KR101429197B1 - Antibacterial Composition Containing Anthriscus sylvestris Extract - Google Patents
Antibacterial Composition Containing Anthriscus sylvestris Extract Download PDFInfo
- Publication number
- KR101429197B1 KR101429197B1 KR1020110122869A KR20110122869A KR101429197B1 KR 101429197 B1 KR101429197 B1 KR 101429197B1 KR 1020110122869 A KR1020110122869 A KR 1020110122869A KR 20110122869 A KR20110122869 A KR 20110122869A KR 101429197 B1 KR101429197 B1 KR 101429197B1
- Authority
- KR
- South Korea
- Prior art keywords
- extract
- present
- falcarindiol
- deoxypodophyllotoxin
- helicobacter pylori
- Prior art date
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Abstract
본 발명은 전호 (Anthriscus sylvestris) 추출물 및 이로부터 분리한 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin)을 유효성분으로 포함하는 항균 조성물에 관한 것이다.
본 발명의 전호 추출물 및 이로부터 분리한 팔카린디올 (falcarindiol) 및 디옥시포도필로톡신 (deoxypodophyllotoxin) 은 헬리코박터 파이로리균, 황색포도상구균 및 대장균에 대한 강한 항균활성을 나타냄으로써, 병원성 세균에 의해 발생하는 질병의 예방 또는 치료에 유용하게 사용될 수 있다. The present invention relates to an antimicrobial composition comprising, as an active ingredient, an Anthriscus sylvestris extract and falcarindiol or deoxypodophyllotoxin isolated therefrom.
The prophylactic extract of the present invention and falcarindiol and deoxypodophyllotoxin isolated therefrom exhibit a strong antimicrobial activity against Helicobacter pylori, Staphylococcus aureus and Escherichia coli, Can be usefully used for preventing or treating diseases.
Description
본 발명은 전호 (Anthriscus sylvestris) 추출물 및 이로부터 분리한 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin)을 유효성분으로 포함하는 항균 조성물에 관한 것이다.
The present invention relates to an antimicrobial composition comprising, as an active ingredient, an Anthriscus sylvestris extract and falcarindiol or deoxypodophyllotoxin isolated therefrom.
병원성 미생물에 의한 직접 혹은 간접적인 피해는 경제, 환경, 의학적으로 많은 문제를 야기하고 있다. 식품산업에서의 식품 유통 과정 중의 부패로 인한 손실, 농산업에서의 농작물에 대한 과량의 화학 살충제의 사용으로 인한 인체의 유해성 및 환경오염, 항생제의 오남용으로 인한 항생제 내성 균주의 출현 등 사회 전반에서 많은 문제들을 야기하고 있다.Direct or indirect damages caused by pathogenic microorganisms cause economic, environmental and medical problems. The loss of food in the food industry due to corruption, the harmfulness and environmental pollution of the human body due to the use of excessive chemical pesticides in the agricultural industry, and the emergence of antibiotic resistant strains due to abuse of antibiotics. .
인체 감염의 가장 흔한 원인균인 황색포도상구균의 마지막 치료제로 알려진 반코마이신에 고도의 내성을 보이는 포도상구균(vancomycin-resistant staphylococcus aureus, VRSA)이 2002년 미국 질병 통제국(Centers for Disease Control)에서 세계 최초로 보고됨으로써 소위 슈퍼 박테리아의 확산 가능성이 매우 높아지고 있다. 이는 반코마이신에 의해서만 치료가 되는 메치실린 내성 황색포도상구균(methicillin-resistants. aureus, MRSA)이 1970년대부터 문제시된 이후 1988년 반코마이신에 내성을 보이는 장구균(vancomycin resistant enterococcus, VRE)이 유럽에서 처음으로 발견되었고, 1990년 후반에는 일본, 미국, 프랑스, 한국에서 보고된 반코마이신에 내성을 보이는 황색포도상구균(vancomycin intermediate-resistants. aureus, VISA)이 발생하면서 범세계적인 위기로 떠오른 항생제 내성의 새로운 예로서 내성 문제가 얼마나 심각한지를 보여 주고 있어 새로운 항생제 개발이 시급히 요구되고 있다(Pfeltz, R. F. and Wilkinson, B. J. 2004. The escalating challenge of vancomycin resistance in Staphylococcus aureus. Drug targets-infect. Disord. 4: 273-294.; Levy, S. B. and Marshall, B. 2004. Antibacterial resistance worldwide: causes, challenges and responses. Nature Med. 10: 122-129.).Vancomycin-resistant staphylococcus aureus (VRSA), a highly resistant strain of vancomycin, is known to be the world's first treatment for Staphylococcus aureus, the most common cause of human infection. It was first reported by the Centers for Disease Control in 2002 The possibility of so-called super-bacteria spreading is becoming very high. This is the first time in Europe that vancomycin resistant enterococcus (VRE) resistant to vancomycin has been found in 1988 after methicillin-resistant aureus (MRSA), which is treated only by vancomycin, And vancomycin intermediate-resistants (aureus, VISA), which is resistant to vancomycin as reported in Japan, the United States, France and Korea in the latter half of 1990, is a new example of resistance to antibiotics, (Pfeltz, RF and Wilkinson, BJ 2004. The escalating challenge of vancomycin resistance in Staphylococcus aureus. Drug targets-infect. Disord. 4: 273-294 .; Levy , SB and Marshall, B. 2004. Antibacterial resistance worldwide: causes, challenges and responses. Nature Med. 10: 122-129.).
현재 사용되고 있는 대부분의 항생제는 화학적인 합성을 통해 제조된 것으로서 고비용이 소요되며 부작용을 유발하는 등의 많은 한계를 가지고 있다. 따라서, 최근에는 천연물로부터 새로운 항균물질을 분리하고자 하는 연구가 활발하게 진행되고 있다. 천연물로부터 새로운 항균물질을 분리하기 위해서는 항균 스펙트럼이 광범위하고 장기간 투여하여도 부작용이 없이 안전하여야 한다는 점 등을 고려해야 한다.
Most of the currently used antibiotics are manufactured through chemical synthesis, which is costly and has many limitations such as causing side effects. Therefore, in recent years, studies for separating new antimicrobial substances from natural products have been actively conducted. In order to isolate new antimicrobial substances from natural products, it should be considered that the antimicrobial spectrum is wide and safe even without long-term administration without adverse effects.
또한, 1982년 호주의 마샬 (Marshall)과 워렌 (Warren) 그리고 굳윈 (Goodwin)에 의해 B형 위염 환자의 위점막에서 순수 분리된 헬리코박터 파이로리균은 B형 만성위염, 위궤양과 십이지장궤양을 유발시키며 위암발생의 일차적 결정 요인으로 알려져 있다. 헬리코박터 파이로리균의 감염에 의한 위 및 십이지장질환의 발병기전 중 특히 위의 염증 유도에 있어 요소 분해효소인 우레아제 (urease)를 주요 인자로 들 수 있다. 헬리코박터 파이로리균은 전체 단백질의 6%에 해당하는 우레아제를 생성하는데, 생성된 우레아제는 요소를 암모니아와 이산화탄소로 분해하여 세균 주위환경을 중화하여 위 내강의 염산에 의한 공격을 방어할 뿐만 아니라, 위 점막에 축적된 암모니아 자체가 직접 위 점막 상피세포에 세포독성을 나타내어 위 점막 손상이 유발된다 (Sidebotham R.L., et al., J. Clin.Pathol.,44, pp 52-57, 1991). 이러한 우레아제의 작용으로 인해, 위 내강의 위산이 점막층 아래로 역류하게 되어 위산이 위 점막 상피세포를 광범위하게 손상시켜 위염과 위궤양이 발생한다. 또한, 암모니아 자체가 위 점액층 세포의 산소 소비와 미토콘드리아의 ATP 생성을 저해하고 (Tsujii M., et al., Gastroenterology, 102, pp 1881-1888, 1992), 궁극적으로 모노클로로아민 (monochloroamine)을 형성하여 반응성 산소종 (reactive oxygen pecies)을 생성하기 때문에 세포 손상을 유발하여 만성염증을 일으키고, 나아가 DNA 손상을 일으켜 암 발생 과정을 촉진시킨다는 보고가 있다 (Hahm K.B., et al., Am. J.Gastroenterol., 92, pp 1853-1857, 1997).In 1982, Helicobacter pylori isolated from gastric mucosa of patients with type B gastritis by Marshall, Warren and Goodwin in Australia induced chronic gastritis type B, gastric ulcer and duodenal ulcer, It is known as a primary determinant of development. A major factor in the pathogenesis of stomach and duodenal diseases caused by Helicobacter pylori infection is urease, an urease, in the induction of gastric inflammation. Helicobacter pylori produces urea, which is equivalent to 6% of the total protein. The resulting urease breaks down the urea into ammonia and carbon dioxide to neutralize the environment surrounding the bacteria to prevent attack by hydrochloric acid in the gastric lumen, (Sidebotham RL, et al., J. Clin. Pathol., 44, pp. 52-57, 1991), which causes cytotoxicity directly to gastric epithelial cells. Due to the action of urease, stomach acid in the gastric lumen is regressed below the mucosal layer, and gastric acid causes gastric mucosal epithelial cells to be extensively damaged, resulting in gastritis and gastric ulcer. In addition, ammonia itself inhibits the oxygen consumption of the gastric mucosal layer and the ATP production of mitochondria (Tsujii M., et al., Gastroenterology, 102, pp 1881-1888, 1992) and ultimately forms monochloroamine (Hahm KB, et al., Am. J. Gastroenterol). In addition, it has been reported that ROS produce reactive oxygen species, which cause cellular damage and cause chronic inflammation, , 92, pp 1853-1857, 1997).
헬리코박터의 전염은 동물 또는 인간을 통하거나, 의료행위시 부주의 또는 식품 등의 다양한 경로를 통하여 이루어지고 (Dunn, B. E., Cohen, H., and Blaser, M. J. (1997). Clinical Microbiology Reviews, 10 (4), 720-7; Kodaira, M.S., Escobar, A. M. U., & Grisi, S. (2002) Revista de Sade Pade Pblica.36: 356-369), 일단 감염되고 나면 쉽게 박멸되지 않는다.Helicobacter infections can be transmitted through animals or humans, through carelessness during medical care or through various routes of food (Dunn, BE, Cohen, H., and Blaser, MJ (1997). Clinical Microbiology Reviews, 10 ), 720-7, Kodaira, MS, Escobar, AMU, & Grisi, S. (2002) Revista de Sade Pade Pblica.36: 356-369).
헬리코박터 파이로리는 인간에게 특이적이며 위장 내의 특정 장소에서 주로 발견되는데, 소화성 궤양 (예를 들면, 위궤양 또는 십이지장 궤양 등), 염증 (예를 들면, 위염 등), 위암 등의 소화관 상부의 질환, MALT (점막-관련 임파조직 (mucosaassociated lymphoid tissue)) 임파종의 병인 또는 만성 심장 질환의 배경 병원성 인자라고 한다. 현재, 헬리코박터 파이로리 감염증 치료에 관한 연구는 활발히 이루어지고 있으며, 그의 치료법으로서는 제거를 목적으로 한 것, 재발 방지를 목적으로 한 것 등이 다수 보고되어 있다.Helicobacter pylori is specific to humans and is found mainly in certain places within the stomach, including diseases of the digestive tract such as peptic ulcers (e.g. gastric ulcer or duodenal ulcer), inflammation (e.g. gastritis) (Mucosa-associated lymphoid tissue) is a pathogenic factor in the pathogenesis of a lymphoma or chronic heart disease. Currently, studies on the treatment of Helicobacter pylori infection have been actively conducted, and many therapies for the purpose of elimination and prevention of recurrence have been reported.
상술한 바와 같이, 헬리코박터 파이로리가 위장 질환에서 매우 위험한 미생물이지만, 천연소재를 이용한 적절한 항균물질 등 개발이 부족한 실정이다. 현재 헬리코박터 파이로리 치료법으로는 비스무스 (bismuth)제제, 메트로니다졸 (metronidazole)과 함께 테트라사이클린 (tetracycline) 또는 아목실린 (amoxicillin)을 방용 처리하는 일반적인 3중 요법과 비스무스 제제, 오메파라졸 (omeparazole), 테트라사이클린 및 메트로니다졸을 혼합한 4중 요법 등이 보고되어 있다. 그러나, 항생제 투여에 의한 내성 균주 출현 및 위 내에서의 약물의 침투성과, 치료 후에 성장이 억제되어 있던 균이 재 증식하는 문제가 지적되고 있다. 이런 이유로 헬리코박터 파이로리에 특이적인 항균물질을 탐색하려는 수많은 노력이 이루어졌으며, 최근에는 식물류에 들어있는 생리활성 성분에 대한 관심이 높아지고 있으며, 이들의 생체 조절 기능 및 질병의 회복이나 예방 등에 관한 가능성이 제시되어 왔다. 최근 백리향, 중국차, Cashew apple, 소목과 황련 등 여러 천연물의 헬리코박터 파이로리에 대한 항균활성이 보고되었으나, 아직은 연구가 미진한 실정이다.As described above, although Helicobacter pylori is a very dangerous microorganism in gastrointestinal diseases, development of an appropriate antibacterial substance using natural materials is lacking. Currently, Helicobacter pylori therapies include bismuth, metronidazole, tetracycline or amoxicillin, bismuth, omeparazole, tetracycline or amoxicillin, And metronidazole have been reported. However, it has been pointed out that the appearance of resistant strains by the administration of antibiotics, the permeability of the drug in the stomach, and the reproductive growth of the bacteria whose growth has been suppressed after treatment are pointed out. For this reason, numerous efforts have been made to search for antibacterial substances specific to Helicobacter pylori. In recent years, there has been a growing interest in physiologically active ingredients in plants and their potential for regulating or preventing diseases Has come. Recently, antimicrobial activity against Helicobacter pylori of various natural products such as Thyme, Chinese tea, Cashew apple, Caboose and Chrysanthemum has been reported, but the research has not been done yet.
이에 본 발명자는 상기한 바와 같은 문제점을 해결하기 위하여, 천연물로부터 새로운 항균물질을 분리하고자 연구를 계속하던 중, 전호 추출물 및 이로부터 분리한 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin)이 병원성 미생물에 대한 뛰어난 항균효과를 갖는 것을 발견함으로써 본 발명을 완성하였다.
In order to solve the above-mentioned problems, the inventor of the present invention has conducted research to separate new antimicrobial substances from natural products, and found that the extracts of the present invention and falcarindiol or deoxypodophyllotoxin, Has an excellent antimicrobial effect on the pathogenic microorganism, thereby completing the present invention.
본 발명의 목적은 본 발명은 전호 (Anthriscus sylvestris) 추출물 및 이로부터 분리한 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin)을 유효성분으로 포함하는 항균 조성물을 제공하는 것이다.
The object of the present invention is to provide an antimicrobial composition comprising an Anthriscus sylvestris extract and falcarindiol or deoxypodophyllotoxin isolated therefrom as an active ingredient.
상기 목적을 달성하기 위하여 본 발명은 전호 (Anthriscus sylvestris) 추출물을 유효성분으로 포함하는 항균용 약학적 조성물을 제공한다. In order to achieve the above object, the present invention provides a pharmaceutical composition for antimicrobial use comprising an extract of Anthriscus sylvestris as an active ingredient.
또한 본 발명은 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin)을 유효성분으로 포함하는 항균용 약학적 조성물을 제공한다.The present invention also provides a pharmaceutical composition for antimicrobial use comprising, as an active ingredient, falcarindiol or deoxypodophyllotoxin.
또한 본 발명은 전호 추출물을 유효성분으로 포함하는 위 및 십이지장질환 예방 및 치료용 약학적 조성물을 제공한다. The present invention also provides a pharmaceutical composition for the prevention and treatment of stomach and duodenal diseases, which comprises a prodrug extract as an active ingredient.
또한 본 발명은 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin)을 유효성분으로 포함하는 위 및 십이지장질환 예방 및 치료용 약학적 조성물을 제공한다. The present invention also provides a pharmaceutical composition for the prevention and treatment of stomach and duodenal diseases comprising falcarindiol or deoxypodophyllotoxin as an active ingredient.
또한 본 발명은 전호 추출물을 유효성분으로 포함하는 위 및 십이지장질환 예방 및 개선용 건강기능식품을 제공한다. The present invention also provides a health functional food for prevention and improvement of stomach and duodenal diseases, which comprises as an active ingredient a prodrug extract.
또한 본 발명은 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin) 을 유효성분으로 포함하는 위 및 십이지장질환 예방 및 개선용 건강기능식품을 제공한다. The present invention also provides a health functional food for preventing and improving stomach and duodenal diseases comprising falcarindiol or deoxypodophyllotoxin as an active ingredient.
또한 본 발명은 전호 추출물을 유효성분으로 포함하는 항균용 제제를 제공한다.The present invention also provides an antimicrobial preparation comprising a prodrug extract as an active ingredient.
또한 본 발명은 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin)을 유효성분으로 포함하는 항균용 제제를 제공한다.
The present invention also provides an antibacterial agent comprising falcarindiol or deoxypodophyllotoxin as an active ingredient.
본 발명의 전호 추출물 및 이로부터 분리한 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin)은 헬리코박터 파이로리균, 황색포도상구균 및 대장균에 대한 강한 항균활성을 나타냄으로써, 병원성 세균에 의해 발생하는 질병의 예방 또는 치료에 유용하게 사용될 수 있다.
The prophylactic extract of the present invention and falcarindiol or deoxypodophyllotoxin isolated therefrom exhibit a strong antimicrobial activity against Helicobacter pylori, Staphylococcus aureus and Escherichia coli, Can be usefully used for preventing or treating diseases.
도 1은 전호 추출물의 분획 모식도이다.
도 2는 전호 메탄올 추출물의 헬리코박터 파이로리균에 대한 항균활성 결과이다.
도 3은 전호 분획물의 황색포도상구균 및 대장균에 대한 항균활성 결과이다.
도 4는 전호 추출물에서 분리한 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin)의 항균활성 결과이다. Fig. 1 is a fragmentary schematic view of the extract of T. hiraku.
Fig. 2 shows the results of antibacterial activity against Helicobacter pylori of the methanol extract of prokinase.
Fig. 3 shows the results of antibacterial activity against the Staphylococcus aureus and Escherichia coli of the former fraction.
FIG. 4 shows the results of antimicrobial activity of falcarindiol or deoxypodophyllotoxin, which was isolated from the extract of Tumor roe.
이하 본 발명에 대하여 보다 상세히 설명한다. Hereinafter, the present invention will be described in more detail.
하나의 양태로서, 본 발명은 전호 (Anthriscus sylvestris) 추출물을 유효성분으로 포함하는 항균용 약학적 조성물을 제공한다. In one embodiment, the present invention provides a pharmaceutical composition for antimicrobial use comprising an extract of Anthriscus sylvestris as an active ingredient.
전호 (Anthriscus sylvestris)는 전국의 산골짜기에서 흔히 볼 수 있고, 일본, 만주 및 중국에 분포하는 여러해살이풀로서, 높이 30-70cm, 긴 갈색 털이 있으며 뿌리줄기는 굵고 짧게 옆으로 뻗는다. 꽃은 7-8월에 피고 홍자색이며, 줄기 끝의 원추꽃차례에 많은 꽃이 달리고, 화축에는 갈색 털이 많고, 꽃받침은 5개로 갈라지고 갈라진 조각은 달걀 모양이며 꽃잎은 5개이다. 전호를 채취하여 말린 것을 소승마 (赤小麻) 또는 적승마 (赤升麻)라고도 부르며, 혈액순환을 좋게 하고, 어혈 (瘀血)을 풀어주며, 열을 내리고, 독을 풀어주며, 경련을 멎게 하고, 통증을 멎게 하는 효능이 있다고 알려져 있다. 또한 과로로 오는 병, 근육과 뼈마디가 시리고 아픈 증상, 타박상, 관절통, 수술 후 통증, 뱀에게 물린 독을 푸는 데 사용한다 (배기환, 한국의 약용식물, 교학사, p204, 2000).Anthriscus sylvestris is a common perennial plant distributed in Japan, Manchuria and China. It is 30-70cm high and has long brown hairs. Its rootstock is thick and short side-to-side. Flowers bloom in July-August, reddish purple, with many flowers on cones of stem at the end of stem, brown hairs on conchs, sepals are divided into 5 pieces, ovate fragments are 5 petals. It is called red horse hemp or red horse head horse which picks up the dried horse and makes dried, improves blood circulation, releases ebony blood, releases fever, releases poison, It is known that it has the effect of stopping and stopping the pain. It is also used to relieve sickness, muscular and bony symptoms, bruises, arthralgia, post-operative pain, and poisonous bites from poisoned snakes (Bae Ki-hwan, Korean Medicinal Plants, Kyongsoo, p204, 2000).
본 명세서에서 사용된 용어 "추출물 (extract)"이란 천연물로부터 분리된 활성성분 즉, 목적하는 활성을 보이는 물질을 의미한다. 상기 추출물은 물, 유기용매 또는 이들의 혼합용매를 이용하는 추출과정으로 획득할 수 있으며, 추출물 이의 건조 분말 또는 이를 이용하여 제형화된 모든 형태를 포함한다. 또한, 상기 추출물에는 상기 추출과정을 거친 추출액을 분획한 것도 포함된다.As used herein, the term "extract" means an active ingredient isolated from a natural product, i.e., a substance exhibiting the desired activity. The extract can be obtained by an extraction process using water, an organic solvent, or a mixed solvent thereof, and includes all the forms that are formulated with the dry powder of the extract. In addition, the above-mentioned extract also includes a fraction obtained by fractionating the extract obtained through the above extraction process.
본 발명에 따른 전호 추출물은 다음과 같은 과정을 거쳐 얻어질 수 있다.The extract according to the present invention can be obtained through the following process.
전호를 알코올, 에틸아세테이트, 메틸린 클로라이드, 메틸에틸케톤, 아세톤 및 에테르로 이루어진 그룹으로부터 선택된 1종 이상의 용매로 추출하여 감압 농축시킨다. 상기 알코올은 저급 또는 고급 알코올일 수 있으며, 바람직하게는 메탄올, 에탄올, 이소프로판올 및 부탄올로 이루어진 그룹으로부터 선택된 저급 알코올이고, 보다 바람직하게는 메탄올이다. 상기 알코올은 물과의 혼합물일 수 있다. 상기 농축물에 추가적으로 헥산, 메틸린 클로라이드, 에틸아세테이트, 부탄올 또는 물로 각각 분획하여 다시 감압농축을 할 수 있다. 상기 분획 농축물을 담체로는 실리카 또는 종이를, 전개용매로는 클로로포름:아세톤:개미산의 혼합용액을 이용하여 크로마토그래피 (종이, TLC, 컬럼 등)를 실시하여 정제하는 단계를 추가로 실시할 수 있다. 여기서, 담체에 함유된 물과 전개용매 간의 추출물 내 물질들의 분배가 일어나고, 분배율의 차이에 따라 물질이 분리된다. 상기 전개용매에서 클로로포름:아세톤:개미산은 50~100:10~20:5~10, 가장 바람직하게는 75:16.5:8.5의 비율로 혼합할 수 있다. 상기 크로마토그래피는 담체로서 실리카를 이용한 박층 크로마토그래피 (TLC) 또는 컬럼 크로마토그래피일 수 있다. 상기 TLC는 유리판 또는 플라스틱과 같은 지지체에 실리카겔을 얇게 입히고, 그 위에 추출물을 점적한 후 전개용매로 전개하여 정제하는 방식이다. 상기 컬럼 크로마토그래피는 컬럼 내에 실리카를 충진하고, 그 위에 추출물을 로딩한 후 전개용매로 전개하여 정제하는 방식이다. 추출물의 대량 제조 시에는 컬럼 크로마토그래피를 이용하는 것이 바람직하다.The precursor is extracted with at least one solvent selected from the group consisting of alcohol, ethyl acetate, methylene chloride, methyl ethyl ketone, acetone and ether, and the mixture is concentrated under reduced pressure. The alcohol may be a lower or higher alcohol, preferably a lower alcohol selected from the group consisting of methanol, ethanol, isopropanol and butanol, and more preferably methanol. The alcohol may be a mixture with water. The concentrate may further be fractionated with hexane, methylene chloride, ethyl acetate, butanol or water, and then concentrated under reduced pressure. The fraction concentrate may be further purified by chromatography (paper, TLC, column, etc.) using silica or paper as a carrier and a mixed solution of chloroform: acetone: formic acid as a developing solvent have. Here, the distribution of the substances in the extract between the water contained in the carrier and the developing solvent takes place, and the substance is separated according to the difference in the distribution ratio. In the developing solvent, chloroform: acetone: formic acid may be mixed at a ratio of 50 to 100: 10 to 20: 5 to 10, and most preferably 75: 16.5: 8.5. The chromatography may be thin layer chromatography (TLC) or column chromatography using silica as a carrier. The TLC is a method in which a silica gel is thinly coated on a support such as a glass plate or a plastic, and the extract is dripped on the support, followed by development with a developing solvent. The column chromatography is a method in which silica is packed in a column, the extract is loaded on the column, and developed with a developing solvent. For mass production of the extract, column chromatography is preferably used.
또한 본 발명은 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin)을 유효성분으로 포함하는 항균용 약학적 조성물을 제공한다. 상기 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin)은 화학식 1 또는 화학식 2의 구조를 가진다. 상기 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin)은 전호 추출물로부터 수득할 수 있으며, 합성 또는 제조사로부터 구입하여 사용할 수 있다. The present invention also provides a pharmaceutical composition for antimicrobial use comprising, as an active ingredient, falcarindiol or deoxypodophyllotoxin. The above-mentioned falcarindiol or deoxypodophyllotoxin has the structure of formula (1) or (2). The above-mentioned falcarindiol or deoxypodophyllotoxin can be obtained from prodrug extract and can be synthesized or purchased from a manufacturer.
본 발명에 따른 전호 추출물 및 이로부터 분리된 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin)은 황색포도상구균 및 대장균에 대하여 강한 항균활성을 나타낸다. 따라서, 본 발명에 따른 전호 추출물 및 이로부터 분리된 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin)은 상기 세균의 예방 또는 치료에 유용하게 사용할 수 있다. The extract according to the present invention and the falcarindiol or deoxypodophyllotoxin isolated therefrom exhibit a strong antimicrobial activity against Staphylococcus aureus and Escherichia coli. Accordingly, the extract according to the present invention and falcarindiol or deoxypodophyllotoxin isolated therefrom may be useful for the prevention or treatment of the bacterium.
또 다른 양태로서 본 발명은 전호 추출물을 유효성분으로 포함하는 위 및 십이지장질환 예방 및 치료용 약학적 조성물을 제공한다. 또한 본 발명은 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin)을 유효성분으로 포함하는 위 및 십이지장질환 예방 및 치료용 약학적 조성물을 제공한다. In another aspect, the present invention provides a pharmaceutical composition for preventing and treating stomach and duodenal diseases, which comprises a prodrug extract as an active ingredient. The present invention also provides a pharmaceutical composition for the prevention and treatment of stomach and duodenal diseases comprising falcarindiol or deoxypodophyllotoxin as an active ingredient.
본 발명에 따른 전호 추출물 및 이로부터 분리한 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin)은 헬리코박터 파이로리균에 대한 항균활성을 보이므로, 헬리코박터 파이로리에 의해 유발되는 위 및 십이지장 질환의 예방 및 치료에 유용하게 사용할 수 있다. 상기 위 및 십이지장 질환이란, 소화성 궤양과 위암을 포함하는 것일 수 있고, 바람직하게는 위염, 십이지장염, 위궤양, 십이지장궤양, 위선암, 위림프종 및 위암으로 이루어진 군에서 선택된 1종 이상일 수 있으며, 상기 위염은 바람직하게는 만성 위축성 위염일 수 있다. 헬리코박터 파이로리가 발견된 이후로, 상기 위 및 십이지장 질환의 주 원인균은 헬리코박터 파이로리로 보고되고 있으며, 헬리코박터 파이로리는 위점막, 구체적으로는 상피세포 및 점막층에 주로 결합하여 서식하는 것으로 알려져 있다. 따라서, 상기 위 및 십이지장 질환을 치료하기 위해 원인균인 헬리코박터 파이로리에 대한 항균활성이 뛰어난 우수한 물질을 처방할 수 있다.The extract according to the present invention and the falcarindiol or deoxypodophyllotoxin isolated therefrom exhibit antimicrobial activity against Helicobacter pylori. Therefore, prevention of gastric and duodenal diseases induced by Helicobacter pylori And may be useful for treatment. The gastric and duodenal diseases may include peptic ulcer and gastric cancer, and preferably one or more selected from the group consisting of gastritis, duodenal ulcer, gastric ulcer, duodenal ulcer, gastric cancer, gastric lymphoma and gastric cancer, May be preferably chronic atrophic gastritis. Since the discovery of Helicobacter pylori, it has been reported that Helicobacter pylori is the main cause of gastric and duodenal diseases, and Helicobacter pylori is known to live mainly in the gastric mucosa, specifically epithelial cells and mucosal layer. Accordingly, it is possible to prescribe an excellent substance having excellent antimicrobial activity against Helicobacter pylori which is a causative organism for treating gastric and duodenal diseases.
본 발명의 약학적 조성물은 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀전, 시럽, 에어로졸 등 경구 투여용 제형, 멸균 주사용액, 좌제 및 경피 투여용 제제로 제형화하여 사용될 수 있다. 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토오스, 덱스트로오스, 수크로오스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로오스, 메틸 셀룰로오스, 미정질 셀룰로오스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. 필요에 따라 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 제형화한다.The pharmaceutical composition of the present invention may be formulated into oral dosage forms, sterile injectable solutions, suppositories, and transdermal dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups and aerosols according to a conventional method have. Examples of carriers, excipients and diluents that can be included in the composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, Microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. If necessary, it is formulated using a diluent such as a filler, an extender, a binder, a wetting agent, a disintegrant, a surfactant, or an excipient.
한 양태로서, 본 발명의 약학적 조성물은 경구 투여용 고상 제제로 제형화할 수 있다. 경구 투여를 위한 고상 제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되는데, 이러한 고상 제제는 상기 추출물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘 카르보네이트, 수크로오스 또는 락토오스, 젤라틴 등을 혼합하여 제형화된다. 또한, 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용될 수 있다.In one embodiment, the pharmaceutical composition of the present invention can be formulated into a solid preparation for oral administration. Solid form preparations for oral administration include tablets, pills, powders, granules, capsules and the like. These solid preparations may contain at least one excipient such as starch, calcium carbonate, sucrose or lactose, gelatin Are mixed and formulated. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used.
다른 양태로서, 본 발명의 약학적 조성물을 경구 투여용 액상 제제로 제형화할 수도 있다. 경구 투여를 위한 액상 제제는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데, 이러한 액상 제제에는 통상적으로 사용되는 불활성 희석제 (예를 들면, 정제수, 에탄올, 리퀴드 파라핀) 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다.In another embodiment, the pharmaceutical composition of the present invention may be formulated into a liquid preparation for oral administration. Liquid preparations for oral administration include suspensions, solutions, emulsions and syrups. These liquid preparations may contain various excipients in addition to commonly used inert diluents (for example, purified water, ethanol, liquid paraffin) For example, wetting agents, sweeteners, fragrances, preservatives and the like may be included.
또 다른 양태로서, 본 발명의 약학적 조성물은 비경구, 바람직하게는 복강내 투여를 위한 제제로 제형화될 수도 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 멸균된 수용액으로는 한스 용액 (Hank's solution), 링거 용액 (Ringer's solution) 또는 물리적으로 완충된 염수와 같은 적절한 완충용액을 이용할 수 있으며, 비수성용제로, 현탁제로는 프로필렌글리콜, 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 이용될 수 있다. 필요에 따라 방부제, 안정화제, 습윤제 또는 유화제, 삼투압 조절을 위한 염 및/또는 완충제를 이용할 수도 있다. 한편, 좌제의 경우에는 이의 통상적인 기제인 위텝솔 (witepsol), 마크로골, 트윈 (tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.In another embodiment, the pharmaceutical composition of the present invention may be formulated into a preparation for parenteral, preferably intraperitoneal administration. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. As the sterilized aqueous solution, a suitable buffer solution such as Hank's solution, Ringer's solution or physically buffered saline can be used. As the non-aqueous solvent, propylene glycol, polyethylene glycol, olive oil, The same vegetable oil, an injectable ester such as ethyl oleate, or the like can be used. If desired, preservatives, stabilizers, wetting or emulsifying agents, salts for controlling osmotic pressure and / or buffers may be used. On the other hand, in the case of suppositories, witepsol, macrogol, tween 61, cacao paper, laurin, glyceroglatin and the like may be used.
상기와 같은 방법으로 제형화된 조성물은 유효량으로 비경구 또는 경구 (경피, 피하, 정맥, 근육, 복강등)를 포함한 여러 경로를 통해 투여될 수 있다. 상기에서 "유효량"이란 환자에게 투여하였을 때, 예방 또는 치료 효과를 나타내는 양을 말한다. 본 발명에 따른 조성물의 투여량은 투여 경로, 투여 대상, 연령, 성별, 체중, 개인차 및 질병 상태에 따라 적절히 선택될 수 있다. 바람직하게는, 본 발명의 조성물은 질환의 정도에 따라 유효성분의 함량을 달리할 수 있으나, 바람직하게는 0.1~10000 mg/체중kg/day, 보다 바람직하게는 10~1000 mg/체중kg/day의 유효량으로 투여될 수 있다.
The composition formulated in the above manner may be administered through various routes including parenteral or oral (transdermal, subcutaneous, intravenous, muscular, abdominal, etc.) in an effective amount. The "effective amount" as used herein refers to an amount that shows a preventive or therapeutic effect when administered to a patient. The dose of the composition according to the present invention can be appropriately selected depending on the route of administration, subject to be administered, age, sex, weight, individual difference, and disease state. Preferably, the composition of the present invention may contain the active ingredient in an amount of 0.1 to 10000 mg / kg body weight / day, more preferably 10 to 1000 mg / kg body weight / day RTI ID = 0.0 > of < / RTI >
또 다른 양태로서, 본 발명은 전호 (Anthriscus sylvestris) 추출물을 유효성분으로 포함하는 위 및 십이지장 질환의 예방 및 개선용 건강기능식품을 제공한다. 또한 본 발명은 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin)을 유효성분으로 포함하는 위 및 십이지장질환 예방 및 개선용 건강기능식품을 제공한다. In another aspect, the present invention provides a health functional food for prevention and improvement of stomach and duodenal diseases comprising an extract of Anthriscus sylvestris as an active ingredient. The present invention also provides a health functional food for preventing and improving stomach and duodenal diseases comprising falcarindiol or deoxypodophyllotoxin as an active ingredient.
본 발명의 조성물을 식품 또는 음료 첨가물로 사용할 경우, 상기 전호 추출물 또는 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin)을 그대로 첨가하거나, 다른 식품 또는 식품 성분과 함께 사용되고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 상기 전호 추출물 또는 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin)의 혼합양은 그의 사용목적 (예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다.When the composition of the present invention is used as a food or beverage additive, the above extract or the falcarindiol or deoxypodophyllotoxin may be directly added, used in combination with other food or food ingredients, Can be appropriately used. The amount of the prophylactic extract or the amount of falcarindiol or deoxypodophyllotoxin can be suitably determined according to its intended use (prevention, health or therapeutic treatment).
건강을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우, 상기 전호 추출물은 안전성 면에서 아무런 문제가 없기 때문에, 장기간 복용이 가능하다.In the case of long-term intake for the purpose of health or for the purpose of controlling health, it is possible to take the prophylactic extract for a long period of time because there is no problem in terms of safety.
상기 식품의 종류에는 특별한 제한은 없다. 상기 물질을 첨가할 수 있는 식품의 예로는 육류, 소세지, 빵, 초콜릿류, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 수프, 음료수, 차, 드링크제, 알코올 음료 및 비타민 복합제 등이 있다.There is no particular limitation on the kind of the food. Examples of foods to which the above substances can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, , Alcoholic beverages and vitamin complexes.
음료수로 제형화할 경우에 전호 추출물 이외에 첨가되는 액체 성분으로는 이제 한정되지는 않으나, 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드 (예, 포도당, 과당 등), 디사카라이드 (예, 말토오스, 수크로오스 등) 및 폴리사카라이드 (예, 덱스트린, 시클로덱스트린 등과 같은 통상적인 당), 및 자일리톨, 소르비톨, 에리스리톨 등의 당알코올이다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100㎖당 일반적으로 약 1 내지 20g, 바람직하게는 약 5 내지 12g이다. 상술한 것 이외의 향미제로서 천연 향미제 (타우마린, 스테비아 추출물 (예, 레바우디오시드A, 글리시르히진 등)) 및 합성 향미제 (예, 사카린, 아스파르탐 등)를 사용할 수 있다.In case of formulation with beverage, the liquid ingredient to be added in addition to the prophylactic extract is not limited to any one, but may include various flavors or natural carbohydrates such as ordinary beverages as an additional ingredient. Examples of such natural carbohydrates include monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose and polysaccharides such as those commonly used in dextrin and cyclodextrins, , Sorbitol, and erythritol. The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention. Natural flavors (taumarin, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.)) and synthetic flavors (e. G., Saccharin, aspartame, etc.) can be used as flavors other than those described above .
다른 양태로서, 본 발명의 식품 조성물은 여러 가지 영양제, 비타민, 광물 (전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 증진제 (치즈, 초콜릿 등), 펙트산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 또한, 본 발명의 식품 조성물은 과일 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 단독으로 또는 조합으로 사용될 수 있으며, 이러한 첨가제의 비율은 조성물 전체 중량당 10 내지 20 중량%의 범위에서 선택할 수 있다.
In another aspect, the food composition of the present invention may be formulated into various flavors such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, colorants and enhancers (cheese, chocolate etc.), pectic acid and its salts, , Protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like. In addition, the food composition of the present invention may contain pulp for the production of fruit and vegetable drinks. These components may be used singly or in combination, and the proportion of such additives may be selected in the range of 10 to 20% by weight based on the total weight of the composition.
또 다른 양태로서, 본 발명은 전호 (Anthriscus sylvestris) 추출물을 유효성분으로 포함하는 항균용 제제을 제공한다. 또한 본 발명은 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin)을 유효성분으로 포함하는 항균용 제제를 제공한다.In another aspect, the present invention provides an antibacterial agent comprising an Anthriscus sylvestris extract as an active ingredient. The present invention also provides an antibacterial agent comprising falcarindiol or deoxypodophyllotoxin as an active ingredient.
상기 제제로는 예를 들면, 이에 한정되지는 않으나 화장품, 소독제, 살균 세정제 및 식품 보존제가 포함된다. 상기에서 화장품은 본 발명의 전호 추출물 또는 이로부터 분리된 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin)과 함께 화장료 조성물의 제조 분야에서 일반적으로 사용되는 하나 이상의 부형제 및 첨가제를 포함하여 당 분야의 공지의 방법에 따라 용이하게 제조될 수 있다. 보다 구체적으로, 상기 화장품은 화장수, 크림, 에센스, 클렌징 폼 및 클렌징 워터와 같은 세안제, 팩, 바디오일 등과 같은 기초 화장품, 화운데이션, 립스틱, 마스카라 및 메이크업 베이스 등과 같은 색조 화장품, 샴푸, 린스, 헤어컨디셔너 및 헤어젤 등과 같은 두발제품 및 비누 등이 포함된다. 바람직하게는, 본 발명의 전호 추출물 또는 이로부터 분리된 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin)을 포함하는 화장료 조성물은 여드름을 치료 또는 예방하는데 사용될 수 있다. 따라서, 본 발명의 화장료 조성물에는 여드름의 치료 효과를 향상시킬 수 있는 파파인(Papain), 브로멜레인(Bromelain) 등 식물 유래의 단백질 분해효소와 미생물 유래의 단백질분해효소 등의 피부각질 제거제를 추가로 첨가할 수 있다. 특히, 살리실산이나 트리클로산 등의 물질을 추가로 첨가할 수 있다.Such preparations include, for example, but are not limited to, cosmetics, disinfectants, sterilizing detergents, and food preservatives. The cosmetic composition may comprise one or more excipients and additives commonly used in the field of cosmetic composition preparation together with the prophylactic extract of the present invention or falcarindiol or deoxypodophyllotoxin isolated therefrom, And can be easily manufactured according to a known method in the field. More specifically, the cosmetic may be at least one selected from the group consisting of basic cosmetics such as cleanser, pack, body oil and the like such as lotion, cream, essence, cleansing foam and cleansing water, color cosmetics such as foundation, lipstick, mascara and makeup base, shampoo, Hair products such as hair gel and soap, and the like. Preferably, cosmetic compositions comprising the prophylactic extract of the present invention or falcarindiol or deoxypodophyllotoxin isolated therefrom may be used to treat or prevent acne. Therefore, the cosmetic composition of the present invention may further comprise a plant-derived proteolytic enzyme such as Papain and Bromelain which can improve the therapeutic effect of acne, and a skin exfoliating agent such as a protease derived from a microorganism Can be added. In particular, substances such as salicylic acid and triclosan can be further added.
상기 소독제는 본 발명의 전호 추출물 또는 이로부터 분리된 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin)을 그대로 사용하거나 적합한 농도가 되도록 피부학적 및 약리학적으로 허용되는 희석제 또는 용매로 희석하여 제조할 수 있다. 상기 소독제는 생물체의 표면 바람직하게는, 포유동물의 피부 가장 바람직하게는 인간의 피부에 사용될 수 있다. 또한, 상기 소독제는 무생물체의 표면 예를 들면, 나무, 금속, 유리, 세라믹, 플라스틱, 종이 및 천의 표면에 사용될 수 있다. 상기 소독제는 침지, 면봉, 분무 및 브러싱을 포함하는 방법을 사용하여 상기 생물체 또는 무생물체의 표면에 처리할 수 있다. 바람직하게는, 상기 소독제는 상처표면, 수술 전 피부소독, 수술기구의 소독, 도관 소독 등의 용도로 병원과 일반 가정에서 사용할 수 있다.The disinfectant may be obtained by diluting the prophylactic extract of the present invention or falcarindiol or deoxypodophyllotoxin isolated therefrom as it is or diluting it with a dermatologically and pharmacologically acceptable diluent or solvent to a suitable concentration Can be manufactured. The disinfectant may be used on the surface of the organism, preferably on the skin of mammals, most preferably on human skin. In addition, the disinfectant may be used on surfaces of non-living organisms such as wood, metal, glass, ceramic, plastic, paper and cloth. The disinfecting agent may be applied to the surface of the organism or organism using methods including immersion, swab, spray and brushing. Preferably, the disinfectant may be used in hospitals and general households for use on wound surfaces, pre-operative skin disinfection, surgical instrument disinfection, and catheter disinfection.
상기 살균 세정제의 경우에는 본 발명에 따른 전호 추출물 또는 이로부터 분리된 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin) 외에 세정제의 제조 분야에서 일반적으로 사용되는 하나 이상의 부형제 및 첨가제를 포함하여 당 분야의 공지의 방법에 따라 용이하게 제조될 수 있다. 상기 살균 세정제는 주방용 또는 식품용으로 사용될 수 있으며, 주방용 살균 세정제에는 전호 추출물 또는 이로부터 분리된 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin)외에 음이온계 계면활성제, 비이온계 계면활성제, 양쪽성 계면활성제 등을 추가로 포함할 수 있다. 음이온계 계면활제의 예로는 알킬벤젠설 포네이트, 알파올레핀설페이트, 소듐 또는 암모늄라우릴에테르설페이트 등이 있으며, 비온온계 계면활성제의 예로는 지방산 아미드, 알킬폴리글루코시드, 에톡시화 지방알콜계, 에톡시화 노닐 페놀계 등이 있다. 양쪽성 계면활성제의 예로는 베타인계 계면활성제, 아민 옥사이드 등이 있다. 상기 계면활성제 외에 향, 색소 및 물과 같은 희석제를 선택적으로 첨가할 수 있다.In the case of the germicidal cleansing agent, in addition to the prophylactic extract according to the present invention or falcarindiol or deoxypodophyllotoxin isolated therefrom, one or more excipients and additives commonly used in the production of detergents And can be easily produced according to methods known in the art. The sterilizing detergent may be used for a kitchen or a food, and the sterilizing detergent for the kitchen may contain an anionic surfactant, a nonionic surfactant, an antioxidant, an antiseptic, an antiseptic, an antiseptic, , An amphoteric surfactant, and the like. Examples of anionic surfactants include alkylbenzenesulfonates, alpha olefin sulfates, sodium or ammonium lauryl ether sulfates, and examples of nonionic surfactants include fatty acid amides, alkylpolyglucosides, ethoxylated fatty alcohols, And the like. Examples of amphoteric surfactants include betaine surfactants, amine oxides, and the like. In addition to the surfactant, a diluent such as fragrance, pigment and water may be optionally added.
식품용 살균 세정제의 경우에는 본 발명에 따른 전호 추출물 또는 이로부터 분리된 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin)에 식품학적으로 허용되는 용매 또는 희석제를 추가로 첨가하여 적절한 농도로 희석함으로써 제조할 수 있다. 상기 식품용 살균 세정제는 예를 들어, 과일류, 어류 및육류 등의 살균 및 세척에 사용될 수 있다.In the case of a food sterilizing detergent, a food-acceptable solvent or diluent is added to the extract of the present invention or falcarindiol or deoxypodophyllotoxin isolated therefrom at an appropriate concentration And then diluted. The food sterilizing detergent can be used for sterilizing and washing fruits, fish and meat, for example.
식품 보존제는 식품류의 보존성을 증강시키기기 위한 목적으로 본 발명의 따른 전호 추출물 또는 이로부터 분리된 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin)에 식품학적으로 허용되는 용매 또는 희석제를 추가로 첨가하여 제조할 수 있다. 본 발명의 식품 보존제는 식품의 제조 공정시 원료와 함께 배합하거나 별도의 수용성 현탁액으로 제조하여 첨가할 수도 있다. 또한, 상기 본 발명에 따른 식품 보존제를 사용하여 대상 식품을 침지시키거나 본 발명의 식품 보존제를 대상 식품에 분무할 수 있다.
For the purpose of enhancing the preservability of foodstuffs, a food preservative may be added to a pharmacologically acceptable solvent or diluent to falcarindiol or deoxypodophyllotoxin isolated from the extract according to the present invention or a pharmacologically acceptable salt thereof And the like. The food preservative of the present invention may be formulated together with the raw material in the process of producing food or may be added as a separate aqueous suspension. In addition, the food preservative according to the present invention can be used to immerse the target food or spray the food preservative of the present invention to the target food.
이하 본 발명의 이해를 돕기 위하여 바람직한 실시예 및 제조예를 제시한다. 그러나 하기의 실시예 및 제조예는 본 발명을 보다 쉽게 이해하기 위하여 제공되는 것일 뿐, 실시예 및 제조예에 의해 본 발명의 내용이 한정되는 것은 아니다.
Hereinafter, preferred embodiments and production examples are shown to facilitate understanding of the present invention. However, the following Examples and Preparation Examples are provided only for the purpose of easier understanding of the present invention, and the present invention is not limited by the Examples and Production Examples.
실시예Example 1. One. 전호No. 메탄올 및 Methanol and 분획물의Fraction 수득 purchase
전호를 음건한 후 메탄올 (methanol)을 이용해 계통적 추출을 실시하며 3회 이상 추출한 다음 40 ℃에서 감압농축기 (CCA-1100, EYELA)로 감압, 농축시켜, 전호 메탄올 추출물을 수득하였다. The shrimp was shaken and then subjected to systematic extraction using methanol. The extract was extracted three times or more, and then concentrated under reduced pressure at 40 ° C with a vacuum concentrator (CCA-1100, EYELA) to obtain a methanol extract.
상기 메탄올 추출물을 헥산, 메틸린 클로라이드, 에틸아세테이트, 부탄올 또는 물로 각각 분획하여, 전호 분획물을 수득하였다. 분획 모식도는 도 1에 나타내었다.
The above methanol extract was fractionated with hexane, methylene chloride, ethyl acetate, butanol or water, respectively, to obtain the former fraction. The fractionation scheme is shown in Fig.
실시예Example 2. 헬리코박터 2. Helicobacter 파이로리Pyory 균에 대한 항균 효과 실험 Antibacterial effect on bacteria
헬리코박터 파이로리 최적 배지 plate에 균분산액 100μL를 분주하여 멸균 유리봉으로 도말한 다음, 멸균된 disc paper (지름 8mm)를 올리고 0.45㎛ membrane filter로 제균한 각 추출물을 vacuum evaporator로 농축한 후 멸균수로 희석하여 추출물 30μL를 disc paper에 흡수시키고, 대조구로는 멸균수를 흡수시킨 후 37℃의 미호기성 조건에서 24시간 동안 incubation한 다음 disc주위의 clear zone 생성 유무를 확인하였다. 100 μL of the fungus dispersion was dispensed on a Helicobacter pylori optimal plate, sterilized by a glass rod, and sterilized disc paper (
전호 메탄올 추출물의 헬리코박터 파이로리균에 대한 항균효과를 살펴본 결과, 도 2에 나타낸 바와 같이, 멸균수에서는 Clear zone 이 8 mm로 나타나 헬리코박터 파이로리균의 항균효과가 없는 것으로 나타났으나, 10 μg/30μL농도의 전호 30μL 즉 10 μg의 전호에서는 Clear zone 이 11 mm 으로 나타나 헬리코박터 파이로리균에 대한 항균효과를 확인 할 수 있었다.
As a result of examining the antimicrobial effect of the methanol extract of the present invention on Helicobacter pylori, as shown in Fig. 2, the clear zone was 8 mm in the sterilized water and showed no antibacterial effect of Helicobacter pylori. However, , The clear zone was 11 mm at 30 μL of 10 μg of total solution, indicating that the antibacterial effect against Helicobacter pylori was confirmed.
실시예Example 3. 병원성 세균에 대한 항균 효과 실험 3. Antibacterial effects on pathogenic bacteria
실시예 2와 동일한 방법으로 전호 추출물이 대표적인 병원성 세균인 황색포도상구균 및 대장균에 대해 항균활성을 보이는지 확인하였다. In the same manner as in Example 2, it was confirmed whether or not the prothyronectin extract had antimicrobial activity against representative pathogenic bacteria such as Staphylococcus aureus and Escherichia coli.
실시예 1에서 수득한 전호 Hx, MC, EtOAc, BuOH 분획물을 각각 10 μg/30 μL의 농도로 24시간 동안 처리하였다. 실험 결과, 도 3에 나타낸 바와 같이, E. coli에 대하여 전호의 Hx, Mc, EtOAc 분획물이 각각 10 mm 의 생육 억제환을 나타내었다. 또한, S. aureus에 대하여 전호의 Hx, Mc 분획물이 11 mm의 생육 억제환을 보여, 항균 효과를 확인하였다. The fractions Hx, MC, EtOAc and BuOH fractions obtained in Example 1 were treated at a concentration of 10 μg / 30 μL for 24 hours, respectively. As shown in FIG. 3, the Hx, Mc, and EtOAc fractions of the present invention showed 10 mM growth inhibition for E. coli , respectively. In addition, the antimicrobial effect of S. aureus was confirmed by the inhibition of Hx and Mc fractions of 11 mM.
실시예Example 4. 활성 성분의 동정 및 항균 효과 실험 4. Identification and Antibacterial Effect of Active Ingredients
항균활성을 나타내는 유효성분을 확인하기 위하여, 활성분획인 MC분획으로부터 항균활성을 나타내는 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin)을 TLC를 통하여 확인하고, 그 구조는 NMR을 통하여 동정하였다.In order to identify the active ingredient showing antimicrobial activity, falcarindiol or deoxypodophyllotoxin, which shows antimicrobial activity from the MC fraction as the active fraction, was identified by TLC and its structure was identified through NMR Respectively.
Falcarindiol; 1H-NMR (500 MHz, CDCl3): δ 5.94 (H-2), 5.61 (H-10), 5.50 (H-9), 5.45 (H-1a), 5.27 (H-1b), 5.21 (H-8), 4.94 (H-3), 0.87 (CH3)Falcarindiol; 1 H-NMR (500 MHz, CDCl 3): δ 5.94 (H-2), 5.61 (H-10), 5.50 (H-9), 5.45 (H-1a), 5.27 (H-1b), 5.21 ( H-8), 4.94 (H -3), 0.87 (CH 3)
[화학식 1][Chemical Formula 1]
Deoxypodophyllotoxin; 1H-NMR (400 MHz, CDCl3): δ 6.67 (1H, s, H-2), 6.52 (1H, s, H-5), 6.34 (2H, s, H-2′, 6′), 5.95 (2H, d, J = 1.0 Hz, OCH2O), 5.93 (2H, d, J = 1.0 Hz, OCH2O), 4.60 (1H, d, J = 2.8 Hz, H-7′), 4.45 (1H, td, H-9), 3.91 (1H, td, H-9), 3.80 (3H, s, 4′-OCH3), 3.75 (6H, s, 3′ & 4′-OCH3), 3.08 (1H, d, J = 11.2 Hz, H-7), 2.77 (1H, m, H-7), 2.74 (2H, m, H-8, 8′)Deoxypodophyllotoxin; 1 H-NMR (400 MHz, CDCl 3): δ 6.67 (1H, s, H-2), 6.52 (1H, s, H-5), 6.34 (2H, s, H-2 ', 6'), 5.95 (2H, d, J = 1.0 Hz, OCH 2 O), 5.93 (2H, d, J = 1.0 Hz, OCH 2 O), 4.60 (1H, d, J = 2.8 Hz, H-7 '), 4.45 (1H, td, H-9 ), 3.91 (1H, td, H-9), 3.80 (3H, s, 4'-OCH 3), 3.75 (6H, s, 3 '&4'-OCH 3), (1H, m, H-8, 8 '), 3.08 (1H, d, J = 11.2 Hz, H-
[화학식 2](2)
상기 과정을 통하여 수득한 활성물질인 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin)의 항균활성을 확인한 결과, 황색 포도상구균, 대장균 및 헬리코박터 파이로리균에 대한 억제환이 확인되었다 (도 4).The antimicrobial activity of falcarindiol or deoxypodophyllotoxin, which is an active substance obtained through the above process, was confirmed, and as a result, inhibitory rings against Staphylococcus aureus, Escherichia coli and Helicobacter pylori were confirmed (Fig. 4) .
따라서, 본 실험을 통하여 국내 자생식물인 전호의 추출물 및 분획물이 헬리코박터 파이로리균, 황색포도상구균 및 대장균에 대해 뛰어난 항균활성을 보임을 확인하였으며, 활성분획으로부터 분리한 팔카린디올 (falcarindiol) 또는 디옥시포도필로톡신 (deoxypodophyllotoxin) 또한 항균 활성을 보임을 확인하였다.
Therefore, it was confirmed through this experiment that the extracts and fractions of the wild plants of Korean native plants showed excellent antimicrobial activity against Helicobacter pylori, Staphylococcus aureus and E. coli, and falcarindiol or dioxy Deoxypodophyllotoxin also showed antimicrobial activity.
이하 본 발명의 상기 조성물을 포함하는 약학적 조성물, 건강기능식품 및 항균 제제의 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.
Hereinafter, examples of pharmaceutical composition, health functional food, and antimicrobial preparation containing the composition of the present invention will be described, but the present invention is not intended to be limited thereto but is specifically described.
제제예Formulation example 1. One. 산제의Sanje 제조 Produce
전호 추출물 또는 팔카린디올 또는 디옥시포도필로톡신 2gOr 2 g of pharmacological or pharmacokinetic
유당 100 mgLactose 100 mg
탈크 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
전호 추출물 또는 팔카린디올 또는 디옥시포도필로톡신 100 mg100 mg of ephedra extract or palmarindiol or deoxyglycolipotoxin
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
전호 추출물 또는 팔카린디올 또는 디옥시포도필로톡신 100 mg100 mg of ephedra extract or palmarindiol or deoxyglycolipotoxin
결정성 셀룰로오스 3 mgCrystalline cellulose 3 mg
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
전호 추출물 또는 팔카린디올 또는 디옥시포도필로톡신 100 mg100 mg of ephedra extract or palmarindiol or deoxyglycolipotoxin
만니톨 180 mg180 mg mannitol
주사용 멸균 증류수 2974 mgSterile sterilized water for injection 2974 mg
Na2HPO42H2O 26 mgNa 2 HPO 4 2H 2 O 26 mg
통상의 주사제의 제조방법에 따라 1 앰플당 (2 ml) 상기의 성분 함량으로 제조한다.
(2 ml) per 1 ampoule in accordance with the usual injection preparation method.
제제예Formulation example 5. 5. 액제의Liquid 제조 Produce
전호 추출물 또는 팔카린디올 또는 디옥시포도필로톡신 100 mg100 mg of ephedra extract or palmarindiol or deoxyglycolipotoxin
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 ml로 조절한 후 갈색병에 충진하여 멸균시켜 액제를 제조한다.
Each component was added and dissolved in purified water according to the usual liquid preparation method, 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 added with purified water to adjust the total volume to 100 ml, And sterilized to prepare a liquid preparation.
제제예Formulation example 6. 건강식품의 제조 6. Manufacture of health food
전호 추출물 또는 팔카린디올 또는 디옥시포도필로톡신 1 gOr 1 g of pharmacological or pharmacokinetic
비타민 혼합물 적량Vitamin mixture quantity
비타민 A 아세테이트 70 μg Vitamin A acetate 70 μg
비타민 E 1.0 mgVitamin E 1.0 mg
비타민 B1 0.13 mgVitamin B1 0.13 mg
비타민 B2 0.15 mg0.15 mg of vitamin B2
비타민 B6 0.5 mgVitamin B6 0.5 mg
비타민 B12 0.2 μg Vitamin B12 0.2 μg
비타민 C 10 mg
비오틴 10 μg Biotin 10 μg
니코틴산아미드 1.7 mgNicotinic acid amide 1.7 mg
엽산 50 μg Folic acid 50 μg
판토텐산 칼슘 0.5 mgCalcium pantothenate 0.5 mg
무기질 혼합물 적량Mineral mixture quantity
황산제1철 1.75 mg1.75 mg of ferrous sulfate
산화아연 0.82 mg0.82 mg of zinc oxide
탄산마그네슘 25.3 mgMagnesium carbonate 25.3 mg
제1인산칼륨 15 mgPotassium monophosphate 15 mg
제2인산칼슘 55 mgSecondary calcium phosphate 55 mg
구연산칼륨 90 mgPotassium citrate 90 mg
탄산칼슘 100 mgCalcium carbonate 100 mg
염화마그네슘 24.8 mgMagnesium chloride 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강식품 조성물 제조에 사용할 수 있다.
Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.
제제예Formulation example 7. 7. 건강음료의Health drink 제조 Produce
전호 추출물 또는 팔카린디올 또는 디옥시포도필로톡신 1 gOr 1 g of pharmacological or pharmacokinetic
비타민 C 15 gVitamin C 15 g
비타민 E(분말) 100 gVitamin E (powder) 100 g
젖산철 19.75 g19.75 g of ferrous lactate
산화아연 3.5 g3.5 g of zinc oxide
니코틴산아미드 3.5 gNicotinic acid amide 3.5 g
비타민 A 0.2 gVitamin A 0.2 g
비타민 B1 0.25 gVitamin B1 0.25 g
비타민 B2 0.3gVitamin B2 0.3g
물 정량Water quantification
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간 동안 85 ℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2 l 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 stirred and heated at 85 DEG C for about 1 hour. The solution thus prepared was filtered and sterilized in a sterilized 2 liter container, It is used in the production of the health beverage composition of the invention.
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.
제제예Formulation example 8. 피부 세안제의 제조 8. Manufacture of skin cleanser
전호 추출물 또는 팔카린디올 또는 디옥시포도필로톡신 0.5중량%0.5% < tb > < tb > < tb >
글리세린 6g Glycerin 6 g
모노알킬포스페이트 2.0g 2.0 g of monoalkyl phosphate
수산화나트륨수용액 0.5gAqueous solution of sodium hydroxide 0.5 g
미리스틴산 1.5g, 향료 미량이 포함된 세안제 베이스12g1.5 g of myristic acid, 12 g of a cleanser base containing a small amount of fragrance
상기 성분을 호모 믹서(homo mixer)에서 교반한 후 60℃에서 3분간 가열한 다음 탈기하고 37℃로 냉각하여 세안제 조성물을 제조한다.
The components were stirred in a homo mixer, heated at 60 ° C for 3 minutes, degassed, and cooled to 37 ° C to prepare a cleanser composition.
제제예Formulation example 9. 비누의 제조 9. Manufacture of soap
전호 추출물 또는 팔카린디올 또는 디옥시포도필로톡신 0.5중량%0.5% < tb > < tb > < tb >
비누 베이스 99.5중량%(수분 포함)Soap base 99.5% by weight (including moisture)
상기 성분을 혼합기로 잘 혼합한 후 비누 제조기에서 압출, 절단 및 형타하여 고형 비누 조성물을 제조한다.
The ingredients are mixed well in a mixer, extruded, cut and pressed in a soap maker to produce a solid soap composition.
제제예Formulation example 10. 주방용 세정제의 제조 10. Manufacture of kitchen cleaner
전호 추출물 또는 팔카린디올 또는 디옥시포도필로톡신 0.5중량%0.5% < tb > < tb > < tb >
알킬에테르술폰산염(alkylethersulfonate) 20중량% 20% by weight alkylethersulfonate (alkylethersulfonate)
알킬폴리글루코시드(alkylpolyglucoside) 4중량% 4% by weight alkylpolyglucoside < RTI ID = 0.0 >
라우릴디메틸아민옥사이드(lauryldimethylamine oxide) 4중량%4% by weight of lauryldimethylamine oxide,
코카미도 프로필베타인(Cocamidopropyl Betaine) 7중량% Cocamidopropyl betaine 7% by weight < RTI ID = 0.0 >
에톡시화라우릴알콜 5중량% 5% by weight of ethoxylated lauryl alcohol
EDTA 0.3중량% EDTA 0.3 wt%
색소 소량 Small amount of pigment
향 0.5중량%Incense 0.5%
정제수 적량Purified water quantity
상기의 성분을 혼합하여 세정제를 제조한다.
The above components are mixed to prepare a cleaning agent.
Claims (12)
An antimicrobial composition for Helicobacter pylori containing an extract of Anthriscus sylvestris as an active ingredient.
The composition according to claim 1, wherein the extract is extracted with an alcohol having 1 to 4 carbon atoms or a mixed solvent thereof.
Antibacterial agent for Helicobacter pylori containing an extract of Anthriscus sylvestris as an active ingredient.
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KR20180065458A (en) | 2016-12-08 | 2018-06-18 | 조선대학교산학협력단 | Composition for Prevention or Treatment of Arthritis Comprising The Anthriscus sylvestris Hoffm extract |
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KR102110966B1 (en) * | 2017-05-12 | 2020-05-14 | 부산대학교 산학협력단 | Process for Producing Deoxypodophilotoxin in Quantity |
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Non-Patent Citations (4)
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Journal of Natural Products. Vol.62, Issue 4, pp.626-628 * |
Journal of Natural Products. Vol.62, Issue 4, pp.626-628* |
Journal of the Korean Society for Applied Biological Chemistry. Vol.52, Issue 6, pp.620-625 * |
Journal of the Korean Society for Applied Biological Chemistry. Vol.52, Issue 6, pp.620-625* |
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KR20180065458A (en) | 2016-12-08 | 2018-06-18 | 조선대학교산학협력단 | Composition for Prevention or Treatment of Arthritis Comprising The Anthriscus sylvestris Hoffm extract |
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