KR101355821B1 - A Composition comprising an extract of Curdrania tricuspidata Bureau for preventing and treating alcoholic gatro-intestinal disease - Google Patents
A Composition comprising an extract of Curdrania tricuspidata Bureau for preventing and treating alcoholic gatro-intestinal disease Download PDFInfo
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- KR101355821B1 KR101355821B1 KR1020110101194A KR20110101194A KR101355821B1 KR 101355821 B1 KR101355821 B1 KR 101355821B1 KR 1020110101194 A KR1020110101194 A KR 1020110101194A KR 20110101194 A KR20110101194 A KR 20110101194A KR 101355821 B1 KR101355821 B1 KR 101355821B1
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- extract
- curdrania
- composition
- gastric
- bureau
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- 229960003495 thiamine Drugs 0.000 description 1
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 1
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
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Classifications
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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
- A61K36/605—Morus (mulberry)
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/32—Alcohol-abuse
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/334—Foods, ingredients or supplements having a functional effect on health treating the effects of consuming alcohol, narcotics or other addictive behavior, e.g. treating hangover or reducing blood alcohol levels
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2250/00—Food ingredients
- A23V2250/20—Natural extracts
- A23V2250/21—Plant extracts
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/10—Preparation or pretreatment of starting material
- A61K2236/15—Preparation or pretreatment of starting material involving mechanical treatment, e.g. chopping up, cutting or grinding
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/37—Extraction at elevated pressure or temperature, e.g. pressurized solvent extraction [PSE], supercritical carbon dioxide extraction or subcritical water extraction
Abstract
본 발명은 꾸지뽕나무(Curdrania tricuspidata Bureau) 추출물을 유효성분으로 함유하는 알콜성 위장관질환의 예방 및 치료를 위한 조성물 및 건강기능식품에 관한 것으로, 상세하게는 본 발명의 추출물이 알콜로 유도된 위 손상에서 염증 및 위액분비관련 유전자 발현를 억제하고 위보호물질인 뮤신(mucin) 합성을 증가시킴을 확인하여 알콜성 위장관질환의 예방 및 치료를 위한 조성물 및 건강기능식품으로 유용하게 이용할 수 있다.The present invention relates to a composition and health functional food for the prevention and treatment of alcoholic gastrointestinal diseases containing Cudrania tricuspidata Bureau extract as an active ingredient, in detail, the extract of the present invention is alcohol-induced gastric damage Inhibits inflammation and gastric secretion-related gene expression and increases the synthesis of mucin (mucin), a gastroprotective agent can be useful as a composition and health functional food for the prevention and treatment of alcoholic gastrointestinal diseases.
Description
본 발명은 꾸지뽕나무 추출물을 유효성분으로 함유하는 알콜성 위장관질환의 예방 및 치료를 위한 조성물 및 건강기능식품에 관한 것이다.
The present invention relates to a composition and a health functional food for the prevention and treatment of alcoholic gastrointestinal diseases, which contains Cucumber extract as an active ingredient.
[문헌 1] Lawrence et al., Anti-inflammatory lipid mediators and insights into the resolution of inflammation, Nat. Rev. Immunol., (2002) 2: pp.787-795; Lawrence et al., Anti-inflammatory lipid mediators and insights into the resolution of inflammation, Nat. Rev. Immunol., (2002) 2 : pp. 787-795;
[문헌 2] 박성철 등, LPS로 활성화된 RAW 264.7 대식세포에서 애기땅빈대의 염증매개물질 억제효과, 한국식품영양과학회지, (2011) 40: pp.486-492.[2] Park, Seong-Cheol et al., LPS-activated RAW 264.7 macrophages inhibit the inflammatory mediators of Arabidopsis, Korean Journal of Food Science and Nutrition, (2011) 40 : pp.486-492.
[문헌 3] Ohshima 등, Prevention of human cancer by modulation of chronicinflammatory processes, Mutat. Res., (2005) 591: pp.110-122[3] Ohshima et al., Prevention of human cancer by modulation of chronic inflammatory processes, Mutat. Res., (2005) 591 : pp. 110-122
[문헌 4] Siurala 등, Chronic gastritis: dynamic and clinical aspects, Scand. J. Gastroenterol. Suppl., (1985) 109: pp.69-76[4] Siurala et al., Chronic gastritis: dynamic and clinical aspects, Scand. J. Gastroenterol. Suppl., (1985) 109 : pp. 69-76
[문헌 5] Dixon, Helicobacter pylori and peptic ulceration: histopathological aspects, J. Gastroenterol. Hepatol., (1991) 6: pp.125-130Dixon, Helicobacter pylori and peptic ulceration: histopathological aspects, J. Gastroenterol. Hepatol., (1991) 6 : pp. 125-130
[문헌 6] El-Zimaity, Recent advances in histopathology of gastritis, Curr. Diagn. Pathol., (2007) 13: pp.340-348El-Zimaity, Recent advances in histopathology of gastritis, Curr. Diagn. Pathol., (2007) 13 : pp. 340-348
[문헌 7] 오은상, 한두석, 팔선주와 알콜의 계속적인 투여가 흰쥐 위점막에 미치는 형태학적 영향, 원광치의학, (2003) 12: pp.421-435[Essay 7] Oh, Sang Doo, Doo Seok Han, Palist Wine and Morphological Effects on Alcoholic Mucosa of Rats, Wonkwang Dentistry, (2003) 12 : pp.421-435
[문헌 8] Iaquinto 등, Role of endogenous endothelin 1 in ethanol-induced gastric mucosal damage in humans, Dig. Dis. Sci. (2003) 48: pp.663-6698 Iaquinto et al., Role of endogenous endothelin 1 in ethanol-induced gastric mucosal damage in humans, Dig. Dis. Sci. (2003) 48 : pp. 663-669
[문헌 9] Rovert 등, Cytoprotection by prostaglandins in rats. Prevention of gastric necrosis produced by alchol, HCl, NaOH, hypertonic NaCl and thermal injury, Gastroenterology (1979) 77: pp.433-443Rovert et al., Cytoprotection by prostaglandins in rats. Prevention of gastric necrosis produced by alchol, HCl, NaOH, hypertonic NaCl and thermal injury, Gastroenterology (1979) 77 : pp.433-443
[문헌 10] Hagel 등, Gastric mucosal cell loss caused by aspirin and alcohol, Hepatogastroenterology, (1987) 34: pp.262-264[10] Hagel et al., Gastric mucosal cell loss caused by aspirin and alcohol, Hepatogastroenterology, (1987) 34 : pp. 262-264
[문헌 11] 박경아 등, 조직학, 고려의학, (1992) pp.393-395[Document 11] Kyung-A Park et al., Histology, Korea Medicine, (1992) pp.393-395
[문헌 12] 오은상, 한두석, 팔선주와 알콜의 계속적인 투여가 흰쥐 위점막에 미치는 형태학적 영향, 원광치의학, (2003) 12: pp.421-435[Essay 12] Oh, Sang Doo, Han, Doo-Suk, Palist, and Morphological Effects of Continuous Administration of Alcohol on Rat Gastric Mucosa, Wonkwang Dentistry, (2003) 12 : pp.421-435
[문헌 13] 정보섭외, 향약대사전, 영림사, (1998) pp.544-545
[Reference 13] Information Interpretation, Hyangjeomsa Dictionary, Younglimsa, (1998) pp.544-545
염증(inflammation)은 외부자극에 대한 체내의 방어기전으로 유해물질이나 화학적 자극에 의한 손상으로 일어난다. 염증반응이 일어나면 염증매개 인자들이 만들어지고 이로 인해 발적, 발열, 종창, 동통, 기능장애 등의 증상이 나타나게 된다(Lawrence 등, Anti-inflammatory lipid mediators and insights into the resolution of inflammation, Nat Rev Immunol (2002) 2: 787-795; 박성철 등, LPS로 활성화된 RAW 264.7 대식세포에서 애기땅빈대의 염증매개물질 억제효과, 한국식품영양과학회지, (2011) 40: 486-492). 염증반응으로부터 발생된 활성산소종은 산화적 스트레스성 전사인자들인 nuclear factor kappa-b(NF-κB)를 활성시킬 수 있을 뿐만 아니라 중요한 신호 전달자인 inducible nitric oxide synthase(iNOS)와 염증성 유도효소인 cyclooxygenase(COX-2)를 활성화시킴으로써 염증반응을 촉진시키고, 비정상적인 변이와 암을 유발하게 된다고 한다(Ohshima 등, Prevention of human cancer by modulation of chronicinflammatory processes, Mutat Res, (2005) 591: 110-122). Inflammation is a defense mechanism in the body against external stimuli that results from damage caused by harmful substances or chemical stimuli. When an inflammatory reaction occurs, inflammatory mediators are produced, causing symptoms such as redness, fever, swelling, pain, and dysfunction (Lawrence et al., Anti-inflammatory lipid mediators and insights into the resolution of inflammation, Nat Rev Immunol (2002). 2: 2: 787-795; Park, Seong-Cheol et al., LPS-activated RAW 264.7 macrophages inhibit the inflammatory mediators of Arabidopsis, Korean Journal of Food Science and Nutrition, (2011) 40: 486-492). Oxygen species from the inflammatory response not only activate nuclear factor kappa-b (NF-κB), which is an oxidative stressor, but also inducible nitric oxide synthase (iNOS), an important signal transmitter, and cyclooxygenase, an inflammatory inducer. Activating (COX-2) promotes the inflammatory response and leads to abnormal mutations and cancer (Ohshima et al., Prevention of human cancer by modulation of chronic inflammatory processes, Mutat Res, (2005) 591: 110-122).
특히 위염은 위점막의 염증성 질환을 총칭하는 것으로 원인으로는 Helicobacter pylori균 감염, NSAID (non-steroid anti-inflammatory drugs), 스트레스, 알콜 등이 알려져 있다(Siurala 등, Chronic gastritis: dynamic and clinical aspects, Scand J Gastroenterol Suppl, (1985) 109: 69-76; Dixon, Helicobacter pylori and peptic ulceration: histopathological aspects, J Gastroenterol Hepatol, (1991) 6: 125-130; El-Zimaity, Recent advances in histopathology of gastritis, Curr Diagn Pathol, (2007) 13: 340-348). In particular, gastritis is a generic term for inflammatory diseases of the gastric mucosa. Helicobacter pylori infection, NSAID (non-steroid anti-inflammatory drugs), stress, alcohol and the like are known (Siurala et al., Chronic gastritis: dynamic and clinical aspects, Scand J Gastroenterol Suppl, (1985) 109: 69-76; Dixon, Helicobacter pylori and peptic ulceration: histopathological aspects, J Gastroenterol Hepatol, (1991) 6: 125-130; El-Zimaity, Recent advances in histopathology of gastritis, Curr Diagn Pathol, (2007) 13: 340-348).
알콜 섭취는 위점막의 파괴인자로 작용하며, 위점막을 보호하는 점액, 혈류촉진 인자인 nitric oxide (NO)와 프로스타글란딘 등의 방어인자와 위점막을 손상시키는 위산, 펩신 등의 공격인자 사이의 균형을 깨뜨려 위염 및 궤양을 유발하는데, 알콜 섭취로 발생하는 위장관질환은 급성 점막손상 및 위궤양 발생과 만성 위염의 형태로 나누어 볼 수 있다. 알콜성 위염은 위점막 보호물질의 감소, 산소라디칼의 증가, mast cell의 histamine 분비 등에 의해 위점막이 손상되어 염증이 악화되는 질병으로, 정확한 분자 생물학적 메커니즘의 규명은 밝혀지지 않았다. (오은상, 한두석, 팔선주와 알콜의 계속적인 투여가 흰쥐 위점막에 미치는 형태학적 영향, 원광치의학, (2003) 12: 421-435; Iaquinto 등, Role of endogenous endothelin 1 in ethanol-induced gastric mucosal damage in humans, Dig Dis Sci (2003) 48: 663-669) Alcohol consumption acts as a destructive factor of the gastric mucosa, and balances the mucus that protects the gastric mucosa, the defense factors such as nitric oxide (NO) and prostaglandin, and the attackers such as gastric acid and pepsin, which damage the gastric mucosa. It causes gastritis and ulcers by breaking the stomach, and gastrointestinal diseases caused by alcohol consumption can be divided into acute mucosal injury and gastric ulcer development and chronic gastritis. Alcoholic gastritis is a disease in which inflammation of the gastric mucosa is exacerbated by a decrease in gastric mucosa protective agents, an increase in oxygen radicals, and histamine secretion in mast cells. The exact molecular biological mechanisms have not been identified. (Oh Sang, Han Doo Seok, Palist Wine and Morphological Effects of Alcohol Administration on Rat Gastric Mucosa, Wonkwang Dentistry, (2003) 12: 421-435; Iaquinto et al., Role of endogenous endothelin 1 in ethanol-induced gastric mucosal damage in humans, Dig Dis Sci (2003) 48: 663-669)
위의 표면을 덮고 있는 상피세포는 점액을 분비하는데 이 점액은 두꺼운 겔 상태의 점액층을 형성하여 강산(strong acid)이나 약물로부터 위점막을 보호한다. 또한 세포표면에서는 윤활작용을 하는 다른 점액도 분비되는데 이들 점액은 내부 파괴인자인 소화과정 중에 일어나는 기계적 자극, 염산, 펩신으로부터 위점막을 보호하며 외부로부터 오는 NaOH, 소금 및 알콜 등으로부터 위점액을 보호하기도 한다. 따라서 위점막과 점막밑조직의 결손에 의한 궤양은 주로 1차 보호장벽인 점액분비 손상에서 기인한다(Rovert 등, Cytoprotection by prostaglandins in rats. Prevention of gastric necrosis produced by alchol, HCl, NaOH, hypertonic NaCl and thermal injury, Gastroenterology (1979) 77: 433-443; Hagel 등, Gastric mucosal cell loss caused by aspirin and alcohol. Hepatogastroenterology, (1987) 34: 262-264; 박경아 등, 조직학, 고려의학, (1992) p393-395; 오은상, 한두석, 팔선주와 알콜의 계속적인 투여가 흰쥐 위점막에 미치는 형태학적 영향, 원광치의학, (2003) 12: 421-435). Epithelial cells covering the surface of the stomach secrete mucus, which forms a thick, gel-like layer of mucus that protects the gastric mucosa from strong acids or drugs. In addition, other lubricating mucus is secreted from the cell surface, which protects the gastric mucosa from mechanical irritation, hydrochloric acid and pepsin, which occur during digestion, an internal destruction factor, and gastric mucus from NaOH, salt and alcohol from the outside. Sometimes. Thus, ulcers caused by defects in the gastric mucosa and submucosa are mainly due to the secretion of mucus secretion, the primary protective barrier (Rovert et al., Cytoprotection by prostaglandins in rats.Prevention of gastric necrosis produced by alchol, HCl, NaOH, hypertonic NaCl and thermal injury, Gastroenterology (1979) 77: 433-443; Hagel et al., Gastric mucosal cell loss caused by aspirin and alcohol.Hepatogastroenterology, (1987) 34: 262-264; Park Kyung-ah et al., Histology, Korean Medicine, (1992) p393- 395; Eun Sang Oh, Doo Seok Han, Palangeum and Morphological Effects of Continuous Administration of Alcohol on Rat Gastric Mucosa, Wonkwang Dentistry, (2003) 12: 421-435).
꾸지뽕나무(Curdrania tricuspidata Bureau)는 뽕나무과(Molaceae)에 속하는 낙엽활엽 소교목으로 한국 등의 동아시아에 주로 분포하며 10여종이 알려져 있는데 우리나라에서는 1종만이 자생하고 있으며, 근경에는 모린(morin), 포퓨닌(populnin), 스타키드린(stachydrine), 카엠페롤(kaempferol)-7-글루코시드(glucoside) 등의 성분이 함유된 것으로 알려져 있다. (정보섭외, 향약대사전, 영림사, 1998년, pp544-545)Kkujippong trees (Curdrania tricuspidata Bureau is a deciduous broad-leaved small arborescent belonging to Molaceae, distributed mainly in East Asia such as Korea, and 10 species are known. Only one species grows in Korea, and morin, populnin, and stark are in the root of root. It is known to contain components such as stachydrine and kaempferol-7-glucoside. (Information Counseling, Hyangjeomsa Dictionary, Younglimsa, 1998, pp544-545)
그러나 상기문헌의 어디에도 꾸지뽕나무 추출물의 알콜성 위염억제 효과에 관한 연구는 보고된 바 없다. However, none of the above documents has been reported on the inhibitory effect of alcoholic gastritis of Cudrania japonica extract.
이에 본 연구에서는 알콜로 유도된 위 손상에서 꾸지뽕나무의 각 부위별, 용매별 추출물의 염증관련 유전자 발현과 위액분비관련 유전자 발현을 측정한 결과, 알콜로 유도된 위 손상에서 염증 및 위액분비관련 유전자 발현를 억제하고 위보호물질인 뮤신(mucin) 합성을 증가시킴을 확인함으로써 알콜성 위장관질환의 예방 및 치료를 위한 조성물 및 건강기능식품으로 유용하게 이용할 수 있음을 확인하여 본 발명을 완성하였다. In this study, we measured the inflammation-related gene expression and gastric secretion-related gene expression of alcohol-induced gastric injuries in each region and solvent. The present invention was completed by confirming that it inhibits expression and increases mucin (mucin) synthesis, which is a gastric protective substance, and can be usefully used as a composition and health functional food for the prevention and treatment of alcoholic gastrointestinal diseases.
상기 목적에 따라, 본 발명은 꾸지뽕나무(Curdrania tricuspidata Bureau) 추출물을 유효성분으로 함유하는 알콜성 위장관질환의 예방 및 치료를 위한 약학조성물을 제공한다.According to the above object, the present invention Cudrania ( Curdrania) It provides a pharmaceutical composition for the prevention and treatment of alcoholic gastrointestinal diseases containing tricuspidata Bureau extract as an active ingredient.
본원에서 정의되는 꾸지뽕나무 추출물은 바람직하게는 국내산, 보다 바람직하게는 강원도 지역에서 재배된 꾸지뽕나무의 잎, 줄기 또는 열매, 바람직하게는 잎 부위를 물, C1 내지 C4의 저급 알콜 용매 또는 이들의 혼합용매, 바람직하게는 물 또는 물 및 에탄올 혼합용매, 보다 바람직하게는, 5 내지 90% 에탄올 혼합용매, 보다 더 바람직하게는 5 내지 30% 에탄올 혼합용매에 가용한 추출물을 포함한다.Cudrania extract as defined herein is preferably a leaf, stem or fruit of the Cudrania tree grown in Korea, more preferably in Gangwon-do region, preferably the leaf portion of water, a lower alcohol solvent of C 1 to C 4 or these Mixed solvent, preferably water or water and ethanol mixed solvent, more preferably 5 to 90% ethanol mixed solvent, even more preferably 5 to 30% ethanol mixed solvent.
본원에서 정의되는 알콜성 위장관질환은 알콜 섭취로 발생하는 위장관질환을 통칭하며 이에 제한되지는 않으나, 알콜과다섭취로 기인한 급성 점막손상, 위궤양, 급성 위염 또는 만성 위염, 바람직하게는 알콜과다섭취로 기인한 만성 위염을 포함한다.Alcoholic gastrointestinal diseases, as defined herein, collectively include, but are not limited to, gastrointestinal diseases resulting from alcohol consumption, including acute mucosal injury, gastric ulcer, acute gastritis or chronic gastritis, preferably alcohol overdose due to alcohol intake. Contains chronic gastritis caused.
이하, 구체적으로 본 발명의 추출물을 수득하는 제조방법을 설명한다.Hereinafter, a production method for obtaining the extract of the present invention will be described in detail.
본 발명의 꾸지뽕나무 추출물은 이물질을 제거한 꾸지뽕나무의 잎, 줄기, 열매 등의 부위를 건조 및 분말화하는 단계; 상기 분말을 시료중량의 약 5 내지 35배, 바람직하게는 약 10 내지 30배, 더욱 바람직하게는 15 내지 25배의 정제수를 포함한, 물, 탄소수 1 내지 4의 저급알콜 또는 이들의 혼합용매, 바람직하게는 물 또는 물 및 에탄올 혼합용매, 보다 바람직하게는 5 내지 90% 에탄올 혼합용매, 보다 더 바람직하게는 5 내지 30% 에탄올 혼합용매에 가용하여 100℃ 내지 400℃, 바람직하게는 200℃ 내지 300℃ 추출온도에서 약 1시간 내지 5시간, 바람직하게는 약 2시간 내지 4시간 동안 냉침추출, 열수추출, 초음파 추출, 환류냉각추출, 가열추출 등의 추출방법, 바람직하게는 초음파 추출법 또는 환류냉각추출법으로 추출한 후, 그 여과물을 여과하고 감압농축 및 건조하여 본 발명의 추출물을 수득할 수 있다. Kudji mulberry extract of the present invention comprises the steps of drying and powdering the parts of leaves, stems, berries and the like of Kudji mulberry removed foreign matter; The powder may be water, lower alcohols having 1 to 4 carbon atoms or mixed solvents thereof, preferably containing about 5 to 35 times, preferably about 10 to 30, more preferably 15 to 25 times the sample weight. Preferably it is water or water and ethanol mixed solvent, more preferably 5 to 90% ethanol mixed solvent, even more preferably 100 to 400 ℃, preferably 200 to 300 ℃ soluble in 5 to 30% ethanol mixed solvent Extraction method such as cold sediment extraction, hot water extraction, ultrasonic extraction, reflux cooling extraction, heating extraction for about 1 hour to 5 hours, preferably about 2 hours to 4 hours at an extraction temperature, preferably ultrasonic extraction or reflux cooling extraction After extraction, the filtrate is filtered, concentrated under reduced pressure and dried to obtain the extract of the present invention.
따라서, 본 발명은 상기의 제조방법 및 상기 제조방법으로 얻어진 꾸지뽕나무 추출물을 유효성분으로 함유하는 알콜성 위장관질환의 예방 및 치료를 위한 약학조성물 및 건강기능식품을 제공한다.Therefore, the present invention provides a pharmaceutical composition and health functional food for the prevention and treatment of alcoholic gastrointestinal diseases, containing the above-mentioned manufacturing method and Cucurbitaceae extract obtained by the manufacturing method as an active ingredient.
본 발명의 꾸지뽕나무 추출물에 대하여 알콜로 유도된 위 손상에서 꾸지뽕나무의 각 부위별, 용매별 추출물의 염증관련 유전자 발현과 위액분비관련 유전자 발현을 측정한 결과, 알콜로 유도된 위 손상에서 염증 및 위액분비관련 유전자 발현를 억제하고 위보호물질인 뮤신(mucin) 합성을 증가시킴을 확인함으로써 알콜성 위장관질환의 예방 및 치료를 위한 조성물 및 건강기능식품으로 유용하게 이용할 수 있음을 확인하였다.Inflammation-related gene expression and gastric juice secretion-related gene expression of the extracts of each region and solvent in the alcoholic-induced gastric injury of the extracts of the present invention was measured. By suppressing gastric secretion-related gene expression and increasing mucin (mucin) synthesis, it was confirmed that it can be useful as a composition and health functional food for the prevention and treatment of alcoholic gastrointestinal diseases.
본 발명의 추출물을 함유하는 약학조성물은 조성물 총 중량에 대하여 상기 추출물을 0.1 내지 50 중량%로 포함한다.The pharmaceutical composition containing the extract of the present invention comprises 0.1 to 50% by weight of the extract based on the total weight of the composition.
그러나 상기와 같은 조성은 반드시 이에 한정되는 것은 아니고, 환자의 상태 및 질환의 종류 및 진행 정도에 따라 변할 수 있다.However, the composition is not limited thereto, and may vary depending on the condition of the patient, the type of disease, and the progress of the disease.
본 발명의 추출물 자체는 독성 및 부작용이 거의 없으므로 예방 목적으로 장기간 복용 시에도 안심하고 사용할 수 있는 약재이다. The extract itself of the present invention is a drug that can be used with confidence even when taken for a long time for the purpose of prevention because there is little toxicity and side effects.
본 발명의 조성물은 약학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다.The compositions of the present invention may further comprise suitable carriers, excipients and diluents conventionally used in the manufacture of pharmaceutical compositions.
본 발명의 조성물은 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있으며, 추출물을 포함하는 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 추출물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(calcium carbonate), 수크로스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔스,사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜 (propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.The composition of the present invention may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterilized injection solutions, Examples of carriers, excipients and diluents that can be included in the composition containing the extract include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate , Cellulose, methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and the solid preparations may include at least one excipient such as starch, calcium carbonate, sucrose in the extract. ) Or lactose, gelatin and the like are mixed. In addition to simple excipients, lubricants such as magnesium stearate talc are also used. Liquid preparations for oral use include suspensions, solvents, emulsions, and syrups, and may include various excipients, for example, wetting agents, sweeteners, fragrances, preservatives, etc. have. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of suppository bases include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin, and the like.
본 발명의 조성물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 그러나 바람직한 효과를 위해서, 본 발명의 추출물은 1일 0.5 g/kg 내지 5 g/kg으로, 바람직하게는 1 g/kg 내지 3 g/kg으로 투여하는 것이 좋다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수 있다. 따라서 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.The preferred dosage of the composition of the present invention varies depending on the condition and the weight of the patient, the degree of disease, the type of drug, the route of administration and the period of time, but can be appropriately selected by those skilled in the art. However, for the desired effect, the extract of the present invention is preferably administered at 0.5 g / kg to 5 g / kg, preferably 1 g / kg to 3 g / kg per day. The administration may be carried out once a day or divided into several doses. Accordingly, the dosage is not limited in any way to the scope of the present invention.
본 발명의 조성물은 쥐, 생쥐, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁내 경막 또는 뇌혈관내 (intracerebroventricular) 주사에 의해 투여될 수 있다.
The composition of the present invention may be administered to mammals such as rats, mice, livestock, humans, and the like in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebroventricular injections.
또한, 본 발명은 꾸지뽕나무 추출물을 유효성분으로 함유하는 알콜성 위장관질환의 예방 및 개선용 건강기능식품을 제공한다. In another aspect, the present invention provides a health functional food for the prevention and improvement of alcoholic gastrointestinal diseases containing kkujimi tree extract as an active ingredient.
따라서, 또한, 본 발명은 알콜성 위장관질환의 예방 및 개선 효과를 갖는 상기 꾸지뽕나무 추출물을 유효성분으로 함유하는 식품 또는 식품첨가제를 제공한다.Therefore, the present invention also provides a food or food additive containing the Cuzipia japonica extract as an active ingredient having an effect of preventing and improving alcoholic gastrointestinal diseases.
본 발명의 추출물을 포함하는 조성물은 알콜성 위장관질환의 예방 및 개선을 위한 약제, 식품 및 음료 등에 다양하게 이용될 수 있다. 본 발명의 추출물을 첨가할 수 있는 식품으로는, 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합제, 건강보조 식품류 등이 있고, 분말, 과립, 정제, 캡슐 또는 음료인 형태로 사용할 수 있다.The composition containing the extract of the present invention can be used in various ways, such as drugs, food and beverages for the prevention and improvement of alcoholic gastrointestinal diseases. Examples of the foods to which the extract of the present invention can be added include various foods, beverages, gums, tea, vitamin complexes, health supplements and the like, and they can be used as powders, granules, tablets, capsules or beverages have.
본 발명의 추출물은 알콜성 위장관질환의 예방 및 개선을 목적으로 식품 또는 음료에 첨가될 수 있다. 이 때, 식품 또는 음료 중의 상기 추출물의 양은 일반적으로 본 발명의 건강식품 조성물은 전체 식품 중량의 1 내지 5 중량%로 가할 수 있으며, 건강 음료 조성물은 100 ㎖를 기준으로 0.02 내지 10 g, 바람직하게는 0.3 내지 1 g의 비율로 가할 수 있다. Extract of the present invention may be added to food or beverage for the purpose of preventing and improving alcoholic gastrointestinal diseases. At this time, the amount of the extract in the food or beverage is generally the health food composition of the present invention can be added to 1 to 5% by weight of the total food weight, the health beverage composition is 0.02 to 10 g, preferably based on 100 ml Can be added in a ratio of 0.3 to 1 g.
본 발명의 건강 음료 조성물은 지시된 비율로 필수 성분으로서 상기 추출물을 함유하는 것 외에 액체성분에는 특별한 제한점은 없으며 통상의 음료서 상이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등의 디사카라이드, 예를 들어 말토스, 슈지 스 등의 및 폴리사카라이드, 예를 들어 덱스트린, 시쥴 덱스트린 등성물은 지통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마틴, 또는 스테비아 추출물(예를 들어 레바우디오시드 A를 함유한 글리시르히진 등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율 지본 발명의 조성물 100 mL당 일반적으로 약 1 내지 20g, 바람직하게는 약 5 내지 12g이다.In addition to containing the extract as an essential ingredient in the indicated ratio, the health beverage composition of the present invention is not particularly limited in the liquid component and may contain various flavors, natural carbohydrates, etc. as additional ingredients in a conventional beverage. Examples of the above-mentioned natural carbohydrates include monosaccharides such as disaccharides such as glucose and fructose such as maltose and sucrose and polysaccharides such as dextrin and sludge dextrin Conventional sugars and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin, or stevia extract (for example, glycyrrhizin containing rebaudioside A) and synthetic flavoring agents (saccharin, aspartame, etc.) are advantageously used. The ratio of said natural carbohydrates is generally about 1 to 20 g, preferably about 5 to 12 g per 100 mL of the composition of the present invention.
상기 외에 본 발명의 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, 알콜, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명의 조성물들은 천연 과일 쥬스 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.
In addition to the above, the composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof, alginic acid and its Salts, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks, and the like. In addition, the compositions of the present invention may contain flesh for the production of natural fruit juices and vegetable beverages. These components may be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.
상술한 바와 같이, 본 발명의 꾸지뽕나무 추출물은 알콜로 유도된 위 손상에서 꾸지뽕나무의 각 부위별, 용매별 추출물의 염증관련 유전자 발현과 위액분비관련 유전자 발현을 측정한 결과, 알콜로 유도된 위 손상에서 염증 및 위액분비관련 유전자 발현를 억제하고 위보호물질인 뮤신(mucin) 합성을 증가시킴을 확인함으로써 알콜성 위장관질환의 예방 및 치료를 위한 조성물 및 건강기능식품으로 유용하게 이용될 수 있다.
As described above, according to the present invention, the Kudji mulberry extract of the present invention measured the inflammation-related gene expression and gastric juice secretion-related gene expression of the extract of each region, solvent by the alcohol-induced gastric damage, gastric-induced stomach By inhibiting inflammation and gastric secretion-related gene expression in the injury and confirming the increase of mucin (mucin) synthesis of gastric protective material can be useful as a composition and health functional food for the prevention and treatment of alcoholic gastrointestinal diseases.
이하, 본 발명을 실시예 및 실험예에 의해 상세히 설명한다. Hereinafter, the present invention will be described in detail with reference to Examples and Experimental Examples.
단, 하기 실시예 및 실험예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실시예 및 실험예에 한정되는 것은 아니다.
However, the following Examples and Experimental Examples are merely illustrative of the present invention, and the present invention is not limited to the following Examples and Experimental Examples.
실시예Example 1. One. 꾸지뽕나무Cudrania 추출물의 제조 Preparation of extract
1-1. 1-1. 꾸지뽕CJ 물 가용추출물의 제조( Preparation of Water Soluble Extracts CTL0CTL0 , , CTS0CTS0 , , CTF0CTF0 ))
영농법인 고성(강원도 고성군 토성면 인흥리 산62-3)에서 구입한 꾸지뽕나무의 잎, 줄기 및 열매를 수세하고, 동결건조기(Ilshin Lab Co., Ltd, FD8512)로 건조시키고 분말화하였다. 상기 꾸지뽕나무의 잎, 줄기 및 열매 분말 50g에 1L의 증류수를 가하여 3시간 동안 250℃에서 환류(reflux)하여 추출을 수행하고 얻어진 추출물을 여과지(ADVANTEC FILTER PAPER 6, 150 mm)로 여과하여 여과액을 회전진공농축기(Sunil EYELA, Rotatory evaporator, N-1N)로 감압 농축하여 동결건조하여 꾸지뽕나무의 잎, 줄기 및 열매의 물가용 추출물을 각각 7.78g, 3.49g 및 6.40g 을 수득하고 이후 하기 실험예의 시료로 사용하였다. (이하, 각각 "CTL0", "CTS0", 및 "CTF0"라 함)
The leaves, stems, and fruits of the coupe mulberry tree purchased from Goseong (Insanheung-ri, 62-3, Inheung-ri, Goseong-gun, Goseong-gun, Gangwon-do) were washed with water, dried and powdered with a freeze dryer (Ilshin Lab Co., Ltd, FD8512). 1 g of distilled water was added to 50 g of the leaves, stems, and fruit powders of the Koji mulberry tree, followed by extraction at reflux at 250 ° C. for 3 hours, and the obtained extract was filtered through filter paper (ADVANTEC FILTER PAPER 6, 150 mm) and filtered. Was concentrated under reduced pressure with a Sunil EYELA, Rotatory evaporator (N-1N), and lyophilized to obtain 7.78 g, 3.49 g, and 6.40 g of water-soluble extracts of leaves, stems, and berries of Cucumis paniculata, respectively. Used as an example sample. (Hereinafter referred to as "CTL0", "CTS0", and "CTF0", respectively)
1-2. 1-2. 꾸지뽕CJ 10% 에탄올 가용추출물의 제조( Preparation of 10% Ethanol Soluble Extract CTL10CTL10 , , CTS10CTS10 , , CTF10CTF10 ))
영농법인 고성(강원도 고성군 토성면 인흥리 산62-3)에서 구입한 꾸지뽕나무의 잎, 줄기 및 열매를 수세 하고, 동결건조기(Ilshin Lab Co., Ltd, FD8512)로 건조시키고, 분말화하였다. 상기 꾸지뽕나무의 잎, 줄기 및 열매 분말 50g에 1L의 10% 에탄올를 가하여 3시간 동안 250℃에서 환류(reflux)하여 추출을 수행하고 얻어진 추출물을 여과지(ADVANTEC FILTER PAPER 6, 150mm)로 여과하여 여과액을 회전진공농축기(Sunil EYELA, Rotatory evaporator, N-1N)로 감압 농축하여 동결건조하여 꾸지뽕 나무의 잎, 줄기 및 열매의 10% 에탄올 가용 추출물을 각각 7.78g, 3.49g 및 6.40g을 수득하고 이후 하기 실험예의 시료로 사용하였다. (이하, 각각 "CTL10", "CTS10", 및 "CTF10"라 함)
The leaves, stems, and fruits of the coupe mulberry tree purchased at Goseong (Incheon-ri, Inheung-ri, Toseong-myeon, Goseong-gun, Gangwon-do) were washed with water, dried with a freeze dryer (Ilshin Lab Co., Ltd, FD8512), and powdered. 1 g of 10% ethanol was added to 50 g of the leaves, stems, and fruit powders of the zigzag tree, followed by extraction at reflux at 250 ° C. for 3 hours, and the obtained extract was filtered through a filter paper (ADVANTEC FILTER PAPER 6, 150 mm). Was concentrated under reduced pressure with a Sunil EYELA, Rotatory evaporator (N-1N) and lyophilized to obtain 7.78 g, 3.49 g and 6.40 g of 10% ethanol soluble extracts of leaves, stems and berries of Cudrania japonica, respectively. It used as the sample of the following experiment example. (Hereinafter referred to as "CTL10", "CTS10", and "CTF10", respectively)
1-3. 1-3. 꾸지뽕CJ 80% 에탄올 가용추출물의 제조( Preparation of 80% Ethanol Soluble Extract CTL80CTL80 , , CTS80CTS80 , , CTF80CTF80 ))
영농법인 고성(강원도 고성군 토성면 인흥리 산62-3)에서 구입한 꾸지뽕나무의 잎, 줄기 및 열매를 수세하고, 동결건조기(Ilshin Lab Co., Ltd, FD8512)로 건조시키고, 분말화하였다. 상기 꾸지뽕 나무의 잎, 줄기 및 열매 분말 50g에 1L의 80% 에탄올를 가하여 3시간 동안 250℃에서 환류(reflux)하여 추출을 수행하고 얻어진 추출물을 여과지(ADVANTEC FILTER PAPER 6, 150mm)로 여과하여 여과액을 회전진공농축기(Sunil EYELA, Rotatory evaporator, N-1N)로 감압 농축하여 동결건조하여 꾸지뽕 나무의 잎, 줄기 및 열매의 80% 에탄올 가용 추출물을 각각 7.78g, 3.49g 및 6.40g을 수득하고 이후 하기 실험예의 시료로 사용하였다. (이하, 각각 "CTL80", "CTS80", 및 "CTF80",라 함)
The leaves, stems, and fruits of the coupe mulberry tree purchased from Goseong (San 62, Inheung-ri, Toseong-myeon, Goseong-gun, Gangwon-do) were washed with water, dried with a lyophilizer (Ilshin Lab Co., Ltd, FD8512), and powdered. 1 g of 80% ethanol was added to 50 g of the leaves, stems, and fruit powders of Cudrania chinensis and refluxed at 250 ° C. for 3 hours, followed by extraction. The obtained extract was filtered through a filter paper (ADVANTEC FILTER PAPER 6, 150 mm) and filtered. Was concentrated under reduced pressure with a Sunil EYELA (Rotatory evaporator, N-1N) and lyophilized to obtain 7.78 g, 3.49 g and 6.40 g of 80% ethanol soluble extracts of leaves, stems, and berries of Cudrania japonica, respectively. It used as the sample of the following experiment example. (Hereinafter referred to as "CTL80", "CTS80", and "CTF80", respectively)
참고예Reference Example 1. 실험준비 1. Preparation for Experiment
1. 실험세포 준비1. Preparation of experimental cells
실험세포는 인간 위암세포주 AGS 세포이며 ATCC(American Type Culture Collection, CRL-1739)에서 구입하였으며, 10% FBS(fetal bovine serum)과 1% penicillin/streptomycin이 함유된 RPMI-1640 배지(Hyclone, SH30027.01)를 사용하여 37℃, 5% CO2 배양기에서 배양하였다.
Experimental cells were human gastric cancer cell line AGS cells and were purchased from the American Type Culture Collection (ATCC), RPMI-1640 medium containing 10% FBS (fetal bovine serum) and 1% penicillin / streptomycin (Hyclone, SH30027. 01) using 37 ° C., 5% CO 2 Lt; / RTI >
실험예Experimental Example 1. One. 꾸지뽕나무Cudrania 추출물의 세포독성 측정 Cytotoxicity of Extracts
상기 실시예의 시료들의 AGS 세포에 대한 세포독성을 확인하기 위하여 문헌에 개시된 MTT 방법을 응용하여 하기와 같이 실험을 수행하였다(Jones and Senft, 1985 K.H. Jones and J.A. Senft, An improved method to determine cell viability by simultaneous staining with fluorescein diacetate and propidium iodide. Histochem. Cytochem., 33 (1985), pp. 7779. ).In order to confirm the cytotoxicity of AGS cells of the samples of the above example, the experiment was performed by applying the MTT method disclosed in the literature (Jones and Senft, 1985 KH Jones and JA Senft, An improved method to determine cell viability by simultaneous staining with fluorescein diacetate and propidium iodide.Histochem.Cytochem., 33 (1985), pp. 7779.
인간 위암세포주인 AGS 세포를 96 웰 플레이트(well plate)에 1 × 104 cells/well로 분주하여 20시간 배양한 후, 배지를 제거하고 3일 동안 꾸지뽕나무 추출물들을 0~ 800 μg/mL로 처리하였다. 3일 후, MTT 용액(SIGMA, M5655)을 넣고 3시간 더 배양한 다음 생성된 formazan을 dimethyl sulfoxide(DMSO)를 첨가하여 용해시킨 후, microplate reader(VERSAmax, Molecular Devices)를 사용하여 540 nm에서 흡광도를 측정하였다. 세포생존율은 무처리 대조군의 흡광도에 대한 시료 처리군의 흡광도 비로 계산하였다.AGS cells, a human gastric cancer cell line, were cultured in 96 well plates at 1 × 10 4 cells / well and incubated for 20 hours, and then the medium was removed and treated with Koji mulberry extract at 0 to 800 μg / mL for 3 days. It was. After 3 days, MTT solution (SIGMA, M5655) was added and incubated for 3 more hours. The resulting formazan was dissolved by adding dimethyl sulfoxide (DMSO), and then absorbed at 540 nm using a microplate reader (VERSAmax, Molecular Devices). Was measured. Cell viability was calculated as the absorbance ratio of the sample treated group to the absorbance of the untreated control group.
본 실험 결과, 잎의 경우, 열수 추출물(CTL0)은 800 μg/mL, 10% 에탄올(CTL10)과 80% 에탄올 추출물(CTL80)은 100 μg/mL 농도까지 독성이 나타나지 않았고, 줄기는 열수 추출물(CTS0)은 100 μg/mL, 10% 에탄올 추출물(CTS10)은 50 μg/mL, 80% 에탄올 추출물(CTS80)은 10 μg/mL 농도까지 세포독성이 나타나지 않았다. 또한 열매 열수 추출물은 800 μg/mL(CTF0), 10% 에탄올(CTF10)과 80% 에탄올 추출물(CTF80)은 200 μg/mL까지 세포독성이 나타나지 않아 이후 실험은 세포독성이 나타나지 않는 최대농도를 선정하여 실험하였다.
In the case of leaves, the hydrothermal extract (CTL0) was not toxic to 800 μg / mL, 10% ethanol (CTL10) and 80% ethanol extract (CTL80) to 100 μg / mL, and the stem was hydrothermal extract ( CTS0) was 100 μg / mL, 10% ethanol extract (CTS10) was 50 μg / mL, 80% ethanol extract (CTS80) showed no cytotoxicity up to 10 μg / mL. In addition, 800 μg / mL (CTF0), 10% ethanol (CTF10) and 80% ethanol extract (CTF80) did not show cytotoxicity up to 200 μg / mL. The experiment was carried out.
실험예Experimental Example 2. 2. 꾸지뽕나무Cudrania 잎 추출물의 Of leaf extract TNFTNF -α 발현 억제 효과-α expression inhibitory effect
상기 실시예의 시료들의 TNF-α 발현에 대한 억제 활성를 확인하기 위하여 문헌에 개시된 방법을 응용하여 하기와 같이 실험을 수행하였다(J Physiol Pharmacol. 2009 Dec;60 Suppl 7:131-7. Beta-carotene inhibits Helicobacter pylori-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 in human gastric epithelial AGS cells. Jang SH, Lim JW, Kim H.).In order to confirm the inhibitory activity on the TNF-α expression of the samples of the above example, the experiment was performed by applying the method disclosed in the literature (J Physiol Pharmacol. 2009 Dec; 60 Suppl 7: 131-7. Beta-carotene inhibitors Helicobacter pylori-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 in human gastric epithelial AGS cells.Jang SH, Lim JW, Kim H.).
AGS 세포를 24 웰 플레이트에 1 × 104 cells/well로 분주하여 20시간 배양한 후, 꾸지뽕나무 부위별, 용매별 추출물을 농도별로 처리하여 2시간 동안 배양한 다음 염증 유발 물질인 리포폴리사카라이드(lipopolysaccharide, 4 μg/mL) 또는 2% 알콜을 처리하였다. 2% EtOH을 24시간 처리 후에 TNF-α 발현량을 정량하기 위하여 ELISA kit (R&D systems, Minneapolis, MN, USA)을 사용하였다. 즉, TNF-α에 반응하는 항체가 코팅된 96 웰 플레이트에 준비된 standard(R&D systems Catalog # DY994) 및 배지 100 μL를 분주하여 실온에서 2시간 배양하고 2회 세척한 다음에 detection antibody(R&D systems Catalog # DY211, Part 840781) 100 μL를 넣어 2시간 배양한 후, 2회 세척하였다. Streptavidin-HRP 용액(R&D systems Catalog # DY211, Part 890803)을 각 웰에 100 μL씩 넣고 20분 동안 실온에서 배양한 후, 2회 세척한 다음에 TMB 기질 용액(R&D systems Catalog # DY999)을 각 웰당 100 μL씩 분주하여 실온 암소에서 20분간 반응시켰다. Stop 용액(2 M H2SO4) 50 μL를 넣어 반응을 정지시키고, microplate reader(VERSAmax, Molecular Devices) 450 nm에서 흡광도를 측정하여 정량하였다.After dispensing AGS cells in a 24-well plate at 1 × 10 4 cells / well and incubating for 20 hours, the extracts were treated by concentrations of extracts for each region and solvent, followed by incubation for 2 hours, and then lipopolysaccharide, an inflammation-inducing substance. (lipopolysaccharide, 4 μg / mL) or 2% alcohol. ELISA kit (R & D systems, Minneapolis, MN, USA) was used to quantify TNF-α expression after 24 hours treatment with 2% EtOH. In other words, 100 μL of standard (R & D systems Catalog # DY994) and medium prepared in a 96 well plate coated with TNF-α-responsive antibody were incubated at room temperature for 2 hours, washed twice, and then detected with detection antibody (R & D systems Catalog). # DY211, Part 840781) 100 μL was added and incubated for 2 hours, followed by washing twice. 100 μL of Streptavidin-HRP solution (R & D systems Catalog # DY211, Part 890803) was added to each well, incubated at room temperature for 20 minutes, washed twice, and then TMB substrate solution (R & D systems Catalog # DY999) was added to each well. 100 μL was aliquoted and allowed to react for 20 minutes in room temperature. 50 μL of Stop solution (2 MH 2 SO 4 ) was added to stop the reaction, and the absorbance was measured and measured at 450 nm of a microplate reader (VERSAmax, Molecular Devices).
본 실험 결과, AGS 세포에 LPS(lipopolysaccharide; SIGMA, L4391)를 처리하여 염증을 유도한 후, 꾸지뽕나무의 잎, 줄기 및 열매의 10% 에탄올, 80% 에탄올, 열수 추출물을 전처리하여 염증유발 물질인 TNF-α 발현을 측정한 결과, 무처리 대조군에 비해 알콜 처리 대조군에서 TNF-α 발현이 유의적으로 증가하였으며, CTL10 전처리에 의해 가장 높은 억제효과가 나타났고, CTS80, CTL80 순으로 높은 억제효과를 보였다. 2% 에탄올 처리에 의한 TNF-α 발현 억제효과 또한 CTL10에서 가장 높게 나타났으며, CTS80, CTL80 순으로 나타났다. 열매 추출물은 2% 에탄올에 의해 유도된 염증유발 물질인 TNF-α 발현 억제효과를 나타내지 않았다.
As a result of this experiment, AGS cells were treated with LPS (lipopolysaccharide; SIGMA, L4391) to induce inflammation, and then pretreated with 10% ethanol, 80% ethanol, and hydrothermal extract of leaves, stems and fruits of Koji mulberry tree. As a result of measuring TNF-α expression, TNF-α expression was significantly increased in the alcohol treated control group compared to the untreated control group, and the highest inhibitory effect was obtained by CTL10 pretreatment, followed by CTS80, CTL80. Seemed. Inhibition of TNF-α expression by 2% ethanol treatment was also highest in CTL10, followed by CTS80 and CTL80. Fruit extract did not show the inhibitory effect of TNF-α expression, an inflammatory-induced substance induced by 2% ethanol.
실험예Experimental Example 3. 3. 꾸지뽕나무Cudrania 잎 추출물의 염증관련 단백질 및 전사인자의 발현 조절 Controlling Expression of Inflammation-related Proteins and Transcription Factors in Leaf Extracts
상기 실시예의 시료들의 염증관련 단백질 및 전사인자 발현에 대한 억제 활성을 확인하기 위하여 문헌에 개시된 방법을 응용하여 하기와 같이 실험을 수행하였다(J Physiol Pharmacol. 2009 Dec;60 Suppl 7:131-7. Beta-carotene inhibits Helicobacter pylori-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 in human gastric epithelial AGS cells. Jang SH, Lim JW, Kim H.).In order to confirm the inhibitory activity on the expression of inflammation-related proteins and transcription factors of the samples of the above example, the experiments were performed by applying the method disclosed in the literature (J Physiol Pharmacol. 2009 Dec; 60 Suppl 7: 131-7. Beta-carotene inhibits Helicobacter pylori-induced expression of inducible nitric oxide synthase and cyclooxygenase-2 in human gastric epithelial AGS cells.Jang SH, Lim JW, Kim H.).
2% 알콜이 처리된 AGS 세포에서 NF-κB, Cox-2, iNOS, Muc5/6 및 β-actin의 발현을 측정하기 위하여 western blot을 실시하였다. AGS 세포를 20시간 배양한 후, 꾸지뽕나무 추출물을 농도별로 처리하여 2시간 동안 배양한 다음 2% 에탄올을 처리하였다. 6시간 후 세포에 lysis buffer(SIGMA, R7757)를 첨가하여 lysis시킨 다음 단백질을 정량하여 50 μg 단백질을 10% SDS-polyacrylamide(USB corporation, 75819)에 loading하여 전기영동하였다. 전기영동하여 분리한 단백질을 nitrocellulose membrane(Whatman, PROTRAN)에 transfer한 후 5% skim milk 용액(BD, Difcoim skim milk, 232100)으로 blocking한 다음 1차 항체와 2차 항체를 붙였다. 항체반응이 끝난 membrane에 ECL detection kit(iNtRON, WEST-ONE, 160-31)을 처리하고 X-ray film(AGFA, CP-BU new 100 NIF)에 노출하여 현상한 후 band를 확인하였다.Western blot was performed to measure the expression of NF-κB, Cox-2, iNOS, Muc5 / 6 and β-actin in AGS cells treated with 2% alcohol. After incubating the AGS cells for 20 hours, the extracts were treated by concentration of Cucumis japonica extract for 2 hours and then treated with 2% ethanol. After 6 hours, the cells were lysed by adding lysis buffer (SIGMA, R7757), and the proteins were quantified and electrophoresed by loading 50 μg protein into 10% SDS-polyacrylamide (USB corporation, 75819). Electrophoresed proteins were transferred to nitrocellulose membrane (Whatman, PROTRAN), blocked with 5% skim milk solution (BD, Difcoim skim milk, 232100), and then attached with primary and secondary antibodies. ECL detection kit (iNtRON, WEST-ONE, 160-31) was treated on the membrane after the antibody reaction was completed and exposed to X-ray film (AGFA, CP-BU new 100 NIF) to develop bands.
본 실험 결과, AGS 세포에서 2% 에탄올에 의해 유도되는 전사인자인 NF-κB와 염증반응에 의해 발현되는 단백질 Cox-2 및 iNOS 발현을 western blot으로 측정한 결과, 알콜 처리 대조군에 비해 CTL10 전처리에 의해 농도 의존적으로 그 발현이 감소하였으며, CTL10의 100 μg/mL 농도에서 가장 높은 발현 억제 효과가 나타났다. 또한 CTL10은 알콜 처리된 AGS 세포에서 위보호물질인 mucin 합성을 증가시킴으로 알콜로 손상된 위벽을 보호하는 효과를 나타내었다.
As a result, we measured the expression of NF-κB, a transcription factor induced by 2% ethanol, and protein Cox-2 and iNOS expressed by inflammatory reaction in AGS cells by western blot. The expression was reduced in a concentration-dependent manner, the highest expression inhibitory effect at 100 μg / mL concentration of CTL10. In addition, CTL10 has been shown to protect alcohol-damaged gastric wall by increasing mucin synthesis, a gastric protective substance in alcohol-treated AGS cells.
실험예Experimental Example 4. 4. 꾸지뽕나무Cudrania 잎 추출물의 위액분비관련 유전자 발현 조절 Gene Expression Control of Gastric Secretion in Leaf Extracts
상기 실시예의 시료들의 위액분비 관련 유전자 발현에 대한 억제 활성을 확인하기 위하여 문헌에 개시된 방법을 응용하여 하기와 같이 실험을 수행하였다(Finley GG, Koski RA, Melhem MF, Pipas JM, Meisler AI. Expression of the gastrin gene in the normal human colon and colorectal adenocarcinoma. Cancer Res 1993;53:2919-2926.).In order to confirm the inhibitory activity of the gastric secretion-related gene expression of the samples of the above example, the experiment was performed as follows (Finley GG, Koski RA, Melhem MF, Pipas JM, Meisler AI. the gastrin gene in the normal human colon and colorectal adenocarcinoma. Cancer Res 1993; 53: 2919-2926.).
2% 알콜이 처리된 AGS 세포에서 위액분비조절 유전인자 mRNA 발현을 측정하기 위하여 RNeasy Mini kit(QIAGEN, 74104)을 사용하여 세포 내 총 RNA를 추출하고 정량하였다. 1 μg RNA를 oligo(dT) primer(BIO-RAD, iScript Select cDNA Synthesis Kit, 170-8897)와 superscript Ⅱ 역전사효소(iScript Select cDNA Synthesis Kit, 170-8897)와 반응시켜 cDNA를 제작하였다. PCR 반응은 1 μg cDNA를 Gold Taq polymerase(BIO-RAD, iQ SYBR Green Supermix, 170-8880)를 첨가하여 32 cycles로 PCR 반응시킨 다음에 1.5% agarose gel(Promega, USA, v3125)에서 전기영동한 후에 ethidium bromide(EtBr,Promega, USA, #H5041)로 염색하여 UV에서 DNA를 확인하였고, DNA의 정량적 분석은 Applied Biosystem Inc.(STEP-ONE Real Time PCR, Foster city, CA, USA)에서 제공된 7500 Systems SD software version 2.1, (STEP-ONE Real Time PCR, Rev A, 1029576)을 이용하여 측정하였다. In order to measure gastric secretion regulatory gene mRNA expression in AGS cells treated with 2% alcohol, total RNA was extracted and quantified using RNeasy Mini kit (QIAGEN, 74104). CDNA was prepared by reacting 1 μg RNA with oligo (dT) primer (BIO-RAD, iScript Select cDNA Synthesis Kit, 170-8897) and superscript II reverse transcriptase (iScript Select cDNA Synthesis Kit, 170-8897). PCR reaction was performed by PCR reaction with 1 μg cDNA in 32 cycles with Gold Taq polymerase (BIO-RAD, iQ SYBR Green Supermix, 170-8880), followed by electrophoresis on 1.5% agarose gel (Promega, USA, v3125). DNA was then confirmed by UV staining with ethidium bromide (EtBr, Promega, USA, # H5041), and quantitative analysis of DNA was carried out by Applied Biosystem Inc. (STEP-ONE Real Time PCR, Foster city, CA, USA) 7500. Measurements were made using Systems SD software version 2.1, (STEP-ONE Real Time PCR, Rev A, 1029576).
사용된 primer는 하기 표 1과 같다.Primers used are shown in Table 1 below.
본 실험 결과, 위액분비에 관여하는 유전자인 gastrin과 somastatin에 대한 mRNA 발현을 RT-PCR로 측정한 결과, 위액분비를 촉진하는 gastrin은 농도 의존적으로 감소하였으며, CTL10의 100 μg/mL에서 가장 높은 억제 효과가 나타났다. In this experiment, mRNA expression of gastrin and somastatin genes involved in gastric secretion was measured by RT-PCR. Effect appeared.
반면에 위액분비를 억제하는 somastatin은 농도 의존적으로 증가하여 100 μg/mL에서 가장 높게 발현되었다. 이상의 결과로 볼 때 CTL10은 알콜로 유도된 위 손상에서 염증 및 위액분비관련 유전자 발현를 억제하고 위보호물질인 뮤신(mucin) 합성을 증가시킴으로써 위염 억제효과를 나타내는 것으로 사료된다.
On the other hand, somastatin, which inhibits gastric secretion, was highest at 100 μg / mL due to its concentration-dependent increase. These results suggest that CTL10 suppresses gastritis by inhibiting gene expression related to inflammation and gastric secretion and increasing mucin synthesis by gastric secretion in alcohol-induced gastric injury.
하기에 본 발명의 꾸지뽕 추출물을 포함하는 약학조성물 및 건강기능식품의 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.
Described below is an example of the preparation of a pharmaceutical composition and health functional food comprising the kkujippong extract of the present invention, the present invention is not intended to limit it, but is intended to explain in detail.
제제예Formulation example 1. One. 산제의Sanje 제조 Produce
CTL10 20 mgCTL10 20 mg
유당 100 mgLactose 100 mg
탈크 10 mgTalc 10 mg
상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 제조한다.
The above components are mixed and filled in airtight bags to prepare powders.
제제예Formulation example 2. 정제의 제조 2. Preparation of tablets
CTS80 10 mg CTS80 10 mg
옥수수전분 100 mgCorn starch 100 mg
유당 100 mgLactose 100 mg
스테아린산 마그네슘 2 mgMagnesium stearate 2 mg
상기의 성분들을 혼합한 후 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조한다.
After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.
제제예Formulation example 3. 캅셀제의 제조 3. Preparation of capsules
CTL80 10 mg CTL80 10 mg
결정성 셀룰로오스 3 mg3 mg of crystalline cellulose
락토오스 14.8 mgLactose 14.8 mg
마그네슘 스테아레이트 0.2 mgMagnesium Stearate 0.2 mg
통상의 캡슐제 제조방법에 따라 상기의 성분을 혼합하고 젤라틴 캡슐에 충전하여 캡슐제를 제조한다.
The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.
제제예Formulation example 4. 주사제의 제조 4. Preparation of injections
CTL10 10 mg CTL10 10 mg
만니톨 180 mg180 mg mannitol
주사용 멸균 증류수 2974 mgSterile sterilized water for injection 2974 mg
Na2HPO412H2O 26 mgNa 2 HPO 4 12H 2 O 26 mg
통상의 주사제의 제조방법에 따라 1 앰플당(2㎖) 상기의 성분 함량으로 제조한다.
(2 ml) per 1 ampoule according to the usual injection preparation method.
제제예Formulation example 5. 5. 액제의Liquid 제조 Produce
CTL10 20 mg CTL10 20 mg
이성화당 10 g10 g per isomer
만니톨 5 g5 g mannitol
정제수 적량Purified water quantity
통상의 액제의 제조방법에 따라 정제수에 각각의 성분을 가하여 용해시키고 레몬향을 적량 가한 다음 상기의 성분을 혼합한 다음 정제수를 가하여 전체를 정제수를 가하여 전체 100㎖로 조절한 후 갈색병에 충진하여 멸균시켜 액제를 제조한다.
Each component was added to purified water in accordance with the usual liquid preparation method and dissolved, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was adjusted to 100 ml with purified water, And sterilized to prepare a liquid preparation.
제제예Formulation example 6. 건강 식품의 제조 6. Manufacture of health food
CTS80 1000 ㎎CTS80 1000 mg
비타민 혼합물 적량Vitamin mixture proper amount
비타민 A 아세테이트 70 ㎍70 μg of Vitamin A Acetate
비타민 E 1.0 ㎎Vitamin E 1.0 mg
비타민 B1 0.13 ㎎Vitamin B1 0.13 mg
비타민 B2 0.15 ㎎Vitamin B2 0.15 mg
비타민 B6 0.5 ㎎Vitamin B6 0.5 mg
비타민 B12 0.2 ㎍0.2 μg of vitamin B12
비타민 C 10 ㎎Vitamin C 10 mg
비오틴 10 ㎍10 μg biotin
니코틴산아미드 1.7 ㎎Nicotinic Acid 1.7 mg
엽산 50 ㎍50 μg folic acid
판토텐산 칼슘 0.5 ㎎Calcium Pantothenate 0.5mg
무기질 혼합물 적량Mineral mixture
황산제1철 1.75 ㎎Ferrous Sulfate 1.75 mg
산화아연 0.82 ㎎Zinc Oxide 0.82 mg
탄산마그네슘 25.3 ㎎Magnesium carbonate 25.3 mg
제1인산칼륨 15 ㎎Potassium monophosphate 15 mg
제2인산칼슘 55 ㎎Dibasic calcium phosphate 55 mg
구연산칼륨 90 ㎎Potassium Citrate 90 mg
탄산칼슘 100 ㎎Calcium Carbonate 100 mg
염화마그네슘 24.8 ㎎Magnesium chloride 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강기능식품 조성물 제조에 사용할 수 있다.
Although the composition ratio of the above-mentioned vitamin and mineral mixtures is mixed with a component suitable for a health food in a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method. The granules may be prepared and used for preparing the nutraceutical composition according to a conventional method.
제제예Formulation example 7. 건강 음료의 제조 7. Manufacture of health drinks
CTL80 1000 ㎎CTL80 1000 mg
구연산 1000 ㎎Citric acid 1000 mg
올리고당 100 ㎎Oligosaccharide 100 mg
매실농축액 2 ㎎Plum concentrate 2 mg
타우린 1 ㎎Taurine 1 mg
정제수를 가하여 전체 900 ㎖Add 900 ml of purified water
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간 동안 85℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2ℓ 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강음료 조성물 제조에 사용한다. The above components were mixed according to a conventional health drink manufacturing method, and the mixture was heated at 85 DEG C for about 1 hour with stirring, and the solution thus prepared was filtered to obtain a sterilized 2-liter container, which was sealed and sterilized, ≪ / RTI >
상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만 수요계층이나, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.
Although the compositional ratio is relatively mixed with a component suitable for a favorite drink, it is also possible to arbitrarily modify the compounding ratio according to the regional or national preference such as the demand class, the demanding country, and the use purpose.
Claims (7)
Curdrania tricuspidata with debris removed Bureau) drying and powdering the leaf area; The powder was dissolved in a 5-30% ethanol mixed solvent of 5 to 35 times the weight of the sample, and extracted by reflux cooling extraction for 1 to 5 hours at 100 ° C to 400 ° C extraction temperature. The filtrate was filtered and concentrated under reduced pressure. And dried Cudrania japonica (Curdrania tricuspidata) Bureau) A pharmaceutical composition for the prevention and treatment of acute mucosal injury caused by excessive intake of alcohol containing 5 to 30% ethanol mixed solvent extract of the leaves as an active ingredient.
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| KR101365017B1 (en) * | 2013-08-07 | 2014-03-04 | 재단법인춘천바이오산업진흥원 | Composition having inhibitory effects on protein tyrosine phosphatase 1b |
| KR102082860B1 (en) | 2018-07-17 | 2020-02-28 | 주식회사한국야쿠르트 | Food composition for prevention and improvment of reflux esophagitis containing Cudrania tricuspidata extract as an effective factor |
| KR102038695B1 (en) | 2018-10-30 | 2019-10-30 | 주식회사 종근당바이오 | Composition for Preventing or Treating Alcoholic Intestinal Damage Comprising Probiotics as Effective Ingredients |
| KR102079731B1 (en) | 2019-08-30 | 2020-02-20 | 주식회사한국야쿠르트 | Composition for Preventing or Improving Functional Dyspepsia comprising Cudrania Tricuspidata Extract |
| KR102465346B1 (en) * | 2020-10-07 | 2022-11-14 | 정읍시 | A composition comprising Chrysanthemum zawadskii and Cudrania tricuspidata Bureau having anti-inflammation activity |
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| KR20110036317A (en) * | 2009-10-01 | 2011-04-07 | 재단법인 제주테크노파크 | Anti-inflammatory composition |
| KR20120058850A (en) * | 2010-11-30 | 2012-06-08 | 주식회사 알엔에스 | Compositions for the antiinflammatory and the antimicrobial activities |
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| KR20110036317A (en) * | 2009-10-01 | 2011-04-07 | 재단법인 제주테크노파크 | Anti-inflammatory composition |
| KR20120058850A (en) * | 2010-11-30 | 2012-06-08 | 주식회사 알엔에스 | Compositions for the antiinflammatory and the antimicrobial activities |
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| KR20180057442A (en) | 2016-11-22 | 2018-05-30 | 건양대학교산학협력단 | Manufacturing Method of Cudrania Tricuspidata Root Extract Having Anti-hangover Effect |
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