가제는 각 제형의 건강기능식품을 제조하는데 첨가되는 것으로서 당업자가 적절히 선택하여 사용할 수 있다. 예를 들어 여러 가지 영양제, 비타민, 광물 (전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 충진제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등이 포함되지만, 상기 예들에 의해 그 종류가 제한되는 것은 아니다.The food additives may be appropriately selected and used by those skilled in the art as being added to prepare health functional foods of each formulation. For example, various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and fillers, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusting agents , stabilizers, preservatives, glycerin, alcohol, carbonation agents used in carbonated beverages, etc. are included, but the types are not limited by the above examples.
이때, 상기 식품에 포함되는 추출물 또는 분획물의 함량은 특별히 이에 제한되지 않으나, 식품 조성물의 총 중량에 대하여 0.01 내지 100 중량%, 구체적으로는 1 내지 80 중량%로 포함될 수 있다.At this time, the content of the extract or fraction contained in the food is not particularly limited thereto, but may be included in 0.01 to 100% by weight, specifically 1 to 80% by weight based on the total weight of the food composition.
식품이 음료인 경우에는 100㎖를 기준으로 1 내지 30g, 구체적으로는 3 내지 20g의 비율로 포함될 수 있다. 또한, 상기 조성물은 식품 조성물에 통상 사용되어 냄새, 맛, 시각 등을 향상시킬 수 있는 추가 성분을 포함할 수 있다. 예를 들어, 비타민 A, C, D, E, B1, B2, B6, B12, 니아신(niacin), 비오틴(biotin), 폴레이트(folate), 판토텐산(panthotenic acid) 등을 포함할 수 있다. 또한, 아연(Zn), 철(Fe), 칼슘(Ca), 크롬(Cr), 마그네슘(Mg), 망간(Mn), 구리(Cu) 등의 미네랄을 포함할 수 있다. 또한, 라이신, 트립토판, 시스테인, 발린 등의 아미노산을 포함할 수 있다. 또한, 방부제(소르빈산 칼륨, 벤조산나트륨, 살리실산, 데히드로초산나트륨 등), 살균제(표백분과 고도 표백분, 차아염소산나트륨 등), 산화방지제(부틸히드록시아니졸(BHA), 부틸히드록시톨류엔(BHT) 등), 착색제(타르색소 등), 발색제(아질산 나트륨, 아초산 나트륨 등), 표백제(아황산나트륨), 조미료(MSG 글루타민산나트륨 등), 감미료(둘신, 사이클레메이트, 사카린, 나트륨 등), 향료(바닐린, 락톤류 등), 팽창제(명반, D-주석산수소칼륨 등), 강화제, 유화제, 증점제(호료), 피막제, 검기초제, 거품억제제, 용제, 개량제 등의 식품 첨가물(food additives)을 첨가할 수 있다. 상기 첨가물은 식품의 종류에 따라 선별되고 적절한 양으로 사용된다.If the food is a beverage, it may be included in a ratio of 1 to 30 g, specifically 3 to 20 g based on 100 ml. In addition, the composition may include additional ingredients that are commonly used in food compositions to improve odor, taste, and visual properties. For example, vitamins A, C, D, E, B1, B2, B6, B12, niacin, biotin, folate, panthotenic acid, and the like may be included. In addition, minerals such as zinc (Zn), iron (Fe), calcium (Ca), chromium (Cr), magnesium (Mg), manganese (Mn), and copper (Cu) may be included. In addition, amino acids such as lysine, tryptophan, cysteine, and valine may be included. In addition, preservatives (potassium sorbate, sodium benzoate, salicylic acid, sodium dehydroacetate, etc.), disinfectants (bleaching powder, high bleaching powder, sodium hypochlorite, etc.), antioxidants (butylhydroxyanisole (BHA), butylhydroxytoluene ( BHT), etc.), coloring agents (tar color, etc.), coloring agents (sodium nitrite, sodium nitrite, etc.), bleach (sodium sulfite, etc.), seasonings (MSG sodium glutamate, etc.), sweeteners (dulcin, cyclemate, saccharin, sodium, etc.) Food additives such as flavoring agents (vanillin, lactones, etc.), expanding agents (alum, D-potassium hydrogen tartrate, etc.), strengthening agents, emulsifiers, thickeners (thickeners), coating agents, gum base agents, foam inhibitors, solvents, improvers, etc. ) can be added. The additive is selected according to the type of food and used in an appropriate amount.
본 발명의 식품 조성물은 당업계에서 통상적으로 사용되는 방법에 의하여 제조가능하며, 상기 제조 시에는 당업계에서 통상적으로 첨가하는 원료 및 성분을 첨가하여 제조할 수 있다. 또한 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용 시 발생할 수 있는 부작용 등이 없는 장점이 있고, 휴대성이 뛰어날 수 있다.The food composition of the present invention can be prepared by a method commonly used in the art, and can be prepared by adding raw materials and components commonly added in the art during the preparation. In addition, unlike general drugs, there is an advantage in that there is no side effect that may occur when taking a drug for a long time by using food as a raw material, and it can be excellent in portability.
상기 목적을 달성하기 위한 본 발명의 또 다른 하나의 양태는 신남산을 유효성분으로 포함하는 조성물을 개체에 투여하는 단계를 포함하는 장내 균총 개선방법을 제공한다.Another aspect of the present invention for achieving the above object provides a method for improving intestinal flora, comprising administering to a subject a composition containing cinnamic acid as an active ingredient.
이때, 상기 “신남산”, “유효성분”, “장내 미생물”, “불균형”, 및 “개선”에 대한 설명은 상기에서 서술한 바와 같다.At this time, the description of the "cinnamic acid", "active ingredient", "intestinal microorganisms", "imbalance", and "improvement" is as described above.
본 발명에서 사용되는 용어, "투여"는 어떠한 적절한 방법으로 환자에게 본 발명의 조성물 도입하는 것을 의미하며, 상기 조성물의 투여 경로는 목적 조직에 도달할 수 있는 한 어떠한 일반적인 경로를 통하여 투여될 수 있다. 복강 내 투여, 정맥 내 투여, 근육 내 투여, 피하 투여, 피내 투여, 경구 투여, 국소 투여, 비 내 투여될 수 있으나, 이에 제한되지는 않는다.As used herein, the term "administration" means introducing the composition of the present invention to a patient by any suitable method, and the administration route of the composition may be administered through any general route as long as it can reach the target tissue. . Intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, oral administration, topical administration, intranasal administration may be administered, but is not limited thereto.
본 발명의 조성물을 매일 투여 또는 간헐적으로 투여해도 좋고, 1일당 투여 횟수는 1회 또는 2 ~ 3회로 나누어 투여하는 것이 가능하다. 또한, 단독으로, 또는 다른 약물 치료와 병용하여 사용할 수 있다. 상기 요소를 모두 고려하여 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 당업자에 의해 용이하게 결정될 수 있다.The composition of the present invention may be administered daily or intermittently, and the number of administrations per day may be administered once or divided into 2 to 3 times. It can also be used alone or in combination with other drug treatments. It is important to administer the amount that can obtain the maximum effect with the minimum amount without side effects in consideration of all the above factors, and can be easily determined by those skilled in the art.
본 발명에서 용어, "개체"는 주름 또는 여성 갱년기 증후군이 발병하였거나 발병할 수 있는 쥐, 생쥐, 가축 등의 모든 동물을 의미한다.In the present invention, the term "individual" refers to all animals such as rats, mice, livestock, etc. that have or may develop wrinkles or female menopausal syndrome.
상기 목적을 달성하기 위한 본 발명의 또 다른 하나의 양태는 신남산을 유효성분으로 포함하는 조성물의 장내 균총 개선 용도를 제공한다.Another aspect of the present invention for achieving the above object provides a composition containing cinnamic acid as an active ingredient for improving intestinal flora.
본 발명의 신남산을 유효성분으로 하는 조성물은 갱년기에 의한 장내 균총 불균형, 장내 균총 다양성 감소, 호기성 장내 미생물 또는 스트레스 내성 미생물의 감소, 또는 장 건강에 도움을 주는 미생물의 감소를 개선하는 효능이 있어, 장내 균총 개선용 조성물로서 유용하게 사용될 수 있다.The composition containing cinnamic acid as an active ingredient of the present invention has the effect of improving intestinal flora imbalance caused by menopause, reduction of intestinal flora diversity, reduction of aerobic intestinal microorganisms or stress-resistant microorganisms, or reduction of microorganisms conducive to intestinal health. , It can be usefully used as a composition for improving intestinal flora.
도 1은 난소 절제술을 통해 갱년기를 유도한 동물 모델에서 신남산 처리에 의한 장내 균총 다양성 인덱스의 변화를 나타내는 그래프이다.
도 2는 난소 절제술을 통해 갱년기를 유도한 동물 모델에서 신남산 처리에 의한 장내 미생물 속(genus)의 변화를 측정한 결과를 나타낸 그래프이다.
도 3는 난소 절제술을 통해 갱년기를 유도한 동물 모델에서 신남산 처리에 의한 장내 호기성 미생물 및 스트레스 내성 미생물의 변화를 나타내는 그래프이다.
도 4은 난소 절제술을 통해 갱년기를 유도한 동물 모델에서 신남산 처리에 의해 여성 갱년기 특이적 장내 미생물인 라크노스피로세 또는 루미노코카새애의 변화를 나타내는 그래프이다.1 is a graph showing changes in the intestinal flora diversity index by cinnamic acid treatment in an animal model in which menopause was induced through ovariectomy.
Figure 2 is a graph showing the results of measuring changes in the genus of intestinal microorganisms by cinnamic acid treatment in an animal model in which menopause was induced through ovariectomy.
3 is a graph showing changes in aerobic microorganisms and stress-resistant microorganisms in the intestine by cinnamic acid treatment in an animal model in which menopause was induced through ovariectomy.
4 is a graph showing changes in female menopausal-specific intestinal microbes, Lachnospirose or Rumi no cocca, by cinnamic acid treatment in an animal model in which menopause was induced through ovariectomy.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 예시하기 위한 것으로서, 본 발명의 범위가 이들 실시예에 의해 제한되는 것으로 해석되지 않는 것은 당업계에서 통상의 지식을 가진 자에게 있어서 자명할 것이다.Hereinafter, the present invention will be described in more detail through examples. These examples are only for exemplifying the present invention, and it will be apparent to those skilled in the art that the scope of the present invention is not to be construed as being limited by these examples.
실험예 1. 신남산 준비Experimental Example 1. Preparation of Sinnamsan
본원에서 사용한 신남산은 Sigma Aldrich 에서 구매하여 사용하였다.Cinnamic acid used herein was purchased from Sigma Aldrich.
실험예 2. 동물 모델 준비 및 신남산 투여Experimental Example 2. Animal model preparation and administration of cinnamic acid
갱년기 동물 모델을 준비하기 위하여 난소 절제를 통해 호르몬 변화를 유도하였다.To prepare a menopausal animal model, hormonal changes were induced through ovarian resection.
보다 구체적으로, 7주된 C57BL/6J 암컷 쥐(mouse)를 구매하여 1주간 적응 시켰다. 이후, 마취과정을 통해 양쪽 난소 절제술을 실행하였다.More specifically, 7-week-old C57BL/6J female mice were purchased and adapted for 1 week. Subsequently, bilateral oophorectomy was performed under anesthesia.
또한, 상기 갱년기를 유도한 동물 모델에 신남산을 투여하였다.In addition, cinnamic acid was administered to the animal model inducing menopause.
보다 구체적으로, 동물 모델을 3 그룹에 나누어, 신남산을 각각 CA 5 mg/kg (CA5), CA 10 mg/kg (CA10), 및 CA 20 mg/kg (CA20)를 처리하였으며, 난소 절제술 후 신남산을 처리하지 않은 난소 절제군(OVX)을 준비하였다. 또한, 양성 대조군(E+P)으로는 0.1 mg/kg β-에스트라디올(β-estradiol) 및 1 mg/kg 프로게스테론(progesterone)을 투여하여 호르몬 변화를 촉진하였으며, 음성 대조군(Sham)으로는 복강 절제 후 난소의 제거 없이 봉합한 군을 준비하여, 2주의 회복기간 후 10주간 CA 50 mg/kg을 구강으로 투여하여 변화를 관찰하였다.More specifically, the animal model was divided into 3 groups, and cinnamic acid was treated with CA 5 mg/kg (CA5), CA 10 mg/kg (CA10), and CA 20 mg/kg (CA20), respectively, after ovariectomy. An ovarian excision group (OVX) not treated with cinnamic acid was prepared. In addition, as a positive control (E+P), 0.1 mg/kg β-estradiol and 1 mg/kg progesterone were administered to promote hormonal changes, and as a negative control (Sham), intraperitoneal After resection, a group in which the ovary was sutured without removal was prepared, and after a 2-week recovery period, CA 50 mg/kg was orally administered for 10 weeks to observe changes.
실험예 3. 미생물 균총의 유전자 분석Experimental Example 3. Genetic analysis of microbial flora
장내 미생물 균총은 상기 동물(쥐) 모델의 맹장(Cecum)에서 미생물 유전체를 QIAamp PowerFecal Pro DNA Kit를 사용하여 추출하여 박테리아 특이적 16S rRNA 부위인341F/805R영역에 대해 유전체 증폭을 수행하였다. 미생물 유전체의 염기서열 분석은 MiSeq (일루미나) 장비를 이용하였고 QIIME2 플랫폼을 통해 유전정보 정제 및 미생물 분류를 수행하였다. 밝혀진 미생물 균총의 정보를 이용하여 2차적으로 MicrobiomeAnalyst, Bugbase 분석도구를 이용하여 군집 다양성, 우점 미생물의 특징 및 통계학적 차이 등을 분석하였다.As for the gut microbiota, the microbial genome was extracted from the cecum of the animal (rat) model using the QIAamp PowerFecal Pro DNA Kit, and genome amplification was performed for the 341F/805R region, which is a bacteria-specific 16S rRNA region. MiSeq (Illumina) equipment was used for sequencing of microbial genomes, and genetic information purification and microbial classification were performed through the QIIME2 platform. MicrobiomeAnalyst and Bugbase analysis tools were used to secondarily analyze community diversity, characteristics of dominant microorganisms, and statistical differences using the information on the microbial flora.
실시예 1. 미생물 균총의 다양성 측정Example 1. Measurement of Diversity of Microbial Flora
신남산이 장내 미생물 균총의 다양성에 미치는 영향을 확인하기 위하여, 동물 모델을 통해 이를 확인하였다.In order to confirm the effect of cinnamic acid on the diversity of intestinal microflora, it was confirmed through an animal model.
구체적으로, 실험예 2의 방법을 통해 동물 모델 실험을 진행한 뒤, 실험예 3의 방법을 통해 분석하였다.Specifically, after the animal model experiment was conducted through the method of Experimental Example 2, it was analyzed through the method of Experimental Example 3.
그 결과, 도 1에서 볼 수 있듯이, 난소 절제를 하지 않은 음성 대조군(Sham)에서는 다양성 인덱스는 전체적으로 높았으나, 난소 절제술군(OVX)에서 인덱스 수치가 현저히 감소하는 것을 확인하였다. 반면, 신남산을 투여한 군에서는 상기 감소된 인덱스 수치가 농도의존적으로 증가하는 것을 확인하였으며, 이는 양성대조군 보다 우수한 효능임을 확인하였다.As a result, as shown in FIG. 1 , the diversity index was generally high in the negative control group (Sham) without ovariectomy, but it was confirmed that the index value significantly decreased in the ovariectomy group (OVX). On the other hand, in the group administered with cinnamic acid, it was confirmed that the decreased index value increased in a concentration-dependent manner, which was confirmed to be superior to the positive control group.
또한, 도 2에서 볼 수 있듯이, 난소 절제를 하지 않은 음성 대조군(Sham)에서 우점하였던 장내 균총이 난소 절제술 이후 상대적으로 감소하고 다른 장내 미생물이 증가한 것을 확인하였다. 반면 신남산을 투여한 군에서는 음성 대조군(Sham)에서 우점하였던 장내 균총이 신남산 투여 농도에 의존적으로 회복되는 것을 확인하였다.In addition, as shown in FIG. 2, it was confirmed that the intestinal flora, which was dominant in the negative control group (Sham) without ovariectomy, was relatively decreased after ovariectomy and other intestinal microorganisms increased. On the other hand, in the group administered with cinnamic acid, it was confirmed that the intestinal flora, which was dominant in the negative control group (Sham), was recovered dependently on the concentration of cinnamic acid administered.
이를 통해, 갱년기를 유도하자 장내 균총 다양성 인덱스 및 균총의 수가 감소하는 것을 확인하였으며, 신남산이 상기 감소된 다양성 인덱스 및 장내 균총의 수를 다시 회복시켜, 장내 균총의 불균형을 개선하고 다양성을 증가시키는 효능이 있음을 확인하였다.Through this, it was confirmed that the intestinal flora diversity index and the number of intestinal flora decreased when menopause was induced, and Sinnamsan restored the reduced diversity index and the number of intestinal flora, improving the imbalance of intestinal flora and increasing diversity It was confirmed that there is efficacy.
실시예 2. 호기성 장내 미생물 및 스트레스 내성 미생물 변화 측정Example 2. Measurement of changes in aerobic intestinal microbes and stress-tolerant microbes
신남산이 호기성 장내 미생물 및 스트레스 내성 미생물 변화에 미치는 영향을 확인하기 위하여, 동물 모델을 통해 이를 확인하였다.In order to confirm the effect of cinnamic acid on changes in aerobic intestinal microbes and stress-resistant microbes, this was confirmed through an animal model.
구체적으로, 실험예 2의 방법을 통해 동물 모델 실험을 진행한 뒤, 실험예 3의 방법을 통해 분석하였다.Specifically, after the animal model experiment was conducted through the method of Experimental Example 2, it was analyzed through the method of Experimental Example 3.
그 결과, 도 3에서 볼 수 있듯이, 난소 절제를 하지 않은 음성 대조군(Sham)에서는 호기성 장내 미생물 및 스트레스 내성 미생물의 수가 낮은 것을 확인하였으나, 난소 절제술군(OVX)에서는 상기 미생물의 수치가 유의하게 증가하는 것을 확인하였다. 반면, 신남산을 처리한 군에서는 상기 증가된 미생물들이 농도의존적으로 감소하는 것을 확인하였으며, CA20을 투여할 경우, 음성 대조군과 유사한 수치로 회복되는 것을 확인하였다. 또한, 이는 양성 대조군보다 우수한 효능임을 확인하였다.As a result, as shown in FIG. 3, it was confirmed that the number of aerobic intestinal microbes and stress-resistant microbes was low in the negative control group (Sham) without ovariectomy, but the number of the microbes significantly increased in the ovariectomy group (OVX). confirmed that. On the other hand, in the group treated with cinnamic acid, it was confirmed that the increased microorganisms decreased in a concentration-dependent manner, and when CA20 was administered, it was confirmed that the number was recovered to a value similar to that of the negative control group. In addition, it was confirmed that the efficacy was superior to that of the positive control group.
이를 통해, 갱년기를 유도하자 호기성 장내 미생물 및 스트레스 내성 미생물이 증가하는 것을 확인하였으며, 신남산이 상기 미생물들의 증가를 다시 감소시켜, 장내 미생물 불균형을 개선하는 효능이 있음을 확인하였다.Through this, it was confirmed that when menopause was induced, aerobic intestinal microbes and stress-resistant microbes increased, and it was confirmed that cinnamic acid had the effect of improving intestinal microbial imbalance by reducing the increase of the microbes again.
실시예 3. 라크노스피로세 (Lachnospiraceae) 및 루미노코카새애 (Ruminococcaceae)의 변화 측정Example 3. Measurement of changes in Lachnospiraceae and Ruminococcaceae
라크노스피로세(Lachnospiraceae) 및 루미노코카새애(Ruminococcaceae)는 여성 갱년기에서 특히 감소하는 것으로 알려져 있다. 따라서, 본 발명의 신남산이 여성 갱년기에서 감소하는 상기 장내 미생물 감소에 미치는 영향을 확인하기 위하여, 동물 모델을 통해 이를 확인하였다.Lachnospiraceae and Ruminococcaceae are known to be particularly reduced during female menopause. Therefore, in order to confirm the effect of the cinnamic acid of the present invention on the decrease in the intestinal microorganisms in female menopause, this was confirmed through an animal model.
구체적으로, 실험예 2의 방법을 통해 동물 모델 실험을 진행한 뒤, 실험예 3의 방법을 통해 분석하였다.Specifically, after the animal model experiment was conducted through the method of Experimental Example 2, it was analyzed through the method of Experimental Example 3.
그 결과, 도 4에서 볼 수 있듯이, 난소 절제를 하지 않은 음성 대조군(Sham)에서는 라크노스피로세 및 루미노코카새애의 수치가 감소하는 것을 확인하였으나, 난소 절제술군(OVX)에서는 상기 미생물의 수가 감소하는 것을 확인하였다. 반면, 신남산을 처리한 군에서는 상기 감소된 미생물들이 농도의존적으로 증가하는 것을 확인하였으며, 이는 양성 대조군보다 우수한 효능임을 확인하였다.As a result, as can be seen in FIG. 4, it was confirmed that the levels of Lachnospirose and Rumi no cocca were decreased in the negative control group (Sham) without ovariectomy, but in the ovariectomy group (OVX), the number of the microorganisms confirmed to decrease. On the other hand, in the group treated with cinnamic acid, it was confirmed that the reduced microorganisms increased in a concentration-dependent manner, which was confirmed to be superior to the positive control group.
이를 통해, 갱년기를 유도하자 라크노스피로세 및 루미노코카새애 미생물이 감소하는 것을 확인하였으며, 신남산이 상기 미생물들의 감소를 다시 증가시켜, 장내 미생물 불균형을 개선하는 효능이 있음을 확인하였다.Through this, it was confirmed that when menopause was induced, the microorganisms of Lachnospirose and Ruminococca were reduced, and it was confirmed that cinnamic acid had the effect of improving the imbalance of microorganisms in the intestine by increasing the decrease of the microorganisms again.
이상의 설명으로부터, 본 발명이 속하는 기술 분야의 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 실시 예들은 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 (12)
상기 신남산은 단리된 것인, 장내 균총 개선용 식품 조성물.
A food composition for improving intestinal flora, comprising cinnamic acid as an active ingredient,
The cinnamic acid is an isolated food composition for improving intestinal flora.
The food composition for improving intestinal flora according to claim 1, wherein the improvement is achieved by restoring intestinal flora imbalance.
The food composition for improving intestinal flora according to claim 1, wherein the improvement is achieved by increasing intestinal flora diversity.
The food composition for improving intestinal flora according to claim 1, wherein the improvement is achieved through reduction of aerobic intestinal microorganisms or stress-resistant microorganisms.
The food composition for improving intestinal flora according to claim 1, wherein the improvement is achieved through an increase in microorganisms conducive to intestinal health.
According to claim 7, wherein the microorganisms that help the intestinal health Lachnospiraceae (Lachnospiraceae) or Ruminococca saae (Ruminococcaceae) will, the intestinal flora improvement food composition.
The food composition for improving intestinal flora according to claim 1, which improves intestinal health by improving the intestinal flora.
The food composition according to claim 1, wherein the composition may include additional prebiotics (prebiotics).
상기 신남산은 단리된 것인, 장내 균총 개선방법.A method for improving intestinal flora comprising the step of administering a composition containing cinnamic acid as an active ingredient to a non-human subject,
The method for improving intestinal flora, wherein the cinnamic acid is isolated.
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