WO2022080523A1 - Composition comprising a mixture of medicinal herbal extracts from indigo pulverata levis, broussonetia kazinoki, and juglans mandshurica for preventing or treating inflammatory bowel disease - Google Patents

Composition comprising a mixture of medicinal herbal extracts from indigo pulverata levis, broussonetia kazinoki, and juglans mandshurica for preventing or treating inflammatory bowel disease Download PDF

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WO2022080523A1
WO2022080523A1 PCT/KR2020/014025 KR2020014025W WO2022080523A1 WO 2022080523 A1 WO2022080523 A1 WO 2022080523A1 KR 2020014025 W KR2020014025 W KR 2020014025W WO 2022080523 A1 WO2022080523 A1 WO 2022080523A1
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mulberry
extract
inflammatory bowel
bowel disease
preventing
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French (fr)
Korean (ko)
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손미원
김신연
최진규
김세웅
박상철
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엠테라파마 주식회사
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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
    • 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)
    • A61K36/52—Juglandaceae (Walnut family)
    • 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
    • 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)
    • A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Definitions

  • the present invention relates to a pharmaceutical composition for the prevention or treatment of inflammatory bowel disease, comprising a complex herbal extract of Qingdao, mulberry, and mulberry as an active ingredient.
  • the present invention also relates to a food composition or feed composition for preventing or improving inflammatory bowel disease comprising the herbal extract as an active ingredient.
  • IBD Inflammatory bowel disease
  • Infiltrating and activated neutrophils are an important cause of reactive oxygen species and reactive nitrogen species, which are cytotoxic substances that induce oxidative stress that degrades cross-linked proteins, lipids and nucleic acids, and cause epithelial dysfunction and damage. do.
  • 5-aminosalicylic acid (5-ASA) drugs that block the production of prostaglandins, such as sulfasalazine, are used, or steroid immunosuppressants are used.
  • Sulfasalazine is prone to side effects or adverse effects such as abdominal fullness, headache, rash, liver disease, leukopenia, agranulocytosis, and male infertility.
  • side effects or adverse effects such as abdominal fullness, headache, rash, liver disease, leukopenia, agranulocytosis, and male infertility.
  • sulfasalazine has sufficient relapse inhibitory effect in patients with intestinal incision or in patients with remission.
  • Steroid immunosuppressants are adrenocortical steroids, and although short-term effects are recognized, they cannot improve long-term prognosis.
  • side effects such as induced infectious disease, secondary adrenocortical insufficiency, peptic ulcer, diabetes, psychiatric disorder, steroidal nephropathy, etc., there is a limitation in that it should be used only in acute cases.
  • cheongdae Indigo Pulverata levis
  • Indigo plant is native to China and India and is a representative plant used as a blue dye for dyeing fabrics and threads. It is a dye obtained by picking leaves around July-August and is used for dyeing by techniques such as the raw juice method and the semi-water method.
  • Cheongdae tastes salty and cold in nature, and is known to have anti-cancer, anti-inflammatory, and detoxifying properties.
  • the mulberry tree ( Broussonetia kazinoki ) is a deciduous broad-leaved tree of the Morus family, of the Nettle family, and is a male and female tree, and the leaves appear in spring and flowers bloom at the same time.
  • the fruit is a ball-shaped drupe similar to a strawberry, and ripens around September. It is mainly grown around cultivated land or in sunny areas at the foot of mountains.
  • the bark is a material for making paper in Korea, China, and Japan, and the fruit is called 'jeosil' or 'gusuja' and is used medicinally, and the young leaves are also eaten.
  • Juglans mandshurica ( Juglans mandshurica ) is classified in the family Juglansaceae or Walnutaceae and exists in the form of trees or shrubs and is native to America, Eurasia or South Asia. It is mainly found in central and northern parts of Korea or northeastern China, and is used as a medicinal plant and herbal medicine.
  • Patent Document 1 Korean Patent Registration No. 10-1710730
  • An object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of inflammatory bowel disease comprising a complex herbal extract of chrysanthemum, mulberry, and/or phlegm as an active ingredient.
  • An object of the present invention is to provide a food composition for the prevention or improvement of inflammatory bowel disease comprising a complex herbal extract of chrysanthemum, mulberry and/or phlegm as an active ingredient.
  • An object of the present invention is to provide a feed composition for the prevention or improvement of inflammatory bowel disease comprising a complex herbal extract of chrysanthemum, mulberry, and/or phlegm as an active ingredient.
  • the present invention relates to (1) Qing dynasty; And (2) provides a pharmaceutical composition for the prevention or treatment of inflammatory bowel disease, comprising one or more herbal extracts selected from the group consisting of mulberry and mulberry.
  • the herbal extract may be a mixture of extracts extracted from each herbal medicine, or may be extracted from a mixture of herbal medicines.
  • the mulberry extract may be a mulberry stem extract, a mulberry fruit extract, a mulberry root extract, or a mulberry leaf extract, preferably a mulberry leaf extract.
  • the shamrock extract may be a shamrock stem extract, a shamrock fruit extract, a shamrock root extract, or a shamrock leaf extract, preferably a shamrock fruit extract.
  • 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.
  • a solvent selected from the group consisting of water, C1 to C6 alcohol, acetic acid, and a mixed solvent thereof.
  • it is a 0.01% to 90% ethanol extract, and most preferably, it is a 60% to 80% ethanol extract.
  • the pharmaceutical composition may include herbal extracts of chrysanthemum, mulberry, and mulberry.
  • the blending weight ratio of the blueberry, mulberry tree, and mulberry tree may be from 1:0.1 to 10:0.1 to 10, preferably from 1:0.5 to 2:0.5 to 2, and more preferably from 1:1:1.
  • the pharmaceutical composition may be to reduce the length or weight of the large intestine.
  • the pharmaceutical composition may reduce the length or weight of the spleen.
  • the present invention relates to (1) Qing dynasty; And (2) it provides a food composition for preventing or improving inflammatory bowel disease, comprising one or more herbal extracts selected from the group consisting of mulberry and mulberry.
  • the present invention relates to (1) Qing dynasty; And (2) provides a feed composition for preventing or improving inflammatory bowel disease, comprising one or more herbal extracts selected from the group consisting of mulberry and mulberry.
  • the pharmaceutical composition comprising the complex herbal extract of chrysanthemum, mulberry and/or phlegm of the present invention as an active ingredient exhibits an excellent therapeutic effect on inflammatory bowel disease, and can be used as a novel therapeutic agent.
  • the pharmaceutical composition of the present invention can be used as a safe therapeutic agent by reducing the side effects of existing therapeutic agents by including a natural product as an active ingredient.
  • 1 and 2 show the change in body weight of mice in each experimental group.
  • 3 and 4 show the length of the large intestine of mice in each experimental group.
  • the present invention relates to (1) Qing dynasty; And (2) it relates to a composition for preventing, treating or improving inflammatory bowel disease, comprising one or more herbal extracts selected from the group consisting of mulberry and mulberry.
  • the composition may be a pharmaceutical composition, a food composition or a feed composition.
  • the mulberry extract may be a mulberry stem extract, a mulberry fruit extract, a mulberry root extract, or a mulberry leaf extract, preferably a mulberry leaf extract.
  • the shamrock extract may be a shamrock stem extract, a shamrock fruit extract, a shamrock root extract, or a shamrock leaf extract, preferably a shamrock fruit extract.
  • the term "crude drug extract” or “composite herbal extract” refers to an active ingredient of the pharmaceutical composition of the present invention, including extracts extracted from crude drugs of chrysanthemum, mulberry and/or spruce, or from a mixture of these herbs. It may contain an extracted extract.
  • the pharmaceutical composition may include herbal extracts of chrysanthemum, mulberry, and mulberry.
  • the blending weight ratio of the blueberry, mulberry tree, and mulberry tree may be from 1:0.1 to 10:0.1 to 10, preferably from 1:0.5 to 2:0.5 to 2, and more preferably from 1:1:1.
  • the herbal extract of the present invention When used together with an additional active ingredient, the herbal extract and the additional active ingredient may be administered simultaneously as one formulation, or may be administered simultaneously or sequentially as separate formulations.
  • composition of the present invention can be used alone or in combination with methods using surgery, hormone therapy, drug therapy, or a biological response modifier to treat inflammatory bowel disease.
  • the herbal extract used in the present invention can be obtained using a conventional extraction solvent known in the art.
  • a polar solvent or a non-polar solvent may be used.
  • Polar solvents include water, C1 to C6 alcohols (eg, methanol, ethanol, propanol, butanol, n-propanol, iso-propanol and n-butanol, etc.), acetic acid, or mixtures of the foregoing 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.
  • 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.
  • a solvent selected from the group consisting of water, C1 to C6 alcohol, acetic acid, and a mixed solvent thereof.
  • it is a 0.01% to 90% ethanol extract, and most preferably, it is a 60% to 80% ethanol extract.
  • the herbal extract used in the present invention may be extracted through hot water extraction, cold extraction, reflux cooling extraction, ultrasonic extraction, or a conventional extraction method known in the art.
  • extract means commonly used in the art as a crude extract, but broadly includes a fraction obtained by further fractionation of the extract. That is, the herbal extract includes not only those obtained using the above-described solvent, but also those obtained by additionally applying a purification process thereto. For example, a fraction obtained by passing the extract through an ultrafiltration membrane having a constant molecular weight cut-off value, separation by various chromatographs (those prepared for separation according to size, charge, hydrophobicity or affinity), etc. The fraction obtained through the purification method is also included in the herbal extract of the present invention.
  • prevention refers to any action that inhibits or delays the onset of inflammatory bowel disease by administration of the composition according to the present invention
  • treatment refers to any activity of suspected and delayed inflammatory bowel disease by administration of the composition. It means any action that improves or beneficially changes the symptoms of the affected individual.
  • improvement refers to any action that at least reduces a parameter, eg, the severity of a symptom, associated with a condition to be treated by administration of a composition comprising an extract of the present invention.
  • the composition may be to reduce the length or weight of the large intestine.
  • the composition may reduce the length or weight of the spleen.
  • the food composition of the present invention includes health functional food and health food.
  • the food composition of the present invention can be taken for a long time.
  • the food composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), synthetic flavoring agents and flavoring agents such as natural flavoring agents, coloring agents and thickening agents (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid and salts thereof , organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like.
  • Washed and dried cheongdae Indigo Pulverata Levis
  • mulberry Broussonetia kazinoki
  • Juglans mandshurica fruits were used round or pulverized according to the crude drug. 10 times 70% ethanol (v/v) aqueous solution was added to each herbal medicine of the blueberry, mulberry leaf, and mulberry fruit, followed by extraction at room temperature for 72 hours. After filtering the extract, it was concentrated under reduced pressure at 50 to 65° C. to obtain a single herbal extract in a powder state, and the following experiment was performed based on the obtained extract.
  • mice 8-week-old C57BL/6 male mice were purchased and pre-bred for 1 week, and then, 8 mice were randomly divided into 7 groups, and the experiment was conducted as follows.
  • DSS Dextran Sulfate Sodium
  • Experimental group 1-3 2.5% DSS administration + 10 mg of cheongdae extract and 10 mg of chrysanthemum extract were mixed and administered orally at a concentration of 50 mg/kg
  • mice Six-week-old C57BL/6N male mice were purchased and pre-bred for 1 week, and then the experiment was conducted by dividing the mice into 8 groups at random, as follows.
  • DSS Dextran Sulfate Sodium
  • Experimental group 2-4 2.5% DSS administration + 10 mg of blueberry extract and 10 mg of mulberry leaf extract were mixed and administered orally at a concentration of 50 mg/kg
  • Weight loss is a typical symptom of inflammatory bowel disease (Scientific Reports volume 10, Article number: 3829 (2020)).
  • the weight of the mouse of Example 1 was measured once a day at the same time (10 am) using an electronic scale.
  • the rate of change in body weight of each group was obtained by adding up the weights of 8 mice per group and dividing by 8. did.
  • the significance was verified by performing a Mann-Whitney test for each group between the negative control group and the experimental group, which were administered with a negative 2.5% DSS.
  • the body weight of the mice in the normal group was 105.31 ⁇ 1.51%, and the body weight of the mice in the negative control group was 81.96 ⁇ 0.84%, which was significantly reduced compared to that of the normal group.
  • mice body weight of the positive control group administered with 5-ASA was 90.29 ⁇ 1.47%, the mouse administered only the cheongdae extract (Experimental group 1-1), the body weight was 86.19 ⁇ 0.71%, and the mouse administered the blueberry and mulberry extract (Experimental group 1-2)
  • the body weight was measured to be 89.51 ⁇ 1.59%, and the body weight of mice treated with chrysanthemum extract and shamrock extract (experimental group 1-3) was measured to be 92.04 ⁇ 1.72%.
  • mice administered with blueberry and mulberry extract had a body weight of 89.25 ⁇ 3.77%, and mice administered with blueberry and mulberry extract (experimental group 2-5) weighed 93.62 ⁇ 3.09%, with blueberry, mulberry and mulberry extract
  • the body weight of mice administered with (experimental group 2-6) was measured to be 95.89 ⁇ 1.53%.
  • mice of Example 1 were sacrificed on the last day of each administration, and the length of the large intestine was measured and the average length is shown in FIG. 3 .
  • the colon length of the normal group was 6.66 ⁇ 0.22 cm
  • the negative control group was 4.17 ⁇ 0.19 cm, which decreased compared to the normal group.
  • the colon length of the positive control group was 4.41 ⁇ 0.16 cm
  • the colon length of mice administered only cheongdae extract (experimental group 1-1) was 4.25 ⁇ 0.25 cm
  • the colon length of mice administered with cheongdae and mulberry extracts (experimental group 1-2) was It was measured to be 4.83 ⁇ 0.17 cm.
  • the colon length of the normal group was 7.56 ⁇ 0.18 cm, and the negative control group was 5.66 ⁇ 0.15 cm, which decreased compared to the normal group.
  • Mice administered with blueberry and mulberry extract had a colon length of 5.97 ⁇ 0.23 cm, and mice administered with blueberry and mulberry extracts (Experimental group 2-5) had a colon length of 5.76 ⁇ 0.19 cm, with blueberry, mulberry and phlegm.
  • the length of the large intestine of mice administered the tree extract (experimental group 2-6) was measured to be 6.23 ⁇ 0.22 cm.
  • the weight of the large intestine is also commonly used as a morphological parameter of the degree of inflammation.
  • the mice of Example 2 were sacrificed on the last day of each administration, and the weight of the large intestine was measured and the average length is shown in FIG. 5 .
  • the colon weight of the normal group was 0.88 ⁇ 0.01 g
  • the negative control group was 0.59 ⁇ 0.03 g, which decreased compared to the normal group.
  • Mice administered with blueberry and mulberry extract had a large intestine weight of 0.65 ⁇ 0.06 g
  • mice administered with blueberry and mulberry extract (experimental group 2-5) with a large intestine weight of 0.69 ⁇ 0.05 g, blueberry, mulberry and phlegm.
  • the weight of the large intestine of mice administered the tree extract (experimental groups 2-6) was measured to be 0.71 ⁇ 0.05 g.
  • a typical symptom that can occur in relation to inflammatory bowel disease is splenitis.
  • the size of the spleen becomes enlarged due to its nature (Nutrients 2019, 11(11), 2776), and in fact, It is known that the spleen is enlarged in the IBD model (Biol. Pharm. Bull. 43, 450-457 (2020)).
  • the weight and length of the spleen of each group compared to the negative control group treated with DDS were expressed as the spleen ratio.
  • the spleen weight and size of the negative control group were increased compared to the normal group.
  • Each single extract administration group (Experimental group 2-1), mulberry tree (Experimental group 2-2), and mulberry tree (experimental group 2-3) decreased the weight and length of the spleen compared to the negative control group.
  • the experimental group 2-6) administration group decreased the weight and length of the spleen to a level similar to that of the normal group, and it was found that the symptoms of enlarged spleen due to splenitis were improved.
  • DAI Disease Activity Index
  • DAI Disease Activity Index
  • mice of Example 2 disease activity was measured in the same manner as in Experimental Example 7, and the results are shown in FIG. 8 .
  • disease activity was significantly increased in the negative control group administered with DSS.
  • superior disease activity in the group administered with extracts of chrysanthemum, mulberry and mulberry extract (experimental group 2-6) compared to each single extract administration group (experimental group 2-1), mulberry tree (experimental group 2-2), and mulberry tree (experimental group 2-3). improvement was confirmed.

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Abstract

The present invention relates to a pharmaceutical composition comprising a mixture of medicinal herbal extracts from Indigo Pulverata Levis, Broussonetia kazinoki, and/or Juglans mandshurica for preventing or treating inflammatory bowel disease. In addition, the present invention relates to a food composition or animal feed composition comprising the medicinal herbal extracts for preventing or treating inflammatory bowel disease.

Description

청대, 닥나무, 및 가래나무의 복합 생약 추출물을 포함하는 염증성 장질환의 예방 또는 치료용 조성물Composition for the prevention or treatment of inflammatory bowel disease, comprising a complex herbal extract of chrysanthemum, mulberry, and mulberry tree
본 발명은 청대, 닥나무, 및 가래나무의 복합 생약 추출물을 유효성분으로 포함하는 염증성 장질환의 예방 또는 치료용 약학 조성물에 관한 것이다. 또한 본 발명은 상기 생약 추출물을 유효성분으로 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 complex herbal extract of Qingdao, mulberry, and mulberry as an active ingredient. The present invention also relates to a food composition or feed composition for preventing or improving inflammatory bowel disease comprising the herbal extract as an active ingredient.
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 intestinal tract of unknown cause, showing a clinical course that repeats aggravation and improvement, and ulcerative colitis and Crohn's disease are representative diseases. Although the cause or pathophysiology of inflammatory bowel disease is not yet known clearly, it is estimated that genetic factors, environmental factors such as intestinal bacteria or food, and immunological factors are involved in the complex development mechanism. Persistent or inappropriate activation of the intestinal immune system plays an important role in the pathophysiology of chronic mucosal inflammation, and in particular, infiltration of neutrophils, macrophages, lymphocytes and mast cells leads to mucosal destruction and ulceration. Infiltrating and activated neutrophils are an important cause of reactive oxygen species and reactive nitrogen species, which are cytotoxic substances that induce oxidative stress that degrades cross-linked proteins, lipids and nucleic acids, and cause 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.A fundamental treatment for inflammatory bowel disease has not yet been established, so drugs that can alleviate symptoms are being used. Mainly, 5-aminosalicylic acid (5-ASA) drugs that block the production of prostaglandins, such as sulfasalazine, are used, or steroid immunosuppressants 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 prone to side effects or adverse effects such as abdominal fullness, headache, rash, liver disease, leukopenia, agranulocytosis, and male infertility. In addition, it is unclear whether sulfasalazine has sufficient relapse inhibitory effect in patients with intestinal incision or in 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 immunosuppressants are adrenocortical steroids, and although short-term effects are recognized, they cannot improve long-term prognosis. In addition, in terms of side effects such as induced infectious disease, secondary adrenocortical insufficiency, peptic ulcer, diabetes, psychiatric disorder, steroidal nephropathy, etc., there is a limitation in that it 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, there is still no reliable treatment for inflammatory bowel disease, so there is a need to develop a new therapeutic agent that has no side effects and is inexpensive and has excellent therapeutic effect. For example, a composition for preventing or treating inflammatory bowel disease using a natural product extract (Korea Registered Patent No. 10-1710730) and the like are being developed.
한편, 청대 (Indigo Pulverata levis)는 쪽이라고도 하는 마디풀목 마디풀과의 한해살이 풀의 잎을 발효시켜 얻은 가루이다. 쪽은 중국과 인도가 원산지이며 옷감이나 실을 물들이는 파란색 염료로 사용하는 대표적인 식물이다. 7~8월 무렵에 잎을 따 얻은 염료로 생즙법, 반물법 등의 기법으로 염색에 사용한다. 청대의 맛은 짜고 성질은 차며 항암, 청열 (淸熱), 해독 등의 작용을 하는 것으로 알려져있다. 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. 가래나무 (Juglans mandshurica)는 가래나무과 또는 호두나무과로 분류되며 나무 또는 관목 형태로 존재하며 아메리카, 유라시아 또는 남아시아가 원산지이다. 이는 한국 중부 이북 또는 중국 북동부 등지에서 주로 서식하며 약용식물, 한방 약재로 이용되고 열매는 9~10월에 익은 것을 약용이나 식용으로 이용한다.On the other hand, cheongdae ( Indigo Pulverata levis ) is a powder obtained by fermenting the leaves of the annual grasses of the genus Indigo plant family, also called indigo plants. Indigo plant is native to China and India and is a representative plant used as a blue dye for dyeing fabrics and threads. It is a dye obtained by picking leaves around July-August and is used for dyeing by techniques such as the raw juice method and the semi-water method. Cheongdae tastes salty and cold in nature, and is known to have anti-cancer, anti-inflammatory, and detoxifying properties. The mulberry tree ( Broussonetia kazinoki ) is a deciduous broad-leaved tree of the Morus family, of the Nettle family, and is a male and female tree, and the leaves appear in spring and flowers bloom at the same time. The fruit is a ball-shaped drupe similar to a strawberry, and ripens around September. It is mainly grown around cultivated land or in sunny areas at the foot of mountains. The bark is a material for making paper in Korea, China, and Japan, and the fruit is called 'jeosil' or 'gusuja' and is used medicinally, and the young leaves are also eaten. Juglans mandshurica ( Juglans mandshurica ) is classified in the family Juglansaceae or Walnutaceae and exists in the form of trees or shrubs and is native to America, Eurasia or South Asia. It is mainly found in central and northern parts of Korea or northeastern China, and is used as a medicinal plant and herbal medicine.
그러나 현재까지 청대, 닥나무 및 가래나무 복합 생약 추출물이 염증성 장질환의 치료에 효과적으로 사용될 수 있는지는 공지된 바 없다. 이와 관련하여, 본 발명의 발명자들은 염증성 장질환의 치료 효능을 갖는 천연물을 개발하기 위하여 지속적인 연구를 거듭한 결과, 청대, 닥나무 및 가래나무 복합 생약 추출물에 우수한 염증성 장질환 개선 효과가 있음을 확인하여 본 발명을 완성하였다.However, to date, it is not known whether the herbal extracts of cheongdae, mulberry and mulberry can be effectively used for the treatment of inflammatory bowel disease. In this regard, the inventors of the present invention conducted continuous research to develop a natural product having therapeutic efficacy for inflammatory bowel disease. The present invention was completed.
[선행기술문헌][Prior art literature]
[특허문헌][Patent Literature]
(특허문헌 1) 한국 등록특허 제10-1710730호(Patent Document 1) Korean Patent Registration No. 10-1710730
본 발명은 청대, 닥나무 및/또는 가래나무의 복합 생약 추출물을 유효성분으로 포함하는 염증성 장질환의 예방 또는 치료용 약학 조성물을 제공하고자 한다.An object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of inflammatory bowel disease comprising a complex herbal extract of chrysanthemum, mulberry, and/or phlegm as an active ingredient.
본 발명은 청대, 닥나무 및/또는 가래나무의 복합 생약 추출물을 유효성분으로 포함하는 염증성 장질환의 예방 또는 개선용 식품 조성물을 제공하고자 한다.An object of the present invention is to provide a food composition for the prevention or improvement of inflammatory bowel disease comprising a complex herbal extract of chrysanthemum, mulberry and/or phlegm as an active ingredient.
본 발명은 청대, 닥나무 및/또는 가래나무의 복합 생약 추출물을 유효성분으로 포함하는 염증성 장질환의 예방 또는 개선용 사료 조성물을 제공하고자 한다.An object of the present invention is to provide a feed composition for the prevention or improvement of inflammatory bowel disease comprising a complex herbal extract of chrysanthemum, mulberry, and/or phlegm as an active ingredient.
본 발명은 (1) 청대; 및 (2) 닥나무 및 가래나무로 이루어진 군에서 선택된 하나 이상의 생약 추출물을 포함하는, 염증성 장질환의 예방 또는 치료용 약학 조성물을 제공한다.The present invention relates to (1) Qing dynasty; And (2) provides a pharmaceutical composition for the prevention or treatment of inflammatory bowel disease, comprising one or more herbal extracts selected from the group consisting of mulberry and mulberry.
일 실시태양에서, 상기 생약 추출물은 각각의 생약으로부터 추출된 추출물의 혼합물이거나, 생약의 혼합물로부터 추출된 것일 수 있다.In one embodiment, the herbal extract may be a mixture of extracts extracted from each herbal medicine, or may be extracted from a mixture of herbal medicines.
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, preferably a mulberry leaf extract.
일 실시태양에서, 상기 가래나무 추출물은 가래나무 줄기 추출물, 가래나무 열매 추출물, 가래나무 뿌리 추출물, 또는 가래나무 잎 추출물일 수 있으며, 바람직하게는 가래나무 열매 추출물일 수 있다.In one embodiment, the shamrock extract may be a shamrock stem extract, a shamrock fruit extract, a shamrock root extract, or a shamrock leaf extract, preferably a shamrock fruit 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, 가장 바람직하게는, 60% 내지 80% 에탄올 추출물이다.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 a 0.01% to 90% ethanol extract, and most preferably, it is a 60% to 80% ethanol extract.
일 실시태양에서, 상기 약학 조성물은 청대, 닥나무 및 가래나무의 생약 추출물을 포함하는 것일 수 있다. 상기 청대, 닥나무 및 가래나무의 배합 중량비는 1 : 0.1 내지 10 : 0.1 내지 10일 수 있으며, 바람직하게는 1 : 0.5 내지 2 : 0.5 내지 2이고, 더욱 바람직하게는 1 : 1 : 1이다.In one embodiment, the pharmaceutical composition may include herbal extracts of chrysanthemum, mulberry, and mulberry. The blending weight ratio of the blueberry, mulberry tree, and mulberry tree may be from 1:0.1 to 10:0.1 to 10, preferably from 1:0.5 to 2:0.5 to 2, and more preferably from 1:1:1.
일 실시태양에서, 상기 약학 조성물은 대장의 길이 또는 무게를 감소시키는 것일 수 있다.In one embodiment, the pharmaceutical composition may be to reduce the length or weight of the large intestine.
또다른 실시태양에서, 상기 약학 조성물은 비장의 길이 또는 무게를 감소시키는 것일 수 있다.In another embodiment, the pharmaceutical composition may reduce the length or weight of the spleen.
본 발명은 (1) 청대; 및 (2) 닥나무 및 가래나무로 이루어진 군에서 선택된 하나 이상의 생약 추출물을 포함하는, 염증성 장질환의 예방 또는 개선용 식품 조성물을 제공한다.The present invention relates to (1) Qing dynasty; And (2) it provides a food composition for preventing or improving inflammatory bowel disease, comprising one or more herbal extracts selected from the group consisting of mulberry and mulberry.
본 발명은 (1) 청대; 및 (2) 닥나무 및 가래나무로 이루어진 군에서 선택된 하나 이상의 생약 추출물을 포함하는, 염증성 장질환의 예방 또는 개선용 사료 조성물을 제공한다.The present invention relates to (1) Qing dynasty; And (2) provides a feed composition for preventing or improving inflammatory bowel disease, comprising one or more herbal extracts selected from the group consisting of mulberry and mulberry.
본 발명의 청대, 닥나무 및/또는 가래나무의 복합 생약 추출물을 유효성분으로 포함하는 약학 조성물은 염증성 장질환에 대하여 우수한 치료 효과를 나타내어, 신규한 치료제로 사용될 수 있다.The pharmaceutical composition comprising the complex herbal extract of chrysanthemum, mulberry and/or phlegm of the present invention as an active ingredient exhibits an excellent therapeutic effect on 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 by reducing the side effects of existing therapeutic agents by including a natural product as an active ingredient.
도 1 및 2는 각 실험군 마우스의 몸무게 변화를 나타낸 것이다.1 and 2 show the change in body weight of mice in each experimental group.
도 3 및 4는 각 실험군 마우스의 대장 길이를 나타낸 것이다.3 and 4 show the length of the large intestine of mice in each experimental group.
도 5는 각 실험군 마우스의 대장 무게를 나타낸 것이다.5 shows the weight of the large intestine of mice in each experimental group.
도 6은 각 실험군 마우스의 비장 무게 및 길이를 나타낸 것이다.6 shows the weight and length of the spleen of mice in each experimental group.
도 7 및 8은 각 실험군 마우스의 질병활성도 (DAI) 측정 결과를 나타낸 것이다.7 and 8 show the disease activity (DAI) measurement results of 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 invention will be described in detail with reference to the accompanying drawings so that those of ordinary skill in the art to which the present invention pertains can easily carry out. However, the present application may be embodied 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.Throughout this specification, when a part "includes" a component, it means that other components may be further included, rather than excluding other components, unless otherwise stated.
본 발명은 (1) 청대; 및 (2) 닥나무 및 가래나무로 이루어진 군에서 선택된 하나 이상의 생약 추출물을 포함하는, 염증성 장질환의 예방, 치료 또는 개선용 조성물에 관한 것이다. 상기 조성물은 약학 조성물, 식품 조성물 또는 사료 조성물일 수 있다.The present invention relates to (1) Qing dynasty; And (2) it relates to a composition for preventing, treating or improving inflammatory bowel disease, comprising one or more herbal extracts selected from the group consisting of mulberry and mulberry. 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, preferably a mulberry leaf extract.
일 실시태양에서, 상기 가래나무 추출물은 가래나무 줄기 추출물, 가래나무 열매 추출물, 가래나무 뿌리 추출물, 또는 가래나무 잎 추출물일 수 있으며, 바람직하게는 가래나무 열매 추출물일 수 있다.In one embodiment, the shamrock extract may be a shamrock stem extract, a shamrock fruit extract, a shamrock root extract, or a shamrock leaf extract, preferably a shamrock fruit extract.
본원에 사용된 용어 "생약 추출물" 또는 "복합 생약 추출물"은 본 발명의 약학 조성물의 유효성분으로서, 청대, 닥나무 및/또는 가래나무의 생약으로부터 추출된 추출물 각각을 포함하거나, 이들 생약의 혼합물로부터 추출된 추출물을 포함할 수 있다.As used herein, the term "crude drug extract" or "composite herbal extract" refers to an active ingredient of the pharmaceutical composition of the present invention, including extracts extracted from crude drugs of chrysanthemum, mulberry and/or spruce, or from a mixture of these herbs. It may contain an extracted extract.
일 실시태양에서, 상기 약학 조성물은 청대, 닥나무 및 가래나무의 생약 추출물을 포함하는 것일 수 있다. 상기 청대, 닥나무 및 가래나무의 배합 중량비는 1 : 0.1 내지 10 : 0.1 내지 10일 수 있으며, 바람직하게는 1 : 0.5 내지 2 : 0.5 내지 2이고, 더욱 바람직하게는 1 : 1 : 1이다.In one embodiment, the pharmaceutical composition may include herbal extracts of chrysanthemum, mulberry, and mulberry. The blending weight ratio of the blueberry, mulberry tree, and mulberry tree may be from 1:0.1 to 10:0.1 to 10, preferably from 1:0.5 to 2:0.5 to 2, and more preferably from 1:1:1.
본 발명의 생약 추출물이 추가의 유효성분과 함께 사용되는 경우, 생약 추출물 및 추가의 유효성분은 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 and the additional active ingredient may be administered simultaneously as one formulation, or may be administered simultaneously or sequentially as 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 can be used alone or in combination with methods using surgery, hormone therapy, drug therapy, or a biological response modifier to treat inflammatory bowel disease.
본 발명에 이용되는 생약 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 herbal 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, n-propanol, iso-propanol and n-butanol, etc.), acetic acid, or mixtures of the foregoing 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 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, 가장 바람직하게는 60% 내지 80% 에탄올 추출물이다.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 a 0.01% to 90% ethanol extract, and most preferably, it is a 60% to 80% 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 extraction, reflux cooling extraction, ultrasonic extraction, or a conventional extraction method 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.As used herein, the term "extract" means commonly used in the art as a crude extract, but broadly includes a fraction obtained by further fractionation of the extract. That is, the herbal extract includes not only those obtained using the above-described solvent, but also those obtained by additionally applying a purification process thereto. For example, a fraction obtained by passing the extract through an ultrafiltration membrane having a constant molecular weight cut-off value, separation by various chromatographs (those prepared for separation according to size, charge, hydrophobicity or affinity), etc. The fraction obtained through the purification method is 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.As used herein, the term “prevention” refers to any action that inhibits or delays the onset of inflammatory bowel disease by administration of the composition according to the present invention, and “treatment” refers to any activity of suspected and delayed inflammatory bowel disease by administration of the composition. It means any action that improves or beneficially changes the symptoms of the affected individual. As used herein, the term “improvement” refers to any action that at least reduces a parameter, eg, the severity of a symptom, associated with a condition to be treated by administration of a composition comprising an extract of the present invention.
일 실시태양에서, 상기 조성물은 대장의 길이 또는 무게를 감소시키는 것일 수 있다.In one embodiment, the composition may be to reduce the length or weight of the large intestine.
또다른 실시태양에서, 상기 조성물은 비장의 길이 또는 무게를 감소시키는 것일 수 있다.In another embodiment, the composition may reduce the length or weight of the spleen.
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 food and health food. 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), synthetic flavoring agents and flavoring agents such as natural flavoring agents, coloring agents and thickening agents (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid and salts thereof , organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents 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 will 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]
단일 생약 추출물의 제조Preparation of single herbal extracts
세척 및 건조된 청대 (Indigo Pulverata Levis), 닥나무 (Broussonetia kazinoki) 잎, 가래나무 (Juglans mandshurica) 열매를 생약에 따라 원형 또는 분쇄하여 사용하였다. 상기 청대, 닥나무 잎, 가래나무 열매 각 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 cheongdae ( Indigo Pulverata Levis ), mulberry ( Broussonetia kazinoki ) leaves, and Juglans mandshurica fruits were used round or pulverized according to the crude drug. 10 times 70% ethanol (v/v) aqueous solution was added to each herbal medicine of the blueberry, mulberry leaf, and mulberry fruit, followed by extraction at room temperature for 72 hours. After filtering the extract, it was concentrated under reduced pressure at 50 to 65° C. to obtain a single herbal extract in a powder state, and the following experiment was performed based on the obtained extract.
[실시예 1] [Example 1]
실험군 및 대조군 (1)Experimental group and control group (1)
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 and pre-bred for 1 week, and then, 8 mice were randomly divided into 7 groups, and the experiment was conducted as follows.
멸균 물에 희석한 2.5% 덱스트란 황산나트륨 (Dextran Sulfate Sodium, DSS)은 총 8일간 음수 투여하였고, 염증성 장질환 치료제인 5-ASA, 또는 각 추출물을 DSS 투여일 2일 전부터 총 10일간 경구 투여하였다.2.5% Dextran Sulfate Sodium (DSS) diluted in sterile water was administered with negative water for a total of 8 days, and 5-ASA, an inflammatory bowel disease treatment, or each extract was orally administered from 2 days before DSS administration to a total of 10 days. .
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-Aminosalicylic acid, 5-ASA) orally administered at a concentration of 100 mg/kg
iv) 실험군 1-1: 2.5% DSS 투여 + 청대 추출물 20mg을 50mg/kg의 농도로 경구 투여iv) Experimental group 1-1: 2.5% DSS administration + Oral administration of 20mg cheongdae extract at a concentration of 50mg/kg
v) 실험군 1-2: 2.5% DSS 투여 + 청대 추출물 10mg 및 닥나무 잎 추출물 10mg을 혼합하여 50mg/kg의 농도로 경구 투여v) Experimental group 1-2: 2.5% DSS administration + 10 mg of cheongdae extract and 10 mg of mulberry leaf extract were mixed and administered orally at a concentration of 50 mg/kg
vi) 실험군 1-3: 2.5% DSS 투여 + 청대 추출물 10mg 및 가래나무 열매 추출물 10mg을 혼합하여 50mg/kg의 농도로 경구 투여vi) Experimental group 1-3: 2.5% DSS administration + 10 mg of cheongdae extract and 10 mg of chrysanthemum extract were mixed and administered orally at a concentration of 50 mg/kg
vii) 실험군 1-4: 2.5% DSS 투여 + 청대 추출물 10mg, 닥나무 잎 추출물 10mg, 및 가래나무 열매 추출물 10mg을 혼합하여 75mg/kg의 농도로 경구 투여vii) Experimental group 1-4: 2.5% DSS administration + 10 mg of blueberry extract, 10 mg of mulberry leaf extract, and 10 mg of mulberry fruit extract were mixed and administered orally at a concentration of 75 mg/kg
[실시예 2] [Example 2]
실험군 및 대조군 (2)Experimental group and control group (2)
6주령의 C57BL/6N 수컷 마우스를 구입하여 1주일간 예비사육한 후 8마리씩 무작위로 총 8그룹으로 하기와 같이 나누어 실험을 진행하였다.Six-week-old C57BL/6N male mice were purchased and pre-bred for 1 week, and then the experiment was conducted by dividing the mice into 8 groups at random, as follows.
멸균 물에 희석한 2.5% 덱스트란 황산나트륨 (Dextran Sulfate Sodium, DSS)은 총 10일간 음수 투여하였고, 각 추출물은 DSS 투여일 2일 전부터 총 12일간 경구 투여하였다.2.5% Dextran Sulfate Sodium (DSS) diluted in sterile water was administered with negative water for a total of 10 days, and each extract was orally administered from 2 days before DSS administration to a total of 12 days.
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) 실험군 2-1: 2.5% DSS 투여 + 청대 추출물 20mg을 50mg/kg의 농도로 경구 투여iii) Experimental group 2-1: 2.5% DSS administration + 20mg cheongdae extract orally administered at a concentration of 50mg/kg
iv) 실험군 2-2: 2.5% DSS 투여 + 닥나무 잎 추출물 20mg을 50mg/kg의 농도로 경구 투여iv) Experimental group 2-2: 2.5% DSS administration + oral administration of 20 mg of mulberry leaf extract at a concentration of 50 mg/kg
v) 실험군 2-3: 2.5% DSS 투여 + 가래나무 열매 추출물 20mg을 50mg/kg의 농도로 경구 투여v) Experimental group 2-3: 2.5% DSS administration + Oral administration at a concentration of 50 mg/kg
vi) 실험군 2-4: 2.5% DSS 투여 + 청대 추출물 10mg 및 닥나무 잎 추출물 10mg을 혼합하여 50mg/kg의 농도로 경구 투여vi) Experimental group 2-4: 2.5% DSS administration + 10 mg of blueberry extract and 10 mg of mulberry leaf extract were mixed and administered orally at a concentration of 50 mg/kg
vii) 실험군 2-5: 2.5% DSS 투여 + 청대 추출물 10mg 및 가래나무 열매 추출물 10mg을 혼합하여 50mg/kg의 농도로 경구 투여vii) Experimental group 2-5: 2.5% DSS administration + 10 mg of cheongdae extract and 10 mg of chrysanthemum extract were mixed and administered orally at a concentration of 50 mg/kg
viii) 실험군 2-6: 2.5% DSS 투여 + 청대 추출물 6.67mg, 닥나무 잎 추출물 6.67mg, 및 가래나무 열매 추출물 6.67mg을 혼합하여 50mg/kg의 농도로 경구 투여viii) Experimental group 2-6: 2.5% DSS administration + 6.67 mg of blueberry extract, 6.67 mg of mulberry leaf extract, and 6.67 mg of mulberry fruit extract were mixed and administered orally at a concentration of 50 mg/kg
[실험예 1][Experimental Example 1]
마우스 몸무게 변화 측정 (1)Mouse weight change measurement (1)
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 (Scientific Reports volume 10, Article number: 3829 (2020)). In this experimental example, the weight of the mouse of Example 1 was measured once a day at the same time (10 am) using an electronic scale. The rate of change in body weight of each group was obtained by adding up the weights of 8 mice per group and dividing by 8. did. The significance was verified by performing a Mann-Whitney test for each group between the negative control group and the experimental group, which were administered with a negative 2.5% DSS.
도 1a 및 도 1b에 나타낸 바와 같이, 정상군 마우스의 체중은 105.31±1.51 %이고, 음성 대조군 마우스의 체중은 81.96±0.84 %로 정상군과 비교하여 체중이 유의하게 감소되었다. 5-ASA를 투여한 양성 대조군의 마우스 체중은 90.29±1.47 %, 청대 추출물만 투여한 마우스 (실험군 1-1) 체중은 86.19±0.71 %, 청대 및 닥나무 추출물을 투여한 마우스 (실험군 1-2) 체중은 89.51±1.59 %, 청대 및 가래나무 추출물을 투여한 마우스 (실험군 1-3) 체중은 92.04±1.72 %로 측정되었다. As shown in FIGS. 1A and 1B , the body weight of the mice in the normal group was 105.31±1.51%, and the body weight of the mice in the negative control group was 81.96±0.84%, which was significantly reduced compared to that of the normal group. The mouse body weight of the positive control group administered with 5-ASA was 90.29±1.47%, the mouse administered only the cheongdae extract (Experimental group 1-1), the body weight was 86.19±0.71%, and the mouse administered the blueberry and mulberry extract (Experimental group 1-2) The body weight was measured to be 89.51±1.59%, and the body weight of mice treated with chrysanthemum extract and shamrock extract (experimental group 1-3) was measured to be 92.04±1.72%.
상기 결과로부터, 청대 단독 추출물에 비하여, 청대 및 닥나무 추출물과 청대 및 가래나무 추출물에서 더욱 우수한 몸무게 감소 억제 효과가 있으며, 이는 양성 대조군과 유사한 수준임을 알 수 있었다. From the above results, it can be seen that there is a more excellent weight loss inhibitory effect in the extracts of cheongdae and mulberry, and extracts of chungdae and mulberry compared to the extract of cheongdae alone, which is at a level similar to that of the positive control.
[실험예 2][Experimental Example 2]
마우스 몸무게 변화 측정 (2)Mouse weight change measurement (2)
실시예 2의 마우스에 대하여, 실험예 1과 동일한 방법으로 몸무게를 측정하고, 그 결과를 도 2에 나타냈다.For the mouse of Example 2, the body weight was measured in the same manner as in Experimental Example 1, and the results are shown in FIG.
도 2에서 확인되는 바와 같이, 정상군 마우스의 체중은 104.79±1.36 %이고, 음성 대조군 마우스의 체중은 91.16±1.63 %로 정상군과 비교하여 체중이 유의하게 감소되었다. 청대 및 닥나무 추출물을 투여한 마우스 (실험군 2-4) 체중은 89.25±3.77 %, 청대 및 가래나무 추출물을 투여한 마우스 (실험군 2-5) 체중은 93.62±3.09 %, 청대, 닥나무 및 가래나무 추출물을 투여한 마우스 (실험군 2-6) 체중은 95.89±1.53 %로 측정되었다.As confirmed in FIG. 2 , the body weight of the normal group mice was 104.79±1.36%, and the body weight of the negative control mice was 91.16±1.63%, which was significantly reduced compared to the normal group. Mice administered with blueberry and mulberry extract (experimental group 2-4) had a body weight of 89.25±3.77%, and mice administered with blueberry and mulberry extract (experimental group 2-5) weighed 93.62±3.09%, with blueberry, mulberry and mulberry extract The body weight of mice administered with (experimental group 2-6) was measured to be 95.89±1.53%.
상기 결과로부터, 청대 및 닥나무 추출물, 청대 및 가래나무 추출물, 청대, 닥나무 및 가래나무 추출물은 모두 마우스 몸무게 감소 억제 효과를 보이며, 특히 청대, 닥나무 및 가래나무 추출물에서 가장 우수한 몸무게 감소 억제 효과를 나타내는 것을 알 수 있었다.From the above results, it was found that cheongdae and mulberry extracts, chungdae and mulberry extracts, chungdae, mulberry and mulberry extracts all showed the effect of inhibiting weight loss in mice, and in particular, the extracts from cheongdae, mulberry and phlegm showed the best weight loss inhibitory effect. Could know.
[실험예 3][Experimental Example 3]
마우스 대장 길이 측정 (1)Mouse colon length measurement (1)
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 길이를 측정하여 평균 길이를 도 3에 나타냈다. It is known that there is a sufficient correlation between the small intestine and histologic changes, and the length of the large intestine is commonly 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 the length of the large intestine was measured and the average length is shown in FIG. 3 .
도 3에서 확인되는 바와 같이, 정상군의 대장 길이는 6.66±0.22 cm이고, 음성 대조군은 4.17±0.19 cm로 정상군과 비교하여 대장의 길이가 감소하였다. 양성 대조군의 대장 길이는 4.41±0.16 cm, 청대 추출물만 투여한 마우스 (실험군 1-1)의 대장 길이는 4.25±0.25 cm, 청대 및 닥나무 추출물을 투여한 마우스 (실험군 1-2)의 대장 길이는 4.83±0.17cm으로 측정되었다. 3 , the colon length of the normal group was 6.66±0.22 cm, and the negative control group was 4.17±0.19 cm, which decreased compared to the normal group. The colon length of the positive control group was 4.41±0.16 cm, the colon length of mice administered only cheongdae extract (experimental group 1-1) was 4.25±0.25 cm, and the colon length of mice administered with cheongdae and mulberry extracts (experimental group 1-2) was It was measured to be 4.83±0.17 cm.
상기 결과로부터, 청대 단독 추출물에 비하여, 청대 및 닥나무 추출물을 투여한 경우 대장 길이가 유의하게 길어졌으며, 이는 양성 대조군보다 더욱 우수한 수준임을 알 수 있었다. From the above results, compared to the extract of cheongdae alone, when the extract of cheongdae and mulberry was administered, the length of the large intestine was significantly increased, which was found to be superior to that of the positive control group.
[실험예 4][Experimental Example 4]
마우스 대장 길이 측정 (2)Mouse colon length measurement (2)
실시예 2의 마우스에 대하여, 실험예 3과 동일한 방법으로 대장 길이를 측정하고, 그 결과를 도 4에 나타냈다.For the mouse of Example 2, the colon length was measured in the same manner as in Experimental Example 3, and the results are shown in FIG. 4 .
도 4에서 확인되는 바와 같이, 정상군의 대장 길이는 7.56±0.18 cm이고, 음성 대조군은 5.66±0.15 cm로 정상군과 비교하여 대장의 길이가 감소하였다. 청대 및 닥나무 추출물을 투여한 마우스 (실험군 2-4) 대장 길이는 5.97±0.23 cm, 청대 및 가래나무 추출물을 투여한 마우스 (실험군 2-5) 대장 길이는 5.76±0.19 cm, 청대, 닥나무 및 가래나무 추출물을 투여한 마우스 (실험군 2-6) 대장 길이는 6.23±0.22 cm로 측정되었다.As can be seen in FIG. 4 , the colon length of the normal group was 7.56±0.18 cm, and the negative control group was 5.66±0.15 cm, which decreased compared to the normal group. Mice administered with blueberry and mulberry extract (Experimental group 2-4) had a colon length of 5.97±0.23 cm, and mice administered with blueberry and mulberry extracts (Experimental group 2-5) had a colon length of 5.76±0.19 cm, with blueberry, mulberry and phlegm. The length of the large intestine of mice administered the tree extract (experimental group 2-6) was measured to be 6.23±0.22 cm.
상기 결과로부터, 청대 및 닥나무 추출물, 청대 및 가래나무 추출물, 청대, 닥나무 및 가래나무 추출물은 모두 마우스 대장 길이 감소 억제 효과를 보이며, 특히 청대, 닥나무 및 가래나무 추출물에서 가장 우수한 대장 길이 감소 억제 효과를 나타내는 것을 알 수 있었다.From the above results, cheongdae and mulberry extract, cheongdae and mulberry extract, cheongdae, mulberry, and phlegm extract all showed an inhibitory effect on the decrease in colon length in mice, and in particular, extracts from cheongdae, mulberry and phlegm showed the most excellent effect of inhibiting the decrease in colon length. could be seen to indicate
[실험예 5][Experimental Example 5]
마우스 대장 무게 측정Weighing the mouse colon
대장의 길이와 마찬가지로, 대장의 무게 또한 통상적으로 염증 정도의 형태학적 매개 변수로서 이용된다. 실시예 2의 마우스를 각 투여 마지막 날 희생시키고, 대장의 무게를 측정하여 평균 길이를 도 5에 나타냈다.As with the length of the large intestine, the weight of the large intestine is also commonly used as a morphological parameter of the degree of inflammation. The mice of Example 2 were sacrificed on the last day of each administration, and the weight of the large intestine was measured and the average length is shown in FIG. 5 .
도 5에서 확인되는 바와 같이, 정상군의 대장 무게는 0.88±0.01 g이고, 음성 대조군은 0.59±0.03 g로 정상군과 비교하여 대장의 무게가 감소하였다. 청대 및 닥나무 추출물을 투여한 마우스 (실험군 2-4) 대장 무게는 0.65±0.06 g, 청대 및 가래나무 추출물을 투여한 마우스 (실험군 2-5) 대장 무게는 0.69±0.05 g, 청대, 닥나무 및 가래나무 추출물을 투여한 마우스 (실험군 2-6) 대장 무게는 0.71±0.05g로 측정되었다.As can be seen in FIG. 5 , the colon weight of the normal group was 0.88±0.01 g, and the negative control group was 0.59±0.03 g, which decreased compared to the normal group. Mice administered with blueberry and mulberry extract (experimental group 2-4) had a large intestine weight of 0.65±0.06 g, and mice administered with blueberry and mulberry extract (experimental group 2-5) with a large intestine weight of 0.69±0.05 g, blueberry, mulberry and phlegm. The weight of the large intestine of mice administered the tree extract (experimental groups 2-6) was measured to be 0.71±0.05 g.
상기 결과로부터, 청대 및 닥나무 추출물, 청대 및 가래나무 추출물, 청대, 닥나무 및 가래나무 추출물은 모두 마우스 대장 무게 감소 억제 효과를 보이며, 특히 청대, 닥나무 및 가래나무 추출물에서 가장 우수한 대장 무게 감소 억제 효과를 나타내는 것을 알 수 있었다.From the above results, cheongdae and mulberry extract, chungdae and mulberry extract, cheongdae, mulberry and phlegm extract all showed the effect of inhibiting the weight loss of the mouse large intestine, and in particular, the most excellent effect of inhibiting the weight loss of the large intestine in the extract of cheongdae, mulberry and phlegm. could be seen to indicate
[실험예 6] [Experimental Example 6]
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 DSS처리후 유도된 IBD 모델에서 비장이 비대해지는 것으로 알려져 있다 (Biol. Pharm. Bull. 43, 450-457 (2020)).A typical symptom that can occur in relation to inflammatory bowel disease is splenitis. When the spleen becomes inflamed, the size of the spleen becomes enlarged due to its nature (Nutrients 2019, 11(11), 2776), and in fact, It is known that the spleen is enlarged in the IBD model (Biol. Pharm. Bull. 43, 450-457 (2020)).
실시예 2의 마우스를 각 투여 마지막날 희생시킨 후 DDS를 처리한 음성대조군 대비 각 그룹의 비장 무게 및 길이를 비장율 (spleen ratio)로 나타냈다. 도 6에서 확인되는 바와 같이, 정상군에 비하여 음성 대조군의 비장 무게 및 크기가 증가되었다. 청대 (실험군 2-1), 닥나무 (실험군 2-2), 가래나무 (실험군 2-3) 각 단일 추출물 투여군은 음성 대조군에 비하여 비장 무게 및 길이가 감소되었으며, 특히 청대, 닥나무 및 가래나무 추출물 (실험군 2-6) 투여군은 정상군과 유사한 수준으로 비장 무게 및 길이가 감소하여 비장염으로 인하여 비장이 비대해지는 증상이 개선된 것을 알 수 있었다.After sacrificing the mice of Example 2 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 the spleen ratio. As can be seen in FIG. 6 , the spleen weight and size of the negative control group were increased compared to the normal group. Each single extract administration group (Experimental group 2-1), mulberry tree (Experimental group 2-2), and mulberry tree (experimental group 2-3) decreased the weight and length of the spleen compared to the negative control group. The experimental group 2-6) administration group decreased the weight and length of the spleen to a level similar to that of the normal group, and it was found that the symptoms of enlarged spleen due to splenitis were improved.
[실험예 7][Experimental Example 7]
질병활성도 (Disease Activity Index, DAI) 평가 (1)Disease Activity Index (DAI) evaluation (1)
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 inflammatory bowel disease animal model treated with the administration method of Example 1, weight change, stool hardness, and the presence or absence of bloody stool visually observed in the stool or anus were evaluated for the disease activity (DAI) in Table 1. ) according to the grade, the disease activity was measured by checking every day during the administration period.
질병활성도 수치 (Disease Activity Index score)Disease Activity Index score
체중감소weight loss 점수score 변의 형태shape of stool 점수score 혈변bloody stool 점수score
<1%<1% 00 딱딱하고 단단함hard and hard 00 없음doesn't exist 00
1-5%1-5% 1One 단단하나 끈적함hard but sticky 1One 숨겨짐hidden 1One
5-10%5-10% 22 부드러우나 형태 유지Soft but retains shape 22 눈에 보이는visible 22
10-15%10-15% 33 부드러우면서 형태 손실Soft and loses shape 33 직장 출혈rectal bleeding 33
15-20%15-20% 44 액체로서 형태가 없음Liquid, no form 44 -- --
도 7a 및 도 7b에 나타낸 바와 같이, DSS를 투여한 음성 대조군에서 질병활성도가 크게 증가하였다. 또한, 청대 단독 추출물 투여군 (실험군 1-1)에 비하여, 청대 및 닥나무 추출물 투여군 (실험군 1-2)과 청대 및 가래나무 추출물 투여군 (실험군 1-3)에서 질병활성도가 더욱 개선되는 것이 확인되었으며, 이는 양성 대조군보다 우수한 수준임을 알 수 있었다. 7A and 7B, disease activity was significantly increased in the negative control group administered with DSS. In addition, it was confirmed that disease activity was further improved in the group administered with cheongdae and mulberry extract (experimental group 1-2) and the group administered with chrysanthemum and mulberry extract (experimental group 1-3), compared to the group administered with the single extract of cheongdae (experimental group 1-1), This was found to be superior to that of the positive control group.
[실험예 8][Experimental Example 8]
질병활성도 (Disease Activity Index, DAI) 평가 (2)Disease Activity Index (DAI) evaluation (2)
실시예 2의 마우스에 대하여, 실험예 7과 동일한 방법으로 질병 활성도를 측정하고, 그 결과를 도 8에 나타냈다.For the mice of Example 2, disease activity was measured in the same manner as in Experimental Example 7, and the results are shown in FIG. 8 .
도 8에서 확인되는 바와 같이, DSS를 투여한 음성 대조군에서 질병활성도가 크게 증가하였다. 또한 청대 (실험군 2-1), 닥나무 (실험군 2-2), 가래나무 (실험군 2-3) 각 단일 추출물 투여군에 비하여 청대, 닥나무 및 가래나무 추출물 (실험군 2-6) 투여군에서 특히 우수한 질병활성도의 개선이 확인되었다.As can be seen in FIG. 8 , disease activity was significantly increased in the negative control group administered with DSS. In addition, especially superior disease activity in the group administered with extracts of chrysanthemum, mulberry and mulberry extract (experimental group 2-6) compared to each single extract administration group (experimental group 2-1), mulberry tree (experimental group 2-2), and mulberry tree (experimental group 2-3). improvement was confirmed.

Claims (15)

  1. (1) 청대; 및(1) Qing Dynasty; and
    (2) 닥나무 및 가래나무로 이루어진 군에서 선택된 하나 이상(2) at least one selected from the group consisting of mulberry and mulberry trees
    의 생약 추출물을 포함하는, 염증성 장질환의 예방 또는 치료용 약학 조성물.A pharmaceutical composition for preventing or treating inflammatory bowel disease, comprising a herbal extract of.
  2. 제1항에 있어서, 상기 생약 추출물은 각각의 생약으로부터 추출된 추출물의 혼합물이거나, 생약의 혼합물로부터 추출된 것을 특징으로 하는, 염증성 장질환의 예방 또는 치료용 약학 조성물.The pharmaceutical composition for preventing or treating inflammatory bowel disease according to claim 1, wherein the herbal extract is a mixture of extracts extracted from each herbal medicine or extracted from a mixture of herbal medicines.
  3. 제1항에 있어서, 상기 닥나무 추출물은 닥나무 잎 추출물인 것을 특징으로 하는, 염증성 장질환의 예방 또는 치료용 약학 조성물.The pharmaceutical composition for preventing or treating inflammatory bowel disease according to claim 1, wherein the mulberry extract is a mulberry leaf extract.
  4. 제1항에 있어서, 상기 가래나무 추출물은 가래나무 열매 추출물인 것을 특징으로 하는, 염증성 장질환의 예방 또는 치료용 약학 조성물.[Claim 2] The pharmaceutical composition for preventing or treating inflammatory bowel disease according to claim 1, wherein the extract of the sputum tree is an extract of the sputum tree fruit.
  5. 제1항에 있어서, 상기 생약 추출물은 물, C1 내지 C6의 알코올, 아세트산, 및 이들의 혼합 용매로 이루어지는 군으로부터 선택되는 용매로 추출된 것을 특징으로 하는, 염증성 장질환의 예방 또는 치료용 약학 조성물.The pharmaceutical composition for preventing or treating inflammatory bowel disease according to claim 1, wherein the herbal extract is extracted with a solvent selected from the group consisting of water, C1 to C6 alcohol, acetic acid, and a mixed solvent thereof. .
  6. 제1항에 있어서, 상기 생약 추출물은 0.01% 내지 90% 에탄올 추출물인 것을 특징으로 하는, 염증성 장질환의 예방 또는 치료용 약학 조성물.The pharmaceutical composition for preventing or treating inflammatory bowel disease according to claim 1, wherein the herbal extract is 0.01% to 90% ethanol extract.
  7. 제1항에 있어서, 상기 생약 추출물은 60% 내지 80% 에탄올 추출물인 것을 특징으로 하는, 염증성 장질환의 예방 또는 치료용 약학 조성물.The pharmaceutical composition for preventing or treating inflammatory bowel disease according to claim 1, wherein the herbal extract is a 60% to 80% ethanol extract.
  8. 제1항에 있어서, 상기 약학 조성물은 청대, 닥나무 및 가래나무의 생약 추출물을 포함하는 것을 특징으로 하는, 염증성 장질환의 예방 또는 치료용 약학 조성물.The pharmaceutical composition for the prevention or treatment of inflammatory bowel disease according to claim 1, wherein the pharmaceutical composition comprises herbal extracts of chrysanthemum, mulberry, and mulberry.
  9. 제8항에 있어서, 청대, 닥나무 및 가래나무의 배합 중량비는 1 : 0.1 내지 10 : 0.1 내지 10인 것을 특징으로 하는, 염증성 장질환의 예방 또는 치료용 약학 조성물.[Claim 9] The pharmaceutical composition for preventing or treating inflammatory bowel disease according to claim 8, wherein the blending weight ratio of chrysanthemum, mulberry and mulberry is 1: 0.1 to 10: 0.1 to 10.
  10. 제8항에 있어서, 청대, 닥나무 및 가래나무의 배합 중량비는 1 : 0.5 내지 2 : 0.5 내지 2인 것을 특징으로 하는, 염증성 장질환의 예방 또는 치료용 약학 조성물.[Claim 9] The pharmaceutical composition for preventing or treating inflammatory bowel disease according to claim 8, wherein the blending weight ratio of cheongdae, mulberry, and mulberry is 1: 0.5 to 2: 0.5 to 2.
  11. 제8항에 있어서, 청대, 닥나무 및 가래나무의 배합 중량비는 1 : 1 : 1인 것을 특징으로 하는, 염증성 장질환의 예방 또는 치료용 약학 조성물.[Claim 9] The pharmaceutical composition for preventing or treating inflammatory bowel disease according to claim 8, wherein the blending weight ratio of cheongdae, mulberry and mulberry is 1: 1: 1.
  12. 제1항에 있어서, 상기 약학 조성물은 대장의 길이 또는 무게를 감소시키는 것을 특징으로 하는, 염증성 장질환의 예방 또는 치료용 약학 조성물.The pharmaceutical composition for preventing or treating inflammatory bowel disease according to claim 1, wherein the pharmaceutical composition reduces the length or weight of the large intestine.
  13. 제1항에 있어서, 상기 약학 조성물은 비장의 길이 또는 무게를 감소시키는 것을 특징으로 하는, 염증성 장질환의 예방 또는 치료용 약학 조성물.The pharmaceutical composition for preventing or treating inflammatory bowel disease according to claim 1, wherein the pharmaceutical composition reduces the length or weight of the spleen.
  14. (1) 청대; 및(1) Qing Dynasty; and
    (2) 닥나무 및 가래나무로 이루어진 군에서 선택된 하나 이상(2) at least one selected from the group consisting of mulberry and mulberry trees
    의 생약 추출물을 포함하는, 염증성 장질환의 예방 또는 개선용 식품 조성물.A food composition for preventing or improving inflammatory bowel disease, comprising a herbal extract of
  15. (1) 청대; 및(1) Qing Dynasty; and
    (2) 닥나무 및 가래나무로 이루어진 군에서 선택된 하나 이상(2) at least one selected from the group consisting of mulberry and mulberry trees
    의 생약 추출물을 포함하는, 염증성 장질환의 예방 또는 개선용 사료 조성물.A feed composition for preventing or improving inflammatory bowel disease, comprising a herbal extract of
PCT/KR2020/014025 2020-10-14 2020-10-14 Composition comprising a mixture of medicinal herbal extracts from indigo pulverata levis, broussonetia kazinoki, and juglans mandshurica for preventing or treating inflammatory bowel disease WO2022080523A1 (en)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060003026A1 (en) * 2002-03-08 2006-01-05 Bihui Wang Chinese preparation for treating enteritis ulcer colitis and preparation method thereof
KR20110078941A (en) * 2009-12-31 2011-07-07 한림대학교 산학협력단 Composition comprising pgg as speicial component of juglans mandshurica for the preventing inflammation-related-molecules induced skin inflammatory diseases
JP2011173857A (en) * 2010-02-26 2011-09-08 Chunyang Paper Co Ltd Immune function-enhancing composition containing paper mulberry extract
KR20160025524A (en) * 2013-06-26 2016-03-08 타슬리 파마슈티컬 그룹 컴퍼니 리미티드 Use of chinese medicine preparation in preparing drug for preventing and/or treating crohn's disease
KR20170128766A (en) * 2017-11-10 2017-11-23 (주)아모레퍼시픽 Cosmetic Composition Containing Broussonetia Extract for Inhibiting Lipogenesis and Decreasing Sebum Secretion of Skin
KR20180071987A (en) * 2016-12-20 2018-06-28 서울대학교병원 Pharmaceutical composition comprising an extract of Indigo Pulverata Levis or fractions thereof for prevention or treatment of inflammatory bowel disease

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060003026A1 (en) * 2002-03-08 2006-01-05 Bihui Wang Chinese preparation for treating enteritis ulcer colitis and preparation method thereof
KR20110078941A (en) * 2009-12-31 2011-07-07 한림대학교 산학협력단 Composition comprising pgg as speicial component of juglans mandshurica for the preventing inflammation-related-molecules induced skin inflammatory diseases
JP2011173857A (en) * 2010-02-26 2011-09-08 Chunyang Paper Co Ltd Immune function-enhancing composition containing paper mulberry extract
KR20160025524A (en) * 2013-06-26 2016-03-08 타슬리 파마슈티컬 그룹 컴퍼니 리미티드 Use of chinese medicine preparation in preparing drug for preventing and/or treating crohn's disease
KR20180071987A (en) * 2016-12-20 2018-06-28 서울대학교병원 Pharmaceutical composition comprising an extract of Indigo Pulverata Levis or fractions thereof for prevention or treatment of inflammatory bowel disease
KR20170128766A (en) * 2017-11-10 2017-11-23 (주)아모레퍼시픽 Cosmetic Composition Containing Broussonetia Extract for Inhibiting Lipogenesis and Decreasing Sebum Secretion of Skin

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