KR101895969B1 - Anti-inflammatory composition comprising corn cob extract - Google Patents
Anti-inflammatory composition comprising corn cob extract Download PDFInfo
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- KR101895969B1 KR101895969B1 KR1020170041540A KR20170041540A KR101895969B1 KR 101895969 B1 KR101895969 B1 KR 101895969B1 KR 1020170041540 A KR1020170041540 A KR 1020170041540A KR 20170041540 A KR20170041540 A KR 20170041540A KR 101895969 B1 KR101895969 B1 KR 101895969B1
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- South Korea
- Prior art keywords
- extract
- inflammatory gastrointestinal
- present
- disease
- colitis
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Abstract
Description
본 발명은 옥수수 속대 추출물을 포함하는 항염증용 조성물에 관한 것으로, 보다 구체적으로는 옥수수 속대 추출물을 포함하는 염증성 위장관 질환의 예방 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for preventing or treating inflammatory gastrointestinal diseases, including corncobs extract, and more particularly to a composition for anti-inflammation comprising corncob activity.
염증 반응은 생체나 조직에 물리적 작용이나 화학적 물질, 세균감염 등의 어떠한 기질적 변화를 가져오는 침습이 가해질 때 그 손상부위를 수복 재생하려는 기전을 의미한다. Inflammation reaction refers to the mechanism of restoration and regeneration of an injured area when an invasion of any physical change such as physical action, chemical substance, bacterial infection, etc. is applied to a living body or tissue.
그 중 대장염은 대장에 염증이 발생하는 질환으로, 다양한 원인에 의해 발생하고, 테네스무스(tenesmus, 시원치 않음), 복부팽만감, 하복부통, 설사 등이 주요 증상으로 나타나며, 분변 중에 점액, 고름이나 혈액이 섞이는 경우도 있다. 대장염은 원인에 따라 크게 감염성 대장염과 비감염성 대장염으로 구분될 수도 있고, 발병 기간에 따라 급성 대장염과 만성 대장염으로 구분될 수도 있다. 급성 대장염에는 아메바성이질, 세균성이질, 살모넬라나 항생물질에 의한 위막성 대장염(pseudomembranous enteritis) 등이 있고 만성 대장염에는 궤양성 대장염, 크론병, 결핵, 매독, X선 등에 의한 것이 있다. 또한, 대장염은 염증성 대장 질환(Inflammatory bowel disease; IBD) 뿐만 아니라 과민성 대장염 증후군(irritable bowel syndrome, IBS)등을 포함한다. 염증성 대장 질환(Inflammatory bowel disease; IBD) 중 대표적인 질환인 궤양성 대장염(ulcerative colitis; UC)과 크론병(Crohn's disease; CD)은 아직 원인이 명확히 밝혀져 있지 않고 있으며, 복통과 더불어 심한 만성 설사와 혈성 설사를 일으킬 수 있으며, 완치가 힘들고 호전과 악화를 반복하는 특성이 있다. 궤양성 대장염은 대장의 점막에 진무름(미란)이나 궤양이 연속적으로 형성되는 질환으로, 혈변, 점혈변, 설사, 복통이 일어나고, 중증인 경우에는 발열, 체중감소, 빈혈 등의 전신성의 증상이 나타난다. 또한, 궤양성 대장염은 위장관 어느 부위에서도 발생할 수 있다. 크론병은 입에서 항문에 이르는 소화관의 임의의 부위에 궤양 등의 병변이 비연속적으로 발생하는 질환으로서, 복통, 설사, 혈변과 더불어, 중증의 경우에는 발열, 하혈, 체중감소, 전신권태감, 빈혈 등의 증상이 나타난다. 궤양성 대장염과 크론병은 병변과 염증 증상에 있어서 차이가 있지만 여러 면에서 유사한 양상을 보이기 때문에 두 질환의 구분이 서로 명확하지 않은 경우가 흔하다.Colitis is an inflammation of the large intestine caused by a variety of causes, including tenesmus, abdominal bloating, lower abdomen, and diarrhea. The main symptoms are mucus, pus or blood There is also a case of mixing. Colitis may be classified into infectious colitis and non - infectious colitis depending on the cause and may be classified into acute colitis and chronic colitis according to the onset period. Acute colitis may be caused by amebic dysentery, bacterial dysentery, salmonella, or pseudomembranous enteritis caused by antibiotics. Chronic colitis may be caused by ulcerative colitis, Crohn's disease, tuberculosis, syphilis, or X-rays. In addition, colitis includes not only inflammatory bowel disease (IBD) but also irritable bowel syndrome (IBS). The causes of ulcerative colitis (UC) and Crohn's disease (CD), the most common inflammatory bowel disease (IBD), have yet to be clearly identified, and severe chronic diarrhea and hemolytic It can cause diarrhea, and it is difficult to cure, and it has the characteristic of repeated improvement and deterioration. Ulcerative colitis is a disease in which erosions (erosions) and ulcers are continuously formed in the mucous membranes of the large intestine. Bleeding, dyspepsia, diarrhea and abdominal pain occur in the colon. In severe cases, systemic symptoms such as fever, weight loss and anemia appear . Ulcerative colitis may also occur anywhere in the gastrointestinal tract. Crohn's disease is a disease in which ulcer and other lesions occur in a random part of the digestive tract from the mouth to the anus. In addition to abdominal pain, diarrhea and stool, severe cases include fever, hemorrhage, weight loss, And the like. Ulcerative colitis and Crohn 's disease are different in terms of lesions and inflammatory symptoms, but they are similar in many respects.
종래, 궤양성 대장염 및 크론병의 발생률은 서양인에게 높다고 알려졌었지만, 최근, 식습관 등의 생활습관의 변화로 인해 우리나라 등 동양에서도 환자 수가 급증하고 있다. 그렇지만, 원인이 불분명한 이유도 있어 근본적 치료법은 확립되어 있지 않다. 이 때문에 완전한 치료를 목표로 하는 것이 아니라, 증상을 완화시키고, 이러한 상태를 가능한 한 장기간 유지하는 약제가 사용되고 있는 실정이다. 이러한 대증요법을 위한 약제로서, 주로 아미노살리실산제제, 부신피질 스테로이드제, 면역억제제 등이 사용되지만, 다양한 부작용이 보고되고 있다. 예를 들어, 아미노살리실산제제로서 자주 사용되는 살라조설파피리딘은 구역질, 구토, 식욕부진, 발진, 두통, 간장해, 백혈구 감소, 이상 적혈구, 단백뇨, 설사 등의 부작용이 보고되고 있다. 또한 부신피질스테로이드제는 일반적으로는 프레드니솔론의 경구투여, 관장, 좌약, 정맥 주사 등으로 사용되지만, 위궤양이나 장기사용에 의한 대퇴골두 괴사 등 부작용이 강하다. 그러나 투약의 중단은 증상을 재발시키기 때문에, 이들 약제는 계속적으로 사용하지 않을 수 없다. In the past, the incidence of ulcerative colitis and Crohn's disease was known to be high in Westerners, but in recent years, the number of patients has also increased in Korea and other countries due to changes in lifestyle such as eating habits. However, there is a reason why the cause is unclear, and fundamental treatment is not established. For this reason, it is not aimed at complete treatment, but medicines which alleviate symptoms and maintain such state as long as possible are used. Aminosalicylic acid preparations, adrenocorticosteroids, immunosuppressants and the like are mainly used as medicines for such symptomatic therapy, but various side effects have been reported. For example, salazosulfapyridine, which is frequently used as an aminosalicylic acid preparation, has been reported to have side effects such as nausea, vomiting, anorexia, rash, headache, liver damage, leukocytosis, abnormal red blood cells, proteinuria and diarrhea. Adrenocortical steroids are generally used for oral administration of prednisolone, enema, suppository, intravenous injection, etc. However, side effects such as gastric ulcer necrosis caused by gastric ulcer or long-term use are strong. However, since discontinuation of the medication recurs, the medicines must be continuously used.
한편, 위는 식도를 통하여 들어온 음식물을 저장하고 소화되기 쉽게 잘게 부수며, 십이지장으로 음식물을 보내는 것을 조절하여 췌장효소의 분비와 조화를 이루어 효율적인 소화와 흡수가 되도록 하는 장기이다. 위는 음식물이 들어오면 이를 소화시키기 위해 강한 산인 위산을 분비하는데, 이때 위점막 보호층이 위산에 의해 위점막이 손상되지 않도록 작용한다. 위를 보호하는 위점막 보호층은 여러 종류의 인자로부터 공격을 받아 손상 받기 쉽다. 대표적인 공격 인자로는 위산, 알콜, 아스피린 등의 비스테로이드성 소염제(NSAID), 헬리코박터 파이롤리(helicobacter pylori) 등의 세균, 스트레스에 의해 유도된 위점막의 미세순환장애와 저혈압 등이 있다. 이러한 요인으로 인해 위점막층이 손상되었을 때 미란, 발적, 출혈, 부종을 동반한 염증이 발생하게 되며, 손상이 심하여 위점막을 뚫고 점막 하단 및 근육층까지 손상되었을 때 위궤양이 발생하게 된다. 또한, 상기 요인에 의해 십이지장 점막이 손상되어 가장 표면에 있는 점막층보다 깊이 패이면서 점막근층 이상으로 손상이 진행되면 십이지장 궤양이 발생하게 된다. 따라서, 상기와 같은 공격인자에 의해 유발된 위염, 위궤양 및 십이지장궤양 등의 위장질환을 치료하기 위해서는 위산 분비 억제, 헬리코박터 파이롤리 균의 증식 억제, 점액 분비 촉진, 상피세포 재생 촉진, 항염증 등의 효능을 가진 약물이 필요하다.On the other hand, the stomach stores the food that comes in through the esophagus, breaks it down easily, and controls the sending of the food to the duodenum, so that the pancreas enzyme is secreted and harmonized to efficiently digest and absorb. The stomach secretes stomach acid, which is strong acid to digest it when food comes in. At this time, the gastric mucosal protective layer acts to prevent the stomach acid from damaging the gastric mucosa. The gastric mucosal protective layer that protects the stomach is susceptible to attack from various kinds of factors. Typical attack factors include non-steroidal anti-inflammatory drugs (NSAIDs) such as gastric acid, alcohol, and aspirin, bacteria such as Helicobacter pylori, stress-induced microcirculatory disorders of gastric mucosa and hypotension. These factors cause erosion with erosion, redness, hemorrhage and edema when the gastric mucosal layer is damaged, and gastric ulcers occur when the damage is severe and the gastric mucosa penetrates to the lower mucosa and muscle layer. In addition, duodenal ulcer occurs when the duodenal mucosa is damaged due to the above factors, and the lesion progresses more than the mucosal layer on the surface most than the mucosal layer. Therefore, in order to treat gastrointestinal diseases such as gastritis, gastric ulcer, and duodenal ulcer induced by the above-described attack factors, it is desirable to inhibit gastric acid secretion, inhibit proliferation of Helicobacter pylori, promote mucous secretion, promote epithelial cell regeneration, Drugs with efficacy are needed.
현재 가장 대표적인 위장질환 치료제로는 과다한 위 분비액을 중화시키는 제산제(antacid), 위산 분비를 억제하는 히스타민 H2 수용체 길항제와 프로톤 펌프 저해제(proton pump inhibitor), 소화액에 대한 위 내막의 내성을 증가시키고 산 분비를 억제할 수 있는 프로스타글란딘(prostaglandin), 또는 위점막 보호제 등이 있다.Currently, the most typical treatment for gastrointestinal diseases is antacid which neutralizes excessive secretion liquid, histamine H2 receptor antagonist which suppresses gastric acid secretion, proton pump inhibitor, Prostaglandin, or gastric mucosal protective agent, which can inhibit the gastric mucosa.
상기 약물 중 제산제는 근본적인 치료가 아닌 일시적인 속효성을 위한 것으로, 위 내의 pH를 상승시켜 펩신의 활성을 저하시킴으로써 약효를 나타낸다. 그러나 제산제를 사용할 시 무기물질 투여에 의해 변비, 설사, 대사성 알칼로시스 (alkalosis), 요로결석증 등과 같은 부작용이 보고되어 있으며, 최근에는 제산제에 의한 산반동(acid rebound) 현상 등이 문제시되고 있다.Antacids among the above drugs are for temporary short-acting, not fundamental treatment, and exhibit drug efficacy by lowering the activity of pepsin by raising the pH in the stomach. However, when using antacids, side effects such as constipation, diarrhea, metabolic alkalosis and urinary nodule have been reported by the administration of inorganic substances. In recent years, acid rebound due to antacids has become a problem.
상기와 같은 한계 때문에 효과가 우수하면서도, 안전하고 부작용을 일으키지 않는 염증성 위장관 질환 치료제의 개발이 요구되고 있다. Due to such limitations, there is a demand for the development of a therapeutic agent for inflammatory gastrointestinal diseases which is excellent in efficacy, safe, and does not cause side effects.
이에 본 발명자들은 우수한 치료 활성을 가진 천연 추출물을 제조하기 위하여 연구한 결과, 옥수수 속대 추출물이 인체에 유해성이 없고, 우수한 위염 및 대장염 등 염증성 위장관 질환에 대한 치료 효과를 보임을 확인함으로써, 본 발명을 완성하였다. Accordingly, the present inventors have conducted studies to produce natural extracts having excellent therapeutic activity, and as a result, they have found that corncobs extract has no harmful effects on the human body and has a therapeutic effect on inflammatory gastrointestinal diseases such as gastritis and colitis, Completed.
본 발명의 목적은 옥수수 속대 추출물을 포함하는 염증성 위장관 질환의 예방 또는 치료용 조성물을 제공하는 것이다. It is an object of the present invention to provide a composition for the prophylaxis or treatment of inflammatory gastrointestinal diseases, including corncobs extract.
상기 과제를 해결하기 위하여, 본 발명은 옥수수 속대 추출물을 포함하는 염증성 위장관 질환의 예방 또는 치료용 약학적 조성물을 제공한다. In order to solve the above problems, the present invention provides a pharmaceutical composition for preventing or treating an inflammatory gastrointestinal tract disease comprising corncob meal extract.
본 발명은 옥수수 속대 추출물을 포함하는 염증성 위장관 질환의 예방 또는 개선용 식품 조성물을 제공한다. The present invention provides a food composition for preventing or ameliorating an inflammatory gastrointestinal tract disease comprising corncob meal extract.
본 발명의 옥수수 속대 추출물은 인체 내 부작용이 없으며, 위염 및 대장염 등 염증성 위장관 질환에 대한 우수한 치료 효과를 가지므로, 의약품 및 건강기능식품 등으로 유용하게 사용될 수 있다.The corncob meal extract of the present invention has no side effects in the human body and has an excellent therapeutic effect on inflammatory gastrointestinal diseases such as gastritis and colitis, and thus can be usefully used as medicines and health functional foods.
도 1은 AGS(랫트 위장점막세포)에서 옥수수 속대 추출물이 염증 인자 발현에 미치는 영향을 확인한 결과를 나타낸 도이다.
도 2는 위염 동물모델에서 옥수수 속대 추출물 투여에 의한 염증 부위의 크기 변화를 확인한 결과를 나타낸 도이다.
도 3은 위염 동물모델에 옥수수 속대 추출물을 투여한 후, 위 조직의 H&E 염색 결과(A) 및 조직 염증도 분석 결과(B)를 나타낸 도이다.
도 4는 위염 동물모델에 옥수수 속대 추출물을 투여한 후, 위 조직 단편을 분리하고 조직면역염색을 수행한 결과를 나타낸 도이다(A: i-NOS, B: TNF-a).
도 5는 대장염 동물모델에서 옥수수 속대 추출물 투여에 의한 체중 변화(A) 및 DAI(B)를 확인한 결과를 나타낸 도이다.
도 6은 대장염 동물모델에서 옥수수 속대 추출물 투여에 의한 대장 길이 변화를 확인한 결과를 나타낸 도이다.
도 7은 대장염 동물모델에 옥수수 속대 추출물을 투여한 후, 대장 조직의 H&E 염색 결과(A) 및 조직 염증도 분석 결과(B)를 나타낸 도이다.
도 8은 대장염 동물모델에 옥수수 속대 추출물을 투여한 후, 대장 조직 단편을 분리하고 조직면역염색을 수행한 결과를 나타낸 도이다(A: i-NOS, B: TNF-a). FIG. 1 is a graph showing the effect of corncobs extract on the expression of inflammatory factors in AGS (rat gastrointestinal mucosa cells). FIG.
FIG. 2 is a graph showing the change in the size of inflammation sites caused by administration of corncob meal extract in an animal model of gastritis. FIG.
FIG. 3 is a graph showing the results of H & E staining (A) and tissue inflammation analysis (B) of stomach tissue after administration of corn borer extract to a gastritis animal model.
FIG. 4 is a graph showing the results of immunohistochemical staining of the gastric tissue after the ingestion of corncob meal extract into a gastric animal model (A: i-NOS, B: TNF-a).
FIG. 5 is a graph showing the change in body weight (A) and DAI (B) by administration of corn borer extract in an animal model of colitis.
FIG. 6 is a diagram showing the results of checking the change in colon length by administration of corncob meal extract in an animal model of colitis. FIG.
FIG. 7 is a diagram showing the results of H & E staining (A) and tissue inflammation analysis (B) of colonic tissues after administration of corn borer extract to an animal model of colitis.
FIG. 8 is a graph showing the result of administration of a corn borer extract to an animal model of colitis, followed by isolation of a colon tissue fragment and tissue immunostaining (A: i-NOS, B: TNF-a).
본 발명은 옥수수 속대 추출물을 포함하는 염증성 위장관 질환의 예방 또는 치료용 조성물을 제공한다. The present invention provides a composition for preventing or treating an inflammatory gastrointestinal tract disease comprising corncob meal extract.
상기 조성물은 약학적 조성물 및 식품 조성물을 포함한다. The composition comprises a pharmaceutical composition and a food composition.
이하 본 발명에 대하여 보다 상세히 설명한다. Hereinafter, the present invention will be described in more detail.
본 발명에 있어서, '옥수수 속대(Corn cob)'는 식물체의 줄기에서 관상으로 배열된 관다발에 둘러싸인 중심에서 볼 수 있는 유조직이다. 상기 옥수수 속대는 건조물 기준으로 수분 6.7~14.9%, 조단백 4.3~12.9%, 조지방 0.5~1.4%, 조회분4.9~13.0% 및 식이섬유 27~54%를 포함하며, 수용성 식이섬유 및 불용성 식이섬유를 포함한다. 본 발명의 유효성분인 옥수수 속대는 일반적으로 버려지는 부산물을 이용하는 것이기에 부가가치가 높다. In the present invention, a 'corn cob' is a soft tissue that is visible at the center surrounded by a vascular bundle arranged in a tubular form at the stem of a plant. The cornstarch comprises 6.7 to 14.9% moisture, 4.3 to 12.9% crude protein, 0.5 to 1.4% crude fat, 4.9 to 13.0% of ash and 27 to 54% of dietary fiber, . The corn borer which is the active ingredient of the present invention has a high added value because it is a generally used by-product.
본 발명에 있어서, "추출물"은 상기 옥수수 속대의 추출처리에 의하여 얻어지는 추출액, 상기 추출액의 희석액이나 농축액, 상기 추출액을 건조하여 얻어지는 건조물, 상기 추출액의 조정제물이나 정제물, 또는 이들의 혼합물 등, 추출액 자체 및 추출액을 이용하여 형성 가능한 모든 제형의 추출물을 포함한다. In the present invention, the term "extract" means an extract obtained by extracting the cornstarch, a diluted solution or concentrate of the extract, a dried product obtained by drying the extract, a controlled preparation or a purified product of the extracted solution, Extracts themselves and extracts of all formulations which can be formed using extracts.
상기 추출물을 수득하기 위해 이용될 수 있는 용매의 종류에는 물, 탄소수 1 내지 4의 알코올 및 이들의 혼합용매 등이 포함되나 이에 제한되지 않는다. Examples of the solvent that can be used to obtain the extract include water, alcohols having 1 to 4 carbon atoms, a mixed solvent thereof, and the like, but are not limited thereto.
상기 추출물의 추출 방법으로는 열수추출법, 냉침추출법, 환류냉각추출법, 용매추출법, 수증기증류법, 초음파추출법, 용출법, 압착법 등의 방법이 사용될 수 있다. 추출물은 추가로 통상의 분획 공정을 수행할 수도 있으며, 통상의 정제 방법을 이용하여 정제될 수도 있다.Examples of the method for extracting the above extract include hot water extraction, cold extraction, reflux cooling, solvent extraction, steam distillation, ultrasonic extraction, elution, and compression. The extract may further be subjected to a conventional fractionation process, and may be purified using a conventional purification method.
본 발명에 있어서, '염증성 위장관 질환'은 위, 소장, 대장 등의 위장관(gastrointestinal tract)에 다양한 원인에 의해 발생된 염증 질환을 의미한다. 상기 염증성 위장관 질환에는 염증성 장질환(inflammatory bowel disease)[구체적으로는 궤양성 대장염(ulcerative colitis), 크론병(Crohn's disease)], 과민성 대장 증후군(irritable bowel syndrome)(특히, 하리형 과민성 대장 증후군), 또는 위염(gastritis)을 포함하며, 이에 제한되지 않는다. In the present invention, 'inflammatory gastrointestinal disease' refers to inflammatory diseases caused by various causes in the gastrointestinal tract such as stomach, small intestine, and large intestine. Inflammatory bowel disease (specifically, ulcerative colitis, Crohn's disease), irritable bowel syndrome (in particular, hyaline type irritable bowel syndrome), inflammatory bowel disease, , Or gastritis. ≪ / RTI >
상기 대장은 직장, S상결장, 하행결장, 횡행결장, 또는 상행결장을 포함하는 개념으로, 대장염은 상기 부위 중 1 이상의 부위에 염증이 발생한 것뿐만 아니라, 상기 부위를 모두 포함하는 부위에 염증이 발생한 것을 포함한다. The large intestine includes the rectum, the S-phase, the descending colon, the transverse colon, or the ascending colon. In the case of colitis, inflammation occurs in at least one site of the site, And the like.
본 발명의 옥수수 속대 추출물은 인체 내 부작용이 없으며, 위염 및 대장염 등 염증성 위장관 질환에 대한 우수한 치료 효과를 가지므로, 의약품 및 건강기능식품 등으로 유용하게 사용될 수 있다.The corncob meal extract of the present invention has no side effects in the human body and has an excellent therapeutic effect on inflammatory gastrointestinal diseases such as gastritis and colitis, and thus can be usefully used as medicines and health functional foods.
일 양태로서, 본 발명은 옥수수 속대 추출물을 포함하는 염증성 위장관 질환의 예방 또는 치료용 약학적 조성물을 제공한다.In one aspect, the invention provides a pharmaceutical composition for the prophylaxis or treatment of inflammatory gastrointestinal diseases, including corncobs extract.
본 발명에 있어서 약학적 조성물은 질병의 예방 또는 치료를 목적으로 제조된 것을 의미하며, 각각 통상의 방법에 따라 다양한 형태로 제형화하여 사용될 수 있다. 본 발명의 조성물이 염증성 위장관 질환의 예방 또는 치료를 목적으로 약학적 조성물로 제형화 될 경우, 약학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다. 또한 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다. 당해 기술 분야에 알려진 적합한 제제는 문헌 (Remington's Pharmaceutical Science, 최근, Mack Publishing Company, Easton PA)에 개시되어 있는 것을 사용하는 것이 바람직하다. 상기 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토오스, 덱스트로오스, 수크로오스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로오스, 메틸 셀룰로오스, 미정질 셀룰로오스, 폴리비닐 피롤리돈, 물, 메틸히드록시 벤조에이트, 프로필히드록시 벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유 등이 있다. 상기 조성물을 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 조성물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트 (calcium carbonate), 수크로오스, 락토오스, 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용된다. 경구투여를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순 희석제인 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 according to the present invention is prepared for the purpose of prevention or treatment of diseases, and can be formulated into various forms according to ordinary methods. When the composition of the present invention is formulated into a pharmaceutical composition for the purpose of preventing or treating inflammatory gastrointestinal diseases, it may further comprise suitable carriers, excipients and diluents conventionally used in the production of pharmaceutical compositions. In addition, it can be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, oral preparations such as syrups and aerosols, external preparations, suppositories and sterilized injection solutions according to a conventional method. Suitable formulations known in the art are preferably those as disclosed in Remington ' s Pharmaceutical Science, recently, Mack Publishing Company, Easton PA. Examples of carriers, excipients and diluents that can be included in the composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose , Microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. When the composition is formulated, it is prepared using a diluent such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, or an excipient usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose, lactose, Gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. 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. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.
본 발명에서 용어, "투여"는 임의의 적절한 방법으로 개체에게 소정의 본 발명의 조성물을 제공하는 것을 의미한다.The term "administering" as used herein means providing the subject invention with a composition of the invention in any suitable manner.
본 발명의 약학적 조성물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 상기 조성물의 투여는 하루에 한번 투여할 수도 있고, 수 회 나누어 투여할 수도 있다. 본 발명의 약학적 조성물의 투여량은 예를 들어, 1일 1 mg/kg 내지 1,000 mg/kg, 바람직하게는 10 mg/kg 내지 500 mg/kg일 수 있으나, 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.The preferred dosage of the pharmaceutical composition of the present invention varies depending on the condition and the weight of the patient, the degree of disease, the type of drug, the route of administration and the period of time, but can be appropriately selected by those skilled in the art. The composition may be administered once a day, or divided into several doses. The dosage of the pharmaceutical composition of the present invention may be, for example, 1 mg / kg to 1,000 mg / kg per day, preferably 10 mg / kg to 500 mg / kg per day, And are not intended to limit the scope of the invention.
본 발명의 약학적 조성물의 투여 경로 및 투여 방식은 각각 독립적일 수 있으며, 그 방식에 있어 특별히 제한되지 아니하며, 목적하는 해당 부위에 상기 약학적 조성물이 도달할 수 있는 한 임의의 투여 경로 및 투여 방식에 따를 수 있다. 상기 약학적 조성물은 경구 투여 또는 비경구 투여 방식으로 투여할 수 있고, 예를 들면, 경구, 직장, 정맥, 근육 또는 피하를 통해 투여될 수 있으며, 바람직하게는 경구로 투여될 수 있다. The route of administration and the mode of administration of the pharmaceutical composition of the present invention may be independent of each other, and the method is not particularly limited, and any route of administration and administration method may be used as long as the pharmaceutical composition can reach the desired site . The pharmaceutical composition may be administered orally or parenterally, for example, orally, rectally, intravenously, intramuscularly or subcutaneously, preferably orally.
본 발명의 약학적 조성물은 옥수수 속대 추출물과 함께 염증성 위장관 질환의 예방 또는 치료 효과를 갖는 공지의 유효성분을 1종 이상 더 함유할 수 있다. The pharmaceutical composition of the present invention may contain one or more known active ingredients having an effect of preventing or treating an inflammatory gastrointestinal tract disease together with a corn borer extract.
본 발명의 약학적 조성물은 염증성 위장관 질환의 예방 및 치료를 위하여 단독으로, 또는 수술, 방사선 치료, 호르몬 치료, 화학 치료 및 생물학적 반응 조절제를 사용하는 방법들과 병용하여 사용할 수 있다.The pharmaceutical composition of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers for the prevention and treatment of inflammatory gastrointestinal diseases.
다른 양태로써, 본 발명은 옥수수 속대 추출물을 포함하는 염증성 위장관 질환의 예방 또는 개선용 식품 조성물을 제공한다. In another aspect, the present invention provides a food composition for preventing or ameliorating an inflammatory gastrointestinal disorder, comprising corncob meal extract.
본 발명에 있어서 식품 조성물은 당업계에서 통상적으로 사용되는 방법에 의하여 제조가능하며, 상기 제조 시에는 당업계에서 통상적으로 첨가하는 원료 및 성분을 첨가하여 제조할 수 있다. 또한 상기 식품 조성물의 제형 또한 식품 조성물로 인정되는 제형이면 제한 없이 제조될 수 있다. In the present invention, the food composition may be prepared by a method commonly used in the art, and may be prepared by adding raw materials and ingredients that are conventionally added in the art. The formulations of the food composition may also be prepared without limitation as long as they are formulations acceptable as food compositions.
본 발명에 따른 식품 조성물은, 예를 들어, 건강기능식품의 형태일 수 있다. The food composition according to the invention may, for example, be in the form of a health functional food.
본 발명에 있어서 “건강기능식품”이란 식품에 물리적, 생화학적, 생물공학적 수법 등을 이용하여 해당 식품의 기능을 특정 목적에 작용, 발현하도록 부가가치를 부여한 식품군이나 식품 조성이 갖는 생체방어리듬조절, 질병방지와 회복 등에 관한 체내조절기능을 생체에 대하여 충분히 발현하도록 설계하여 가공한 식품을 의미한다. 본 발명의 목적상 상기 건강기능식품은 염증성 위장관 질환을 예방 또는 개선시키기 위한 것으로, 예를 들어, 위염 또는 대장염 등을 예방 및 개선하기 위한 건강기능식품을 의미한다.In the present invention, the term " health functional food " refers to a food group imparted with added value to function or express the function of the food by physical, biochemical, biotechnological techniques or the like, Means a food which has been designed and manufactured so that the body's control function regarding disease prevention and recovery is sufficiently expressed to the living body. For the purpose of the present invention, the health functional food is intended to prevent or ameliorate inflammatory gastrointestinal diseases, for example, a health functional food for preventing and improving gastritis or colitis.
본 발명에 따른 식품으로는 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합제, 기능성 식품 등이 있다. 또한 식품에는 특수영양식품 (예, 조제유류, 영, 유아식 등), 식육가공품, 어육제품, 두부류, 묵류, 면류 (예, 라면류, 국수류 등), 빵류, 건강보조식품, 조미식품 (예, 간장, 된장, 고추장, 혼합장 등), 소스류, 과자류 (예, 스넥류), 캔디류, 쵸코렛류, 껌류, 아이스크림류, 유가공품 (예, 발효유, 치즈 등), 기타 가공식품, 김치, 절임식품 (각종 김치류, 장아찌 등), 음료 (예, 과실 음료, 채소류 음료, 두유류, 발효음료류 등), 천연조미료 (예, 라면 스프 등), 식품첨가제 등이 포함되나 이에 제한되지 않는다. 상기 식품, 음료 또는 식품첨가제는 통상의 제조방법으로 제조될 수 있다.Foods according to the present invention include, for example, various foods, beverages, gums, tea, vitamin complexes, and functional foods. Foods also include special nutritional foods (eg crude oil, spirits, baby food, etc.), processed meat products, fish meat products, tofu, jelly, noodles (eg, ramie noodles, (For example, soy sauce), candy, chocolate, gum, ice cream, milk products (eg fermented milk, cheese), other processed foods, kimchi, pickled foods (Eg, fruit juices, etc.), beverages (eg fruit drinks, vegetable beverages, beverages, fermented beverages, etc.), natural seasonings (eg, ramen soup, etc.), food additives. The food, beverage or food additive may be prepared by a conventional production method.
본 발명의 조성물을 건강기능식품 첨가물로 사용할 경우, 상기 조성물을 그대로 첨가하거나 다른 건강기능식품 성분과 함께 사용할 수 있고, 통상적인 방법에 따라 적절하게 사용할 수 있다. 유효성분의 혼합량은 사용 목적에 따라 적합하게 결정될 수 있다. 일반적으로, 식품 또는 음료의 제조 시에 본 발명의 조성물은 원료에 대하여 바람직하게는 50 중량부 이하, 보다 바람직하게는 25 중량부 이하의 양으로 첨가할 수 있다. 그러나, 건강 조절 및 위생을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하일 수 있으며, 안정성 면에서 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로도 사용할 수 있다.When the composition of the present invention is used as a health functional food additive, the composition may be added as it is or may be used together with other health functional food ingredients, and may be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be appropriately determined depending on the purpose of use. In general, the composition of the present invention may be added in an amount of preferably 50 parts by weight or less, more preferably 25 parts by weight or less, with respect to the raw material in the production of food or beverage. However, in the case of long-term intake intended for health control and hygiene, the amount may be less than the above range, and since there is no problem in terms of stability, the active ingredient may be used in an amount in the above range.
본 발명의 식품 조성물은 유효성분인 옥수수 속대 추출물을 함유하는 것 외에 통상의 식품 조성물과 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트리톨 등의 당 알코올이다. 상술한 향미제는 천연 향미제 (타우마틴), 스테비아 추출물 (예를 들어 레바우디오시드 A, 글리시르히진 등) 및 합성 향미제 (사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. The food composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient as well as conventional food compositions in addition to the corncob activity extract which is an effective ingredient. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And polysaccharides such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. The above-described flavors can be advantageously used as natural flavorings (tau martin), stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.).
또한 상기 식품 조성물은 옥수수 속대 추출물 외에 여러 가지 영양제, 비타민, 광물 (전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제 (치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명의 식품 조성물은 천연 과일 주스 및 과일 주스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. In addition to the corncob meal extract, the food composition may contain various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and heavies (cheese, chocolate etc.), pectic acid and its salts, And salts thereof, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like. In addition, the food composition of the present invention may contain flesh for the production of natural fruit juices and fruit juice drinks and vegetable drinks.
이하 본 발명을 실시예 및 실험예에 의해 상세히 설명한다. 하기 실시예 및 실험예는 본 발명을 예시하기 위한 것일 뿐 본 발명이 하기 실시예 및 실험예에 의해 한정되는 것은 아니다.Hereinafter, the present invention will be described in detail with reference to Examples and Experimental Examples. The following Examples and Experimental Examples are provided only for illustrating the present invention, but the present invention is not limited by the following Examples and Experimental Examples.
실시예Example 1. 옥수수 1. Corn 속대An innocent 추출물의 제조 Preparation of extract
옥수수로부터 옥수수 속대를 분리하였다. 건조된 옥수수 속대 50g을 1L 병에 넣고 옥수수 속대 양의 10배인 500ml dH2O을 가하고 혼합하였다. 이후 110℃ 및 0.4kgf/cm3 (5.69PSI)의 고온 고압 조건에서 15분 동안 열수 추출한 후, 0.2 um 실린지 필터로 여과하였다. 상기 과정을 통해 수득한 옥수수 속대 추출물(Zm extract)을 이하 실험에 이용하였다.Corn corps was isolated from corn. 50 g of dried cornstarch were placed in a 1 L bottle and 500 mL dH 2 O, 10 times the amount of corn inoculated, was added and mixed. After that, the mixture was subjected to hydrothermal extraction for 15 minutes under high temperature and high pressure conditions of 110 ° C and 0.4 kgf / cm 3 (5.69 PSI), followed by filtration with a 0.2 μm syringe filter. The Zm extract obtained through the above procedure was used in the following experiments.
실시예Example 2. 옥수수 2. Corn 속대An innocent 추출물의 성분 분석 Analysis of components of extract
2-1. 옥수수 2-1. corn 속대An innocent 추출액의 동결건조 및 건조 중량 분석 Freeze-drying and dry weight analysis of extract
상기 실시예 1에서 수득한 옥수수 속대 추출액 1ml을 1.5ml 튜브에 넣은 뒤 동결 건조기(Martin Christ, Alpha 1-4 LDplus, Osterode am Harz, Germany)를 이용하여 24시간 동안 동결건조하였다(-56°C, 0.021mbar). 이후 시료의 건조 중량을 측정하였으며, 총 3개 세트(A, B, C)의 건조 중량의 평균값을 산출하였다. 그 결과를 표 1에 나타내었다. 1 ml of the corncob meal extract obtained in Example 1 was placed in a 1.5 ml tube and lyophilized for 24 hours using a freeze dryer (Martin Christ, Alpha 1-4 LDplus, Osterode am Harz, Germany) , 0.021 mbar). Then, the dry weight of the sample was measured, and the average value of the dry weights of the three sets (A, B, C) was calculated. The results are shown in Table 1.
(A,B,C)Average
(A, B, C)
(mg/ml)Dry powder
(mg / ml)
2-2. 옥수수 2-2. corn 속대An innocent 추출물 내 폴리페놀 함량 분석 Analysis of Polyphenol Contents in Extracts
먼저, 갈릭산(SIGMA, G7384-100G, USA) 0.17012g을 최종 부피가 1ml이 되도록 메탄올(ARMRESCO, K977-1L, USA)에 녹여 1M 갈릭산을 제조하였다. 이를 메탄올에 희석하여 다양한 농도(1uM, 5uM, 10uM, 25uM, 75uM, 0.3mM, 0.7mM, 2mM, 6mM)로 제조한 후 폴리페놀 함량 분석을 위한 스탠다드 용액으로 사용하였다. First, 0.17012 g of gallic acid (SIGMA, G7384-100G, USA) was dissolved in methanol (ARMRESCO, K977-1L, USA) to a final volume of 1 ml to prepare 1M gallic acid. (1uM, 5uM, 10uM, 25uM, 75uM, 0.3mM, 0.7mM, 2mM, 6mM) were diluted in methanol and used as a standard solution for polyphenol content analysis.
다음으로, 2N Folin&Ciocalteu's phenol reagent(SIGMA, F9252-1L, USA) 80ul를 99.98ml의 dH2O에 희석하여 10%의 Folin&Ciocalteu's phenol reagent 반응액 (Solution A)을 제조하였다. 한편, 0.74g의 탄산나트륨(SIGMA, 223484-500G, USA)을 dH2O에 녹여 700mM 탄산나트륨 반응액 (Solution B)를 제조하였다. 1.5ml 튜브에 상기 스탠다드 용액 또는 옥수수 속대 추출물을 각각 100ul씩 넣어준 뒤 Solution A를 200ul과 혼합하고 상온에서 1분간 반응시켰다. 상기 혼합액에 Solution B 800ul을 넣고 혼합한 뒤 37°C에서 30분간 다시 반응시켰다. 반응이 끝난 뒤 얼음에 넣어 반응을 멈추게 하고, 큐벳(HellmaAnalytics, 104-10-46, Germany)에 1ml씩 넣고 분광광도계(Optizen, Optizen POP Bio, Korea)를 이용하여 765 nm에서 흡광도를 측정하였다. 그 결과를 표 2에 나타내었다. Next, 80 μl of 2N Folin and Ciocalteu's phenol reagent (SIGMA, F9252-1L, USA) was diluted in 99.98 ml of dH 2 O to prepare a 10% solution of Folin and Ciocalteu's phenol reagent (Solution A). On the other hand, 0.74 g of sodium carbonate (SIGMA, 223484-500G, USA) was dissolved in dH 2 O to prepare a 700 mM sodium carbonate reaction solution (Solution B). The standard solution or the cornstarch extract was added to a 1.5 ml tube in an amount of 100 μl each, followed by mixing with 200 μl of Solution A and reacting at room temperature for 1 minute. 800 Solution of Solution B was added to the mixed solution, and the mixture was reacted at 37 캜 for 30 minutes. After the reaction was completed, the reaction was stopped by adding ice to 1 ml of cuvette (HellmaAnalytics, 104-10-46, Germany) and absorbance was measured at 765 nm using a spectrophotometer (Optizen, Optizen POP Bio, Korea). The results are shown in Table 2.
(A,B,C)Average
(A, B, C)
2-3. 옥수수 2-3. corn 속대An innocent 추출물 내 카테킨 함량 분석 Analysis of catechin content in extracts
먼저 1mg의 카테킨을 1ml의 메탄올에 녹인 후, 1.5ml 튜브에 0, 1, 5, 10, 20ul씩 나누어주고 최종 부피가 20ul가 되도록 메탄올을 각 튜브에 20, 19, 15, 10, 0ul씩 넣어 전체 폴리페놀 중 카테킨(Catechin) 함량 분석을 위한 스탠다드 용액으로 사용하였다. First, 1 mg of catechin was dissolved in 1 ml of methanol, and the mixture was divided into 0, 1, 5, 10, and 20 ul in a 1.5 ml tube. Methanol was added to each tube in an amount of 20, 19, 15, It was used as a standard solution for catechin content analysis of whole polyphenols.
다음으로, 바닐린(JUNSEI, Japan) 0.1g을 10ml 메탄올(ARMRESCO, USA)에 녹여 1% vanillin 용액을 제조하였다 (solution A). 한편, 메탄올에 희석한 8% HCl (Daejung, Korea)과 solution A를 1:1의 부피비로 혼합하여 반응액을 제조하였다 (solution B). 상기 반응액(Solution B)을 30°C에서 15분간 유지하고, 스탠다드 20ul와 옥수수속대 추출물 20ul를 30°C에서 5분간 전 배양(pre-incubation)한 후, 상기 반응액(Solution B) 100ul와 스탠다드 용액 또는 옥수수 속대 추출물 20ul를 혼합한 뒤, 30°C에서 20분간 반응시키고 얼음에 넣어 반응을 멈춰주었다. 이후, 96 웰 플레이트 (SPL Life Sciences, Korea)에 각 용액을 110ul씩 넣어준 후, 마이크로 플레이트 리더기(SunriseTM, Tecan, Switzerland)를 이용하여 492 nm에서 흡광도를 측정하였다. 그 결과를 표 3에 나타내었다. Next, 0.1 g of vanillin (JUNSEI, Japan) was dissolved in 10 ml of methanol (ARMRESCO, USA) to prepare a 1% vanillin solution (solution A). Meanwhile, 8% HCl (Daejung, Korea) diluted in methanol and solution A were mixed at a volume ratio of 1: 1 to prepare a reaction solution (solution B). The reaction solution (Solution B) was maintained at 30 ° C for 15 minutes, 20 μl of the standard and 20 μl of the cornstarch extract were pre-incubated at 30 ° C for 5 minutes. Then, 100 μl of the reaction solution (Solution B) 20ul of standard solution or corncob meal extract was mixed and reacted at 30 ° C for 20 minutes, and the reaction was stopped by adding ice. Then, 110 ul of each solution was added to a 96-well plate (SPL Life Sciences, Korea), and the absorbance was measured at 492 nm using a microplate reader (Sunrise ™ , Tecan, Switzerland). The results are shown in Table 3.
(A,B,C)Average
(A, B, C)
(ug/ml)Catechin
(ug / ml)
실험예Experimental Example 1. 위장 점막 세포에서 항염증 활성 검증 1. Anti-inflammatory activity assay in gastric mucosa cells
생체 외에서 옥수수 속대 추출물의 항염증 활성을 확인하기 위하여, 랫트의 위장점막세포인 AGS (ATCC® CRL-1739™)를 이용하였다. 보다 구체적으로, AGS 세포를 L-글루타민, 10% FBS(Fetal Bovine Serum; GemCell, California, USA), 1% 페니실린/스트렙토마이신(Thermo Fisher Scientific, Massachusetts, USA)을 포함하는 RPMI1640 1X(RPMI1640; CORNING, Utah, USA) 배지에 넣고, 36.5℃, 5% CO2 조건의 인큐베이터(Thermo scientific, Massachusetts, USA)에서 유지하였다. 상기 AGS 세포 5x105개를 100mm 플레이트에 시딩하고, 12시간 동안 배양하였다. 각 웰에 비히클 또는 옥수수 속대 추출물(10-2, 10-3, 10-4 희석액)을 처리한 후, 다시 12시간 동안 반응시켰다. 이후 세포를 수거한 후, RIPA 버퍼(50mM Tris, 150mM Nacl, 0.1%SDS, 0.5% Sodium deoxycholate, 1% Nonidet P-40)와 1% PMSF를 넣어 준 뒤 30분 동안 처리하고 상층액을 회수하여 단백질을 분리하였다. 상기 단백질을 이용하여 당업계에 공지된 방법에 따라 웨스턴 블랏을 수행하였다. 이때 1차 항체로는 염증 표지단백질인 COX2(Santa Cruz Biotechnology, California, USA) 및 IL-6(Santa Cruz Biotechnology, California, USA)에 대한 것을 이용하였다. 그 결과를 도 1에 나타내었다. AGS (ATCC® CRL-1739 ™), a gastric mucosal cell of the rat, was used to confirm the anti-inflammatory activity of the corncobs extract in vitro. More specifically, AGS cells were suspended in RPMI 1640 1X (RPMI 1640; CORNING, USA) containing L-glutamine, 10% FBS (Fetal Bovine Serum; GemCell, California, USA), 1% penicillin / streptomycin (Thermo Fisher Scientific, , Utah, USA) and maintained in an incubator (Thermo scientific, Massachusetts, USA) at 36.5 ° C and 5% CO 2 . 5x10 5 of the AGS cells were seeded on a 100 mm plate and cultured for 12 hours. Each well was treated with vehicle or cornstarch extract (10 -2 , 10 -3 , 10 -4 dilution) and allowed to react for another 12 hours. After the cells were collected, the cells were treated with RIPA buffer (50 mM Tris, 150 mM NaCl, 0.1% SDS, 0.5% sodium deoxycholate, 1% Nonidet P-40) and 1% PMSF for 30 minutes, Proteins were isolated. Western blotting was performed according to methods known in the art using the protein. The primary antibodies were COX2 (Santa Cruz Biotechnology, California, USA) and IL-6 (Santa Cruz Biotechnology, California, USA) as the primary antibodies. The results are shown in Fig.
도 1에 나타낸 바와 같이, 옥수수 속대 추출물의 처리에 따라 위장 점막 세포에서 염증 마커인 COX2와 IL-6의 발현이 통계적으로 유의하게 감소하는 등 항염증 효과가 나타남을 확인하였다. As shown in FIG. 1, it was confirmed that anti-inflammatory effects such as COX2 and IL-6 expression, which are inflammation markers, in the gastric mucosal cells were statistically decreased by the treatment of corncob meal extract.
실험예Experimental Example 2. 위염 동물 모델에서 항염증 활성 검증 2. Anti-inflammatory activity test in gastric animal model
6주령의 수컷 랫트에 경구를 통해 80mg/kg의 인도메타신(Indomethacin)을 투여하고 6시간 지속시킴으로써 위염 동물 모델을 제작하였다(G2). 상기 위염 동물 모델에 실시예 1에서 수득한 옥수수 속대 추출물(추출물의 10배 희석[G4], 100배 희석[G5])을 각각 투여하여 그 치료 효과를 확인하였다. G1은 아무것도 처리하지 않는 정상군의 랫트이며, G3는 위염 치료제인 란소프라졸(lansoprazole)을 투여한 군이다. 실험 종료 후 각 랫트를 부검하여 위 염증 부위를 측정하였으며, 위 조직을 분리하여 H&E 염색 및 조직 관찰을 통해 염증 수치를 계산하였다. 또한, 위 조직 단편을 이용하여 i-NOS 및 TNF-a에 대한 조직면역염색(immunohistochemistry)을 수행하였다. 이상의 실험 결과를 도 2 내지 도 4에 나타내었다. A gastritis model was prepared by administering 80 mg / kg of indomethacin to 6-week-old male rats via oral route and continuing for 6 hours (G2). To the above gastrointestinal animal model, the corncob meal extract (10-fold dilution [G4], 100-fold dilution [G5]) of the extract obtained in Example 1 was respectively administered to confirm the therapeutic effect. G1 is a normal group of rats that does nothing, and G3 is a group administered with lansoprazole, a gastritis treatment. After the end of the experiment, each rat was autopsied and gastric inflammation site was measured. The gastric tissues were separated, and the inflammation level was calculated by H & E staining and tissue observation. In addition, immunohistochemistry for i-NOS and TNF-a was performed using gastric tissue sections. The results of the above experiments are shown in FIG. 2 to FIG.
도 2에 나타낸 바와 같이, 인도메타신에 의한 위 염증 정도가 옥수수 속대 추출물의 투여에 의해 통계적으로 유의(P>0.05)하게 감소하였음을 확인하였다. As shown in Fig. 2, it was confirmed that the degree of gastric inflammation by indomethacin was statistically significant (P > 0.05) by administration of corncob meal extract.
또한, 도 3에 나타낸 바와 같이, H&E 염색 및 조직관찰(inflammation, ulceration, hyperplasia) 결과, 옥수수 속대 추출물의 투여에 의해 염증수치가 현저하게 개선됨을 확인하였다. In addition, as shown in FIG. 3, the results of H & E staining and tissue observation (inflammation, ulceration, hyperplasia) showed that inflammation levels were remarkably improved by administration of corn borer extract.
또한, 도 4에 나타낸 바와 같이, 옥수수 속대 추출물의 투여에 의해 대표적인 염증 마커인 i-NOS(A) 및 TNF-a(B)의 발현이 현저하게 감소함을 확인하였다. In addition, as shown in Fig. 4, the expression of i-NOS (A) and TNF-a (B), which are typical inflammation markers, was remarkably decreased by administration of corncob activity.
이를 통해, 본 발명에 따른 옥수수 속대 추출물이 위염 동물 모델에서 우수한 치료 효과를 가지고 있음을 확인하였다. Thus, it was confirmed that the corncob meal extract according to the present invention has an excellent therapeutic effect in a gastritis animal model.
실험예Experimental Example 3. 대장염 동물 모델에서 항염증 활성 검증 3. Anti-inflammatory activity assay in colitis animal model
5주령의 수컷 마우스에 1주일간 2% DSS(dextran sulfate sodium)를 자유급이로 공급하여 대장염을 유발하였다. 예방군(prevention group)은 DSS 투여 1주일 전부터 1회/일씩 옥수수 속대 추출물(추출물의 10배 희석[G3], 100배 희석[G5)])을 경구투여한 군을 의미하며, 처치군(therapy group)은 DSS 투여와 동시에 1회/일씩 옥수수 속대 추출물(추출물의 10배 희석[G4], 100배 희석[G6)])을 경구투여한 군을 의미한다. G1은 아무것도 투여하지 않은 정상 마우스이며, G2는 DSS만 투여한 질병유발군이다. 실험 종료 후 각 마우스를 희생시킨 후 체중을 측정하고, DAI(Disease activity index)를 분석하였다. 이때 DAI는 다음과 같은 3가지 항목으로 측정하였다: [Body weight loss]: none=0; 1-5%=1; 5-10%=2; 10-15%=3; above 15%=4, [Stool consistency]: normal=0; soft=2; diarrhea=4, [Presence of blood in stool]: none=0; slight bleeding=2; massive bleeding=4. 또한, 각 마우스의 대장 길이를 측정하고, 대장 조직을 분리한 후 H&E 염색 및 조직 관찰을 통해 염증 수치를 계산하였다. 또한, 대장 조직 단편을 이용하여 i-NOS 및 TNF-a에 대한 조직면역염색(immunohistochemistry)을 수행하였다. 이상의 실험 결과를 도 5 내지 도 8에 나타내었다.5-week-old male mice were fed with 2% DSS (dextran sulfate sodium) for 1 week at free-feeding to induce colitis. The prevention group means a group of oral administration of corncobs extract (10 times diluted [G3], 100 times diluted [G5])] once a day / day from 1 week before administration of DSS, group) refers to a group obtained by oral administration of corncob meal extract (10-fold diluted [G4], 100-fold diluted [G6])] at a time / day at the same time as DSS administration. G1 is a normal mouse to which nothing is administered, and G2 is a disease-induced group administered only DSS. After the completion of the experiment, each mouse was sacrificed and the body weight was measured, and the DAI (Disease activity index) was analyzed. At this time, DAI was measured by the following three items: [Body weight loss]: none = 0; 1-5% = 1; 5-10% = 2; 10-15% = 3; above 15% = 4, [Stool consistency]: normal = 0; soft = 2; diarrhea = 4, [Presence of blood in stool]: none = 0; slight bleeding = 2; massive bleeding = 4. In addition, colon length of each mouse was measured, colon tissue was separated, and the inflammation level was calculated by H & E staining and tissue observation. In addition, immunohistochemistry for i-NOS and TNF-a was performed using a colon tissue fragment. The results of the above experiments are shown in Figs.
도 5에 나타낸 바와 같이, 대장염의 발병에 의해 발생하는 급격한 체중 감소가 옥수수 속대 추출물의 투여에 의해 완화되었음을 확인하였으며(A), 옥수수 속대 추출물 투여군의 DAI가 질병유발군에 비해 유의적으로 낮음을 확인하였다(B). As shown in FIG. 5, it was confirmed that the rapid weight loss caused by the incidence of colitis was alleviated by the administration of the corn borer extract (A), and the DAI of the corn borer extract-administered group was significantly lower than that of the disease-induced group (B).
또한, 도 6에 나타낸 바와 같이, 질병유발군은 대장염의 발병에 의해 대장 길이가 유의하게 줄어들었으나, 옥수수 속대 추출물 투여군은 정상군과 큰 차이가 없음을 확인하였다. In addition, as shown in FIG. 6, colon length was significantly reduced by the onset of colitis in the disease-induced group, but it was confirmed that there was no significant difference between the group treated with corn onion extract and the normal group.
또한, 도 7에 나타낸 바와 같이, H&E 염색 및 조직관찰(inflammation, ulceration, hyperplasia) 결과, 옥수수 속대 추출물의 투여에 의해 염증 수치가 현저하게 개선됨을 확인하였고, 도 8에 나타낸 바와 같이, 대표적인 염증 마커인 i-NOS(A) 및 TNF-a(B)의 발현이 옥수수 속대 추출물의 투여에 의해 현저하게 감소함을 확인하였다. 7, as a result of H & E staining and tissue observation (inflammation, ulceration, hyperplasia), it was confirmed that the inflammation level was remarkably improved by the administration of corncob meal extract. As shown in FIG. 8, The expression of i-NOS (A) and TNF-a (B) was remarkably decreased by the administration of corn borer extract.
이를 통해, 본 발명에 따른 옥수수 속대 추출물이 대장염 동물 모델에서 우수한 예방 및 치료 효과를 가지고 있음을 확인하였다. Thus, it was confirmed that the corncobs extract according to the present invention has excellent preventive and therapeutic effects in an animal model of colitis.
이상의 실험 결과를 통해, 옥수수 속대 추출물은 위염 및 대장염을 비롯한 염증성 위장관 질환 동물모델에서 현저하게 우수한 항염증 효과를 가지고 있음을 확인하였다. From the above results, it was confirmed that corncobs extract had a remarkably excellent anti-inflammatory effect in an animal model of inflammatory gastrointestinal tract diseases including gastritis and colitis.
이하 본 발명의 약학적 조성물 및 식품 조성물의 제제예를 설명하나, 본 발명을 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Hereinafter, the pharmaceutical composition of the present invention and the preparation example of the food composition will be described, but the present invention is not intended to be limited but is specifically described.
제제예Formulation example 1. 약학적 조성물의 제조 1. Preparation of pharmaceutical compositions
1-1. 1-1. 산제의Sanje 제조 Produce
옥수수 속대 추출물 2 gCorn onion extract 2 g
유당 1 gLactose 1 g
상기의 성분을 혼합하고 기밀포에 충진하여 산제를 제조하였다.The above components were mixed and packed in airtight bags to prepare powders.
1-2. 정제의 제조1-2. Manufacture of tablets
옥수수 속대 추출물 100 mgCorn onion extract 100 mg
옥수수전분 100 mgCorn starch 100 mg
유당 100 mgLactose 100 mg
스테아린산 마그네슘 2 mg
상기의 성분을 혼합한 후, 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조하였다.After mixing the above components, tablets were prepared by tableting according to a conventional method for producing tablets.
1-3. 캡슐제의 제조1-3. Preparation of capsules
옥수수 속대 추출물 100 mgCorn onion extract 100 mg
옥수수전분 100 mgCorn starch 100 mg
유당 100 mgLactose 100 mg
스테아린산 마그네슘 2 mg
상기의 성분을 혼합한 후, 통상의 캡슐제의 제조방법에 따라서 젤라틴 캡슐에 충전하여 캡슐제를 제조하였다.After mixing the above components, the capsules were filled in gelatin capsules according to the conventional preparation method of capsules.
제제예Formulation example 2. 식품 조성물의 제조 2. Preparation of food composition
2-1. 건강기능식품의 제조2-1. Manufacture of Health Functional Foods
옥수수 속대 추출물 100 mgCorn onion extract 100 mg
비타민 혼합물 적량Vitamin mixture quantity
비타민 A 아세테이트 70 μg Vitamin A acetate 70 μg
비타민 E 1.0 mgVitamin E 1.0 mg
비타민 B1 0.13 mgVitamin B1 0.13 mg
비타민 B2 0.15 mg0.15 mg of vitamin B2
비타민 B6 0.5 mgVitamin B6 0.5 mg
비타민 B12 0.2 μg Vitamin B12 0.2 μg
비타민 C 10 mgVitamin C 10 mg
비오틴 10 μg Biotin 10 μg
니코틴산아미드 1.7 mgNicotinic acid amide 1.7 mg
엽산 50 μg Folic acid 50 μg
판토텐산 칼슘 0.5 mgCalcium pantothenate 0.5 mg
무기질 혼합물 적량Mineral mixture quantity
황산제1철 1.75 mg1.75 mg of ferrous sulfate
산화아연 0.82 mg0.82 mg of zinc oxide
탄산마그네슘 25.3 mgMagnesium carbonate 25.3 mg
제1인산칼륨 15 mgPotassium monophosphate 15 mg
제2인산칼슘 55 mgSecondary calcium phosphate 55 mg
구연산칼륨 90 mgPotassium citrate 90 mg
탄산칼슘 100 mgCalcium carbonate 100 mg
염화마그네슘 24.8 mgMagnesium chloride 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강식품 조성물 제조에 사용할 수 있다.Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.
Claims (6)
A pharmaceutical composition for the prophylaxis or treatment of inflammatory gastrointestinal diseases, comprising corncobacca high-pressure hot-water extract containing polyphenols and catechins.
The pharmaceutical composition for preventing or treating inflammatory gastrointestinal diseases according to claim 1, wherein the corncob meal extract contains polyphenols in a concentration of 0.311 to 0.314 mg / ml.
The pharmaceutical composition for preventing or treating inflammatory gastrointestinal diseases according to claim 1, wherein the corncoble high-pressure hot-water extract contains catechin at a concentration of 0.059 to 0.063 μg / ml.
The pharmaceutical composition according to claim 1, wherein the inflammatory gastrointestinal disorder is at least one selected from the group consisting of gastritis, ulcerative colitis, Crohn's disease and irritable bowel syndrome.
A food composition for preventing or ameliorating an inflammatory gastrointestinal tract disease comprising corncobacca high-pressure hot-water extract containing polyphenols and catechins.
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KR102614182B1 (en) | 2023-06-16 | 2023-12-15 | 주식회사 사임당화장품 | Cosmetic Compositions Comprising Extract of Zea mays husk |
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KR20130011111A (en) * | 2011-07-20 | 2013-01-30 | 신일제약주식회사 | Pharmaceutical compositions for preventing or treating inflammatory diseases comprising phytosterol compound |
KR20160036202A (en) | 2014-09-25 | 2016-04-04 | 코웨이 주식회사 | UV Protecting Cosmetic Composition Comprising Corn Cob Extract As Active Ingredient |
KR20160066279A (en) * | 2014-12-02 | 2016-06-10 | 임인자 | Oral Cavity Cleaning Composition |
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KR20130011111A (en) * | 2011-07-20 | 2013-01-30 | 신일제약주식회사 | Pharmaceutical compositions for preventing or treating inflammatory diseases comprising phytosterol compound |
KR20160036202A (en) | 2014-09-25 | 2016-04-04 | 코웨이 주식회사 | UV Protecting Cosmetic Composition Comprising Corn Cob Extract As Active Ingredient |
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KR102614182B1 (en) | 2023-06-16 | 2023-12-15 | 주식회사 사임당화장품 | Cosmetic Compositions Comprising Extract of Zea mays husk |
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