KR101054943B1 - Phenolic Compounds with Antioxidant Activity from Coding Tea Extract and Functional Foods Comprising the Same as Active Ingredients - Google Patents
Phenolic Compounds with Antioxidant Activity from Coding Tea Extract and Functional Foods Comprising the Same as Active Ingredients Download PDFInfo
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- KR101054943B1 KR101054943B1 KR1020080113632A KR20080113632A KR101054943B1 KR 101054943 B1 KR101054943 B1 KR 101054943B1 KR 1020080113632 A KR1020080113632 A KR 1020080113632A KR 20080113632 A KR20080113632 A KR 20080113632A KR 101054943 B1 KR101054943 B1 KR 101054943B1
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- compound
- acid
- epi
- tea
- methyl ester
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Abstract
본 발명은 베트남 전통차로서 사용되고 있는 Ilex kudingcha(bitter tea)로부터 항산화 활성을 갖는 페놀릭계 성분을 함유하는 조성물에 관한 것이다. 더욱 상세하게는 베트남에서 전통차로 사용하여 왔지만 항산화 활성을 나타내는 물질에 대한 보고가 없었던 쿠딩차의 알코올 조추출물을 용매 분획한 후, 항산화 활성을 보이는 에틸아세테이트 분획으로부터 분리한 항산화 활성을 갖는 화합물 1 내지 화합물 9를 포함하는 쿠딩차 추출물을 유효성분으로 포함하는 항산화용 기능성 식품에 관한 것이다. 쿠딩차 추출물은 산화적 스트레스를 저해하는 기능이 우수하므로 쿠딩차 추출물을 포함하는 본 발명의 기능성 식품은 활성산소에 의해 유발되는 질환을 예방 또는 치료하기 위한 기능성 식품의 제조에 유용하게 사용될 수 있다. The present invention relates to a composition containing a phenolic component having antioxidant activity from Ilex kudingcha (bitter tea) used as a Vietnamese traditional tea. More specifically, after the solvent fractionation of the crude crude extract of the cudding tea, which has been used as a traditional tea in Vietnam but has not been reported for its antioxidant activity, the compound 1 having antioxidant activity isolated from the ethyl acetate fraction showing antioxidant activity. The present invention relates to a functional food for antioxidant containing a cudding tea extract containing compound 9 as an active ingredient. Since the cudding tea extract has an excellent function of inhibiting oxidative stress, the functional food of the present invention including the cudding tea extract may be usefully used for the production of a functional food for preventing or treating diseases caused by free radicals.
식물소재, 항산화, 일렉스 쿠딩차, 추출물 Plant Material, Antioxidant, Ilex Coding Tea, Extract
Description
본 발명은 베트남 전통차로서 사용되고 있는 Ilex kudingcha(bitter tea)로부터 항산화 활성을 갖는 페놀릭계 성분을 함유하는 조성물에 관한 것이다. 더욱 상세하게는 베트남에서 전통차로 사용하여 왔지만 항산화 활성에 관한 물질에 대하여 연구가 없었던 쿠딩차의 알코올 조추출물을 용매 분획한 후, 항산화 활성을 보이는 에틸아세테이트 분획으로부터 분리한 항산화 활성을 갖는 화합물 1 내지 화합물 9을 포함하는 쿠딩차 추출물을 유효성분으로 포함하는 항산화용 기능성 식품에 관한 것이다.The present invention relates to a composition containing a phenolic component having antioxidant activity from Ilex kudingcha (bitter tea) used as a Vietnamese traditional tea. In more detail, after the solvent fractionation of the crude crude extract of Cudding tea, which has been used as a traditional tea in Vietnam but has not been studied for its antioxidant activity, the
인간의 몸은 정상적인 에너지를 생성하는 대사과정에서 활성산소라는 입자가 부수적으로 생산된다. 이러한 활성산소는 화학적 반응성이 뛰어나므로 이들에 의하여 유도된 프리라디칼(free radical) 반응은 생체내의 각종 반응에 영향을 미치며 생체에 치명적인 산소독성을 일으킨다. 즉, 이들 활성산소는 세포구성 성분들인 지 질, 단백질, 당 및 인체 유전체의 구성물질인 DNA 등에 영향을 주어 암을 비롯한 노화, 동맥경화, 관절염, 뇌졸중, 파키슨병, 알츠하이병 등의 각종 질병의 원인으로 작용하고 있다[Physiol Rev., 82(1), 47-95 (2002); Science, 307, 384-387 (2005)].The human body additionally produces particles called free radicals in the metabolic processes that produce normal energy. Since these free radicals have excellent chemical reactivity, the free radical reaction induced by them affects various reactions in vivo and causes deadly oxygen toxicity in the living body. In other words, these free radicals affect cell components such as lipids, proteins, sugars, and DNA, which is a component of the human genome. Act as a cause of [Physiol Rev., 82 (1), 47-95 (2002); Science, 307, 384-387 (2005)].
지금까지 알려진 항산화제로는 BHA(Butylated hydroxy anisole), BHT(Buthylated hydroxy toluene) 및 PG(3,4,5-Trihydroxy benzoic acid propyl ester) 등이 있으며 천연 항산화제로는 비타민 E, 비타민 C, 글루타치온 등의 물질이 있다. 그러나 식생활과 생활수준의 향상에 따라 합성 항산화제에 대한 사용은 소비자들이 거부감을 일으키는 단점이 존재한다. 천연 항산화제의 사용은 합성 항산화제에 비하여 생체에 안전하다는 장점은 있으나 그 효과가 약하다는 단점이 있다[FASEB J., 2, 2867-2870 (1988)]. 또한, 최근 합성 항산화제로서 널리 사용되던 BHT가 50mg/㎏/day 이상을 섭취시 암을 유발한다는 보고가 있을 정도로 천연 소재로부터 새로운 항산화제의 개발 필요성이 존재한다. 일반적으로, 새로운 성분의 약제를 개발하기 위한 여러 가지 방법 중 기존 약제의 실험적 변형에 의한 노력보다는 전통 의학에서 사용되고 있는 천연물 약제들로부터 새로운 활성 성분을 발견할 수 있는 가능성이 매우 높으며 오랫동안 사용되어 왔기 때문에 개발된 약물들에 의한 독성 염려가 적은 장점이 있다. 따라서 본 연구자들은 독성이 적은 항산화제를 개발하기 위하여 식용으로 사용한 천연물로부터 항산화제 화합물의 탐색을 시도하였다. Antioxidants known to date include BHA (Butylated hydroxy anisole), BHT (Buthylated hydroxy toluene) and PG (3,4,5-Trihydroxy benzoic acid propyl ester). Natural antioxidants include vitamin E, vitamin C and glutathione. There is a substance. However, there are drawbacks to the use of synthetic antioxidants in response to improvements in diet and living standards. The use of natural antioxidants has the advantage of being safe for the human body compared to synthetic antioxidants, but the disadvantages are weak. [FASEB J., 2, 2867-2870 (1988)]. In addition, there is a need for the development of new antioxidants from natural materials to the extent that BHT, which has been widely used as a synthetic antioxidant recently, causes cancer when ingested more than 50 mg / kg / day. In general, there is a high possibility of finding new active ingredients from natural medicines used in traditional medicine rather than the efforts of experimental modifications of existing drugs among the various methods for the development of new ingredients of medicine. There is less concern about toxicity due to the drugs developed. Therefore, the present inventors attempted to search for antioxidant compounds from edible natural products to develop low-toxic antioxidants.
쿠딩차(Ilex kudingcha C.J. Tzeng)는 남부 중국이나 베트남에서 사용되어온 차로 그것의 쓴맛에 기인하여 bitter tea로 불리어져 왔다. 베트남에서는 전통적으로 이 차를 두통, 감기, 고혈압, 고열, 당뇨 등의 치료에 처방하여 왔을 정도로 안전성이 보장된 식물이다. 이러한 쿠딩차와 관계된 특허 및 문헌으로는 acyl-CoA cholesteryl acyl transferase(ACAT)를 저해하는 트리터페노이드 계열의 화합물[J. Nat. Prod., 62(7), 1061-1064 (1999)], 피부염을 치료하는 차 조성물[미국특허 제2005/0186293호], 사포닌과 ACAT 저해 화합물[일본특허공개 제2000-44594호]등과 본 연구진들이 베트남에서 발표한 본 발명외의 몇몇 화합물의 항산화 효과에 대한 보고[International workshop on herbal medicinal plants and traditional herb remedies, 2007] 등이 있으며, 동속식물로서 남미에서 사용되는 Ilex paraguarariensis(mate tea)에 관한 항산화 활성[European Journal of Nutrition, 42, 50-54 (2003)]에 대한 보고는 있으나, 쿠딩차 분획물의 화학구조, 물리화학적 특성 및 항산화 활성에 관한 제시나 보고는 없다. Ilex kudingcha CJ Tzeng is a tea that has been used in southern China or Vietnam and has been called bitter tea due to its bitter taste. In Vietnam, the plant has been traditionally prescribed for the treatment of headache, cold, high blood pressure, high fever and diabetes. Patents and documents related to such cuding teas include triterpenoid compounds that inhibit acyl-CoA cholesteryl acyl transferase (ACAT) [J. Nat. Prod., 62 (7), 1061-1064 (1999)], tea composition for treating dermatitis [US Patent No. 2005/0186293], saponin and ACAT inhibitory compounds [Japanese Patent Publication No. 2000-44594] and the like International Journal on herbal medicinal plants and traditional herb remedies (2007), which are published in Vietnam, have published reports on the antioxidant effects of Ilex paraguarariensis (mate tea) used in South America as a homologous plant. There have been reports of activity [European Journal of Nutrition, 42, 50-54 (2003)], but there are no reports or reports on the chemical structure, physicochemical properties and antioxidant activity of the Coding tea fraction.
이에, 본 발명자들은 각종 자생식물 및 한약재를 채집하여 조사하던 중 쿠딩차를 메탄올 추출한 후 크로마토그래피를 이용하여 순수 분리, 정제하여 페놀릭 계열의 화합물 1 내지 화합물 9 를 얻고, 이들의 화학구조, 물리화학적 특성 및 항산화 활성을 조사함으로써 본 발명을 완성하였다.Accordingly, the present inventors collected and extracted various native plants and herbal medicines, and extracted couping tea with methanol, purified and purified by chromatography to obtain
따라서, 본 발명의 목적은 쿠딩차 유래의 항산화 화합물을 제공하는 것이다. Accordingly, it is an object of the present invention to provide an antioxidant compound derived from cudding tea.
또한, 본 발명의 다른 목적은 상기 항산화 화합물을 유효성분으로 함유하는 활성산소에 의해 유발되는 질환을 예방 또는 치료하기 위한 조성물을 제공하는 것이다. In addition, another object of the present invention is to provide a composition for preventing or treating a disease caused by active oxygen containing the antioxidant compound as an active ingredient.
상기한 목적을 달성하기 위하여, 본 발명은 쿠딩차 추출물을 유효성분으로 함유하는 항산화용 기능성 식품을 제공한다.In order to achieve the above object, the present invention provides a functional food for antioxidant containing a cudding tea extract as an active ingredient.
본 발명자들은 활성산소를 저해하는 화합물을 찾기 위하여 1,000 여종의 자생식물 및 외국식물을 대상으로 항산화 활성을 검색하여 쿠딩차를 후보물질로 이용하였다. 본 발명에 사용한 쿠딩차 식물은 2004년 봄에 베트남의 카오방(Caobang) 지역에서 채집한 것을 확인하여 확증식물은 베트남 의약물질연구소에 보관되어 있다. The present inventors searched for antioxidant activity of about 1,000 native plants and foreign plants to find compounds that inhibit the active oxygen, and used the cud tea as a candidate. Cudding tea plant used in the present invention was confirmed in the spring of 2004 in the Caobang (Vietnam) region of Vietnam confirmed plant is stored in Vietnam Pharmaceutical Research Institute.
본 발명의 기능성식품에 포함되는 쿠딩차 추출물은 알코올 수용액을 이용하여 추출하는 것을 특징으로 한다. 쿠딩차 추출물은 알코올 조추출물, 바람직하게는 에탄올(EtOH) 조 추출물을 얻은 뒤 에틸아세테이트로 분획하며, 크로마토그래피 과 정을 거쳐서 하기 화학식 1 내지 3으로 표시되는 화합물 9 종을 포함하는 추출물을 얻는다. 또한 구조분석 결과, 본 발명에서 수득한 화학식 3으로 기재되는 화합물 9(3,5-di-O-caffeoyl-epi-quinic acid n-butyl ester)는 자연계로부터 처음으로 분리한 신규화합물 임을 확인하였다. Kuding tea extract included in the functional food of the present invention is characterized in that the extraction using an aqueous alcohol solution. Coding tea extract is obtained by obtaining a crude alcohol extract, preferably ethanol (EtOH) crude extract and fractionated with ethyl acetate, and through the chromatography process to obtain an extract comprising nine compounds represented by the following formula (1). In addition, as a result of the structural analysis, the compound 9 (3,5-di- O- caffeoyl epi- quinic acid n -butyl ester) described in Chemical Formula 3 obtained in the present invention was confirmed to be a novel compound first isolated from nature.
[화학식 1][Formula 1]
1. R2 = Caffeoyl, R1 = R3 = R4 = H 1 . R2 = Caffeoyl, R1 = R3 = R4 = H
2. R4 = Caffeoyl, R1 = R2 = R3 = H 2 . R4 = Caffeoyl, R1 = R2 = R3 = H
3. R3 = Caffeoyl, R1 = R2 = R4 = H 3 . R3 = Caffeoyl, R1 = R2 = R4 = H
4. R3 = Caffeoyl, R1 = CH3, R2 = R4 = H 4 . R3 = Caffeoyl, R1 = CH3, R2 = R4 = H
5. R3 = R4 = Caffeoyl, R1 = CH3, R2 = H 5 . R3 = R4 = Caffeoyl, R1 = CH3, R2 = H
6. R2 = R4 = Caffeoyl, R1 = CH3, R3 = H 6 . R2 = R4 = Caffeoyl, R1 = CH3, R3 = H
8. R2 = R3 = Caffeoyl, R1 = CH3, R4 = H 8 . R2 = R3 = Caffeoyl, R1 = CH3, R4 = H
[화학식 2][Formula 2]
[화학식 3](3)
상기 화학식 1 내지 화학식 3으로 표시되는 본 발명의 화합물의 경우 쿠딩차 추출물 총 중량에 대하여 화합물 4 로 표시되는 화합물은 0.1 내지 10.00 중량%, 화합물 2 로 표시되는 화합물은 0.01 내지 1.00 중량%를 함유하는 것이 바람직하다.In the case of the compound of the present invention represented by Formula 1 to
상기 화학식 1 내지 화학식 3으로 표시되는 본 발명의 화합물은 DPPH(1,1-diphenyl-2-Picrylhydrazyl) 라디칼 소거 활성, 하이드록실 라디칼(hydroxyl), 슈퍼옥사이드(superoxide)(도 1 참조), 지질 과산화 억제 활성, LDL (low density lipoprotein) 산화의 저해작용을 갖는다. Compounds of the present invention represented by
본 발명의 항산화 활성을 갖는 기능성 식품에 포함되는 쿠딩차 추출물은 화합물 1 (3-caffeoylquinic acid, 3-CQA), 화합물 2 (5-CQA), 화합물 3 (4-CQA), 화합물 4 (4-CQA methyl ester), 화합물 5 (4,5-diCQA methyl ester), 화합물 6 (3,5-diCQA methyl ester), 화합물 7 (CA methyl ester), 화합물 8 (3,4-diCQA methyl ester), 화합물 9 (3,5-di-O-caffeoyl-epi-quinic acid n-butyl ester)로 표시되는 화합물로 구성된 군으로부터 선택된 화합물을 포함하는 것이 바람직하다. Coding tea extract included in the functional food having antioxidant activity of the present invention is Compound 1 (3-caffeoylquinic acid, 3-CQA), Compound 2 (5-CQA), Compound 3 (4-CQA), Compound 4 (4- CQA methyl ester), compound 5 (4,5-diCQA methyl ester), compound 6 (3,5-diCQA methyl ester), compound 7 (CA methyl ester), compound 8 (3,4-diCQA methyl ester), compound It is preferable to include a compound selected from the group consisting of compounds represented by 9 (3,5-di- O- caffeoyl epi- quinic acid n -butyl ester).
본 발명의 항산화용 활성을 갖는 페놀릭 화합물은 쿠딩차로부터 알코올, 에테르, 아세톤 등의 유기용매에 의하여 추출, 에틸아세테이트과 물의 분배, 칼럼크로마토그래피 등 식물체 성분의 분리 추출에 이용되는 공지의 방법을 단독 또는 적합하게 조합하여 용이하게 얻을 수 있다. 또한, 조추출물은 필요에 따라 상기 방법에 따라서 더욱 정제할 수 있다.The phenolic compound having antioxidant activity according to the present invention may be extracted from a cudding tea by an organic solvent such as alcohol, ether, acetone, distribution of ethyl acetate and water, separation of plant components such as column chromatography, and the like. Or it can obtain easily by combining suitably. In addition, the crude extract can be further purified according to the above method if necessary.
본 발명에서 사용하는 크로마토그래피에는 실리카겔 칼럼 크로마토그래피(silica gel column chromatography), 엘에이치-20 칼럼 크로마토그래피(LH-20 column chromatography), 박층 크로마토그래피(TLC; thin layer chromatography) 및 고성능 액체 크로마토그래피(high performance liquid chromatography) 등이 이용될 수 있다.The chromatography used in the present invention includes silica gel column chromatography, L-20 column chromatography, thin layer chromatography and high performance liquid chromatography. performance liquid chromatography) and the like.
본 발명의 쿠딩차는 전통적으로 차로서 사용되었을 뿐만 아니라 안정도도 높으므로 식품, 의약품 등의 첨가제로 이용할 수 있다.The cudding tea of the present invention has not only been used as a tea traditionally, but also has high stability, and thus can be used as an additive for food and medicine.
본 발명에 따른 추출물을 포함하는 약학조성물은, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다. 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. 제제화 할 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, 탄산칼슘, 수크로스 또는 락토오스, 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 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, 동결건조 제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜, 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다. Pharmaceutical compositions comprising extracts according to the invention, in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterile injectable solutions, respectively, according to conventional methods. Can be formulated and used. Carriers, excipients and diluents that may be included in the composition comprising the extract include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate , Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, 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 include at least one excipient such as starch, calcium carbonate, sucrose or lactose, gelatin, and the like. Mix is prepared. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, 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. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
상기 활성성분의 투여량은 치료 받을 대상의 연령, 성별, 체중과, 치료할 특정 질환 또는 병리 상태, 질환 또는 병리 상태의 심각도, 투여경로 및 처방자의 판단에 따라 달라질 것이다. 이러한 인자에 기초한 투여량 결정은 당업자의 수준 내에 있으며, 일반적으로 투여량은 0.001㎎/㎏/일 내지 대략 2000㎎/㎏/일의 범위이 다. 더 바람직한 투여량은 0.1㎎/㎏/일 내지 100㎎/㎏/일이다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다. 본 발명의 추출물은 쥐, 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 주사에 의해 투여될 수 있다. 본 발명의 추출물은 독성 및 부작용은 거의 없으므로 예방 목적으로 장기간 복용시에도 안심하고 사용할 수 있는 약제이다. The dosage of the active ingredient will vary depending on the age, sex and weight of the subject to be treated, the particular disease or pathology to be treated, the severity of the disease or pathology, the route of administration and the judgment of the prescriber. Dosage determination based on these factors is within the level of those skilled in the art, and generally the dosage ranges from 0.001 mg / kg / day to approximately 2000 mg / kg / day. More preferred dosage is 0.1 mg / kg / day to 100 mg / kg / day. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect. The extract of the present invention can be administered to mammals such as mice, livestock, humans, etc. by various routes. All modes of administration can be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or cerebrovascular injections. Since the extract of the present invention has little toxicity and side effects, it is a drug that can be used safely even when taken for long periods of time.
또한, 본 발명은 상기 쿠딩차 추출물 및 식품학적으로 허용 가능한 식품보조 첨가제를 포함하는 비만 예방을 위한 건강 기능 식품을 제공한다. 본 발명의 건강기능식품은 정제, 캡슐제, 환제 또는 액제 등의 형태를 포함하며, 본 발명의 화합물을 첨가할 수 있는 식품으로는, 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합제, 건강 기능성 식품류 등이 있다. 상세하게는, 본 발명은 쿠딩차 추출물을 유효성분으로 함유하는 추출물 및 식품학적으로 허용 가능한 식품보조 첨가제를 포함하는 비만 예방 및 치료용 건강 기능 식품을 제공한다. The present invention also provides a dietary supplement for the prevention of obesity, including the Kudding tea extract and a food supplement acceptable food supplement. The health functional food of the present invention includes the form of tablets, capsules, pills or liquids, and the food to which the compound of the present invention can be added, for example, various foods, beverages, gums, teas, vitamin complexes, etc. And health functional foods. Specifically, the present invention provides a dietary supplement for the prevention and treatment of obesity, including an extract containing a cudding tea extract as an active ingredient and a food acceptable additive.
이상에서 설명한 바와 같이, 본 발명의 쿠딩차(Ilex kudincha) 유래의 추출물 및 이로부터 분리한 화학식 1 내지 화학식 3으로 표시되는 화합물은 합성 항산화제보다 저해 활성이 강하고 전통적으로 베트남에서 차로 사용되어 왔기에 안전성이 우수하므로 활성산소에 의해 유발되는 질환인 암을 비롯하여 동맥경화, 관절염, 뇌졸중, 파킨슨병, 알츠하이머병, 자가면역질환 등의 각종 질병에 대한 예방 및 치 료와 피부 노화 억제를 위한 식품, 화장품 및 의약품의 소재로서 산업적으로 널리 이용될 수 있다.As described above, the extract derived from Ilex kudincha of the present invention and the compounds represented by the formula (1) to the formula (3) separated therefrom have a stronger inhibitory activity than synthetic antioxidants and have been traditionally used as tea in Vietnam Its excellent safety prevents various diseases such as cancer, arteriosclerosis, arthritis, stroke, Parkinson's disease, Alzheimer's disease and autoimmune diseases, including cancer, which is caused by active oxygen, And it can be widely used industrially as a material of medicines.
이하, 실시예를 들어 본 발명을 보다 상세히 설명하지만, 본 발명의 권리범위가 이들 예로만 한정되는 것은 아니다. Hereinafter, the present invention will be described in more detail with reference to Examples, but the scope of the present invention is not limited only to these examples.
<실시예 1: 항산화 활성물질의 분리 및 정제>Example 1 Isolation and Purification of Antioxidant Active Substances
쿠딩차의 건조된 잎 2 kg을 잘게 부순 후 메탄올에 2 일간 침지하여 실온에서 추출하였다. 상기 메탄올 추출물을 감압농축한 후, 농축물(680 g)을 물에 용해시킨뒤 헥산, 에틸아세테이트, 부탄올 등의 용매를 사용하여 분획하여 항산화 활성이 강한 에틸아세테이트 분획물(113 g)을 얻었다. 항산화 작용을 갖는 활성물질을 분리 정제 후 구조를 확인하기 위하여 에틸아세테이트 분획물(1 g)을 메탄올(A)과 물(B)을 이동상으로, 분취용 HPLC[ODS-H80 컬럼(20×150 mm), 유속: 3 ml/min. 용매조건: 0-30 min (45% A), 30-45 min (45→55% A), 45-60 min (55→100% A)]을 실시하였다. 이때 도 3 의 HPLC 그림을 참조하여 실시하였다. 각각 화합물의 칼럼상에서 머무름 시간(tR)과 활성을 고려하여, 화합물 1 (tR, 10.2 min), 화합물 2 (tR, 11.9 min), 화합물 3 (tR, 12.9 min), 화합물 4 (tR, 17.9 min), 화합물 5 (tR, 36.0 min), 화합물 6 (tR, 38.2 min), 화합물 7 (tR, 42.0 min), 화합물 8 (tR, 48.9 min)과 화합물 9 (tR, 51.8 min)를 얻었다. 2 kg of dried leaves of the cudding tea were crushed finely and then immersed in methanol for 2 days and extracted at room temperature. The methanol extract was concentrated under reduced pressure, and then the concentrate (680 g) was dissolved in water and fractionated using a solvent such as hexane, ethyl acetate, butanol to obtain an ethyl acetate fraction (113 g) having strong antioxidant activity. In order to confirm the structure after separating and purifying the active substance having antioxidant activity, ethyl acetate fraction (1 g) was extracted with methanol (A) and water (B) as a mobile phase, and preparative HPLC [ODS-H80 column (20 × 150 mm) Flow rate: 3 ml / min. Solvent conditions: 0-30 min (45% A), 30-45 min (45 → 55% A), 45-60 min (55 → 100% A)]. At this time it was carried out with reference to the HPLC picture of FIG. Compound 1 (t R, 10.2 min), Compound 2 (t R, 11.9 min), Compound 3 (t R, 12.9 min), Compound 4 (in consideration of retention time (t R ) and activity on the column of the compound, respectively) t R, 17.9 min), compound 5 (t R, 36.0 min), compound 6 (t R, 38.2 min), compound 7 (t R, 42.0 min), compound 8 (t R, 48.9 min) and compound 9 ( t R, 51.8 min).
<실시예 2: 분리된 화합물의 구조 분석>Example 2: Structural Analysis of Isolated Compound
상기 실시예 1에서 쿠딩차로부터 분리된 9 종 화합물의 구조를 분석하였다. 화합물의 화학적 구조를 ESI 질량분석기(Electrospray Ionization mass spectrometer)을 사용하여 얻은 분자량 및 핵자기 공명 분석의 1H 및 13C-NMR 분석 결과를 토대로 화합물의 구조를 분석하였다. 신규 화합물 9 의 화합물의 구조는 추가적인 핵자기공명(NMR) 분석을 통하여 1H-NMR, 13C-NMR, HMQC(1H-detected heteronuclear multiple-quantum coherence), HMBC(heteronuclear multiple-bond coherence), DEPT(distortionless enhancement by polarization) 스펙트럼을 얻고 분자구조를 결정하였다. In Example 1, the structure of 9 compounds isolated from the cudding car was analyzed. The chemical structure of the compound was analyzed based on 1 H and 13 C-NMR analysis of molecular weight and nuclear magnetic resonance analysis obtained using an ESI mass spectrometer. The structure of the compound of novel compound 9 was further analyzed by 1 N-NMR, 13 C-NMR, 1 H-detected heteronuclear multiple-quantum coherence (HMQC), heteronuclear multiple-bond coherence (HMBC), Distortionless enhancement by polarization (DEPT) spectra were obtained and molecular structure was determined.
그 결과, 구조 결정된 화합물은 상기 실시예 1에서 보여준 구조를 갖는 것으로 결정 되었으며 신규 화합물인 화합물 9 의 기기 분석값을 표1 에 표시하였다. 또한, 분리된 물질 중 화합물 9 는 신규 화합물로 3,5-di-O-caffeoyl-epi-quinic acid n-butyl ester로 구조 결정하였으며 하기와 같은 특성을 갖고 있었다.As a result, the structure-determined compound was determined to have the structure shown in Example 1, and the instrumental analysis of Compound 9 , a novel compound, is shown in Table 1. In addition, the compound 9 of the isolated material was a new compound, 3,5-di- O -caffeoyl epi- quinic acid n -butyl ester structure was determined and had the following characteristics.
(화학적 특성)(Chemical properties)
3,5-디-오-카페오일 에피-퀴닉 산 노르말-부틸에스테르(3,5-di-O-caffeoyl-epi-quinic acid n-butylester, 9).3,5-di-o-cafeoyl epi -quinic acid normal-butyl ester (3,5-di- O- caffeoyl epi- quinic acid n -butylester, 9 ).
HR-EIMS m/z 572.1886[M]+, calcd.for C29H32O12 572.1894 HR-EIMS m / z 572.1886 [M] + , calcd.for C 29 H 32 O 12 572.1894
[α]D 143.4 (c 0.1, MeOH)[α] D 143.4 ( c 0.1, MeOH)
IR(KBr)νmax 3370, 2930, 1720, 1700, 1605, 1540, 1470, 1190 cm1 IR (KBr) νmax 3370, 2930, 1720, 1700, 1605, 1540, 1470, 1190 cm 1
13C-NMR(CD3OD, 125 MHz): δ(ppm)175.4 (C-7),168.8 and 168.1 (C-9′),149.9 and 149.7 (C-4′),147.6 and 147.3 (C-3′),147.0 (2C, C-7′),128.0 and 127.8 (C-1′),123.2 and 123.1 (C-6′),116.7 and 116.6 (C-5′),115.6 and 115.0 (C-8′), 115.3 (2C, C-2′), 74.7 (C-1), 72.5 (C-5), 72.0 (C-3), 69.6 (C-4), 36.5 (C-2), 35.7 (C-6), 66.6 (C-1″), 31.7 (C-2″), 20.2 (C-3″), 14.2 (C-3″). 13 C-NMR (CD 3 OD, 125 MHz): δ (ppm) 175.4 (C-7), 168.8 and 168.1 (C-9 '), 149.9 and 149.7 (C-4'), 147.6 and 147.3 (C- 3 ′), 147.0 (2C, C-7 ′), 128.0 and 127.8 (C-1 ′), 123.2 and 123.1 (C-6 ′), 116.7 and 116.6 (C-5 ′), 115.6 and 115.0 (C- 8 ′), 115.3 (2C, C-2 ′), 74.7 (C-1), 72.5 (C-5), 72.0 (C-3), 69.6 (C-4), 36.5 (C-2), 35.7 (C-6), 66.6 (C-1 ″), 31.7 (C-2 ″), 20.2 (C-3 ″), 14.2 (C-3 ″).
표1. 화합물 9의 핵자기 공명 분석 결과 Table 1. Nuclear Magnetic Resonance Assay for Compound 9
Position
Position
3,5diCepiQA nbutyl ester (9)
3,5diCepiQA nbutyl ester (9)
2ax2eq
2ax
2.30 m2.18 m
2.30
6eq6ax
6eq
2.34 m2.13 m
2.34 m
<실시예 3: DPPH 라디칼 소거 활성(DPPH radical scavenging activity)의 측정>Example 3: Measurement of DPPH radical scavenging activity
본 발명자들은 상기 실시예 1에서 수득한 메탄올 추출물 등의 DPPH 라디칼 소거 활성(DPPH radical scavenging activity)을 1,1-diphenyl-picrylhydrazyl (DPPH)를 이용하여 측정하여 표2 에 나타내었다. 표2 는 쿠딩차의 메탄올 추출물, 상기 메탄올 추출물을 헥산, 에틸아세테이트, 부탄올로 분획한 각각의 분획물과, 실시예 1의 방법에 따르되 메탄올 대신 물을 사용한 물 추출물의 항산화 활성을 나타내는 도표이다. The present inventors measured DPPH radical scavenging activity of the methanol extract obtained in Example 1 using 1,1-diphenyl-picrylhydrazyl (DPPH), and are shown in Table 2. Table 2 is a table showing the antioxidant activity of the methanol extract of the cudding tea, each fraction of the methanol extract fractions hexane, ethyl acetate, butanol, and water extract using water instead of methanol according to the method of Example 1.
DPPH radical 소거활성법은 시료의 free radical 소거능력이나 수소 공여능력을 평가하는 방법으로서 식품을 비롯한 여러 분야에서 널리 사용되고 있는 방법이다. 대부분의 라디칼들은 반응성이 매우 커서 불안정하지만 DPPH 라디칼은 안정한 free 라디칼로서 517 nm에서 강한 흡수를 갖는 화합물이다. DPPH radical scavenging activity is a method for evaluating free radical scavenging ability or hydrogen donating ability of a sample and is widely used in various fields including foods. Most of the radicals are very unstable due to their high reactivity, but DPPH radicals are stable free radicals with strong absorption at 517 nm.
표2. Table 2.
시료
sample
(IC50, ㎍/㎖)Lipid peroxidation
(IC 50 , μg / ml)
측정 결과, 표2 를 참조하면, 쿠딩차의 에틸아세테이트 층이 다른 용매 분획물에 비하여 DPPH 라디칼 소거활성에 강한 저해활성(16.3 ± 0.1 ㎍/㎖)을 나타내었다. 분리한 화합물 1 - 9은 시행된 항산화활성에 대하여 농도 의존적으로 강한 라디칼 저해 활성을 보여 주었다. 이 수치들은 표3 에 나타내었다. 표3 은 쿠딩차의 에틸 아세테이트 분획으로부터 분리 정제한 화합물의 항산화 활성을 측정한 표이다. As a result, referring to Table 2, the ethyl acetate layer of the cudding tea showed a strong inhibitory activity (16.3 ± 0.1 μg / ml) on DPPH radical scavenging activity compared to other solvent fractions. Separating compounds 1 - 10 showed a dose dependent manner with a strong inhibitory activity against radicals undertaken antioxidant activity. These values are shown in Table 3. Table 3 is a table measuring the antioxidant activity of the compound purified from the ethyl acetate fraction of the cudding tea.
표3.Table 3.
화합물
compound
peroxidationLipid
peroxidation
chin(+) Cate
chin
27.6±2.1
27.6 ± 2.1
3.6±1.1
3.6 ± 1.1
2.7±0.2
2.7 ± 0.2
13.2±2.3
13.2 ± 2.3
18.6±1.3
18.6 ± 1.3
14.7±3.8
14.7 ± 3.8
4.6±0.3
4.6 ± 0.3
herolαTocop
herol
26.8±1.1
26.8 ± 1.1
NA
NA
NA
NA
NA
NA
44.9±8.3
44.9 ± 8.3
NA
NA
17.7±1.6
17.7 ± 1.6
구체적으로 표3 을 참조하면 화합물 2 (5CQA)와 화합물 4 (4CQA methyl ester)는 쿠딩차에 들어있는 항산화 활성을 갖는 주요성분(도 3 참조)으로 지질 과산화 작용을 저해하는 활성으로 양성 대조군인 α-tocopherol (IC50 = 44.9 ± 8.3 μM)보다 강하였으며 DPPH, OH, O2등에 강한 저해 활성을 보여 주었다. Specifically, referring to Table 3, Compound 2 (5CQA) and Compound 4 (4CQA methyl ester) are the main components (see Fig. 3) which have antioxidant activity in the Cudding tea, and inhibit the lipid peroxidation activity. It was stronger than -tocopherol (IC 50 = 44.9 ± 8.3 μM) and showed strong inhibitory activity on DPPH, OH and O 2 .
<실시예 4: 하이드록실 라디칼 라디칼 소거 활성(hydroxyl radical scavenging activity) 측정>Example 4: Determination of hydroxyl radical scavenging activity
Hydroxyl radical (OH)은 생체내에서 생성되는 활성산소 중 가장 반응성이 높은 것으로 알려져 있다. 하이드록시 라디칼은 이온화 방사선을 조사하거나 금속이온의 H2O2의 분해로부터 생성 가능한데 FeCl3를 사용하여 측정하였다. 구체적으로 살펴보면, 0.1 mM FeCl3, 0.1 mM ascorbic acid, 0.1 mM EDTA, 10 mM H2O2 , 2.8 mM 데옥시리보스에 시료를 첨가한 포스페이트 버퍼 (PBS,20 mM, pH 7.4)를 1시간동안 상온에서 반응시켰다. 이후 각각 trichloroacetic acid (10%, w/v) 와 thiobacbituric acid (1%, w/v) 250 ㎕를 첨가하여 532 ㎚에서 흡광도를 측정하였고 그 결과를 표3 에 나타내었다.Hydroxyl radicals (OH) are known to be the most reactive free radicals produced in vivo. Hydroxy radicals can be generated from irradiation of ionizing radiation or from decomposition of H 2 O 2 of metal ions, measured using FeCl 3 . Specifically, 0.1 mM FeCl 3 , 0.1 mM ascorbic acid, 0.1 mM EDTA, 10 mM H 2 O 2 , 2.8 mM deoxyribose added the sample in phosphate buffer (PBS, 20 mM, pH 7.4) for 1 hour. The reaction was carried out at room temperature. After that, 250 µl of trichloroacetic acid (10%, w / v) and thiobacbituric acid (1%, w / v) were added, and the absorbance was measured at 532 nm. The results are shown in Table 3.
하이드록실 라디칼은 생체내에서 생성되는 활성산소 중 반응성이 높은 라디칼로 직접적으로 체내 단백질, 지질 및 DNA의 산화적 손상을 일으키는 것으로 알려져 있다. 측정 결과, 표 3을 참조하면, 분리한 화합물 1 - 9은 농도 의존적으로 강한 하이드록실 라디칼 저해 활성을 보여 주었다. 구체적으로 보면 화합물 5 (4,5diCQA methyl ester, IC50 = 2.2 ± 0.4 μM)와 화합물 6 (3,5diCQA methyl ester, IC50 = 2.6 ± 0.1 μM)은 양성 대조군으로 사용한 catechin (IC50 = 2.7 ± 0.2 μM)과 비슷한 저해 활성을 보여 주었다. Hydroxyl radicals are highly reactive radicals in free radicals produced in vivo and are known to directly cause oxidative damage to proteins, lipids and DNA in the body. If the measurement results, see Table 3, and compounds isolated 1 - 6 showed a concentration-dependent manner with a strong hydroxyl radical inhibitory activity. Specifically, compound 5 (4,5diCQA methyl ester, IC 50 = 2.2 ± 0.4 μM) and compound 6 (3,5diCQA methyl ester, IC 50 = 2.6 ± 0.1 μM) were used as positive controls for catechin (IC 50 = 2.7 ± 0.2 μM) showed similar inhibitory activity.
<실시예 5: 슈퍼옥사이드 라디칼 라디칼 소거 활성(superoxide radical scavenging activity) 측정Example 5 Determination of Superoxide Radical Scavenging Activity
슈퍼옥사이드 라디칼 자체는 비교적 반응성이 낮지만, 쉽게 과산화수소수로 변화되어 반응성이 강한 하이드록실 라디칼을 생성하는 것으로 알려져 있다. 슈퍼옥사이드 라디칼은 크산틴/크산틴 산화 효소(xanthine/xanthine oxidase)의 효소반응에 의하여 생성한 라디칼의 저해 정도를 측정하여 표3 에 나타내었다. 구체적으로 보면 20 mM xanthine oxidase, 100 M nitro blue tetrazolium(NBT), 50 M xanthine에 시료를 첨가하여 반응시켰다. Superoxide radicals themselves are relatively low in reactivity, but are known to readily convert into hydrogen peroxide to produce highly reactive hydroxyl radicals. Superoxide radicals are shown in Table 3 by measuring the degree of inhibition of radicals produced by the enzymatic reaction of xanthine / xanthine oxidase. Specifically, a sample was added to 20 mM xanthine oxidase, 100 M nitro blue tetrazolium (NBT), and 50 M xanthine for reaction.
측정 결과, 표3 을 참조하면, 분리한 화합물 1 - 9 는 농도 의존적으로 강한 슈퍼옥사이드라디칼 저해 활성을 보여 주었다. 구체적으로 쿠딩차에 들어있는 주요 성분인 화합물 4 (4CQA methyl ester, IC50 = 16.2 ± 0.7 μM)은 양성 대조군으로 사용한 catechin (IC50 = 13.2 ± 2.3 μM)과 비슷한 저해 활성을 보여 주었다.If the measurement results, see Table 3, and compounds isolated 1 - 6 showed a concentration-dependent manner with a strong superoxide radical inhibitory activity. Specifically, compound 4 (4CQA methyl ester, IC 50 = 16.2 ± 0.7 μM), which is a major component in the cudding tea, showed similar inhibitory activity to catechin (IC 50 = 13.2 ± 2.3 μM) used as a positive control.
<실시예 6: 화합물의 저밀도 지질단백질(low density lipoprotein, LDL) 산화 활성 측정>Example 6 Determination of Low Density Lipoprotein (LDL) Oxidation Activity of Compounds
LDL 산화는 동맥경화를 유발하는 인자로 중요시 되고 있다. 생체내에서 산화적 스트레스는 혈액 내의 LDL을 산화된-LDL(oxidized-LDL)로 변형시키게 되고, 이것은 혈관의 내막(intima)내로 유입된다. 유입된 산화된-LDL을 단핵구(monocyte)가 탐식하여 거품세포(foam cell)를 형성하면서 동맥경화의 초기단계를 발생시킨다. 항산화제는 이러한 산화된-LDL의 발생을 낮출 수 있는 가능성을 가질 수 있기에 화합물의 LDL 산화 정도를 측정하여 도 2 와 표3 에 나타내었다.LDL oxidation is becoming an important factor in inducing atherosclerosis. In vivo, oxidative stress transforms LDL in the blood into oxidized-LDL, which enters the intima of blood vessels. Monocytes are introduced into the oxidized-LDL and form foam cells to generate early stages of atherosclerosis. Antioxidants may have the possibility of lowering the occurrence of such oxidized-LDL, and thus the degree of LDL oxidation of the compound is measured and shown in FIG. 2 and Table 3. FIG.
항산화 활성은 저밀도 지질단백질의 산화를 유도하는 것으로 알려져 있는 Cu2+로 생성된 불포화 지방산의 산화 산물인 디알데하이드를 TBARS(thiobarbituric acid reactive substance)법으로 측정하였다. 구체적으로 보면 사람으로부터 채취한 혈장을 채취하여 초원심분리기로 1.02 - 1.06 g/㎖ 사이의 비중을 갖는 분획을 분리하였다. 이후 일정량의 LDL(0.1 ㎎ protein/㎖)을 첨가한 후 5 mM CuSO4나 2,2′-azobis-(2-amidinopropane)dihydrochloride(AAPH)10 mM PBS 용액을 이용하여 활성을 측정하여 표3 에 나타내었다. Antioxidant activity was measured by the thiobarbituric acid reactive substance (TBARS) method of dialdehyde, an oxidation product of unsaturated fatty acids produced with Cu 2+ , which is known to induce oxidation of low density lipoproteins. Specifically, plasma was collected from humans and fractions having specific gravity between 1.02 and 1.06 g / ml were separated by ultracentrifuge. After adding a certain amount of LDL (0.1 mg protein / ㎖) and measured the activity using 5 mM CuSO 4 or 2,2′-azobis- (2-amidinopropane) dihydrochloride (AAPH) 10 mM PBS solution to Table 3 Indicated.
측정 결과, 표3 을 참조하면, 분리한 화합물 1 - 9 는 농도 의존적으로 AAPH 나 Cu2+에 유도되는 저밀도 지질단백질의 산화를 저해하였다. 구체적으로 쿠딩차에 들어있는 페놀릭 계열의 화합물은 양성 대조군으로 사용한 (+)-catechin이나 BHT가 AAPH와 Cu2+에 유도된 산화를 저해하는 것과 같이 비슷하거나 강한 활성을 나타내었다. 더욱이 양성 대조군으로 사용한 α-tocopherol이 Cu2+에 유도되는 저밀도 지질단백질의 산화만을 저해(IC50 = 17.7 ± 1.6 μM)하는 것에 강한 분리된 화합물들은 AAPH와 Cu2+에 의한 산화를 모두 저해하였다.If the measurement results, see Table 3, and compounds isolated 1 - 10 it is inhibited the oxidation of low density lipoprotein that is a concentration-dependent manner induce the AAPH or Cu 2+. Specifically, the phenolic compounds in Cuddingcha showed similar or strong activity, such as (+)-catechin or BHT used as a positive control to inhibit oxidation induced by AAPH and Cu 2+ . Furthermore, isolated compounds resistant to α-tocopherol used as a positive control only inhibited the oxidation of Cu 2 + -induced low-density lipoproteins (IC 50 = 17.7 ± 1.6 μM), which inhibited both AAPH and Cu 2+ oxidation. .
<실시예 7: 독성시험>Example 7: Toxicity Test
상기 실시예 1에서 항산화 활성이 강한 에틸아세테이트 분획물의 랫트에 대한 경구투여에 의한 독성 존재유무를 조사하기 위해 SD계통의 웅성 및 자성 랫트에 각각 1 g/㎏, 2 g/㎏ 및 5 g/㎏ 3개의 투여용량으로 5 마리씩 단회 경구투여하고 14 일간의 사망예, 일반증상, 체중변화 및 부검소견을 관찰하였다. 이와 같이 시험한 결과는 본 발명의 조성물의 모든 투여군에서 시험 전 기간동안 관찰시 사망예는 없었으며, 대조군에 비해 특이적으로 관찰된 일반증상의 변화도 없었다. In order to examine the presence of toxicity by oral administration to rats of the ethyl acetate fraction having strong antioxidant activity in Example 1, 1 g / kg, 2 g / kg and 5 g / kg in male and female rats of the SD system, respectively. Five doses of three doses were orally administered and observed for 14 days of death, general symptoms, weight change, and autopsy findings. As a result of the test, all the administration groups of the composition of the present invention was observed no deaths during the entire test period, there was no change in the general symptoms observed compared to the control group.
따라서 경구투여에 의한 랫트에서의 LD50 (lethal dose)은 5 g/㎏ 이상인 것으로 판단된다.Therefore, LD50 (lethal dose) in rats by oral administration is determined to be 5 g / kg or more.
<실시예 8: 약학적 제제예>Example 8: Pharmaceutical Formulation
8-1. 정제의 제조8-1. Manufacture of tablets
본 발명에 따른 쿠딩차 추출물 또는 이로부터 분리된 화합물을 250 g을 락토 오스 175.9 g, 감자전분 180 g 및 콜로이드성 규산 32 g과 혼합하였다. 이 혼합물에 10% 젤라틴 용액을 첨가시킨 후, 분쇄해서 14 메쉬체를 통과시켰다. 이것을 건조시키고 여기에 감자전분 160 g, 활석 50 g 및 스테아린산 마그네슘 5 g을 첨가해서 얻은 혼합물을 정제로 만들었다. The cudding tea extract according to the present invention or the compound isolated therefrom was mixed with 250 g of lactose 175.9 g, potato starch 180 g and colloidal silicic acid 32 g. 10% gelatin solution was added to the mixture, which was then ground and passed through a 14 mesh sieve. It was dried and the mixture obtained by adding 160 g of potato starch, 50 g of talc and 5 g of magnesium stearate was made into a tablet.
8-2. 주사액제의 제조8-2. Preparation of Injection
본 발명에 따른 쿠딩차 추출물 또는 이로부터 분리된 화합물 1 g, 염화나트륨 0.6 g 및 아스코르브산 0.1 g을 증류수에 용해시켜서 100 ㎖를 만들었다. 이 용액을 병에 넣고 20 ℃에서 30 분간 가열하여 멸균시켰다.1 g of the cudding tea extract according to the present invention or a compound isolated therefrom, 0.6 g of sodium chloride and 0.1 g of ascorbic acid were dissolved in distilled water to make 100 ml. The solution was bottled and sterilized by heating at 20 ° C. for 30 minutes.
<실시예 9: 식품 제조예>Example 9: Food Preparation Example
9-1. 조리용 양념의 제조9-1. Preparation of Cooking Seasonings
본 발명에 따른 쿠딩차 추출물 또는 이로부터 분리된 화합물 각각 0.2~10 중량부로 건강 증진용 조리용 양념을 제조하였다.Coding tea extract according to the present invention or a compound isolated therefrom 0.2 to 10 parts by weight of a health promotion cooking seasoning was prepared.
9-2. 밀가루 식품의 제조9-2. Manufacture of flour food products
본 발명에 따른 쿠딩차 추출물 또는 이로부터 분리된 화합물 각각 0.1~5.0 중량부를 밀가루에 첨가하고, 이 혼합물을 이용하여 빵, 케이크, 쿠키, 크래커 및 면류를 제조하여 건강 증진용 식품을 제조하였다.0.1 to 5.0 parts by weight of each of the cudding tea extract or the compound isolated therefrom was added to the flour, and bread, cake, cookies, crackers and noodles were prepared using the mixture to prepare foods for health promotion.
9-3. 스프 및 육즙(gravies)의 제조9-3. Preparation of soups and gravy
본 발명에 따른 쿠딩차 추출물 또는 이로부터 분리된 화합물 각각 0.1~1.0 중량부를 스프 및 육즙에 첨가하여 건강 증진용 육가공 제품, 면류의 수프 및 육즙을 제조하였다.Coding tea extract according to the present invention or compounds separated therefrom were added 0.1 to 1.0 parts by weight to soups and broth to prepare meat products for health promotion, soups and noodles of noodles.
9-4. 유제품(dairy products)의 제조9-4. Manufacture of dairy products
본 발명에 따른 쿠딩차 추출물 또는 이로부터 분리된 화합물 각각 0.1~1.0 중량부를 우유에 첨가하고, 상기 우유를 이용하여 버터 및 아이스크림과 같은 다양한 유제품을 제조하였다.Coding tea extract according to the present invention or 0.1 to 1.0 parts by weight each of the compounds separated therefrom were added to milk, and various dairy products such as butter and ice cream were prepared using the milk.
<실시예 10: 음료 제조예>Example 10 Beverage Preparation Example
10-1. 야채쥬스 제조10-1. Vegetable Juice Manufacturing
본 발명에 따른 쿠딩차 추출물 또는 이로부터 분리된 화합물 0.5 g을 토마토 또는 당근 쥬스 1,000 ㎖에 가하여 건강 증진용 야채쥬스를 제조하였다.0.5 g of a cudding tea extract or a compound isolated therefrom was added to 1,000 ml of tomato or carrot juice to prepare a vegetable juice for health promotion.
10-2. 과일쥬스 제조10-2. Fruit juice manufacturing
본 발명에 따른 쿠딩차 추출물 또는 이로부터 분리된 화합물 0.1 g을 사과 또는 포도 쥬스 1,000 ㎖에 가하여 건강 증진용 과일쥬스를 제조하였다.Cushion tea extract according to the present invention or 0.1 g of a compound isolated therefrom was added to 1,000 ml of apple or grape juice to prepare a fruit juice for health promotion.
도 1은 쿠딩차로부터 메탄올 추출물 및 에틸아세테이트 분획의 Cu2+, AAPH에 의해 유도된 LDL 산화 저해활성을 측정한 그래프이다.1 is a graph measuring the LDL oxidation inhibitory activity induced by Cu 2+ , AAPH of methanol extract and ethyl acetate fraction from Coding tea.
도 2는 쿠딩차로부터 메탄올 추출물 및 에틸아세테이트 분획의 Cu2+, AAPH에 의해 유도된 LDL 산화에 있어서의 TBARS 저해활성을 측정한 그림이다.FIG. 2 shows TBARS inhibitory activity in LDL oxidation induced by Cu 2+ and AAPH of methanol extract and ethyl acetate fraction from Coding tea.
도 3은 쿠딩차의 에틸아세테이트 분획으로부터 항산화 활성을 갖는 화합물을 분석하기 위한 HPLC 그림이다.3 is an HPLC diagram for analyzing a compound having antioxidant activity from the ethyl acetate fraction of the cudding tea.
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