KR102136662B1 - Composition for preventing or treating ileus comprising humulus japonicus extract - Google Patents
Composition for preventing or treating ileus comprising humulus japonicus extract Download PDFInfo
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- KR102136662B1 KR102136662B1 KR1020190017212A KR20190017212A KR102136662B1 KR 102136662 B1 KR102136662 B1 KR 102136662B1 KR 1020190017212 A KR1020190017212 A KR 1020190017212A KR 20190017212 A KR20190017212 A KR 20190017212A KR 102136662 B1 KR102136662 B1 KR 102136662B1
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- Prior art keywords
- intestinal obstruction
- extract
- composition
- preventing
- yulcho
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Abstract
Description
본 발명은 율초 추출물을 유효성분으로 함유하는 장폐색증 예방 또는 치료용 조성물에 관한 것이다.The present invention relates to a composition for the prevention or treatment of intestinal obstruction containing the extract of Yulcho as an active ingredient.
장폐색증(ileus)이란, 소장이나 대장의 일부가 막혀서 음식물이나 소화액, 가스 등이 빠져나가지 못하는 질병으로, 배변과 가스가 장내에 축적되어 복통을 일으키는 상태를 말한다. 장폐색증은 장의 유착으로 인한 기계적 장폐색증, 장 이외의 기관에서 일어난 장애로 인해 장운동이 마비되는 마비성 장폐색증으로 구분할 수 있다. Intestinal obstruction (ileus) is a condition in which parts of the small intestine or large intestine are blocked and food, digestive fluids, gas, etc. cannot escape, and refers to a condition in which bowel movement and gas accumulate in the intestine and cause abdominal pain. Intestinal obstruction can be divided into mechanical intestinal obstruction due to adhesion of the intestine and paralytic intestinal obstruction in which intestinal movement is paralyzed due to disorders occurring in organs other than the intestine.
기계적 장폐색증은 장이 유착되어 움직일 때마다 장이 끌어당겨지면서 통증과 장애가 일어나는데, 대부분 복부 수술로 인해 발생한다. 개복 수술 시, 복막이나 장 등 복강 내 조직에 손상이 생길 수 있는데, 이 부위가 아물면서 염증이 발생하고 섬유화 과정을 거치는 과정에서 장들이 서로 들러붙어 장 내용물이 내려가지 못하는 장폐색증이 발생할 수 있다. 수술 후 수일 이내에 나타나기도 하고, 수년 이후에도 나타날 수 있다. 그 외에도 탈장, 종양, 농양, 크론병이나 장결핵 등의 염증성 질환, 외상으로 인한 장별 혈종, 장염전 등으로 인해 기계적 장폐색증이 발생할 수 있다.Mechanical intestinal obstruction causes pain and disability as the intestines are attracted and moved, causing pain and disability, most often due to abdominal surgery. During open surgery, tissues in the abdominal cavity, such as the peritoneum or intestine, may be damaged, and this area may heal, causing inflammation and intestinal obstruction in which the intestinal contents cannot descend due to the intestines sticking together during the fibrosis process. It may appear within a few days after surgery, or even years later. In addition, mechanical intestinal obstruction may occur due to inflammatory diseases such as hernia, tumor, abscess, Crohn's disease or intestinal tuberculosis, intestinal hematoma due to trauma, and enterocolitis.
마비성 장폐색증의 경우 복부 수술을 시행한 후 나타나는 것이 대부분으로, 마취 및 수술로 인해 장의 운동이 일시적으로 마비되나, 수일 이내 회복이 가능하다. 이 외에도 위 또는 십이지장 궤양 천공, 급성 복막염, 급성 췌장염, 급성 담낭염, 복부 외상으로 인한 복막 자극 등에 의해 발생할 수 있다.In the case of paralytic intestinal obstruction, most of them appear after performing abdominal surgery, and anesthesia and surgery temporarily paralyze the bowel movement, but recovery is possible within a few days. In addition to this, it may be caused by perforation of the stomach or duodenal ulcer, acute peritonitis, acute pancreatitis, acute cholecystitis, peritoneal irritation due to abdominal trauma.
개복 수술을 받은 환자에게 이러한 수술 후 장폐색이 발생할 경우, 환자의 육체적 고통은 물론 입원 기간 및 비용이 크게 증가될 수 있다. 장폐색이 발생한 경우, 우선적으로 내과적 처치를 시행하고, 증상의 호전이 없거나 종양 등으로 인한 폐색 시에는 수술적 처치를 시행하는데, 장폐색증은 천공과 같은 합병증이 나타날 수 있고 저혈성 쇼크로 사망할 수 있기 때문에 빠른 진단과 응급처치가 필요하다. If intestinal obstruction occurs after the surgery in a patient undergoing open surgery, the physical pain of the patient as well as the length and cost of hospitalization can be significantly increased. If intestinal obstruction occurs, medical treatment is given first, and surgical treatment is performed when symptoms do not improve or when obstruction occurs due to tumors, etc. Intestinal obstruction may result in complications such as perforation and death from hypotensive shock. Because of this, quick diagnosis and first aid is necessary.
상기와 같은 문제점을 해결하기 위하여, 본 발명은 율초 추출물을 함유하는 장폐색증 예방 또는 치료용 약학 조성물을 제공한다.In order to solve the above problems, the present invention provides a pharmaceutical composition for preventing or treating intestinal obstruction containing yulcho extract.
또한, 본 발명은 율초 추출물을 함유하는 장폐색증 예방 또는 개선용 건강기능식품 조성물을 제공한다.In addition, the present invention provides a health functional food composition for preventing or improving intestinal obstruction containing yulcho extract.
본 발명은 율초(Humulus japonicus) 추출물을 유효성분으로 함유하는 장폐색증 예방 또는 치료용 약학 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing or treating intestinal obstruction, which contains an extract of Yulcho (Humulus japonicus) as an active ingredient.
본 발명은 율초(Humulus japonicus) 추출물을 유효성분으로 함유하는 장폐색증으로 인한 염증 예방 또는 치료용 약학 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing or treating inflammation due to intestinal obstruction, which contains an extract of Yulcho (Humulus japonicus) as an active ingredient.
본 발명은 율초(Humulus japonicus) 추출물을 유효성분으로 함유하는 장폐색증 예방 또는 개선용 건강기능식품 조성물을 제공한다.The present invention provides a health functional food composition for preventing or improving intestinal obstruction, which contains an extract of Yulcho (Humulus japonicus) as an active ingredient.
본 발명은 율초(Humulus japonicus) 추출물을 유효성분으로 함유하는 장폐색증으로 인한 염증 예방 또는 개선용 건강기능식품 조성물을 제공한다.The present invention provides a health functional food composition for preventing or improving inflammation due to intestinal obstruction, which contains an extract of Yulcho (Humulus japonicus) as an active ingredient.
본 발명에 따른 조성물은 위장 운동 능력을 증가시키고, 항산화 및 항염 활성을 가져 효과적으로 장폐색증을 예방 또는 치료할 수 있다. The composition according to the present invention increases gastrointestinal motility, has antioxidant and anti-inflammatory activity, and can effectively prevent or treat intestinal obstruction.
보다 상세하게는 상기 조성물에 함유된 율초 추출물은 말론디알데하이드(Malondialdehyde, MDA)를 감소시키고, 슈퍼옥사이드 디스무타아제(Superoxide dismutase, SOD) 및 글루타치온(Glutathione, GSH)을 증가시켜 항산화 작용을 할 수 있고, 종양괴사인자(Tumor necrosis factor-α, TNF-α) 또는 인터류킨-1베타(Interleukin-1β, IL-1β)를 감소시켜 항염 활성을 증가시킬 수 있다.In more detail, the yulcho extract contained in the composition can decrease the malondialdehyde (MDA), increase superoxide dismutase (SOD) and glutathione (Glutathione, GSH) and act as an antioxidant. In addition, it can increase anti-inflammatory activity by reducing tumor necrosis factor-α (TNF-α) or interleukin-1β (IL-1β).
또한, 본 발명에 따른 조성물은 천연물을 이용함으로써 부작용이 적어 보다 안전한 장점이 있다.In addition, the composition according to the present invention has the advantage of less safety by using fewer natural products.
도 1은 본 발명의 일 실험예에 따른 율초 추출물 처리한 장폐색증 유도 동물 모델의 위 배출(Gastric emptying) 그래프이다.
도 2는 본 발명의 일 실험예에 따른 율초 추출물 처리한 장폐색증 유도 동물 모델의 평균 기하학 중심(Mean geometric center) 그래프이다.
도 3은 본 발명의 일 실험예에 따른 율초 추출물 처리한 장폐색증 유도 동물 모델의 말론디알데하이드(malondialdehyde, MDA)의 변화 그래프이다.
도 4는 본 발명의 일 실험예에 따른 율초 추출물 처리한 장폐색증 유도 동물 모델의 슈퍼옥사이드 디스무타아제(Superoxide dismutase, SOD)의 변화 그래프이다.
도 5는 본 발명의 일 실험예에 따른 율초 추출물 처리한 장폐색증 유도 동물 모델의 글루타치온(Glutathione, GSH)의 변화 그래프이다.
도 6은 본 발명의 일 실험예에 따른 율초 추출물 처리한 장폐색증 유도 동물 모델의 종양괴사인자(Tumor necrosis factor-α, TNF-α)의 변화 그래프이다.
도 7은 본 발명의 일 실험예에 따른 율초 추출물 처리한 장폐색증 유도 동물 모델의 인터류킨-1베타(Interleukin-1β, IL-1β)의 변화 그래프이다.1 is a gastric emptying graph of an intestinal obstruction-induced animal model treated with Yulcho extract according to an experimental example of the present invention.
Figure 2 is a mean geometric center (Mean geometric center) graph of the intestinal obstruction induced animal model treated with Yulcho extract according to an experimental example of the present invention.
Figure 3 is a graph of the change of malondialdehyde (malondialdehyde, MDA) in the intestinal obstruction-induced animal model treated with Yulcho extract according to an experimental example of the present invention.
4 is a graph of changes in superoxide dismutase (SOD) in an intestinal obstruction-induced animal model treated with Yulcho extract according to an experimental example of the present invention.
Figure 5 is a graph of the change in glutathione (Glutathione, GSH) of intestinal obstruction-induced animal model treated with Yulcho extract according to an experimental example of the present invention.
6 is a graph showing changes in tumor necrosis factor-α and TNF-α in an intestinal obstruction-induced animal model treated with Yulcho extract according to an experimental example of the present invention.
7 is a graph showing changes in interleukin-1beta (IL-1β) in an intestinal obstruction-induced animal model treated with Yulcho extract according to an experimental example of the present invention.
이하, 본 발명을 상세하게 설명하기로 한다.Hereinafter, the present invention will be described in detail.
본 명세서에서 "율초(Humulus japonicus)"란 삼과 또는 뽕나무과에 속하는 한해살이풀로, "환삼덩굴", "한삼덩굴" 등으로 불리기도 하여, 이와 혼용하여 사용될 수 있다.In the present specification, "Humulus japonicus" refers to a perennial plant belonging to the family of the triaceae or mulberry family, and may also be used interchangeably with the term "hwansam vine", "hansam vine", and the like.
본 명세서에서 "추출물"이란, 추출 방법, 추출 용매, 추출된 성분 또는 추출물의 형태를 불문하고 천연물의 성분을 뽑아냄으로써 얻어진 물질을 의미하는 것으로, 천연물의 성분을 뽑아내어 얻어진 물질을 추출 후 다른 방법으로 가공 또는 처리하여 얻어질 수 있는 물질을 모두 포함할 수 있다.As used herein, "extract" refers to a material obtained by extracting a component of a natural product regardless of an extraction method, an extraction solvent, an extracted component or a form of an extract, and extracting a component obtained by extracting a component of a natural product and then extracting another material It may include any material that can be obtained by processing or processing.
본 명세서에서 "예방"이란, 본 발명에 따른 약학 조성물 또는 건강기능식품 조성물의 투여에 의해 장폐색증 또는 장폐색증의 적어도 하나 이상의 증상의 발생을 억제시키거나 발병을 지연시키는 모든 행위를 의미한다. 또한, 재발을 예방하거나 방지하기 위해 상기 질병에 차도가 있는 대상의 치료를 포함한다.In the present specification, "prevention" refers to all actions that inhibit the occurrence of at least one symptom of intestinal obstruction or intestinal obstruction or delay the onset of disease by administration of the pharmaceutical composition or dietary supplement composition according to the present invention. It also includes treatment of subjects with remission to the disease to prevent or prevent recurrence.
본 명세서에서 "치료"란, 본 발명에 따른 약학 조성물의 투여에 의해 장폐색증 또는 장폐색증의 적어도 하나 이상의 증상을 완화, 감소, 또는 소멸시키는 등 그 증세를 호전시키거나 이롭게 변경하는 모든 행위를 의미한다."Treatment" as used herein refers to any act of improving or beneficially modifying the symptoms, such as alleviating, reducing, or extinguishing at least one symptom of intestinal obstruction or intestinal obstruction by administration of a pharmaceutical composition according to the present invention.
본 명세서에서 "개선"이란, 본 발명에 따른 건강기능식품 조성물의 섭취에 의해 장폐색증 또는 장폐색증의 적어도 하나 이상의 증상이 완화, 감소, 또는 소멸시키는 등 그 증세를 호전시키거나 이롭게 변경하는 모든 행위를 의미한다.As used herein, "improvement" means any act of improving or beneficially improving the symptoms, such as relief, reduction, or disappearance of at least one symptom of intestinal obstruction or intestinal obstruction by ingestion of the health functional food composition according to the present invention. do.
본 명세서에서 "약학 조성물"이란, 특정한 목적을 위해 투여되는 조성물로, 본 발명의 목적상 장폐색증 또는 장폐색증의 적어도 하나 이상의 증상을 예방하거나 또는 치료하기 위해 투여되는 것을 의미한다.As used herein, "pharmaceutical composition" means a composition that is administered for a specific purpose, and is administered to prevent or treat intestinal obstruction or at least one symptom of intestinal obstruction for the purposes of the present invention.
본 명세서에서 "건강기능식품"이란, 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 제조 및 가공한 식품으로, 영양 공급 외에도 생체 조절 기능이 효율적으로 나타나도록 가공된 의학, 의료 효과가 높은 식품을 의미하며 기능성 식품 등 당업계에 알려진 용어와 혼용할 수 있다.In this specification, "health functional food" is a food manufactured and processed using ingredients or ingredients having useful functions for the human body, and foods with high medical and medical effects processed to efficiently exhibit bio-control functions in addition to nutritional supply. Means and can be used interchangeably with terms known in the art, such as functional food.
본 발명은 율초(Humulus japonicus) 추출물을 유효성분으로 함유하는 장폐색증 예방 또는 치료용 약학 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing or treating intestinal obstruction, which contains an extract of Yulcho (Humulus japonicus) as an active ingredient.
본 발명에 따른 약학 조성물에 있어서, 상기 율초 추출물은 메탄올 또는 메탄올 수용액을 이용하여 추출된 것으로, 이 외에도 추출 시 당업계에서 통상적으로 사용되는 알코올을 이용하여 통상적인 방법으로 추출될 수 있다. In the pharmaceutical composition according to the present invention, the yulcho extract is extracted using methanol or an aqueous methanol solution, in addition to extraction, it can be extracted by a conventional method using alcohol commonly used in the art.
본 발명에 따른 약학 조성물에 있어서, 상기 장폐색증은, 바람직하게는 수술후 장폐색증(Postoperative ileus) 일 수 있다. 상기 수술후 장폐색증은 복부 장기와 골반 내 장기 등을 수술 받은 후에 생기는 흔한 합병증으로, 이러한 개복 수술 후 발생하는 위장관 운동 기능의 저해 상황을 의미하나, 이에 제한되는 것은 아니다. In the pharmaceutical composition according to the present invention, the intestinal obstruction may be postoperative ileus, preferably after surgery. The intestinal obstruction after surgery is a common complication that occurs after surgery on the abdominal organs and organs in the pelvis, and refers to a situation in which gastrointestinal motor function is inhibited after the open surgery, but is not limited thereto.
본 발명에 따른 약학 조성물은 위장 운동 능력을 증가시킬 수 있다. 본 발명의 일 실험예에 따르면, 수술후 장폐색증 유도 동물 모델에 대해 본 발명에 따른 율초 추출물을 처리한 경우, 위 배출(Gastric emptying) 값이 농도 의존적으로 유의하게 증가하였고, 평균 기하학 중심(mean geometric center) 값 또한 증가함으로써, 위 및 소장의 운동능력이 회복되는 것을 확인할 수 있었다. 특히, 율초 추출물의 농도가 높을수록 상기 운동능력이 더욱 향상되었다. 보다 상세한 것은 하기 실험예에서 후술될 것이다.The pharmaceutical composition according to the present invention can increase gastrointestinal motility. According to one experimental example of the present invention, in the case of treatment with the extract of ulcho according to the present invention for an intestinal obstruction induced animal model, gastric emptying value was significantly increased in a concentration-dependent manner, and mean geometric center ) By increasing the value, it was confirmed that the athletic ability of the stomach and small intestine was restored. In particular, the higher the concentration of Yulcho extract, the more the exercise ability was improved. More details will be described later in the following experimental examples.
본 발명에 따른 약학 조성물은 항산화 활성을 가질 수 있다. 보다 상세하게, 상기 조성물은 말론디알데하이드(Malondialdehyde, MDA)를 감소시키고, 슈퍼옥사이드 디스무타아제(Superoxide dismutase, SOD) 및 글루타치온(Glutathione, GSH)을 증가시킬 수 있다. 본 발명의 일 실험예에 따르면, 수술후 장폐색증 유도 동물에 대해 본 발명에 따른 율초 추출물을 처리한 경우, 산화 스트레스 지표인 말론디알데하이드(MDA)가 감소하였고, 항산화 효소인 슈퍼옥사이드 디스무타아제(SOD)와 비효소성 항산화 물질인 글루타치온(GSH) 값이 유의적으로 증가하여 이를 통해, 상기 조성물이 항산화 활성을 가지는 것을 확인할 수 있었다. 보다 상세한 것은 하기 실험예에서 후술될 것이다.The pharmaceutical composition according to the present invention may have antioxidant activity. In more detail, the composition may reduce malondialdehyde (MDA) and increase superoxide dismutase (SOD) and glutathione (GSH). According to an experimental example of the present invention, in the case of treating the intestinal obstruction-inducing animal after surgery, the extract of Yulcho according to the present invention has reduced the oxidative stress index, malondialdehyde (MDA), the antioxidant enzyme superoxide dismutase (SOD) ) And the non-enzymatic antioxidant glutathione (GSH) value was significantly increased, thereby confirming that the composition has antioxidant activity. More details will be described later in the following experimental examples.
본 발명은 율초(Humulus japonicus) 추출물을 유효성분으로 함유하는 장폐색증으로 인한 염증 예방 또는 치료용 약학 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing or treating inflammation due to intestinal obstruction, which contains an extract of Yulcho (Humulus japonicus) as an active ingredient.
본 발명에 따른 약학 조성물은 항염증 활성을 가져 염증의 예방 또는 치료용 약학 조성물로 사용될 수 있다. 상기 염증은 장폐색증 또는 상기 장폐색증의 하나의 증상 등에 의해 발병된 염증을 포함할 수 있다. 또한, 상기 염증은 장폐색증의 발병 기전으로의 염증을 더 포함할 수 있어, 상기 염증을 예방 또는 치료함으로써, 상기 장폐색증을 예방 또는 치료할 수 있다.The pharmaceutical composition according to the present invention has anti-inflammatory activity and can be used as a pharmaceutical composition for preventing or treating inflammation. The inflammation may include inflammation caused by intestinal obstruction or one symptom of the intestinal obstruction. In addition, the inflammation may further include inflammation to the mechanism of onset of intestinal obstruction, thereby preventing or treating the intestinal obstruction by preventing or treating the inflammation.
보다 상세하게는, 상기 조성물은 종양괴사인자(Tumor necrosis factor-α, TNF-α) 또는 인터류킨-1베타(Interleukin-1β, IL-1β)를 감소시킬 수 있다. 본 발명의 일 실험예에 따르면, 수술후 장폐색증 유도 동물에 대해 본 발명에 따른 율초 추출물을 처리한 경우, 염증성 사이토카인인 TNF-α 및 IL-1β가 유의적으로 감소하였고 이를 통해, 상기 조성물이 항염증 활성을 가짐을 확인할 수 있었다. 보다 상세한 것은 하기 실험예에서 후술될 것이다.More specifically, the composition may reduce tumor necrosis factor-α (TNF-α) or interleukin-1β (IL-1β). According to one experimental example of the present invention, when treating the intestinal obstruction-induced animal after surgery, the ulcho extract according to the present invention, the inflammatory cytokines TNF-α and IL-1β were significantly reduced, and through this, the composition was anti- It was confirmed to have inflammatory activity. More details will be described later in the following experimental examples.
본 발명에 따른 약학 조성물은 약학적 분야의 통상적인 방법에 따라 제조될 수 있다.The pharmaceutical composition according to the present invention can be prepared according to conventional methods in the pharmaceutical field.
본 발명에 따른 약학 조성물은 상기 제형에 따라 약학적으로 허용가능한 적절한 담체와 배합될 수 있고, 필요에 따라, 부형제, 희석제, 분산제, 유화제, 완충제, 안정제, 결합제, 붕해제, 용제 등을 더 포함하여 제조할 수 있다. 상기 "약학적으로 허용 가능한"이란, 상기 약학 조성물에 노출되는 세포나 인간에게 독성이 없는 것을 의미하고, 상기 적절한 담체 등은 본 발명에 따른 율초 추출물의 활성 및 특성을 저해하지 않는 것으로, 투여 형태 및 제형에 따라 달리 선택될 수 있다.The pharmaceutical composition according to the present invention may be combined with a suitable pharmaceutically acceptable carrier according to the formulation, and if necessary, further include excipients, diluents, dispersants, emulsifiers, buffers, stabilizers, binders, disintegrants, solvents, etc. Can be produced. The "pharmaceutically acceptable" means that there is no toxicity to cells or humans exposed to the pharmaceutical composition, and the appropriate carrier or the like does not inhibit the activity and properties of the yulcho extract according to the present invention. And depending on the formulation.
본 발명에 따른 약학 조성물은 어떠한 제형으로도 적용될 수 있고, 보다 상세하게는 통상의 방법에 따라 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 비경구형 제형로 제형화하여 사용될 수 있다.The pharmaceutical composition according to the present invention can be applied in any dosage form, and more specifically, it can be used by formulating into a parenteral dosage form of an oral dosage form, an external preparation, a suppository, and a sterile injectable solution according to a conventional method.
상기 경구형 제형 중 고형 제형은 정제, 환제, 산제, 과립제, 캡슐제 등의 형태로, 적어도 하나 이상의 부형제, 예를 들면, 전분, 칼슘카보네이트, 수크로스, 락토오스, 솔비톨, 만니톨, 셀룰로오스, 젤라틴 등을 섞어 조제할 수 있고, 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 포함될 수 있다. 또한, 캡술제형의 경우 상기 언급한 물질 외에도 지방유와 같은 액체 담체를 더 포함할 수 있다.Among the oral dosage forms, solid dosage forms are in the form of tablets, pills, powders, granules, capsules, etc., at least one excipient, for example starch, calcium carbonate, sucrose, lactose, sorbitol, mannitol, cellulose, gelatin, etc. Can be prepared by mixing, and may include lubricants such as magnesium stearate and talc in addition to simple excipients. In addition, in the case of the capsul formulation, in addition to the above-mentioned substances, a liquid carrier such as fatty oil may be further included.
상기 경구형 제형 중 액상 제형은 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.Among the oral formulations, liquid formulations include suspensions, intravenous solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used as diluents, various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, can be included. have.
상기 비경구 제형은 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함될 수 있다. 비수성용제, 현탁제로는 프로필렌글리콜, 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다. 이에 제한되지 않고, 당해 기술 분야에 알려진 적합한 제제를 모두 사용 가능하다.The parenteral formulation may include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, and suppositories. Non-aqueous solvents and suspensions may include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate. As a base for suppositories, witepsol, macrogol, Tween 61, cacao butter, laurin butter, and glycerogelatin may be used. Without being limited thereto, any suitable formulation known in the art may be used.
또한, 본 발명에 따른 약학 조성물은 치료 효능의 증진을 위해 칼슘이나 비타민 D3 등을 더 첨가할 수 있다. In addition, the pharmaceutical composition according to the present invention may further add calcium, vitamin D3, and the like to improve the therapeutic efficacy.
본 발명에 따른 약학 조성물에 있어서, 상기 약학 조성물은 약학적으로 유효한 양으로 투여될 수 있다. 상기 "약학적으로 유효한 양"이란, 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분하며 부작용을 일으키지 않을 정도의 양을 의미한다.In the pharmaceutical composition according to the present invention, the pharmaceutical composition may be administered in a pharmaceutically effective amount. The "pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit/risk ratio applicable to medical treatment and does not cause side effects.
상기 약학 조성물의 유효 용량 수준은 사용 목적, 환자의 연령, 성별, 체중 및 건강 상태, 질환의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 방법, 투여 시간, 투여 경로 및 배출 비율, 치료기간, 배합 또는 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 달리 결정될 수 있다. 예를 들어, 일정하지는 않지만 일반적으로 0.001 내지 100mg/kg으로, 바람직하게는 0.01 내지 10mg/kg을 일일 1회 내지 수회 투여될 수 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.The effective dosage level of the pharmaceutical composition is intended for use, age of the patient, sex, weight and health status, type of disease, severity, drug activity, sensitivity to the drug, administration method, administration time, administration route and discharge rate, treatment The duration, combination, or factors including the drug used concurrently and other factors well known in the medical field can be determined differently. For example, although not constant, it is generally 0.001 to 100 mg/kg, preferably 0.01 to 10 mg/kg once to several times a day. The above dosage does not limit the scope of the invention in any aspect.
본 발명에 따른 약학 조성물은 장폐색증 등이 발생할 수 있는 임의의 동물에 투여할 수 있고, 상기 동물은 예를 들어, 인간 및 영장류뿐만 아니라 소, 돼지, 말, 개 등의 가축 등을 포함할 수 있다.The pharmaceutical composition according to the present invention may be administered to any animal capable of intestinal obstruction or the like, and the animal may include, for example, humans and primates, as well as livestock such as cattle, pigs, horses, and dogs. .
본 발명에 따른 약학 조성물은 제제 형태에 따른 적당한 투여 경로로 투여될 수 있고, 목적 조직에 도달할 수 있는 한 경구 또는 비경구의 다양한 경로를 통하여 투여될 수 있다. 투여 방법은 특히 한정할 필요 없이, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 기관지내 흡입, 자궁내 경막 또는 뇌혈관내(intracere-broventricular) 주사 등의 통상적인 방법으로 투여될 수 있다.The pharmaceutical composition according to the present invention can be administered by a suitable route of administration according to the form of the formulation, and can be administered through various routes, oral or parenteral, as long as it can reach the target tissue. The method of administration is not particularly limited, and may be administered by conventional methods such as, for example, oral, rectal or intravenous, intramuscular, subcutaneous, intrabronchial inhalation, intrauterine epidural or intracere-broventricular injection. .
본 발명에 따른 약학 조성물은 장폐색증 예방 또는 치료를 위하여 단독으로 사용될 수 있고, 수술 또는 다른 약물 치료 등과 병용하여 사용될 수 있다.The pharmaceutical composition according to the present invention may be used alone for the prevention or treatment of intestinal obstruction, and may be used in combination with surgery or other drug treatment.
또한, 본 발명은 율초(Humulus japonicus) 추출물을 유효성분으로 함유하는 장폐색증 예방 또는 개선용 건강기능식품 조성물, 율초 추출물을 유효성분으로 함유하는 장폐색증으로 인한 염증 예방 또는 개선용 건강기능식품 조성물을 제공한다. 상기 조성물은 위장 운동 능력을 증가시킬 수 있고, 항산화 활성 및 항염증 활성을 가지므로, 장폐색증 또는 장폐색증으로 인한 염증의 예방 또는 개선을 위한 건강기능식품 조성물로 사용될 수 있다.In addition, the present invention provides a health functional food composition for preventing or improving inflammation due to intestinal obstruction containing yulcho (Humulus japonicus) extract as an active ingredient, and an inflammation preventing or improving intestinal obstruction containing yulcho extract as an active ingredient. . The composition may increase gastrointestinal motility, has antioxidant activity and anti-inflammatory activity, and thus may be used as a health functional food composition for preventing or improving intestinal obstruction or inflammation caused by intestinal obstruction.
본 발명에 따른 건강기능식품 조성물에 있어서, 상기 건강기능식품은 분말, 과립, 정제, 캡슐, 시럽 또는 음료 등으로 제조될 수 있고, 상기 건강기능식품이 취할 수 있는 형태에는 제한이 없으며, 통상적인 의미의 식품을 모두 포함할 수 있다. 예를 들어, 음료 및 각종 드링크, 과실 및 그의 가공식품(과일통조림, 잼 등), 어류, 육류 및 그 가공식품(햄, 베이컨 등), 빵류 및 면류, 쿠키 및 스낵류, 유제품(버터, 치즈 등) 등이 가능하며, 통상적인 의미에서의 기능성 식품을 모두 포함할 수 있다. 또한 동물을 위한 사료로 이용되는 식품도 포함할 수 있다.In the dietary supplement composition according to the present invention, the dietary supplement may be prepared as a powder, granule, tablet, capsule, syrup or beverage, and there is no limitation in the form that the dietary supplement can take, and is conventional It can include all foods of meaning. For example, beverages and various drinks, fruits and processed foods thereof (canned fruit, jam, etc.), fish, meat and processed foods (ham, bacon, etc.), breads and noodles, cookies and snacks, dairy products (butter, cheese, etc.) ) And the like, and may include all functional foods in a conventional sense. It may also include food used as feed for animals.
본 발명에 따른 건강기능식품 조성물은 당업계에서 통상적으로 사용되는 식품학적으로 허용 가능한 식품 첨가제 및 적절한 기타 보조 성분을 더 포함하여 제조될 수 있다. 예를 들어, 향미제, 천연 탄수화물, 감미제, 비타민, 전해질, 착색제, 펙트산, 알긴산, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산화제 등을 추가로 함유할 수 있다. 특히, 상기 천연 탄수화물로는 포도당, 과당과 같은 모노사카라이드, 말토스, 수크로오스와 같은 디사카라이드, 및 덱스트린, 사이클로덱스트린과 같은 폴리사카라이드, 자일리톨, 소르비톨, 에리트리톨 등의 당알콜을 사용할 수 있으며, 감미제로서는 타우마틴, 스테비아 추출물과 같은 천연 감미제나 사카린, 아스파르탐과 같은 합성 감미제 등을 사용할 수 있다.The dietary supplement composition according to the present invention may be prepared by further including a food-acceptable food additive commonly used in the art and other suitable auxiliary ingredients. For example, it may further contain flavoring agents, natural carbohydrates, sweeteners, vitamins, electrolytes, colorants, pectic acids, alginic acids, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonic acid, etc. Can. In particular, as the natural carbohydrate, monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, sugar alcohols such as xylitol, sorbitol, and erythritol may be used. , As a sweetener, natural sweeteners such as taumatin and stevia extract, synthetic sweeteners such as saccharin and aspartame can be used.
본 발명에 따른 건강기능식품 조성물은 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용 시 발생할 수 있는 부작용 등이 없는 장점이 있고, 휴대성이 뛰어나, 장폐색증 또는 장폐색증으로 인한 염증의 예방 또는 개선을 위한 보조제로 섭취될 수 있다.The health functional food composition according to the present invention has an advantage that there is no side effect or the like that may occur when taking the drug for a long time by using food as a raw material, unlike a general drug, and is excellent in portability, preventing or improving inflammation due to intestinal obstruction or intestinal obstruction It can be taken as a supplement for.
이하, 본 발명의 이해를 돕기 위하여 실시예를 들어 상세하게 설명하기로 한다. 다만 하기의 실시예는 본 발명의 내용을 예시하는 것일 뿐 본 발명의 범위가 하기 실시예에 한정되는 것은 아니다. 본 발명의 실시예는 당업계에서 평균적인 지식을 가진 자에게 본 발명을 보다 완전하게 설명하기 위해 제공되는 것이다.Hereinafter, examples will be described in detail to help understanding of the present invention. However, the following examples are merely illustrative of the contents of the present invention, and the scope of the present invention is not limited to the following examples. The embodiments of the present invention are provided to more fully describe the present invention to those skilled in the art.
<실시예 1> 율초(Humulus japonicus) 추출물의 제조<Example 1> Preparation of Yulcho (Humulus japonicus) extract
율초 400 g을 메탄올 6 L에 넣고 3일 간 추출한 후, 추출물을 거즈로 1차 여과하고 3000×g에서 3분간 원심분리하였다. 원심분리 후, 상층액만을 취하여 0.2 ㎛ 필터(Nalgene, New York, USA)로 여과하였다. 상기 여과액을 증발기(Rotary evaporator, EYELA, Tokyo, Japan)로 동결 건조하여 28.81 g의 율초 추출물 분말을 획득하였으며, 사용하기 전까지 -20 ℃에서 보관하였다. 율초 추출물의 수율은 7.20 %이며, 생체 외(in vitro) 실험에서는 디메틸설폭사이드(dimethyl sulfoxide; DMSO)에, 생체 내(in vivo) 실험에서는 폴리에틸렌글리콜(polyethylene glycol; PEG)에 녹여서 사용하였다.400 g of Yulcho was added to 6 L of methanol, extracted for 3 days, and the extract was first filtered with gauze and centrifuged at 3000 x g for 3 minutes. After centrifugation, only the supernatant was taken and filtered with a 0.2 μm filter (Nalgene, New York, USA). The filtrate was freeze-dried with an evaporator (Rotary evaporator, EYELA, Tokyo, Japan) to obtain 28.81 g of Yulcho extract powder, and stored at -20°C until use. Yield of the extract was 7.20%, and dissolved in dimethyl sulfoxide (DMSO) in an in vitro experiment and polyethylene glycol (PEG) in an in vivo experiment.
<실시예 2> 수술 후 장폐색증(Postoperative ileus) 유도 동물 모델<Example 2> Postoperative ileus induced animal model after surgery
7 주령(200-250 g)의 SD 래트(rat)를 24 시간 절식시킨 후 마취를 실시하였다. 마취된 래트의 복강을 2-3cm 개복한 후, 생리식염수(normal saline)에 적신 거즈 위에 소장~맹장을 꺼내어 놓고 1분 동안 면봉으로 마사지를 한 후, 15분 동안 장이 마르지 않도록 주의하였다. 이후 장을 다시 복부에 집어넣고 개복한 부분을 꿰매어 수술 후 장폐색증 유도 동물 모델을 만들었다.SD rats of 7 weeks of age (200-250 g) were fasted for 24 hours and then anesthetized. After 2-3 cm of the abdominal cavity of the anesthetized rat, the small intestine-blind was removed on gauze soaked in normal saline, massaged with a cotton swab for 1 minute, and the intestine was not dried for 15 minutes. Afterwards, the intestine was put back into the abdomen, and the open area was sewn to create an animal model for gut obstruction after surgery.
<실험예 1> 위 배출(Gastric emptying)을 통한<Experimental Example 1> Gastric emptying 위 운동능력 회복 효과 확인Confirm the effect of restoring gastric ability
상기 실시예 2에 따른 수술 후 장폐색증 유도 동물 모델에 대하여, 상기 실시예 1에 따른 율초 추출물을 처리하여 위 배출(Gastric emptying) 값의 변화를 통해 위의 운동능력 회복 효과를 관찰하였다.For the animal model of intestinal obstruction after surgery according to Example 2, the effect of restoring gastric motility was observed by changing the gastric emptying value by treating the extract of Yulcho according to Example 1.
도 1은 본 발명의 일 실험예에 따른 율초 추출물 처리한 장폐색증 유도 동물 모델의 위 배출(Gastric emptying) 그래프이다. 위 배출(Gastric emptying)은 소화관의 운동능력을 평가하는 지표 중의 하나로, 소화관 중 위의 운동능력 감소와 회복 정도를 평가하기에 적합하다. 개복을 진행하거나 소화관에 조작이 발생할 때 위의 운동능력이 감소하여 위 배출이 위의 운동능력의 이상 여부를 파악하는 지표가 된다.1 is a gastric emptying graph of an intestinal obstruction-induced animal model treated with Yulcho extract according to an experimental example of the present invention. Gastric emptying is one of the indicators for evaluating the gastrointestinal motility, and is suitable for evaluating the reduction and recovery of gastric motility in the gastrointestinal tract. As the gastric motility decreases when the laparotomy is performed or manipulation occurs in the digestive tract, gastric emptying is an indicator to determine whether the gastric motility is abnormal.
도 1을 참조하면, 본 발명의 일 실시예에 따른 수술 후 장 폐색증을 유도한 모델(Postoperative ileus, POI 모델)에서 위 배출(%) 값이 현저히 감소하였고, 장 내 조작 없이 개복만을 진행한 sham POI 유도 모델에서도 위 배출 값이 감소하여 운동 능력이 어느 정도 감소되었음을 확인할 수 있었다. 위장관 운동능력을 증가시키는 5-HT4 수용체 작용제(receptor antagonist)인 모사프리드(mosapride)를 투여했을 때, 위 배출 값이 유의하게 증가하여 위의 운동능력이 회복되는 것을 관찰할 수 있었고, 율초 추출물 50 mg/kg, 150 mg/kg, 300 mg/kg를 투여한 모든 군에서도 농도 의존적으로 위 배출이 유의하게 증가하여 위의 운동능력이 회복되는 것을 확인할 수 있었으며, 특히 300 mg/kg 투여군에서 위의 운동능력이 더욱 향상된 것을 확인할 수 있었다.Referring to FIG. 1, in the model inducing intestinal obstruction after surgery (Postoperative ileus, POI model) according to an embodiment of the present invention, the gastric emptying (%) value was significantly reduced, and only the open sham without intestinal manipulation In the POI-induced model, it was confirmed that the gastric emptying value was decreased, and the exercise capacity was reduced to some extent. When administered with 5-HT4 receptor antagonist, mosapride, which increases gastrointestinal motility, it was observed that gastric excretion value was significantly increased and gastric motility was recovered, and Yulcho extract 50 In all groups administered with mg/kg, 150 mg/kg, and 300 mg/kg, gastric emptying was significantly increased depending on the concentration, and it was confirmed that gastric motor capacity was restored, especially in the 300 mg/kg administered group. It was confirmed that the athletic ability was further improved.
<실험예 2> 평균 기하학 중심(Mean geometric center) 분석을 통한 소장 운동능력 회복 효과 확인<Experimental Example 2> Confirmation of the effect of restoring small intestinal motility through analysis of mean geometric center
상기 실시예 2에 따른 수술 후 장폐색증 유도 동물 모델에 대하여, 상기 실시예 1에 따른 율초 추출물을 처리하여 평균 기하학 중심(Mean geometric center)값의 변화를 통해 소장의 운동능력 회복 효과를 관찰하였다.For the animal model inducing intestinal obstruction after surgery according to Example 2, the effect of restoring the small intestine was observed by changing the average geometric center value by treating the extract of Yulcho according to Example 1.
도 2는 본 발명의 일 실험예에 따른 율초 추출물 처리한 장폐색증 유도 동물 모델의 평균 기하학 중심(Mean geometric center) 그래프이다. 평균 기하학 중심은 소화관의 운동능력을 평가하는 지표 중의 하나로, 소장의 운동능력 감소와 회복 정도를 평가하기에 적합하다. 개복을 진행하고 소화관에 조작이 발생할 때 소장의 운동능력이 크게 감소하여, 평균 기하학 중심이 소장의 운동능력 이상을 파악하는 지표가 된다. Figure 2 is a mean geometric center (Mean geometric center) graph of the intestinal obstruction induced animal model treated with Yulcho extract according to an experimental example of the present invention. The center of average geometry is one of the indices for evaluating the exercise capacity of the digestive tract. When the laparotomy progresses and manipulation occurs in the digestive tract, the intestinal motility is greatly reduced, and the center of the average geometry is an index to grasp the abnormality of the intestinal motility.
도 2를 참조하면, 본 발명의 일 실시예에 따른 수술 후 장 폐색증을 유도한 모델(POI)에서 평균 기하학 중심 값이 감소하였고, 장 내 조작 없이 개복만을 진행한 sham POI 유도 모델에서도 평균 기하학 중심 값이 감소하여 운동능력이 어느 정도 감소되었음을 것을 확인할 수 있었다. 위장관 운동능력을 증가시키는 5-HT4 수용체 작용제인 모사프리드를 투여했을 때 평균 기하학 중심 값이 증가하여 유의하게 소장의 운동능력이 회복되는 것을 관찰할 수 있었고, 율초 추출물 150 mg/kg와 300 mg/kg를 투여한 군에서 평균 기하학 중심 값이 증가하여 유의하게 소장의 운동능력이 회복되는 것을 확인할 수 있었으며, 특히 300 mg/kg 투여군에서 소장의 운동능력이 더욱 향상된 것을 확인할 수 있었다.Referring to FIG. 2, the mean geometric center value in the model (POI) inducing intestinal obstruction after surgery according to an embodiment of the present invention was reduced, and the mean geometric center in the sham POI induction model in which only open sham was performed without intestinal manipulation. It was confirmed that the exercise capacity was reduced to a certain extent by decreasing the value. When administered with the 5-HT4 receptor agonist, mosapride, which increases the gastrointestinal motility, it was observed that the mean geometric center value increased and the intestinal motility was significantly restored, and Yulcho extract 150 mg/kg and 300 mg/ In the group administered with kg, it was confirmed that the mean geometric center value increased and significantly improved the ability of the small intestine to recover. In particular, it was confirmed that the exercise ability of the small intestine further improved in the group administered with 300 mg/kg.
<실험예 3> 말론디알데하이드(malondialdehyde, MDA) 감소 효과 확인<Experimental Example 3> Check the effect of reducing malondialdehyde (MDA)
상기 실시예 2에 따른 수술 후 장폐색증 유도 동물 모델에 대하여, 상기 실시예 1에 따른 율초 추출물을 처리하여 말론디알데하이드(malondialdehyde, MDA)의 변화를 관찰하였다.For the intestinal obstruction-induced animal model according to Example 2, the change of malondialdehyde (MDA) was observed by treating the extract of Yulcho according to Example 1.
도 3은 본 발명의 일 실험예에 따른 율초 추출물 처리한 장폐색증 유도 동물 모델의 말론디알데하이드(malondialdehyde, MDA)의 변화 그래프이다. 말론디알데하이드(이하, MDA)는 염증 시 발생하는 활성 산소종(reactive oxygen species; 이하, ROS)이 지질과 반응하여 생성된 지질 과산화물로, 산화 스트레스(Oxidative stress)의 지표로 잘 알려져 있다. Figure 3 is a graph of the change of malondialdehyde (malondialdehyde, MDA) in the intestinal obstruction-induced animal model treated with Yulcho extract according to an experimental example of the present invention. Malondialdehyde (hereinafter referred to as MDA) is a lipid peroxide produced by reacting reactive oxygen species (ROS) with lipids, and is well known as an indicator of oxidative stress.
도 3을 참조하면, 본 발명의 일 실시예에 따른 수술 후 장 폐색증 유도가 된 모델(POI)의 회장 조직에서 MDA 농도 수치가 급격히 증가하였고, 모사프리드가 투여된 군 및 율초 추출물이 투여된 군에서는 MDA 농도 수치가 감소하였다. 특히, 율초 추출물이 150 mg/kg, 300 mg/kg 투여된 군에서는 유의성 있게 MDA 농도가 감소되었음을 확인할 수 있었다.Referring to FIG. 3, the MDA concentration level in the ileal tissue of the model (POI) after induction of intestinal obstruction after surgery according to an embodiment of the present invention was rapidly increased, the group administered with mosapride and the group administered with yulcho extract In the MDA concentration level decreased. In particular, it was confirmed that the MDA concentration was significantly decreased in the group in which the Yulcho extract was administered at 150 mg/kg and 300 mg/kg.
<실험예 4> 슈퍼옥사이드 디스무타아제(Superoxide dismutase, SOD) 활성 증가 효과 확인<Experimental Example 4> Superoxide dismutase (Superoxide dismutase, SOD) activity increase effect confirmed
상기 실시예 2에 따른 수술 후 장폐색증 유도 동물 모델에 대하여, 상기 실시예 1에 따른 율초 추출물을 처리하여 항산화 효소인 슈퍼옥사이드 디스무타아제(Superoxide dismutase, SOD)의 변화를 관찰하였다.For the animal model inducing intestinal obstruction after surgery according to Example 2, the extract of Yulcho according to Example 1 was treated to observe changes in the antioxidant enzyme Superoxide dismutase (SOD).
도 4는 본 발명의 일 실험예에 따른 율초 추출물 처리한 장폐색증 유도 동물 모델의 슈퍼옥사이드 디스무타아제(Superoxide dismutase, SOD)의 변화 그래프이다. 슈퍼옥사이드 디스무타아제(이하, SOD)는 초과산화이온을 산소와 과산화수소로 바꿔주는 불균등화 반응을 촉매하는 효소이다. 산소에 노출되는 거의 모든 세포에서 SOD가 항산화 방어 기작을 하는 것으로 알려져 있어 SOD의 활성도(activity)가 항산화 효과(Anti-oxidative effect)의 지표로 사용된다. 4 is a graph of changes in superoxide dismutase (SOD) in an intestinal obstruction-induced animal model treated with Yulcho extract according to an experimental example of the present invention. Superoxide dismutase (hereinafter SOD) is an enzyme that catalyzes the disproportionation reaction that converts excess oxidizing ions into oxygen and hydrogen peroxide. It is known that SOD acts as an antioxidant defense mechanism in almost all cells exposed to oxygen, so the activity of SOD is used as an indicator of the anti-oxidative effect.
도 4를 참조하면, 본 발명의 일 실시예에 따른 수술 후 장 폐색증 유도가 된 모델(POI)의 회장 조직에서 SOD의 활성도 수치가 급격히 감소되었고, 율초 추출물을 투여한 군에서는 농도 의존적으로 SOD 활성도 수치가 증가하였으며, 특히 율초 추출물 300 mg/kg를 투여한 군에서는 유의성 있게 SOD 활성도가 증가되었음을 확인하였다.Referring to FIG. 4, the activity value of SOD in the ileal tissue of the model (POI) after induction of intestinal obstruction after surgery according to an embodiment of the present invention was rapidly reduced, and the concentration of SOD activity was dependent on concentration in the group administered with Yulcho extract The number increased, and it was confirmed that SOD activity was significantly increased in the group administered with 300 mg/kg of Yulcho extract.
<실험예 5> 글루타치온(Glutathione, GSH) 증가 효과 확인<Experimental Example 5> Check the effect of increasing glutathione (Glutathione, GSH)
상기 실시예 2에 따른 수술 후 장폐색증 유도 동물 모델에 대하여, 상기 실시예 1에 따른 율초 추출물을 처리하여 비효소성 항산화 물질인 글루타치온(Glutathione, GSH)의 변화를 관찰하였다.For the animal model inducing intestinal obstruction after surgery according to Example 2, the extract of Yulcho according to Example 1 was treated to observe the change of glutathione (GSH), a non-enzymatic antioxidant.
도 5는 본 발명의 일 실험예에 따른 율초 추출물 처리한 장폐색증 유도 동물 모델의 글루타치온(Glutathione, GSH)의 변화 그래프이다. 글루타치온(이하, GSH)은 대부분의 생물에서 생합성되는 존재하는 비효소성 항산화 물질로, 자유 라디칼이나 과산화물, 지질 과산화물과 같은 ROS와 중금속과 같은 물질에 의해 야기되는 세포의 손상을 예방한다. GSH가 전자를 제공하는 환원제로 작용하며 항산화 방어 기작을 하는 것으로 알려져 있어 항산화 효과의 지표로 사용된다. Figure 5 is a graph of the change in glutathione (Glutathione, GSH) of intestinal obstruction-induced animal model treated with Yulcho extract according to an experimental example of the present invention. Glutathione (hereinafter, GSH) is a non-enzymatic antioxidant that is biosynthesized in most organisms and prevents cell damage caused by substances such as free radicals, peroxides, lipid peroxides and ROS and heavy metals. GSH acts as a reducing agent that provides electrons and is known to act as an antioxidant defense mechanism, so it is used as an indicator of antioxidant effects.
도 5를 참조하면, 본 발명의 일 실시예에 따른 수술 후 장 폐색증 유도가 된 모델(POI)의 회장 조직에서 GSH 값이 급격히 감소하였고, 율초 추출물을 투여한 군에서는 농도 의존적으로 GSH 값이 증가하였으며, 특히, 율초 추출물 300 mg/kg를 투여한 군에서는 가장 유의성 있게 GSH 값이 증가함을 확인할 수 있었다.Referring to FIG. 5, the GSH value was rapidly decreased in the ileal tissue of the model (POI) inducing intestinal obstruction after surgery according to an embodiment of the present invention, and the GSH value was increased in a concentration-dependent manner in the group administered with Yulcho extract In particular, it was confirmed that the GSH value increases most significantly in the group administered with 300 mg/kg Yulcho extract.
<실험예 6> 종양괴사인자(Tumor necrosis factor-α, TNF-α) 감소 효과 확인<Experimental Example 6> confirm the effect of reducing tumor necrosis factor (Tumor necrosis factor-α, TNF-α)
상기 실시예 2에 따른 수술 후 장폐색증 유도 동물 모델에 대하여, 상기 실시예 1에 따른 율초 추출물을 처리하여 염증성 사이토카인인 종양괴사인자(Tumor necrosis factor-α, TNF-α)의 변화를 관찰하였다.For the animal model inducing intestinal obstruction after surgery according to Example 2, a change in the inflammatory cytokine tumor necrosis factor (α, TNF-α) was observed by treating the extract of Yulcho according to Example 1.
도 6은 본 발명의 일 실험예에 따른 율초 추출물 처리한 장폐색증 유도 동물 모델의 종양괴사인자(Tumor necrosis factor-α, TNF-α)의 변화 그래프이다. 종양괴사인자(이하, TNF-α)는 염증의 급성 상태를 촉진시키는 염증성 사이토카인이다. TNF-α는 혈관 투과성을 증가시키고, 이로 인하여 감염 부위로 대식세포 및 호중구를 재소집한다. TNF-α는 세포 증식, 분화, 자가사멸 등을 포함한 생물학적으로 광범위한 조절을 하며 염증을 유도한다. 이러한 기전으로 질환 발생 시 환부의 염증성 지표로 사용된다. 6 is a graph showing changes in tumor necrosis factor-α and TNF-α in an intestinal obstruction-induced animal model treated with Yulcho extract according to an experimental example of the present invention. Tumor necrosis factor (hereinafter, TNF-α) is an inflammatory cytokine that promotes the acute state of inflammation. TNF-α increases vascular permeability, thereby re-engaging macrophages and neutrophils to the site of infection. TNF-α regulates biologically, including cell proliferation, differentiation, and apoptosis, and induces inflammation. This mechanism is used as an inflammatory indicator of the affected area when a disease occurs.
도 6을 참조하면, 본 발명의 일 실시예에 따른 수술 후 장 폐색증 유도가 된 모델(POI)의 회장 조직에서 TNF-α의 수치가 급격히 증가하였고, 율초 추출물을 투여한 군에서는 농도 의존적으로 TNF-α의 수치가 감소하였다. 상세하게는 율초 추출물 150 mg/kg, 300 mg/kg을 투여한 군에서 유의성 있게 TNF-α 수치가 감소하였고, 특히 300 mg/kg 투여군에서 수치가 가장 크게 감소하였다.Referring to FIG. 6, the level of TNF-α in the ileal tissue of a model (POI) inducing intestinal obstruction after surgery according to an embodiment of the present invention was rapidly increased, and the concentration of TNF-dependently in the group administered with Yulcho extract The level of -α decreased. In detail, the TNF-α level was significantly decreased in the group administered with Yulcho extract 150 mg/kg, 300 mg/kg, and the value was significantly decreased in the 300 mg/kg group.
<실험예 7> 인터류킨-1베타(Interleukin-1β, IL-1β) 감소 효과 확인<Experimental Example 7> Interleukin-1 beta (Interleukin-1β, IL-1β) reduction effect confirmed
상기 실시예 2에 따른 수술 후 장폐색증 유도 동물 모델에 대하여, 상기 실시예 1에 따른 율초 추출물을 처리하여 염증성 사이토카인인 인터류킨-1베타(Interleukin-1β, IL-1β)의 변화를 관찰하였다.For the animal model inducing intestinal obstruction after surgery according to Example 2, a change of the inflammatory cytokine, Interleukin-1β, IL-1β was observed by treating the extract of Yulcho according to Example 1.
도 7은 본 발명의 일 실험예에 따른 율초 추출물 처리한 장폐색증 유도 동물 모델의 인터류킨-1베타(Interleukin-1β, IL-1β)의 변화 그래프이다. 인터류킨-1베타(이하, IL-1β)는 IL-1 패밀리에 속하는 염증성 사이토카인으로 단핵구와 대식세포에 의해 생산되는 모노카인이다. TNF-α와 유사하게 염증의 급성 상태를 확인 가능하며, T세포와 B세포의 증식 및 분화, 섬유아세포의 증식, 프로스타글란딘 E2의 생산, 발열 등 생체 내 염증과 면역반응에 광범위하게 작용한다. 이러한 기전들로 질환의 발생시에 급성 염증성 지표로 사용된다. 7 is a graph showing changes in interleukin-1beta (IL-1β) in an intestinal obstruction-induced animal model treated with Yulcho extract according to an experimental example of the present invention. Interleukin-1 beta (hereinafter, IL-1β) is an inflammatory cytokine belonging to the IL-1 family and is a monokine produced by monocytes and macrophages. Similar to TNF-α, it is possible to check the acute state of inflammation, and it functions extensively in inflammation and immune responses in vivo, such as proliferation and differentiation of T cells and B cells, proliferation of fibroblasts, production of prostaglandin E2, fever, etc. These mechanisms are used as acute inflammatory markers in the event of a disease.
도 7을 참조하면, 본 발명의 일 실시예에 따른 수술 후 장 폐색증 유도가 된 모델(POI)의 회장 조직에서 IL-1β의 수치가 급격히 증가하는 것을 확인하였다. 율초 추출물을 투여한 군에서는 150 mg/kg, 300 mg/kg를 투여한 군에서 유의성 있게 IL-1β수치가 감소한 것을 확인할 수 있었다. Referring to FIG. 7, it was confirmed that the level of IL-1β in the ileal tissue of the model (POI) that induces intestinal obstruction after surgery according to an embodiment of the present invention increases rapidly. In the group administered with Yulcho extract, it was confirmed that the IL-1β level was significantly decreased in the group administered with 150 mg/kg and 300 mg/kg.
이상으로 본 발명 내용의 특정한 부분을 상세히 기술하였는 바, 당업계의 통상의 지식을 가진 자에게 있어서, 이러한 구체적 기술은 단지 바람직한 실시양태일 뿐이며, 이에 의해 본 발명의 범위가 제한되는 것이 아닌 점은 명백하다. 즉, 본 발명의 실질적인 범위는 첨부된 청구항들과 그것들의 등가물에 의하여 정의된다.Since the specific parts of the present invention have been described in detail above, for those skilled in the art, it is obvious that this specific technique is only a preferred embodiment, and the scope of the present invention is not limited thereby. Do. That is, the substantial scope of the present invention is defined by the appended claims and their equivalents.
Claims (9)
상기 장폐색증은,
수술후 장폐색증(Postoperative ileus)인 것을 특징으로 하는 장폐색증 예방 또는 치료용 약학 조성물. According to claim 1,
The intestinal obstruction,
A pharmaceutical composition for preventing or treating intestinal obstruction, characterized in that it is postoperative ileus.
상기 율초 추출물은,
메탄올에 의해 추출된 것을 특징으로 하는 장폐색증 예방 또는 치료용 약학 조성물.According to claim 1,
The yulcho extract,
Pharmaceutical composition for the prevention or treatment of intestinal obstruction, characterized in that extracted by methanol.
상기 조성물은,
위장 운동 능력을 증가시키는 것을 특징으로 하는 장폐색증 예방 또는 치료용 약학 조성물.According to claim 1,
The composition,
Pharmaceutical composition for preventing or treating intestinal obstruction, characterized by increasing the gastrointestinal motility.
상기 조성물은,
말론디알데하이드(Malondialdehyde, MDA)를 감소시키고, 슈퍼옥사이드 디스무타아제(Superoxide dismutase, SOD) 및 글루타치온(Glutathione, GSH)을 증가시키는 것을 특징으로 하는 장폐색증 예방 또는 치료용 약학 조성물.According to claim 1,
The composition,
A pharmaceutical composition for the prevention or treatment of intestinal obstruction, characterized by reducing malondialdehyde (MDA) and increasing superoxide dismutase (SOD) and glutathione (GSH).
상기 조성물은,
종양괴사인자(Tumor necrosis factor-α, TNF-α) 또는 인터류킨-1베타(Interleukin-1β, IL-1β)를 감소시키는 것을 특징으로 하는 장폐색증으로 인한 염증 예방 또는 치료용 약학 조성물.The method of claim 6,
The composition,
A pharmaceutical composition for preventing or treating inflammation due to intestinal obstruction, characterized by reducing tumor necrosis factor-α, TNF-α or interleukin-1β, IL-1β.
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| KR1020190017212A KR102136662B1 (en) | 2019-02-14 | 2019-02-14 | Composition for preventing or treating ileus comprising humulus japonicus extract |
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| KR1020190017212A KR102136662B1 (en) | 2019-02-14 | 2019-02-14 | Composition for preventing or treating ileus comprising humulus japonicus extract |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100635658B1 (en) | 2003-07-14 | 2006-10-18 | 재단법인서울대학교산학협력재단 | Herbal medicinal composition for the treatment of postoperative ileus |
| KR20130102295A (en) * | 2012-03-07 | 2013-09-17 | 손원록 | Composition comprising extract of humulus japonicus or humulus scandens for preventing or treating of metabolic diseases |
| KR20160008042A (en) * | 2014-07-11 | 2016-01-21 | 한국생명공학연구원 | Compostion for preventing or treating the neurodegenerative disease comprising Humulus japonicus extract as active ingredient |
| KR102098264B1 (en) * | 2017-04-04 | 2020-04-10 | (주)솔빛피앤에프 | Composition for preventing, improving or treating fatty liver diseases, hyperlipidemia and constipation comprising Phragmitis Rhizoma and Humulus japonicus extract |
-
2019
- 2019-02-14 KR KR1020190017212A patent/KR102136662B1/en active IP Right Grant
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100635658B1 (en) | 2003-07-14 | 2006-10-18 | 재단법인서울대학교산학협력재단 | Herbal medicinal composition for the treatment of postoperative ileus |
| KR20130102295A (en) * | 2012-03-07 | 2013-09-17 | 손원록 | Composition comprising extract of humulus japonicus or humulus scandens for preventing or treating of metabolic diseases |
| KR20160008042A (en) * | 2014-07-11 | 2016-01-21 | 한국생명공학연구원 | Compostion for preventing or treating the neurodegenerative disease comprising Humulus japonicus extract as active ingredient |
| KR102098264B1 (en) * | 2017-04-04 | 2020-04-10 | (주)솔빛피앤에프 | Composition for preventing, improving or treating fatty liver diseases, hyperlipidemia and constipation comprising Phragmitis Rhizoma and Humulus japonicus extract |
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