KR20140004935A - Pharmaceutical composition for preventing or treating inflammatory bowel disease comprising gallnut extract - Google Patents
Pharmaceutical composition for preventing or treating inflammatory bowel disease comprising gallnut extract Download PDFInfo
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- KR20140004935A KR20140004935A KR1020120072392A KR20120072392A KR20140004935A KR 20140004935 A KR20140004935 A KR 20140004935A KR 1020120072392 A KR1020120072392 A KR 1020120072392A KR 20120072392 A KR20120072392 A KR 20120072392A KR 20140004935 A KR20140004935 A KR 20140004935A
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- Prior art keywords
- bowel disease
- inflammatory bowel
- pharmaceutical composition
- extract
- present
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- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/22—Anacardiaceae (Sumac family), e.g. smoketree, sumac or poison oak
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
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- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
Abstract
Description
본 발명은 오배자 추출물을 포함하는 염증성 장질환의 예방 또는 치료효과를 갖는 약학 조성물에 관한 것으로, 보다 구체적으로 본 발명은 오배자 추출물을 포함하고, 담배연기로 인한 염증성 장질환의 발병을 억제할 수 있는 약학 조성물, 오배자 추출물을 포함하고, 담배연기로 인한 염증성 장질환을 예방 또는 개선시킬 수 있는 식품 조성물 및 상기 약학 조성물을 이용하여 염증성 사이토카인의 발현을 억제하는 방법에 관한 것이다.
The present invention relates to a pharmaceutical composition having a prophylactic or therapeutic effect of an inflammatory bowel disease comprising a gall bladder extract, and more particularly, the present invention comprises a gall bladder extract, which can suppress the development of inflammatory bowel disease caused by tobacco smoke. It relates to a pharmaceutical composition, a food composition comprising a gall bladder extract, which can prevent or ameliorate inflammatory bowel disease caused by tobacco smoke, and a method of inhibiting the expression of inflammatory cytokines using the pharmaceutical composition.
염증성 장질환(Inflammatory bowel disease, IBD)은 위장관 내에 만성적인 염증을 유발하는 질환으로, 비교적 청년층부터 발병하며 복통, 발열, 설사, 하혈 등의 증상을 수반한다. 대체로, 궤양성 대장염(Ulcerative colitis, UC)과 크론병(Cron's disease, CD)의 2가지 형태로 분류되는데, 궤양성 대장염은 주로 점막을 침범하여, 자주 문드러짐이나 궤양을 형성하는 대장의 원인불명의 확산성 비특이성 염증(diffuse nonspecific inflammation)의 일종으로서, 혈성 설사를 비롯하여 다양한 전신 증상을 수반하고, 크론병은 구강에서 항문까지 전 소화관을 비연속성으로 점막에서 장관(腸管) 전 층에 궤양, 섬유화, 협착과 병변(病變)이 진전되는 원인불명의 육아종성 염증성 병변으로, 복통, 만성 설사, 발열, 영양장애 등의 전신 증상을 수반한다.Inflammatory bowel disease (IBD) is a disease that causes chronic inflammation in the gastrointestinal tract. It occurs from a relatively young age and is accompanied by symptoms such as abdominal pain, fever, diarrhea and bleeding. In general, there are two types of ulcerative colitis (UC) and Crohn's disease (CD). Ulcerative colitis mainly involves the mucous membranes, often causing unstable colon or ulcers. Is a type of diffuse nonspecific inflammation of the brain, which is accompanied by a variety of systemic symptoms, including bloody diarrhea, and Crohn's disease is discontinuous from the oral cavity to the anus, with ulcers from the mucous membrane to the entire intestinal tract, Unexplained granulomatous inflammatory lesions that develop fibrosis, narrowing and lesions, accompanied by systemic symptoms such as abdominal pain, chronic diarrhea, fever and dystrophy.
상기 염증성 장질환의 발병원인은 아직까지 구체적으로 밝혀져 있지 않으나, 면역기능의 이상이 관여하는 것으로 알려져 있는데, 이에 관여하는 면역학적 요인으로는 선천적 면역성, 사이토카인(Cytokine)의 생성, CD4의 활성화 등이 알려져 있다. 특히, 사이토카인이 중요한 역할을 수행하는 것으로 알려져 있는데, 염증 부위에서 종양괴사인자(Tumor nerosis cytokine; TNF-α), 인터루킨(Interluekin; IL)-1, IL-6, IL-8 생성이 궤양성 대장염과 크론병 환자에게 현저하게 증가되는 것이 확인되었다. The pathogenesis of the inflammatory bowel disease is not yet known in detail, but it is known that abnormalities in immune function are involved. Immunological factors involved in this include innate immunity, cytokine production, activation of CD4, and the like. This is known. In particular, cytokines play an important role. Tumor nerosis cytokine (TNF-α), Interluekin (IL) -1, IL-6, and IL-8 production at the site of inflammation are ulcerative Significantly increased in patients with colitis and Crohn's disease.
이러한 염증성 장질환을 치료하기 위하여 사용되는 약물로는 스테로이드성 면역억제제, 프로스타글란딘(prostaglandins)의 생성을 차단하는 5-아미노살리실산(5-aminosalicylic acid; 5-ASA) 계통 약물(예, 설파살라진 등), 메살라진 등이 사용되고 있는데, 이들은 염증성 장질환의 치료효과가 미미할 뿐만 아니라 복부허실(fullness), 두통, 발진, 간질환, 백혈구 감소증, 무과립구증, 남성 불임 등의 심각한 부작용을 유발하기 때문에, 상기 치료제의 사용이 제한되고 있다.Drugs used to treat these inflammatory bowel diseases include 5-aminosalicylic acid (5-ASA) -based drugs (eg, sulfasalazine) that block the production of steroidal immunosuppressants, prostaglandins, Mesalazine and the like are used, and they are not only effective in treating inflammatory bowel disease but also cause serious side effects such as fullness, headache, rash, liver disease, leukopenia, agranulocytosis, and male infertility. Use is limited.
만일, 부작용을 유발하지 않는 염증성 장질환 치료제를 개발할 수 있다면, 보다 안전하면서도 효과적으로 염증성 장질환 환자들을 치료할 수 있을 것으로 예상되고 있으나, 아직까지는 부작용이 없는 치료제가 개발되지 못하고 있는 실정이다.
If it is possible to develop an inflammatory bowel disease treatment agent that does not cause side effects, it is expected to be able to treat patients with inflammatory bowel disease more safely and effectively, but there is no development of a drug without side effects so far.
이러한 배경하에서, 본 발명자들은 부작용을 유발하지 않는 천연물로부터 유래된 염증성 장질환 치료제를 개발하기 위하여 예의 연구노력한 결과, 오배자 추출물이 염증성 사이토카인 및 엘라스틴과 콜라겐을 파괴하는 것으로 알려진 MMP12의 발현을 억제하고, 장내 유산균의 감소를 억제할 수 있어, 염증성 장질환의 치료에 사용될 수 있음을 확인하고 본 발명을 완성하였다.
Against this background, the present inventors have made intensive studies to develop therapeutic agents for inflammatory bowel disease derived from natural products that do not cause side effects. As a result, the gall extracts inhibit the expression of inflammatory cytokines and MMP12, which are known to destroy elastin and collagen. In addition, it is possible to suppress the reduction of intestinal lactic acid bacteria, confirming that it can be used for the treatment of inflammatory bowel disease and completed the present invention.
본 발명의 하나의 목적은 오배자 추출물을 포함하는 염증성 장질환의 예방 또는 치료용 약학 조성물을 제공하는 것이다.One object of the present invention to provide a pharmaceutical composition for the prevention or treatment of inflammatory bowel disease comprising a gall bladder extract.
본 발명의 다른 목적은 오배자 추출물을 포함하는 염증성 장질환의 예방 또는 개선용 식품 조성물을 제공하는 것이다.Another object of the present invention to provide a food composition for the prevention or improvement of inflammatory bowel disease comprising a gall bladder extract.
본 발명의 또 다른 목적은 상기 약학 조성물을 이용하여 염증성 사이토카인의 발현을 억제하는 방법을 제공하는 것이다.
Still another object of the present invention is to provide a method of inhibiting the expression of inflammatory cytokines using the pharmaceutical composition.
상술한 목적을 달성하기 위한 일 실시양태로서, 본 발명은 오배자 추출물을 포함하는, 염증성 장질환 예방 또는 치료용 약학 조성물을 제공한다.
As one embodiment for achieving the above object, the present invention provides a pharmaceutical composition for preventing or treating inflammatory bowel disease, comprising a gall bladder extract.
본 발명의 용어 "오배자(五倍子, gallnut)"란, 매미목[同翅目] 진딧물과의 오배자면충이 옻나무과의 붉나무(오배자나무)의 잎에 기생하여 만든 벌레혹을 의미하는데, 형태학적으로, 불규칙적인 주머니 형상이고, 사람의 귀와 유사한 형상을 가지며, 속이 비어 있다. 한방에서는 수렴, 지혈, 해독, 항균의 효력이 있어, 설사, 탈항, 위궤양, 십이지장궤양, 도한, 유정, 혈변, 혈뇨, 구내염 등의 치료에 사용되어 왔다.The term "gallnut" of the present invention refers to an insect worm formed by parasitic nematode insects of the cicada aphid and parasitic on the leaves of Rhozophyllum (October japonica), morphologically and irregularly. It is an in-pocket shape, has a shape similar to a human ear, and is hollow. In oriental medicine, it has the effect of astringent, hemostasis, detoxification, antibacterial, and has been used for the treatment of diarrhea, prolapse, gastric ulcer, duodenal ulcer, cold, oil well, bloody stool, hematuria, stomatitis.
본 발명의 용어 "오배자 추출물"이란, 상기 오배자를 물 또는 유기용매로 추출하여 수득한 추출물을 의미하며, 본 발명의 목적상 염증성 장질환의 예방, 치료 또는 개선용 조성물의 유효성분이 될 수 있다. 상기 오배자 추출물은 물, 탄소수 1 내지 6의 알코올, 핵산, 클로로포름, 메틸아세테이트, 부탄올 등의 용매를 사용하여 추출된 것을 사용함이 바람직하다. 보다 바람직하게는 본 발명의 오배자 추출물은 물, 탄소수 1 내지 6의 알코올 또는 이들의 혼합용매인 추출용매를 사용하여 추출된 것일 수 있으며, 가장 바람직하게는 오배자의 열수 추출물 또는 70% 에탄올 추출물이 될 수 있으나, 특별히 이에 제한되지는 않는다.As used herein, the term "gall bladder extract" refers to an extract obtained by extracting the gall bladder with water or an organic solvent, and may be an active ingredient for the prevention, treatment or improvement of inflammatory bowel disease for the purposes of the present invention. The five gall extract is preferably extracted using a solvent such as water, alcohol having 1 to 6 carbon atoms, nucleic acid, chloroform, methyl acetate, butanol. More preferably, the gall bladder extract of the present invention may be extracted using water, an alcohol having 1 to 6 carbon atoms, or a mixed solvent thereof, and most preferably, gall bladder extract or 70% ethanol extract. It may be, but is not particularly limited thereto.
본 발명의 용어 "염증성 장질환(Inflammatory bowel disease, IBD)"이란, 복통, 발열, 설사, 하혈 등의 증상을 수반하면서, 위장관 내에 만성적인 염증을 유발하는 질환을 의미한다. 상기 염증성 장질환은 궤양성 대장염(Ulcerative colitis, UC)과 크론병(Cron's disease, CD)의 2가지 형태로 분류되는데, 궤양성 대장염은 주로 점막을 침범하여, 자주 문드러짐이나 궤양을 형성하는 대장의 원인불명의 확산성 비특이성 염증(diffuse nonspecific inflammation)의 일종으로서, 혈성 설사를 비롯하여 다양한 전신 증상을 수반하고, 크론병은 구강에서 항문까지 전 소화관을 비연속성으로 점막에서 장관(腸管) 전 층에 궤양, 섬유화, 협착과 병변(病變)이 진전되는 원인불명의 육아종성 염증성 병변으로, 복통, 만성 설사, 발열, 영양장애 등의 전신 증상을 수반한다.The term “Inflammatory bowel disease (IBD)” of the present invention refers to a disease causing chronic inflammation in the gastrointestinal tract, accompanied by symptoms such as abdominal pain, fever, diarrhea and bleeding. The inflammatory bowel disease is classified into two types of ulcerative colitis (UC) and Crohn's disease (CD). Ulcerative colitis mainly invades mucous membranes, and frequently causes ulcers or ulcers. A type of diffuse nonspecific inflammation of unknown origin, which is accompanied by various systemic symptoms, including bloody diarrhea. Unexplained granulomatous inflammatory lesions in which ulcers, fibrosis, stenosis and lesions progress, accompanied by systemic symptoms such as abdominal pain, chronic diarrhea, fever and dystrophy.
본 발명의 용어 "예방"이란, 상기 약학 조성물의 투여로 염증성 장질환을 억제 또는 지연시키는 모든 행위를 의미한다. The term "prevention" of the present invention means any action that inhibits or delays inflammatory bowel disease by administration of the pharmaceutical composition.
본 발명의 용어 "치료"란, 치료하고자 하는 개개인 또는 세포의 천연 과정을 변경시키기 위해 임상적으로 개입하는 모든 행위를 의미하는데, 임상 병리 상태가 진행되는 동안 또는 이를 예방하기 위해 수행할 수 있다. 목적하는 치료 효과에는 질병의 발생 또는 재발을 예방하고, 증상을 완화시키며, 질병에 따른 모든 직접 또는 간접적인 병리학적 결과를 저하시키며, 전이를 예방하고, 질병 진행 속도를 감소시키며, 질병 상태를 경감 또는 일시적 완화시키며, 차도시키거나 예후를 개선시키는 것이 포함된다. 본 발명의 목적상 상기 치료는 상기 약학 조성물의 투여로 염증성 장질환의 증세가 호전되거나 완치되는 모든 행위를 포함하는 것으로 해석될 수 있으나, 특별히 이에 제한되지는 않는다.
As used herein, the term "treatment" refers to any activity that is clinically involved in altering the natural process of an individual or cell to be treated, which can be performed during or to prevent a clinical pathology. The desired therapeutic effect includes preventing the occurrence or recurrence of the disease, alleviating the symptoms, reducing all direct or indirect pathological consequences of the disease, preventing metastasis, slowing the progression of the disease, and reducing the disease state. Or temporarily alleviate, drive off, or improve the prognosis. For the purpose of the present invention, the treatment may be interpreted as including all the actions of the symptoms of inflammatory bowel disease improved or cured by administration of the pharmaceutical composition, but is not particularly limited thereto.
본 발명에서 제공하는 약학 조성물은 유효성분으로서 오배자 추출물을 포함하는데, 상기 약학 조성물은 담배연기로 인한 염증성 장질환의 발병시에 증가하는 염증성 사이토카인 및 엘라스틴과 콜라겐을 파괴하는 것으로 알려진 MMP12의 발현량을 감소시킬 수 있고, 상기 염증성 장질환에 의한 장내 유산균수의 감소를 억제할 수 있다.
The pharmaceutical composition provided by the present invention comprises a gall bladder extract as an active ingredient, wherein the pharmaceutical composition has an expression level of MMP12, which is known to destroy inflammatory cytokines and elastin and collagen, which are increased at the onset of inflammatory bowel disease caused by tobacco smoke. It can be reduced, it is possible to suppress the reduction of the number of intestinal lactic acid bacteria by the inflammatory bowel disease.
본 발명의 일 실시예에 의하면, 오배자의 분말을 수 추출하여 오배자 추출물을 수득하고(실시예 1), 상기 오배자 추출물을 경구투여한 마우스를 담배연기에 노출시킨 결과, 담배연기로 인해 발병된 염증성 장질환의 증상이 완화되고(도 1a 내지 도 1e), 상기 염증성 장질환에 의해 유발되는 장내 유산균수의 감소가 억제되며(도 2), 상기 염증성 장질환에 의해 유발되는 체중의 감소가 억제됨(도 3)을 확인하였다.
According to one embodiment of the present invention, by extracting the powder of the gall of the gallant to obtain a gallant extract (Example 1), as a result of exposing the mouse orally administered the gallant extract to tobacco smoke, inflammatory diseases caused by tobacco smoke Symptoms of intestinal disease are alleviated (FIGS. 1A-1E), a decrease in the number of intestinal lactic acid bacteria caused by the inflammatory bowel disease is suppressed (FIG. 2), and a decrease in body weight caused by the inflammatory bowel disease is suppressed ( 3) was confirmed.
상기 약학 조성물은 약학 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 추가로 포함할 수 있다. 상기 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. The pharmaceutical composition may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions. Examples of the carrier, excipient and diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
한편, 본 발명의 약학 조성물은, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제제화하여 사용될 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 상기 적소두 추출물과 이의 분획물들에 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.
On the other hand, the pharmaceutical compositions of the present invention, respectively, in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, oral formulations, external preparations, suppositories, and sterile injectable solutions, respectively, may be used according to conventional methods. Can be. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one excipient such as starch, calcium carbonate, in the red bean extract and fractions thereof. , Sucrose or lactose, gelatin and the like are mixed and prepared. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral use may include various excipients such as wetting agents, sweetening agents, fragrances, preservatives, etc. in addition to water and liquid paraffin, which are simple diluents commonly used in suspension, liquid solutions, emulsions and syrups have. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
상술한 목적을 달성하기 위한 다른 실시양태로서, 본 발명은 상기 약학 조성물을 개체에 투여하는 단계를 포함하는 염증성 장질환의 예방 또는 치료방법을 제공한다.
As another embodiment for achieving the above object, the present invention provides a method for preventing or treating inflammatory bowel disease, comprising administering the pharmaceutical composition to a subject.
본 발명의 용어 "개체"란, 상기 염증성 장질환이 발병될 가능성이 있거나, 또는 발병된 인간을 포함한 모든 동물을 의미한다. 본 발명의 조성물을 개체에 투여함으로써, 염증성 장질환을 완화 또는 치료할 수 있다. The term "individual" of the present invention means all animals, including humans, which may or may not develop the inflammatory bowel disease. By administering a composition of the present invention to an individual, inflammatory bowel disease can be alleviated or treated.
본 발명에서 용어, "완화"는 본 발명에 따른 조성물의 투여로 염증성 장질환이 호전되거나 이롭게 되는 모든 행위를 말한다.As used herein, the term "relaxation" refers to any action in which an inflammatory bowel disease is improved or benefited by administration of a composition according to the present invention.
상기 본 발명의 조성물은 약학적으로 유효한 양으로 투여한다.The composition of the present invention is administered in a pharmaceutically effective amount.
본 발명에서 용어, "투여"는 어떠한 적절한 방법으로 대상에게 본 발명의 약학적 조성물을 도입하는 것을 말하며, 투여 경로는 목적 조직에 도달할 수 있는 한 경구 또는 비경구의 다양한 경로를 통하여 투여될 수 있다.As used herein, the term "administration" refers to introducing a pharmaceutical composition of the present invention to a subject in any suitable manner, and the route of administration may be administered via various routes, oral or parenteral, as long as the target tissue can be reached. .
상기 약학적 조성물은 목적 또는 필요에 따라 당업계에서 사용되는 통상적인 방법, 투여 경로, 투여량에 따라 적절하게 개체에 투여될 수 있다. 투여 경로의 예로는 경구, 비경구, 피하, 복강 내, 폐 내, 및 비강 내로 투여될 수 있으며, 비경구 주입에는 근육 내, 정맥 내, 동맥 내, 복강 내 또는 피하투여가 포함된다. 또한 당업계에 공지된 방법에 따라 적절한 투여량 및 투여 횟수가 선택될 수 있으며, 실제로 투여되는 본 발명의 약학적 조성물의 양 및 투여 횟수는 치료하고자 하는 증상의 종류, 투여 경로, 성별, 건강 상태, 식이, 개체의 연령 및 체중, 및 질환의 중증도와 같은 다양한 인자에 의해 적절하게 결정될 수 있다.The pharmaceutical composition may be appropriately administered to a subject according to conventional methods, routes of administration, and dosages used in the art, depending on the purpose or need. Examples of routes of administration may be administered orally, parenterally, subcutaneously, intraperitoneally, pulmonary, and intranasally, and parenteral infusions include intramuscular, intravenous, intraarterial, intraperitoneal or subcutaneous administration. In addition, an appropriate dosage and frequency of administration may be selected according to methods known in the art, and the amount and frequency of administration of the pharmaceutical composition of the present invention to be actually administered may include the type of symptom to be treated, route of administration, sex, and health condition. , Diet, the age and weight of the individual, and the severity of the disease may be appropriately determined.
본 발명에서의 용어 "약학적으로 유효한 양"은 의학적 용도에 적용 가능한 합리적인 수혜/위험 비율로 혈관 투과성 증가를 억제 또는 완화하기에 충분한 양을 의미하며, 유효 용량 수준은 개체 종류 및 중증도, 연령, 성별, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출 비율, 치료기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 본 발명의 조성물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고 종래의 치료제와는 순차적 또는 동시에 투여될 수 있다. 그리고 단일 또는 다중 투여될 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.
As used herein, the term “pharmaceutically effective amount” means an amount sufficient to inhibit or mitigate the increase in vascular permeability at a reasonable benefit / risk ratio applicable to medical use, and the effective dose level may include the type and severity, age, It may be determined according to sex, activity of the drug, sensitivity to the drug, time of administration, route of administration and rate of release, duration of treatment, factors including concurrently used drugs, and other factors well known in the medical arts. The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. And can be administered singly or multiply. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without adverse effect, and can be easily determined by those skilled in the art.
상술한 목적을 달성하기 위한 또 다른 실시양태로서, 본 발명은 오배자 추출물을 포함하는, 염증성 장질환 예방 또는 개선용 식품 조성물을 제공한다.
As another embodiment for achieving the above object, the present invention provides a food composition for preventing or ameliorating inflammatory bowel disease, comprising a gall bladder extract.
본 발명의 오배자는 종래로부터 약재로 사용되어 그의 안전성이 입증되었으므로, 상기 성분을 식품 조성물로 사용할 수 있다.
Since the gall of the present invention has been conventionally used as a medicinal herb and its safety has been proved, the ingredient can be used as a food composition.
상기 오배자 추출물을 포함하는 조성물은 식품 조성물의 총 중량에 대하여 0.01 내지 100 중량%, 보다 바람직하게는 1 내지 80 중량%로 포함한다. 식품이 음료인 경우에는 100㎖를 기준으로 1~30g, 바람직하게는 3 ~ 20g의 비율로 포함될 수 있다. 또한, 상기 조성물은 식품 조성물에 통상 사용되어 냄새, 맛, 시각 등을 향상시킬 수 있는 추가 성분을 포함할 수 있다. 예들 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), 크륨(Cr) 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.
The composition comprising the gall bladder extract comprises 0.01 to 100% by weight, more preferably 1 to 80% by weight relative to the total weight of the food composition. When food is a beverage, it may be included in a ratio of 1 to 30 g, preferably 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 the smell, taste, time and the like. For example, it may include vitamins A, C, D, E, B1, B2, B6, B12, niacin, biotin, folate, panthotenic acid, and the like. In addition, minerals such as zinc (Zn), iron (Fe), calcium (Ca), chromium (Cr), magnesium (Mg), manganese (Mn), copper (Cu) and chromium (Cr) may be included. It may also contain amino acids such as lysine, tryptophan, cysteine, valine and the like. In addition, preservatives (potassium sorbate, sodium benzoate, salicylic acid, sodium dehydroacetate, etc.), fungicides (bleaching powder and highly bleaching powder, sodium hypochlorite, etc.), antioxidants (butylhydroxyanisol (BHA), butylhydroxytoluene ( BHT), etc.), colorants (such as tar pigments), colorants (such as sodium nitrite, sodium nitrite), bleach (sodium sulfite), seasonings (such as MSG glutamate), sweeteners (ducin, cyclate, saccharin, sodium, etc.) Food additives such as flavors (vanillin, lactones, etc.), swelling agents (alum, potassium D-tartrate, etc.), reinforcing agents, emulsifiers, thickeners (pigments), coatings, gum herbicides, foam inhibitors, solvents, improvers, etc. ) Can be added. The additive is selected according to the type of food and used in an appropriate amount.
한편, 상기 오배자 추출물을 포함하는 식품 조성물을 이용하여 염증성 장질환의 예방 또는 개선용 기능성식품을 제조할 수 있다.On the other hand, by using a food composition comprising the gall bladder extract can be prepared functional food for the prevention or improvement of inflammatory bowel disease.
구체적인 예로, 상기 조성물을 이용하여 농산물, 축산물 또는 수산물의 특성을 살려 변형시키는 동시에 저장성을 좋게한 가공식품을 제조할 수 있다. 이런 가공식품에는 예들 들어, 과자, 음료, 주류, 발효식품, 통조림, 우유가공식품, 육륙가공식품, 국수 등을 포함한다. 과자는 비스킷, 파이, 케익, 빵, 캔디, 젤리, 껌, 시리얼(곡물푸레이크 등의 식사대용품류 포함) 등을 포함한다. 음료는 탄산음료, 기능성이온음료, 쥬스(예들 들어, 사과, 배, 포도, 알로에, 감귤, 복숭아, 당근, 토마토 쥬스 등), 식혜 등을 포함한다. 주류는 청주, 위스키, 소주, 맥주, 양주, 과실주 등을 포함한다. 발효식품은 간장, 된장, 고추장 등을 포함한다. 통조림은 수산물 통조림(예들 들어, 참치, 고등어, 꽁치, 소라 통조림 등), 축산물 통조림(쇠고기, 돼지고기, 닭고기, 칠면조 통조림 등), 농산물 통조림(옥수수, 복숭아, 파일애플 통조림 등)을 포함한다. 우유가공식품은 치즈, 버터, 요구르트 등을 포함한다. 육류가공식품은 돈까스, 비프까스, 치킨까스, 소세지. 탕수육, 너겟류, 너비아니 등을 포함한다. 밀봉포장생면 등의 국수를 포함한다. 이 외에도 상기 조성물은 레토르트식품, 스프류 등에 사용될 수 있다.As a specific example, it is possible to prepare a processed food with improved shelf life while modifying the properties of agricultural products, livestock products or aquatic products using the composition. Such processed foods include, for example, sweets, beverages, alcoholic beverages, fermented foods, canned foods, milk processed foods, land processed foods, noodles and the like. Confections include biscuits, pies, cakes, breads, candies, jelly, gum, cereals (including meal substitutes such as grain flour). Beverages include carbonated drinks, functional hot drinks, juices (eg, apples, pears, grapes, aloes, citrus fruits, peaches, carrots, tomato juices, etc.), Sikhye, and the like. The mainstream includes sake, whiskey, shochu, beer, liquor, and fruit wine. Fermented foods include soy sauce, miso, and kochujang. Canned food includes canned seafood (e.g., tuna, mackerel, saury, canned seashells, etc.), canned animal products (beef, pork, chicken, canned turkey, etc.), canned produce (corn, peaches, canned apples, etc.). Milk processed foods include cheese, butter, yogurt and the like. Meat processed foods are pork cutlet, beef cutlet, chicken cutlet, sausage. Includes sweet and sour pork, nuggets, breadfruits and more. And noodles such as sealed packaging raw noodles. In addition, the composition may be used in retort food, soup and the like.
본 발명의 용어 "기능성식품(functional food)"이란, 특정보건용 식품(food for special health use, FoSHU)와 동일한 용어로, 영양 공급 외에도 생체조절기능이 효율적으로 나타나도록 가공된 의학, 의료효과가 높은 식품을 의미한다. 본 발명에서 용어,“건강식품(health food)"은 일반식품에 비해 적극적인 건강유지나 증진 효과를 가지는 식품을 의미하고, 건강보조식품(health supplement food)는 건강 보조 목적의 식품을 의미한다. 경우에 따라, 기능성식품, 건강식품, 건강보조식품의 용어는 호용된다. 상기 식품은 치주질환의 예방 또는 개선에 유용한 효과를 얻기 위하여 정제, 캅셀, 분말, 과립, 액상, 환 등의 다양한 형태로 제조될 수 있다.
The term "functional food" of the present invention is the same term as a food for special health use (FOSHU), and in addition to the nutritional supply, the medical and medical effects are processed so that the bioregulatory function appears efficiently Means high food. As used herein, the term "health food" refers to a food having an active health maintenance or promotion effect compared to a general food, and a health supplement food refers to a food for health supplement purposes. Accordingly, the terms functional foods, health foods, and health supplements are widely used.These foods may be prepared in various forms such as tablets, capsules, powders, granules, liquids, pills, etc. in order to obtain useful effects in the prevention or improvement of periodontal disease. Can be.
상술한 목적을 달성하기 위한 또 다른 실시양태로서, 본 발명은 상기 약학 조성물을 염증성 사이토카인의 발현이 과다한 조직 또는 세포에 처리하는 단계를 포함하는 염증성 사이토카인의 발현을 억제하는 방법을 제공한다.
As another embodiment for achieving the above object, the present invention provides a method for inhibiting the expression of inflammatory cytokines comprising the step of treating the pharmaceutical composition to tissues or cells with excessive expression of inflammatory cytokines.
본 발명의 용어 "염증성 사이토카인(proinflammatory cytokine)"이란, 체내에서 발생하는 염증반응을 유발시키는 사이토카인을 의미하는데, 이들 염증성 사이토카인은 특별히 이에 제한되지 않으나, IL-1β, TNF-α, IL-6, MCP-1 등이 될 수 있다.
The term "proinflammatory cytokine" of the present invention means a cytokine that causes an inflammatory response occurring in the body, but these inflammatory cytokines are not particularly limited thereto, but IL-1β, TNF-α, IL -6, MCP-1, and the like.
본 발명의 일 실시예에 의하면, 담배연기에 노출된 마우스에서는 염증성 장질환이 유발되어, 대장조직에서 염증성 사이토카인인 TNF-α, IL-6 및 IL-1β의 발현수준이 증가하지만, 본 발명의 약학 조성물을 투여할 경우, TNF-α, IL-6 및 IL-1β의 발현 증가가 억제됨을 확인하였다(도 1a 내지 도 1c). 뿐만 아니라, 엘라스틴과 콜라겐을 파괴하는 것으로 알려진 MMP12의 mRNA 수준 역시 동일한 양상을 나타냄을 확인하였다(도 1d).
According to one embodiment of the present invention, inflammatory bowel disease is induced in mice exposed to tobacco smoke, so that the expression levels of inflammatory cytokines TNF-α, IL-6 and IL-1β in the colon tissue are increased. When administering the pharmaceutical composition of TNF-α, it was confirmed that increased expression of IL-6 and IL-1β is inhibited (Fig. 1a to 1c). In addition, it was confirmed that mRNA levels of MMP12 known to destroy elastin and collagen also showed the same pattern (FIG. 1D).
상술한 목적을 달성하기 위한 또 다른 실시양태로서, 상기 약학 조성물을 유산균수가 감소하는 환경에 노출된 유산균에 처리하는 단계를 포함하는 유산균수의 감소를 억제하는 방법을 제공한다.
As another embodiment for achieving the above object, there is provided a method for inhibiting the decrease in the number of lactic acid bacteria comprising the step of treating the pharmaceutical composition to the lactic acid bacteria exposed to an environment in which the number of lactic acid bacteria is reduced.
본 발명의 용어 "유산균"이란, 젖산균이라고도 하며, 당류를 발효하여 에너지를 획득하고 다량의 젖산을 생성하는 세균을 포괄적으로 의미한다. 상기 유산균은 형태적으로는 구균(Lactococcus, Pediococcus, Leuconostoc)과 간균(Lactobacillus, Bifidobacterim)으로 나누어지고 그람(Gram) 염색성은 양성이며, 산에 내성을 나타내는 것이 많고 영양요구성은 매우 복잡하여 당류 이외에 많은 종류의 아미노산이나 비타민을 요구하는데, 대체로 산소가 적은 환경에서 잘 발육하여 각종 당으로부터 젖산을 생성한다. 상기 유산균에 포함되는 균주는 특별히 이에 제한되지 않으나, 락토바실러스 속(Lactobacillus sp .), 락토코커스 속(Lactococcus sp.), 류코노스톡 속(Leuconostoc sp .), 페디오코커스 속(Pediococcus sp .), 비피도박테리움 속(Bifidobacterium sp .) 균주 등이 될 수 있다.
The term "lactic acid bacterium" of the present invention, also referred to as lactic acid bacteria, means a bacterium that obtains energy by fermenting saccharides and produces a large amount of lactic acid. The lactic acid bacteria are morphologically divided into Lactococcus , Pediococcus , Leuconostoc and Lactobacillus , Bifidobacterim . It requires a variety of amino acids and vitamins, which usually develop well in low-oxygen environments, producing lactic acid from various sugars. The strain contained in the lactic acid bacteria is not particularly limited thereto, but the genus Lactobacillus sp . ), Lactococcus sp .), Leuconostoc sp . Pediococcus sp . ), The genus Bifidobacterium sp . ) Strains and the like.
본 발명의 일 실시예에 의하면, 담배연기에 노출된 마우스에서는 염증성 장질환이 유발되어, 장내 유산균의 수가 감소하지만, 본 발명의 약학 조성물을 투여할 경우, 장내 유산균수의 감소가 억제됨을 확인하였다(도 2).
According to one embodiment of the present invention, mice exposed to tobacco smoke induced inflammatory bowel disease, thereby reducing the number of enteric lactic acid bacteria, but when the pharmaceutical composition of the present invention is administered, it was confirmed that the decrease in the number of enteric lactic acid bacteria was suppressed. (FIG. 2).
본 발명의 오배자 추출물을 포함하는 약학 조성물은 염증성 장질환의 발병에 수반되는 염증성 사이토카인인 IL-1β, TNF-α 및 IL-6와, 엘라스틴과 콜라겐을 파괴하는 것으로 알려진 MMP12의 발현수준을 감소시키고, 장내 유산균수의 감소를 억제할 수 있으므로, 안전하면서도 효과적인 염증성 장질환 치료제의 개발에 널리 활용될 수 있을 것이다.
The pharmaceutical composition comprising the gall bladder extract of the present invention reduces the expression levels of inflammatory cytokines IL-1β, TNF-α and IL-6, and MMP12, known to destroy elastin and collagen, associated with the development of inflammatory bowel disease. It is possible to suppress the reduction of the intestinal lactic acid bacteria, it will be widely used in the development of a safe and effective inflammatory bowel disease treatment.
도 1a는 오배자 추출물의 처리에 따른 IL-6의 mRNA 수준의 변화를 나타내는 그래프이다.
도 1b는 오배자 추출물의 처리에 따른 TNF-α의 mRNA 수준의 변화를 나타내는 그래프이다.
도 1c는 오배자 추출물의 처리에 따른 IL-1β의 mRNA 수준의 변화를 나타내는 그래프이다.
도 1d는 오배자 추출물의 처리에 따른 MMP12의 mRNA 수준의 변화를 나타내는 그래프이다.
도 2는 오배자 추출물의 처리에 따른 유산균수의 변화를 비교한 그래프이다.
도 3은 오배자 추출물의 처리에 따른 마우스 체중의 변화를 비교한 그래프이다. Figure 1a is a graph showing the change in the mRNA level of IL-6 according to the treatment of the gall bladder extract.
Figure 1b is a graph showing the change in mRNA level of TNF-α according to the treatment of the gall bladder extract.
Figure 1c is a graph showing the change in the mRNA level of IL-1β according to the treatment of the gall bladder extract.
Figure 1d is a graph showing the change in mRNA level of MMP12 according to the treatment of the gall bladder extract.
Figure 2 is a graph comparing the change in the number of lactic acid bacteria according to the treatment of the gallengja extract.
Figure 3 is a graph comparing the change in the weight of the mouse according to the treatment of the gall bladder extract.
이하 본 발명을 실시예를 통하여 보다 상세하게 설명한다. 그러나 이들 실시예는 본 발명을 예시적으로 설명하기 위한 것으로 본 발명의 범위가 이들 실시예에 한정되는 것은 아니다.
Hereinafter, the present invention will be described in more detail with reference to examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited to these examples.
실시예Example
1: 시료의 준비 1: Preparation of Sample
SUN TEN(Taipei, 대만)에서 구입한 오배자 파우더를 물에 용해시키고 여과하여 수득한 오배자 추출물 용액을 마우스에 경구투여하는데 사용하였다.
The gall bladder powder purchased from SUN TEN (Taipei, Taiwan) was dissolved in water, and the gall bladder extract solution obtained by filtration was used for oral administration to mice.
실시예Example
2: 담배연기 처리에 의한 염증성 장질환( 2: inflammatory bowel disease caused by tobacco smoke treatment
InfalmmationInfalmmation
bowelbowel
dieases, dieases,
IBDIBD
)의 유발Induction of)
담배가 염증성 장질환(Infalmmation bowel dieases, IBD)을 유발할 수 있다고 알려져 있으므로(Gareth A O Thomas, et al., Postgrad. Med. J., 76(895):273-279, 2000 May), 담배연기에 마우스를 노출시켜서 IBD를 유발시키고자 하였다.Cigarettes are known to cause inflammatory bowel dieases (IBD) (Gareth AO Thomas, et al., Postgrad. Med. J., 76 (895): 273-279, 2000 May). The mice were exposed to try to induce IBD.
먼저, 체중 20-25g의 6주령 암컷 C57BL/6 마우스(Orient Bio Inc, South Korea)를 물과 사료는 자유롭게 먹도록 하였으며, 사육실 내의 온도는 21-24℃ 및 습도는 40-60%로 유지하였고 낮과 밤 주기는 각각 12시간으로 하여 사육하였다. First, 6-week-old female C57BL / 6 mice (Orient Bio Inc, South Korea) weighing 20-25 g were allowed to eat free of water and feed. The temperature in the cage was maintained at 21-24 ℃ and humidity 40-60%. The day and night cycles were 12 hours each.
상기 사육된 마우스에 상기 실시예 1에서 수득한 오배자 추출물 용액을 100mg/kg의 용량으로 경구투여한 다음, 이를 Smoking chamber에 넣고, Reference cigarette 3R4F(University of Kentucky, Lexington, Kentuchy)를 3개피 피운 연기에 30분동안 노출시키고, 연기를 제거한 상태에서 다시 30분간 방치하는 단계를 4회 반복하는 담배연기 처리과정을 수행하였고, 이러한 처리과정을 하루에 1회씩 일주일 동안 5회 수행하는 단계를 3주동안 수행하여 염증성 장질환(Infalmmation bowel dieases, IBD)을 유발시켜 이를 실험군으로 사용하였다. 이때, 음성대조군으로는 담배연기를 처리하지 않은 마우스를 사용하고, 양성대조군으로는 담배연기를 처리하고 오배자 추출물 용액을 투여하지 않은 마우스를 사용하였으며, 음성대조군과 양성대조군은 각각 3마리, 실험군은 2마리로 설정하였다.
The raised mouse was orally administered with the gall extract extract obtained in Example 1 at a dose of 100 mg / kg, and then placed in a smoking chamber, and smoked three cigarettes of Reference cigarette 3R4F (University of Kentucky, Lexington, Kentuchy). After 30 minutes of exposure to smoke, the smoke was removed and left for another 30 minutes. The cigarette smoke treatment process was repeated four times, and this process was performed once a day for five times a week for three weeks. Inflammation bowel dieases (IBD) were induced and used as experimental groups. At this time, the negative control group was used as a mouse not treated with tobacco smoke, and the positive control group was used as a mouse treated with tobacco smoke and not administered the gall extract extract, the negative control group and the positive control group of three, respectively, the experimental group It was set to two.
실시예Example
3: 염증성 장질환에 대한 오배자 추출물의 효과 3: Effect of Mellitus Extracts on Inflammatory Bowel Disease
실시예Example
3-1: 염증성 사이토카인 및 3-1: inflammatory cytokines and
MMP12MMP12
의 발현수준 비교Level of expression
먼저, 상기 실시예 2에서 수득한 각 음성대조군, 양성대조군 및 실시예의 마우스를 희생시키고, 이로부터 각각의 대장조직을 적출한 다음, RNeasy Mini kit (QIAGEN, USA)를 사용하여 상기 적출된 대장조직으로부터 총 RNA를 수득하였다. 구체적으로, 각각의 대장조직에 600㎕의 RLT 완충액을 가하여 세포를 파괴하고, 다시 600㎕의 70% 에탄올을 가하여 혼합하였다. 이어, 상기 혼합물 700㎕를 상기 키트의 RNeasy mini column에 담고, 8,000 ×g에서 15초간 원심분리한 다음, 잔류액에 상기 키트에 포함된 700㎕의 RW1 완충액을 가하고, 다시 8,000 ×g에서 15초간 원심분리하여 잔류액을 수득하였다. 다음으로, 상기 잔류액에 상기 키트에 포함된 500㎕ RPE 완충액을 가하고, 8,000 ×g에서 15초간 원심분리하여 잔류액을 수득하였으며, 상기 잔류액에 상기 키트에 포함된 50㎕ RNase free water를 가하고, 8,000 ×g에서 1분간 원심분리하여 총 RNA를 수득하였다. 상기 수득한 총 RNA를 spectrophotometer(ND-1000, NanoDrop Technologies Inc. USA)로 정량하고, 1% agarose gel에서 전기영동하고 ethidium-bromide(Et-Br, Sigma-Aldrich, USA)로 염색하여 상태를 평가하였다.First, each negative control group, the positive control group and the mouse of the example obtained in Example 2 were sacrificed, and each colon tissue was extracted therefrom, and then the colon tissue extracted using the RNeasy Mini kit (QIAGEN, USA). Total RNA was obtained from. Specifically, 600 μl of RLT buffer was added to each colon tissue to disrupt the cells, and 600 μl of 70% ethanol was added thereto and mixed. Subsequently, 700 μl of the mixture was placed in the RNeasy mini column of the kit, centrifuged at 8,000 × g for 15 seconds, and 700 μl of RW1 buffer included in the kit was added to the residue, followed by 15 seconds at 8,000 × g. Centrifugation gave a residue. Next, 500 μl RPE buffer included in the kit was added to the residue, and centrifuged at 8,000 × g for 15 seconds to obtain a residue. 50 μl RNase free water included in the kit was added to the residue. , Centrifuged for 1 minute at 8,000 × g to give total RNA. Total RNA obtained was quantified with a spectrophotometer (ND-1000, NanoDrop Technologies Inc. USA), electrophoresed on a 1% agarose gel and stained with ethidium-bromide (Et-Br, Sigma-Aldrich, USA) to assess the condition. It was.
한편, 상기 수득한 총 RNA를 이용하여 실시간 RT-PCR 분석을 수행하였다. 상기 분석을 위하여 상기 수득한 총 RNA 2㎍, SYBR Green I Master Mix (Applied Biosystems, Foster City, CA, USA) 및 primers(Genotech Inc., Korea)를 사용한 RT-PCR(95℃: 15sec 및 60℃: 1min, 40 cycles)을 수행하여 cDNA를 수득하고, 상기 수득한 cDNA를 Applied Biosystems 7300 Real time PCR System에 적용하여 실시간 PCR을 수행하여, 각 대조군 및 실험군에서 염증성 사이토카인인 IL-6, TNF-α 및 IL-1β와, 엘라스틴과 콜라겐을 파괴하는 것으로 알려진 MMP12의 mRNA 수준을 비교하였다(도 1a 내지 1d). Meanwhile, real-time RT-PCR analysis was performed using the obtained total RNA. RT-PCR (95 ° C .: 15 sec and 60 ° C.) using 2 μg of the total RNA obtained above, SYBR Green I Master Mix (Applied Biosystems, Foster City, CA, USA) and primers (Genotech Inc., Korea) for the assay : 1min, 40 cycles) to obtain a cDNA, the obtained cDNA was applied to the Applied Biosystems 7300 Real time PCR System to perform real-time PCR, inflammatory cytokines IL-6, TNF- in each control group and experimental group mRNA levels of α and IL-1β and MMP12, known to destroy elastin and collagen, were compared (FIGS. 1A-1D).
도 1a는 오배자 추출물의 처리에 따른 IL-6의 mRNA 수준의 변화를 나타내는 그래프이고, 도 1b는 오배자 추출물의 처리에 따른 TNF-α의 mRNA 수준의 변화를 나타내는 그래프이며, 도 1c는 오배자 추출물의 처리에 따른 IL-1β의 mRNA 수준의 변화를 나타내는 그래프이고, 도 1d는 오배자 추출물의 처리에 따른 MMP12의 mRNA 수준의 변화를 나타내는 그래프이다. 도 1a 내지 1d에서 보듯이, 담배연기를 처리하지 않은 음성대조군에서는 IL-6, TNF-α, IL-1β 및 MMP12의 mRNA 수준이 낮은 수준을 나타내었으나, 담배연기만을 처리한 양성대조군에서는 IL-6, TNF-α, IL-1β 및 MMP12의 mRNA 수준이 급격히 증가하였고, 담배연기를 처리하기 전에 오배자 추출물을 투여한 실험군에서는 담배연기에 의하여 유발된 IL-6, TNF-α, IL-1β 및 MMP12의 mRNA 수준의 증가가 억제됨을 확인하였다.Figure 1a is a graph showing the change in the mRNA level of IL-6 according to the treatment of the gall bladder extract, Figure 1b is a graph showing the change in the mRNA level of TNF-α according to the treatment of the gall bladder extract, Figure 1c It is a graph showing the change of mRNA level of IL-1β with treatment, Figure 1d is a graph showing the change of mRNA level of MMP12 according to the treatment of the gall bladder extract. As shown in FIGS. 1A to 1D, mRNA levels of IL-6, TNF-α, IL-1β and MMP12 were low in the negative control group without tobacco smoke, but IL- in the positive control group treated with tobacco smoke only. 6, mRNA levels of TNF-α, IL-1β and MMP12 increased rapidly, and in the experimental group treated with the Gallja extract before treatment of tobacco smoke, IL-6, TNF-α, IL-1β and It was confirmed that the increase of the mRNA level of MMP12 is suppressed.
상기 결과로부터, 본 발명에서 제공하는 오배자 추출물이 담배연기에 의한 염증성 장질환의 발병을 억제하는 효과를 나타냄을 알 수 있었다.
From the above results, it can be seen that the gall extract provided in the present invention has an effect of suppressing the onset of inflammatory bowel disease caused by tobacco smoke.
실시예Example
3-2: 유산균 3-2: lactic acid bacteria
총균수Total number of bacteria
비교 compare
염증성 장질환이 발병된 경우 장내 미생물의 수준이 감소된다고 알려져 있으므로, 본 발명의 오배자 추출물 용액이 장내 유산균수에 미치는 영향을 확인하고자 하였다.Since it is known that the level of intestinal microorganisms is reduced when inflammatory bowel disease occurs, it was intended to confirm the effect of the gall bladder extract solution on the intestinal lactic acid bacteria count.
구체적으로, 상기 실시예 2에서 수득한 각 음성대조군, 양성대조군 및 실시예의 마우스를 희생시키고, 이로부터 각각의 맹장조직을 적출한 다음, 적출된 맹장조직 1g과 생리식염수 9㎖을 혼합하고 물리적으로 파쇄한 다음, 상기 파쇄물에 10배 부피의 생리식염수를 가하여 희석하는 과정을 3회 수행하여 각각의 희석액을 수득하였다. 상기 수득한 각각의 희석액 100㎕을 유산균 배양용 고체배지(MRS agar plate)에 도말하고, 37℃에서 48시간 동안 배양한 다음, 상기 고체배지에 형성된 유산균 콜로니의 수를 계수하여 비교하였다(도 2).Specifically, each of the negative control group, the positive control group and the mouse obtained in Example 2 was sacrificed, and each cecum tissue was extracted therefrom, and then 1 g of the extracted cecum tissue and 9 ml of physiological saline were mixed and physically After crushing, the dilutions were performed three times by diluting the lysate by adding 10-fold volume of physiological saline to obtain respective dilutions. 100 μl of each dilution obtained above was plated on a solid medium for lactic acid bacteria culture (MRS agar plate), incubated for 48 hours at 37 ° C., and the number of lactic acid colonies formed on the solid medium was counted and compared (FIG. 2). ).
도 2는 오배자 추출물의 처리에 따른 유산균수의 변화를 비교한 그래프이다. 도 2에서 보듯이, 담배연기를 처리하지 않은 음성대조군에서는 유산균수가 높은 수준을 유지하였으나, 담배연기만을 처리한 양성대조군에서는 유산균수가 급격히 감소하였으며, 담배연기를 처리하기 전에 오배자 추출물을 투여한 실험군에서는 담배연기에 의한 유산균수의 감소가 억제됨을 확인하였다.Figure 2 is a graph comparing the change in the number of lactic acid bacteria according to the treatment of the gall bladder extract. As shown in Figure 2, in the negative control group not treated with tobacco smoke maintained a high level of lactic acid bacteria, but in the positive control group treated only with tobacco smoke, the number of lactic acid bacteria was sharply reduced, in the experimental group administered the five-fold extract before treatment of tobacco smoke It was confirmed that the reduction of the number of lactic acid bacteria by tobacco smoke was suppressed.
상기 결과로부터, 본 발명에서 제공하는 오배자 추출물이 담배연기에 의한 유산균수의 감소를 유도하는 염증성 장질환의 발명을 억제하는 효과를 나타냄을 알 수 있었다.
From the above results, it can be seen that the gall extract provided in the present invention has an effect of inhibiting the invention of inflammatory bowel disease which induces a decrease in the number of lactic acid bacteria by tobacco smoke.
실시예Example
3-3: 체중변화 비교 3-3: Comparison of weight change
염증성 장질환이 유발된 동물에서는 체중이 감소한다고 알려져 있으므로, 체중의 변화의 측면에서 본 발명의 오배자 추출물이 염증성 장질환에 미치는 영향을 확인하고자 하였다.Since it is known that the body weight is reduced in animals induced with inflammatory bowel disease, the aim of the present invention was to identify the effect of the gall bladder extract on inflammatory bowel disease in terms of weight change.
즉, 상기 실시예 2에서 수득한 각 음성대조군, 양성대조군 및 실시예의 마우스를 대상으로 하여, 실험 시작일(0일)에 체중을 정밀 저울 E06120을 이용하여 측정하고, 2일 간격으로 체중변화를 측정한 후, 비교하였다(도 3). 도 3은 오배자 추출물의 처리에 따른 마우스 체중의 변화를 비교한 그래프이다. 도 3에서 보듯이, 담배연기를 처리하지 않은 음성대조군에서는 체중이 높은 수준을 유지하였으나, 담배연기만을 처리하여 염증성 장질환을 유발시킨 양성대조군에서는 체중이 급격히 감소하였으며, 담배연기를 처리하기 전에 오배자 추출물을 투여한 실험군에서는 담배연기에 의한 체중의 감소가 억제됨을 확인하였다.That is, for each negative control group, the positive control group and the mouse of the example obtained in Example 2, the body weight was measured using the precision balance E06120 at the start of the experiment (day 0), and the weight change was measured at two-day intervals. After that, the comparison was made (FIG. 3). Figure 3 is a graph comparing the change in body weight of the mouse according to the treatment of gall bladder extract. As shown in Figure 3, in the negative control group not treated with tobacco smoke, the body weight was maintained at a high level, but in the positive control group that induced inflammatory bowel disease only by treating tobacco smoke, the weight was drastically reduced before the tobacco smoke treatment. In the experimental group to which the extract was administered, it was confirmed that the weight loss caused by tobacco smoke was suppressed.
상기 결과로부터, 본 발명에서 제공하는 오배자 추출물이 담배연기에 의한 체중의 감소를 유도하는 염증성 장질환의 발명을 억제하는 효과를 나타냄을 알 수 있었다.From the above results, it can be seen that the gall extract provided in the present invention has an effect of inhibiting the invention of inflammatory bowel disease that induces weight loss due to tobacco smoke.
Claims (7)
A pharmaceutical composition for preventing or treating inflammatory bowel disease, comprising a gall bladder extract.
상기 오배자 추출물은 오배자의 수 추출물인 것인 조성물.
The method of claim 1,
The gall bladder extract is a composition of the gall bladder extract.
상기 염증성 장질환은 궤양성 대장염 또는 크론병인 것인 조성물.
The method of claim 1,
The inflammatory bowel disease is ulcerative colitis or Crohn's disease composition.
약학적으로 허용되는 담체, 부형제 또는 희석제를 추가로 포함하는 것인 조성물.
The method of claim 1,
The composition further comprises a pharmaceutically acceptable carrier, excipient or diluent.
Food composition for preventing or improving inflammatory bowel disease, comprising a gall bladder extract.
A method of inhibiting the expression of an inflammatory cytokine comprising the step of treating the pharmaceutical composition of any one of claims 1 to 4 to a tissue or cell in which the expression of the inflammatory cytokine is excessive.
염증성 사이토카인은 IL-1β, TNF-α, IL-6, MCP-1 및 이의 조합으로 구성된 군으로부터 선택되는 것인 방법.The method according to claim 6,
Inflammatory cytokines are selected from the group consisting of IL-1β, TNF-α, IL-6, MCP-1 and combinations thereof.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20160059753A (en) | 2014-11-19 | 2016-05-27 | 주식회사 엘지생활건강 | Cosmetics compositions for hair strengthening |
| KR20200101823A (en) | 2019-02-19 | 2020-08-28 | 군산대학교산학협력단 | Composition for preventing, ameliorating or treating inflammatory bowel disease comprising extract of Turbinaria ornata |
| KR20200101561A (en) | 2019-02-19 | 2020-08-28 | 군산대학교산학협력단 | Composition for preventing, ameliorating or treating inflammatory bowel disease comprising extract of Ircinia species |
| KR20210043067A (en) | 2019-10-10 | 2021-04-21 | 주식회사 헬릭스미스 | Composition for preventing or treating inflammatory bowel diseases comprising mixed herbal extracts |
-
2012
- 2012-07-03 KR KR1020120072392A patent/KR20140004935A/en not_active Application Discontinuation
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20160059753A (en) | 2014-11-19 | 2016-05-27 | 주식회사 엘지생활건강 | Cosmetics compositions for hair strengthening |
| KR20200101823A (en) | 2019-02-19 | 2020-08-28 | 군산대학교산학협력단 | Composition for preventing, ameliorating or treating inflammatory bowel disease comprising extract of Turbinaria ornata |
| KR20200101561A (en) | 2019-02-19 | 2020-08-28 | 군산대학교산학협력단 | Composition for preventing, ameliorating or treating inflammatory bowel disease comprising extract of Ircinia species |
| KR20210043067A (en) | 2019-10-10 | 2021-04-21 | 주식회사 헬릭스미스 | Composition for preventing or treating inflammatory bowel diseases comprising mixed herbal extracts |
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