KR102252129B1 - Composition for preventing or treating inflammatory bowel disease comprising herbal extract of broussonetia kazinoki - Google Patents
Composition for preventing or treating inflammatory bowel disease comprising herbal extract of broussonetia kazinoki Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/60—Moraceae (Mulberry family), e.g. breadfruit or fig
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K10/00—Animal feeding-stuffs
- A23K10/30—Animal feeding-stuffs from material of plant origin, e.g. roots, seeds or hay; from material of fungal origin, e.g. mushrooms
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/32—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the digestive tract
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- A—HUMAN NECESSITIES
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- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/324—Foods, ingredients or supplements having a functional effect on health having an effect on the immune system
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Abstract
Description
본 발명은 닥나무 추출물을 유효성분으로 포함하는 염증성 장질환의 예방 또는 치료용 약학 조성물에 관한 것이다. 또한 본 발명은 상기 닥나무 추출물을 포함하는 염증성 장질환의 예방 또는 개선용 식품 조성물 또는 사료 조성물에 관한 것이다.The present invention relates to a pharmaceutical composition for the prevention or treatment of inflammatory bowel disease, comprising a mulberry extract as an active ingredient. In addition, the present invention relates to a food composition or feed composition for preventing or improving inflammatory bowel disease comprising the mulberry extract.
염증성 장질환 (Inflammatory bowel disease, IBD)은 장관에 원인미상의 만성 염증을 일으키는 질환으로 악화와 호전을 반복하면서 진행하는 임상경과를 보이며, 궤양성 대장염과 크론병이 대표적인 질환이다. 염증성 장질환의 발생 원인이나 병태생리에 대해서는 아직까지 명확히 알려져 있지 않지만, 유전적 요인, 장내 세균이나 음식물 등의 환경적 요인, 면역학적 요인 등이 복합적으로 발생기전에 관여하는 것으로 추정되고 있다. 장 면역계의 지속적이거나 부적절한 활성화는 만성 점막성 염증의 병태생리에 중요한 역할을 하며, 특히 호중구, 대식세포, 림프구 및 비만세포의 침윤에 의해 결국 점막 파괴 및 궤양을 초래한다. 침윤되고 활성화된 호중구는 활성산소종 및 활성질소종의 중요한 원인이 되며, 이러한 활성종은 세포독성 물질로서 가교 단백질, 지질 및 핵산을 분해하는 산화적 스트레스를 유도하고 상피성 기능장애 및 손상을 초래한다.Inflammatory bowel disease (IBD) is a disease that causes chronic inflammation of the intestine of unknown cause. It has a clinical progression with repeated exacerbation and improvement, and ulcerative colitis and Crohn's disease are representative diseases. The cause or pathophysiology of inflammatory bowel disease is not yet clearly known, but it is estimated that genetic factors, environmental factors such as intestinal bacteria and food, and immunological factors are complexly involved in the development mechanism. Persistent or inappropriate activation of the intestinal immune system plays an important role in the pathophysiology of chronic mucosal inflammation, in particular, by infiltration of neutrophils, macrophages, lymphocytes and mast cells, eventually leading to mucosal destruction and ulcers. Infiltrated and activated neutrophils are an important cause of reactive oxygen species and reactive nitrogen species, and these active species are cytotoxic substances that induce oxidative stress that degrades crosslinking proteins, lipids and nucleic acids, and causes epithelial dysfunction and damage. do.
염증성 장질환의 근본적 치료법은 아직 확립되어 있지 않아 증상을 완화시킬 수 있는 약제가 사용되고 있다. 주로 프로스타글란딘 (prostaglandins)의 생성을 차단하는 5-아미노살리실산 (5-aminosalicylic acid, 5-ASA) 계통 약물, 예를 들어 설파살라진 (sulfasalazine) 등을 이용하거나, 스테로이드류의 면역억제제를 사용하고 있다.The fundamental treatment for inflammatory bowel disease has not yet been established, so drugs that can relieve symptoms are being used. Mainly, 5-aminosalicylic acid (5-ASA) drugs that block the production of prostaglandins, such as sulfasalazine, are used, or immunosuppressants such as steroids are used.
설파살라진은 복부허실 (fullness), 두통, 발진, 간질환, 백혈구 감소증, 무과립구증, 남성 불임 등과 같은 부작용 또는 역효과를 일으키기 쉽다. 또한, 설파살라진이 장의 환부를 절개한 환자 또는 차도가 있는 환자에게 충분한 재발 억제 효과가 있는지는 불분명하다.Sulfasalazine is likely to cause side effects or adverse effects such as fullness, headache, rash, liver disease, leukopenia, agranulocytosis, and male infertility. In addition, it is unclear whether sulfasalazine has a sufficient inhibitory effect on recurrence in patients with incisions in the intestine or patients with remission.
스테로이드류의 면역억제제는 부신피질 스테로이드로서, 단기적인 효과는 인정받고 있지만, 장기적인 예후를 향상시킬 수는 없다. 또한, 유도된 감염성 질환, 2차 부신피질 부전증, 소화성 궤양, 당뇨병, 정신장애, 스테로이드성 신장병 등과 같은 부작용의 측면에서 단지 급성인 경우에만 사용되어야 하는 한계가 있다.Steroid-type immunosuppressants are adrenal cortical steroids, which are recognized for their short-term effects, but cannot improve long-term prognosis. In addition, in terms of side effects such as induced infectious diseases, secondary adrenal insufficiency, peptic ulcer, diabetes, mental disorders, steroidal nephropathy, etc., there is a limitation that should be used only in acute cases.
즉, 아직까지 염증성 장질환에 대해 신뢰할 만한 치료요법이 없으므로, 부작용이 없고 저렴하면서도 치료 효과가 우수한 새로운 치료제의 개발이 필요한 실정이며, 그 예로 천연물 추출물을 사용한 염증성 장질환 예방 또는 치료용 조성물 (한국 등록특허 제10-1710730호) 등이 개발되고 있다.That is, since there is still no reliable therapy for inflammatory bowel disease, there is a need to develop a new therapeutic agent that has no side effects, is inexpensive, and has excellent therapeutic effect. For example, a composition for preventing or treating inflammatory bowel disease using natural extracts (Korea Registered Patent No. 10-1710730) and the like are being developed.
한편, 닥나무 (Broussonetia kazinoki)는 쐐기풀목 뽕나무과의 낙엽활엽 교목으로 암수한그루이며, 봄에 잎이 나면서 동시에 꽃이 핀다. 열매는 뱀딸기 비슷한 공 모양의 핵과로 9월경에 익으며 주로 경작지 주변이나 산기슭 양지 쪽에서 자생한다. 나무껍질은 대한민국, 중국, 일본 등에서 종이를 만드는 재료가 되며, 열매는 '저실' 또는 '구수자'라고 하여 약재로 쓰이고, 어린 잎은 먹기도 한다. On the other hand, Broussonetia kazinoki is a deciduous broad-leaved arboreous tree of the family Nettle, Moraceae, and is a male and female tree, and blossoms at the same time as leaves appear in spring. The fruit is a ball-shaped drupe that resembles a snake strawberry, ripens around September, and grows naturally around the cultivated area or in the sunny side of the foot of the mountain. The bark is a material for making paper in Korea, China, and Japan, and the fruit is called'jeosil'or'gusuja' and is used as a medicinal material, and young leaves are sometimes eaten.
그러나 현재까지 닥나무 추출물이 염증성 장질환의 치료에 효과적으로 사용될 수 있는지 여부가 알려진 바 없다. 이와 관련하여, 본 발명의 발명자들은 염증성 장질환의 치료 효능을 갖는 천연물을 개발하기 위하여 지속적인 연구를 거듭한 결과, 닥나무 추출물에 우수한 염증성 장질환 개선 효과가 있음을 확인하여 본 발명을 완성하였다.However, until now, it has not been known whether or not the extract of mulberry can be used effectively for the treatment of inflammatory bowel disease. In this regard, the inventors of the present invention completed the present invention by confirming that the mulberry extract has excellent inflammatory bowel disease improvement effects as a result of continuing research to develop natural products having therapeutic efficacy for inflammatory bowel disease.
본 발명은 닥나무 추출물을 포함하는 염증성 장질환의 예방 또는 치료용 약학 조성물을 제공하고자 한다.An object of the present invention is to provide a pharmaceutical composition for preventing or treating inflammatory bowel disease, comprising a mulberry extract.
본 발명은 닥나무 추출물을 포함하는 염증성 장질환의 예방 또는 개선용 식품 조성물을 제공하고자 한다.An object of the present invention is to provide a food composition for preventing or improving inflammatory bowel disease, comprising a mulberry extract.
본 발명은 닥나무 추출물을 포함하는 염증성 장질환의 예방 또는 개선용 사료 조성물을 제공하고자 한다.An object of the present invention is to provide a feed composition for preventing or improving inflammatory bowel disease, comprising a mulberry extract.
본 발명은 닥나무 추출물을 포함하는 염증성 장질환의 예방 또는 치료용 약학 조성물을 제공한다.The present invention provides a pharmaceutical composition for the prevention or treatment of inflammatory bowel disease, comprising a mulberry extract.
일 실시태양에서, 상기 닥나무 추출물은 닥나무 줄기 추출물, 닥나무 열매 추출물, 닥나무 뿌리 추출물, 또는 닥나무 잎 추출물일 수 있으며, 바람직하게는 닥나무 잎 추출물일 수 있다.In one embodiment, the mulberry extract may be a mulberry stem extract, a mulberry fruit extract, a mulberry root extract, or a mulberry leaf extract, and preferably may be a mulberry leaf extract.
일 실시태양에서, 상기 생약 추출물은 물, C1 내지 C6의 알코올, 아세트산, 및 이들의 혼합 용매로 이루어지는 군으로부터 선택되는 용매로 추출된 것일 수 있다. 바람직하게는, 0.01% 내지 90% 에탄올 추출물이며, 바람직하게는 60% 내지 80% 에탄올 추출물이고, 가장 바람직하게 70% 에탄올 추출물일 수 있다.In one embodiment, the herbal extract may be extracted with a solvent selected from the group consisting of water, C1 to C6 alcohol, acetic acid, and a mixed solvent thereof. Preferably, it is 0.01% to 90% ethanol extract, preferably 60% to 80% ethanol extract, and most preferably 70% ethanol extract.
일 실시태양에서, 상기 약학 조성물은 염증성 장질환으로 인한 대장의 길이 또는 무게의 감소를 억제할 수 있다.In one embodiment, the pharmaceutical composition may suppress a decrease in the length or weight of the large intestine due to inflammatory bowel disease.
또다른 실시태양에서, 상기 약학 조성물은 염증성 장질환으로 인한 비장의 길이 또는 무게의 증가를 억제할 수 있다.In another embodiment, the pharmaceutical composition may inhibit an increase in the length or weight of the spleen due to inflammatory bowel disease.
본 발명은 닥나무 추출물을 포함하는 염증성 장질환의 예방 또는 개선용 식품 조성물을 제공한다.The present invention provides a food composition for the prevention or improvement of inflammatory bowel disease comprising a mulberry extract.
본 발명은 닥나무 추출물을 포함하는 염증성 장질환의 예방 또는 개선용 사료 조성물을 제공한다.The present invention provides a feed composition for the prevention or improvement of inflammatory bowel disease comprising a mulberry extract.
본 발명의 닥나무 추출물을 포함하는 약학 조성물은 염증성 장질환에 대하여 우수한 치료 효과를 나타내어, 신규한 치료제로 사용될 수 있다.The pharmaceutical composition comprising the mulberry extract of the present invention exhibits an excellent therapeutic effect against inflammatory bowel disease, and can be used as a novel therapeutic agent.
또한, 본 발명의 약학 조성물은 천연물을 유효성분으로 포함함으로써 기존 치료제의 부작용을 줄이고 안전한 치료제로 사용될 수 있다.In addition, the pharmaceutical composition of the present invention can be used as a safe therapeutic agent to reduce side effects of existing therapeutic agents by including a natural product as an active ingredient.
도 1은 각 실험군 마우스의 몸무게 변화를 나타낸 것이다.
도 2는 각 실험군 마우스의 대장 사진이다.
도 3은 각 실험군 마우스의 대장 평균 길이를 나타낸 것이다.
도 4는 각 실험군 마우스의 질병활성도 (DAI) 측정 결과를 나타낸 것이다.
도 5는 각 실험군 마우스의 비장 무게 및 길이를 나타낸 것이다.Figure 1 shows the weight change of each experimental group mice.
2 is a picture of the large intestine of mice in each experimental group.
3 shows the average length of the large intestine of mice in each experimental group.
4 shows the results of measuring disease activity (DAI) of mice in each experimental group.
Figure 5 shows the spleen weight and length of the mice in each experimental group.
이하, 첨부한 도면을 참조하여 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자가 용이하게 실시할 수 있도록 본원의 실시태양 및 실시예를 상세히 설명한다. 그러나 본원은 여러 가지 형태로 구현될 수 있으며 여기에서 설명하는 실시태양 및 실시예에 한정되지 않는다.Hereinafter, embodiments and examples of the present disclosure will be described in detail with reference to the accompanying drawings so that those of ordinary skill in the art may easily implement the present disclosure. However, the present application may be implemented in various forms and is not limited to the embodiments and examples described herein.
본원 명세서 전체에서, 어떤 부분이 어떤 구성 요소를 "포함" 한다고 할 때, 이는 특별히 반대되는 기재가 없는 한 다른 구성 요소를 제외하는 것이 아니라 다른 구성 요소를 더 포함할 수 있는 것을 의미한다.In the entire specification of the present application, when a certain part "includes" a certain constituent element, it means that other constituent elements may be further included rather than excluding other constituent elements unless otherwise specified.
닥나무 추출물을 포함하는 염증성 장질환의 예방, 치료 또는 개선용 조성물에 관한 것이다. 상기 조성물은 약학 조성물, 식품 조성물 또는 사료 조성물일 수 있다.It relates to a composition for the prevention, treatment or improvement of inflammatory bowel disease, comprising a mulberry extract. The composition may be a pharmaceutical composition, a food composition or a feed composition.
일 실시태양에서, 상기 닥나무 추출물은 닥나무 줄기 추출물, 닥나무 열매 추출물, 닥나무 뿌리 추출물, 또는 닥나무 잎 추출물일 수 있으며, 바람직하게는 닥나무 잎 추출물일 수 있다.In one embodiment, the mulberry extract may be a mulberry stem extract, a mulberry fruit extract, a mulberry root extract, or a mulberry leaf extract, and preferably may be a mulberry leaf extract.
본원에 사용된 용어 "닥나무 추출물"은 본 발명의 약학 조성물의 유효성분으로서, 닥나무 생약으로부터 추출된 추출물을 의미할 수 있다.The term "bushroom extract" as used herein is an active ingredient of the pharmaceutical composition of the present invention, and may mean an extract extracted from a prickly pear.
본 발명의 생약 추출물이 추가의 유효성분과 함께 사용되는 경우, 생약 추출물은 하나의 제형으로 동시에 투여되거나, 또는 별개의 제형으로 동시에 또는 순차적으로 투여되는 것일 수 있다.When the herbal extract of the present invention is used together with an additional active ingredient, the herbal extract may be administered simultaneously in one formulation, or administered simultaneously or sequentially in separate formulations.
또한, 본 발명의 조성물은 염증성 장질환을 치료하기 위하여 단독 또는 수술, 호르몬 치료, 약물 치료 또는 생물학적 반응 조절제를 사용하는 방법들과 병용하여 사용할 수 있다.In addition, the composition of the present invention may be used alone or in combination with surgery, hormone therapy, drug therapy, or methods of using a biological response modifier to treat inflammatory bowel disease.
본 발명에 이용되는 닥나무 추출물은 당업계에서 공지된 통상적인 추출용매를 이용하여 얻을 수 있다. 추출용매로는 극성 용매 또는 비극성 용매를 이용할 수 있다. 극성 용매로는 물, C1 내지 C6의 알코올(예: 메탄올, 에탄올, 프로판올, 부탄올, 노말-프로판올, 이소-프로판올 및 노말-부탄올 등), 아세트산, 또는 상기 극성 용매들의 혼합물을 포함한다. 비극성 용매로는 아세톤, 아세토나이트릴, 에틸아세테이트, 메틸아세테이트, 부틸아세테이트, 플루오로알칸, 헥산, 에테르, 클로로포름, 디클로로메탄 또는 상기 비극성 용매들의 혼합물을 포함한다.The mulberry extract used in the present invention can be obtained using a conventional extraction solvent known in the art. As the extraction solvent, a polar solvent or a non-polar solvent may be used. Polar solvents include water, C1 to C6 alcohols (eg, methanol, ethanol, propanol, butanol, normal-propanol, iso-propanol and normal-butanol, etc.), acetic acid, or a mixture of the polar solvents. Non-polar solvents include acetone, acetonitrile, ethyl acetate, methyl acetate, butyl acetate, fluoroalkane, hexane, ether, chloroform, dichloromethane, or mixtures of the above non-polar solvents.
일 실시태양에서, 상기 닥나무 추출물은 물, C1 내지 C6의 알코올, 아세트산, 및 이들의 혼합 용매로 이루어지는 군으로부터 선택되는 용매로 추출된 것일 수 있다. 바람직하게 0.01% 내지 90% 에탄올 추출물이며, 더욱 바람직하게는 60% 내지 80% 에탄올 추출물이고, 가장 바람직하게 70% 에탄올 추출물일 수 있다.In one embodiment, the mulberry extract may be extracted with a solvent selected from the group consisting of water, C1 to C6 alcohol, acetic acid, and a mixed solvent thereof. It is preferably 0.01% to 90% ethanol extract, more preferably 60% to 80% ethanol extract, and most preferably 70% ethanol extract.
본 발명에 이용되는 생약 추출물은 열수 추출, 냉침 추출, 환류 냉각 추출, 초음파 추출 또는 당업계에 알려진 통상적인 추출방법을 통해 추출한 것일 수 있다.The herbal extract used in the present invention may be extracted through hot water extraction, cold needle extraction, reflux cooling extraction, ultrasonic extraction, or conventional extraction methods known in the art.
본원에 사용된 용어 "추출물"은 당업계에서 조추출물(crude extract)로 통용되는 것을 의미하지만, 광의적으로 추출물을 추가적으로 분획(fractionation)한 분획물도 포함한다. 즉 생약 추출물은 상술한 용매를 이용하여 얻은 것뿐만 아니라, 여기에 정제 과정을 추가적으로 적용하여 얻은 것을 포함한다. 예컨대, 상기 추출물을 일정한 분자량 컷-오프 값을 갖는 한외여과막을 통과시켜 얻은 분획, 다양한 크로마토그래프(크기, 전하, 소수성 또는 친화성에 따른 분리를 위해 제작된 것)에 의한 분리 등, 추가적으로 실시된 다양한 정제 방법을 통해 얻어진 분획도 본 발명의 생약 추출물에 포함된다.The term "extract" as used herein means commonly used as a crude extract in the art, but also includes a fraction obtained by further fractionating the extract in a broad sense. That is, the herbal extract includes not only those obtained by using the above-described solvent, but also those obtained by additionally applying a purification process thereto. For example, fractions obtained by passing the extract through an ultrafiltration membrane having a certain molecular weight cut-off value, separation by various chromatographs (made for separation according to size, charge, hydrophobicity or affinity), etc. Fractions obtained through the purification method are also included in the herbal extract of the present invention.
본원에 사용된 용어 "예방"은 본 발명에 따른 조성물의 투여에 의해 염증성 장질환의 발병을 억제 또는 지연시키는 모든 행위를 의미하고, "치료"는 상기 조성물의 투여에 의해 염증성 장질환의 의심 및 발병 개체의 증상이 호전되거나 이롭게 변경되는 모든 행위를 의미한다. 본원에 사용된 용어 "개선"은 본 발명의 추출물을 포함하는 조성물의 투여로 치료되는 상태와 관련된 파라미터, 예를 들면 증상의 정도를 적어도 감소시키는 모든 행위를 의미한다.The term "prevention" as used herein refers to any action that suppresses or delays the onset of inflammatory bowel disease by administration of the composition according to the present invention, and "treatment" refers to suspicion of inflammatory bowel disease and It refers to any action in which symptoms of an affected individual are improved or beneficially altered. As used herein, the term “improvement” refers to any action that at least reduces the severity of a parameter, such as a symptom, associated with the condition being treated by administration of a composition comprising an extract of the present invention.
일 실시태양에서, 상기 조성물은 염증성 장질환으로 인한 대장의 길이 또는 무게의 감소를 억제할 수 있다.In one embodiment, the composition may suppress a decrease in the length or weight of the large intestine due to inflammatory bowel disease.
또다른 실시태양에서, 상기 조성물은 염증성 장질환으로 인한 비장의 길이 또는 무게의 증가를 억제할 수 있다.In another embodiment, the composition may suppress an increase in the length or weight of the spleen due to inflammatory bowel disease.
본 발명의 식품 조성물은 건강기능식품 및 건강식품 등을 포함한다. 본 발명의 식품 조성물은 장기 복용할 수 있다.The food composition of the present invention includes health functional foods and health foods. The food composition of the present invention can be taken for a long time.
본 발명의 식품 조성물은 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.The food composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and thickeners (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid and salts thereof. , Organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonates used in carbonated beverages, and the like.
이하 실시예를 통하여 본 발명을 더욱 상세하게 설명하고자 하나, 하기의 실시예는 단지 설명의 목적을 위한 것이며 본원 발명의 범위를 한정하고자 하는 것은 아니다.The present invention is to be described in more detail through the following examples, but the following examples are for illustrative purposes only and are not intended to limit the scope of the present invention.
[제조예 1][Production Example 1]
닥나무 잎 생약 추출물의 제조Preparation of herbal extracts from mulberry leaves
세척 및 건조된 닥나무(Broussonetia kazinoki Siebold) 잎을 분쇄하여 사용하였다. 상기 닥나무 잎 생약에 10배의 70% 에탄올(v/v) 수용액을 가하여 상온에서 72시간 동안 추출하였다. 추출액을 여과한 후 50-65℃에서 감압농축하여 분말 상태의 단일 생약추출물을 수득하였고, 수득한 추출물을 토대로 이하의 실험을 진행하였다.Washed and dried oak (Broussonetia kazinoki Siebold ) leaves were crushed and used. A 10-fold 70% ethanol (v/v) aqueous solution was added to the herbal medicine of mulberry leaves, followed by extraction at room temperature for 72 hours. The extract was filtered and then concentrated under reduced pressure at 50-65° C. to obtain a powdery single herbal extract, and the following experiment was performed based on the obtained extract.
[실시예 1] [Example 1]
실험군 및 대조군Experimental group and control group
8주령의 C57BL/6 수컷 마우스를 구입하여 1주일간 예비사육한 후 8마리씩 무작위로 총 7그룹으로 하기와 같이 나누어 실험을 진행하였다.8-week-old C57BL/6 male mice were purchased, pre-raised for 1 week, and then randomly divided into 7 groups of 8 mice as follows to conduct the experiment.
멸균 물에 희석한 2.5% 덱스트란 황산나트륨 (Dextran Sulfate Sodium, DSS)은 총 8일간 음수 투여하였고, 염증성 장질환 치료제인 5-ASA, 또는 추출물을 DSS 투여일 2일 전부터 총 10일간 경구 투여하였다.2.5% Dextran Sulfate Sodium (DSS) diluted in sterile water was administered negatively for a total of 8 days, and 5-ASA, or extract, which is a treatment for inflammatory bowel disease, was administered orally for a total of 10 days from 2 days before DSS administration.
i) 정상군: 멸균 물 경구 투여i) Normal group: oral administration of sterile water
ii) 음성 대조군: 2.5% DSS 투여ii) negative control: 2.5% DSS administration
iii) 양성 대조군: 2.5% DSS 투여 + 5-아미노살리실산 (5-Aminosalicylic acid, 5-ASA)을 100mg/kg의 농도로 경구 투여iii) Positive control: 2.5% DSS administration + 5-aminosalicylic acid (5-ASA) administered orally at a concentration of 100 mg/kg
iv) 실험군 1: 2.5% DSS 투여 + 닥나무 잎 추출물 20mg을 50mg/kg의 농도로 경구 투여iv) Experimental group 1: 2.5% DSS administration + 20 mg of oak leaf extract orally administered at a concentration of 50 mg/kg
[실험예 1][Experimental Example 1]
마우스 몸무게 변화 측정Mouse weight change measurement
체중 감소 현상은 염증성 장질환의 대표적인 증상이다 (Scientific Reports volume 10, Article number: 3829 (2020)). 본 실험예에서는 실시예 1의 마우스에 대하여 1일 1회 동일한 시간 (오전 10시)에 전자저울을 사용하여 몸무게를 측정하였다. 각 그룹의 몸무게의 변화율은 그룹당 8마리 마우스의 몸무게를 합산한 후 8로 나누어 구하였고, 2.5% DSS 음수 투여 시작 직전의 평균 몸무게를 100%로 정하고 매일 각 그룹의 평균 몸무게를 구하여 몸무게 변화율을 측정하였다. 2.5% DSS를 음수 투여한 음성 대조군과 실험군 간의 집단 별 맨-휘트니 검정 (Mann-Whitney test)을 실시하여 그 유의성을 검증하였다. Weight loss is a typical symptom of inflammatory bowel disease (
도 1에 나타낸 바와 같이, 정상군 마우스의 체중은 105.44±0.72 %이고, 음성 대조군 마우스의 체중은 85.38±1.62 %로 정상군과 비교하여 체중이 유의하게 감소되었다. 5-ASA를 투여한 양성 대조군의 마우스 체중은 89.68±1.8 %, 닥나무 잎 추출물만 투여한 마우스 (실험군 1) 체중은 88.49±0.8 %로 측정되었다. As shown in FIG. 1, the weight of the mice in the normal group was 105.44±0.72%, and the weight of the mice in the negative control group was 85.38±1.62%, which was significantly reduced compared to the normal group. The weight of mice in the positive control group administered with 5-ASA was 89.68±1.8%, and the weight of mice administered with only the mulberry leaf extract (Experimental Group 1) was 88.49±0.8%.
상기 결과로부터, 음성 대조군 마우스의 체중에 비하여 닥나무 잎 추출물에서 우수한 몸무게 감소 억제 효과가 나타났으며, 이는 양성 대조군과 유사한 수준임을 알 수 있었다.From the results, compared to the weight of the negative control mice, a superior weight loss inhibitory effect was observed in the oak leaf extract, which was found to be similar to that of the positive control group.
[실험예 2][Experimental Example 2]
마우스 대장 길이 측정Mouse colon length measurement
대장의 단소화와 조직적 변화는 충분한 상관 관계가 있는 것으로 알려져 있고, 대장의 길이는 통상적으로 염증 정도의 형태학적 매개 변수로서 이용된다. 실시예 1의 마우스를 각 투여 마지막 날 희생시키고, 대장의 사진을 찍어 도 2에 나타내었고, 대장의 길이를 측정하여 평균 길이를 도 3에 나타냈다. It is known that there is a sufficient correlation between the shortening of the large intestine and histological changes, and the length of the large intestine is usually used as a morphological parameter of the degree of inflammation. The mice of Example 1 were sacrificed on the last day of each administration, and a picture of the large intestine was taken and shown in FIG. 2, and the length of the large intestine was measured and the average length was shown in FIG. 3.
도 2 및 도 3에서 확인되는 바와 같이, 정상군의 대장 길이는 7.01±0.67 cm이고, 음성 대조군은 4.31±0.39 cm로 정상군과 비교하여 대장의 길이가 감소하였다. 양성 대조군의 대장 길이는 4.78±0.5 cm, 닥나무 잎 추출물만 투여한 마우스 (실험군 1)의 대장 길이는 4.76±0.49 cm로 측정되었다. As can be seen in FIGS. 2 and 3, the length of the colon of the normal group was 7.01±0.67 cm, and that of the negative control group was 4.31±0.39 cm, which decreased the length of the colon compared to the normal group. The colon length of the positive control group was measured to be 4.78±0.5 cm, and the colon length of the mouse (Experimental group 1) administered with only the mulberry leaf extract was 4.76±0.49 cm.
상기 결과로부터, 음성 대조군 마우스의 대장길이에 비하여, 닥나무 잎 추출물을 투여한 경우 대장 길이가 유의하게 길어졌으며, 이는 양성 대조군과 유사한 수준임을 알 수 있었다.From the above results, compared to the colon length of the negative control mice, when the mulberry leaf extract was administered, the colon length was significantly longer, which was found to be similar to that of the positive control group.
[실험예 3][Experimental Example 3]
질병활성도 (Disease Activity Index, DAI) 평가Disease activity index (DAI) evaluation
실시예 1의 투여 방법으로 처리된 염증성 장질환 동물모델의 염증성 장질환의 강도를 측정하기 위하여 체중 변화, 변의 굳기, 변이나 항문에서 육안적으로 관찰되는 혈변의 유무를 표 1의 질병활성도 (DAI) 등급에 따라 투여 기간 동안 매일 확인하여 질병활성도를 측정하였다.In order to measure the intensity of inflammatory bowel disease in the animal model of inflammatory bowel disease treated by the administration method of Example 1, weight change, stool hardening, and the presence or absence of bloody stool visually observed in the stool or anus are shown in Table 1 for disease activity (DAI). ) According to the grade, disease activity was measured by checking every day during the administration period.
도 4에 나타낸 바와 같이, DSS를 투여한 음성 대조군에서 질병활성도가 크게 증가하였고, 음성 대조군에 비하여 닥나무 잎 추출물 투여군 (실험군 1)에서 질병활성도가 개선되는 것이 확인되었으며, 이는 양성 대조군과 유사한 수준임을 알 수 있었다.As shown in Figure 4, it was confirmed that the disease activity was significantly increased in the negative control group administered with DSS, and the disease activity was improved in the group (Experimental Group 1) administered with the mulberry leaf extract compared to the negative control group, which was similar to that of the positive control group. Could know.
[실험예 4] [Experimental Example 4]
마우스 비장 염증 감소 확인Confirmation of reduction in mouse spleen inflammation
염증성 장질환과 관련하여 발생할 수 대표적인 병증으로는 비장염 (splenitis)이 있는데 비장에 염증이 생기면 그 특성상 비장의 크기가 비대해지고 (Nutrients 2019, 11(11), 2776), 실제로 DSS 처리후 유도된 IBD 모델에서 비장이 비대해지는 것으로 알려져 있다 (Biol. Pharm. Bull. 43, 450-457 (2020)).A representative condition that can occur in relation to inflammatory bowel disease is splenitis. When the spleen is inflamed, the size of the spleen increases due to its characteristics (Nutrients 2019, 11(11), 2776), and actually induced after DSS treatment. It is known that the spleen becomes enlarged in the IBD model (Biol. Pharm. Bull. 43, 450-457 (2020)).
실시예 1의 마우스를 각 투여 마지막날 희생시킨 후 DDS를 처리한 음성대조군 대비 각 그룹의 비장 무게 및 길이를 비장율 (spleen ratio)로 나타냈다. 도 5에서 확인되는 바와 같이, 정상군에 비하여 음성 대조군의 비장 무게 및 크기가 증가되었다. 닥나무 잎 추출물 투여군 (실험군1)은 음성 대조군에 비하여 비장 무게 및 길이가 감소하여 비장염으로 인하여 비장이 비대해지는 증상이 개선된 것을 알 수 있었다.After the mice of Example 1 were sacrificed on the last day of each administration, the weight and length of the spleen of each group compared to the negative control group treated with DDS were expressed as a spleen ratio. As can be seen in Figure 5, compared to the normal group, the weight and size of the spleen of the negative control group were increased. Compared to the negative control group, the weight and length of the spleen were decreased in the group administered with the extract of mulberry leaves (Experimental Group 1), and it was found that the symptoms of the spleen enlarged due to the spleen were improved.
Claims (9)
A pharmaceutical composition for the prevention or treatment of inflammatory bowel disease, comprising a mulberry extract.
The pharmaceutical composition for preventing or treating inflammatory bowel disease according to claim 1, wherein the mulberry extract is a mulberry leaf extract.
The pharmaceutical composition for preventing or treating inflammatory bowel disease according to claim 1, wherein the mulberry extract is extracted with a solvent selected from the group consisting of water, C1 to C6 alcohol, acetic acid, and a mixed solvent thereof. .
The pharmaceutical composition for preventing or treating inflammatory bowel disease according to claim 1, wherein the mulberry extract is an ethanol extract of 0.01% to 90%.
The pharmaceutical composition for preventing or treating inflammatory bowel disease according to claim 1, wherein the mulberry extract is an ethanol extract of 60% to 80%.
The pharmaceutical composition for preventing or treating inflammatory bowel disease according to claim 1, wherein the pharmaceutical composition inhibits a decrease in the length or weight of the large intestine.
The pharmaceutical composition for preventing or treating inflammatory bowel disease according to claim 1, wherein the pharmaceutical composition inhibits an increase in length or weight of the spleen.
A food composition for preventing or improving inflammatory bowel disease, comprising a mulberry extract.
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