KR100850474B1 - Pharmaceutical composition for cancer chemoprevention comprising the extracts of cutleria cylindrica - Google Patents
Pharmaceutical composition for cancer chemoprevention comprising the extracts of cutleria cylindrica Download PDFInfo
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- KR100850474B1 KR100850474B1 KR1020080046221A KR20080046221A KR100850474B1 KR 100850474 B1 KR100850474 B1 KR 100850474B1 KR 1020080046221 A KR1020080046221 A KR 1020080046221A KR 20080046221 A KR20080046221 A KR 20080046221A KR 100850474 B1 KR100850474 B1 KR 100850474B1
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- extract
- cutleria
- cylindrical
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- whip
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Abstract
Description
본 발명은 해조류인 채찍말(Cutleria cylindrica) 추출물을 유효성분으로 함유하는 화학적 암 예방(cancer chemoprevention)을 위한 조성물에 관한 것으로서, 더욱 상세하게는 채찍말을 에탄올의 유기용매로 추출하여 제조되는 추출물이 암 예방 지표효소인 퀴논 리덕타아제(Quinone reductase)의 활성을 유도하며 세포독성이 없고, 1상 해독효소계의 활성은 유도하지 않지만 2상 해독효소계의 활성을 유도함으로서 화학적 암 예방 효과를 나타내므로, 이를 유효성분으로 함유하는 암 예방을 위한 의약품의 조성물에 관한 것이다.The present invention is a seaweed whip ( Cutleria) cylindrica ) relates to a composition for chemical cancer prevention (cancer chemoprevention) containing the extract as an active ingredient, more specifically, the extract prepared by extracting the whip with an organic solvent of ethanol is quinone reductase which is a cancer prevention indicator enzyme Induces the activity of (Quinone reductase) and has no cytotoxicity, but does not induce the activity of single-phase detoxifying enzyme system, but shows the chemical cancer prevention effect by inducing the activity of two-phase detoxifying enzyme system. It relates to a composition of medicine for.
암에 대한 연구가 30년 이상 심도 있게 이루어진 현재에도 환경오염, 잘못된 식생활습관 등으로 인하여 암 발생률은 계속 증가하여 전 세계적으로 매년 1,000만 명 정도 발생하며 세계보건기구(WHO)는 사망의 주요원인 중 하나로 암을 꼽고 있다. 암은 중년층의 질환으로서 새로운 임상예의 70% 이상이 60세 이상에서 진단되어 세계인구가 고령화됨에 따라 암 발생률이 증가하게 되는 것은 피할 수 없는 현 상이다. 국내에서도 보건복지부에 따르면 매년 10만 명 정도의 암 환자가 발생하는 것으로 알려져 있다.Even after more than 30 years of cancer research, the incidence of cancer continues to increase due to environmental pollution and poor dietary habits, causing about 10 million people worldwide each year. The World Health Organization (WHO) is one of the leading causes of death. Cancer is counted as one. Cancer is a middle-aged disease, and it is unavoidable that more than 70% of new clinical cases are diagnosed at
일반적인 암의 치료법으로는 수술, 방사선 치료, 항암제 치료 등이 있다. 암의 확실한 치료를 위해서는 조기에 암을 진단하여 수술하고, 방사선 또는 항암제 치료를 병행하는 것이다. 그러나 암의 진단이 늦어지거나 암이 전이된 경우에는 치료 방법이 복잡해지며 치료에 소요되는 정신적, 경제적 부담이 훨씬 커지게 된다. 따라서 화학적 암 예방과 암을 초기에 발견하기위한 진단방법 개발이 최근 암 연구의 중요 분야이다.Common treatments for cancer include surgery, radiation, and chemotherapy. To reliably treat cancer, cancer is diagnosed and operated early, and radiation or chemotherapy is combined. However, when the diagnosis of cancer is delayed or the cancer has spread, the treatment methods are complicated and the mental and economic burden of the treatment is much greater. Therefore, chemical cancer prevention and the development of diagnostic methods for early detection of cancer are important areas of recent cancer research.
기존의 항암제 치료는 암세포뿐만 아니라 정상세포에도 손상을 입혀 심각한 독성 및 부작용을 나타내는 경우가 있는 반면 화학적 암 예방은 비교적 독성이 없는 안전한 화학물질을 이용하여 발암과정을 인위적으로 억제하거나 지연 또는 역전시킴으로서 정상세포가 암세포로 전환하는 것을 예방하려는 암 연구의 새로운 전략이다. 화학적 암 예방 물질의 후보군이 되기 위해서는 독성이 없거나 미약해야 하며 다수에게 널리 보급될 수 있도록 천연물로부터 분리나 합성이 용이한 화학물질들이 이용되므로 몇몇 비타민 대사물질들을 제외하고는 주로 식물성 화합물이 이용되고 있다(Surh YJ, Nature Rev Cancer, 3, 768-780, 2003).Conventional anticancer treatments can cause serious toxicity and side effects by damaging not only cancer cells but also normal cells, whereas chemical cancer prevention is achieved by artificially inhibiting, delaying or reversing the carcinogenic process using safe chemicals that are relatively nontoxic. It's a new strategy in cancer research to prevent cells from turning into cancer cells. In order to be a candidate for a chemical cancer prevention substance, the compound should be non-toxic or weak and vegetable compounds are mainly used except for some vitamin metabolites because chemicals that can be easily separated or synthesized from natural products are used for widespread use. Sur YJ, Nature Rev Cancer , 3, 768-780, 2003).
암은 개시단계(initiation), 촉진단계(promotion), 진행단계(progression), 전이단계(metastasis)와 같은 다단계로 되어있는데 화학적 암 예방은 주로 개시단계와 촉진단계에서 암 발생을 억제하는 것을 목표로 하며 그 기전에 따라 크게 두 가지로 구분된다. 즉, 발암물질이 세포내 표적물과 반응하거나 목적물에의 도달을 억제하는 기전을 가진 블록킹 에이전트(blocking agent)와 발암물질에 노출된 세포가 신생물(neoplasia)로 나타나는 과정을 억제하는 서프레싱 에이전트(suppressing agent)이다(Surh YJ, Nature Rev Cancer, 3, 768-780, 2003). 블록킹 에이전트로는 1) 사이토크롬 P-450(cytochrome P-450) 효소의 억제물질인 디알릴 설파이드(diallyl sulfide), 이소티오시아네이트(isothiocyanate), 에라직 액시드(ellagic acid) 등이 알려져 있으며, 2) 2상 해독효소계의 유도제인 페닐에틸 이소티오시아네이트(phenylethyl isothiocyanate), 설포라판(sulforaphane), 올티프라즈(oltipraz) 등이 알려져 있다. 서프레싱 에이전트로는 1)폴리아민(polyamine) 대사 억제물질로 DFMO, 2) 세포분화촉진제로 레티노이드(retinoid) 계열, 3) 프로틴 키나아제 C(protein kinase C) 억제물질로 제니스테인(genistein), 4) 산화성 DNA 손상억제물질로 EGCG 등이 알려져 있다.Cancer has multiple stages, such as initiation, promotion, progression and metastasis. Chemical cancer prevention aims primarily at suppressing cancer initiation and promotion. It is divided into two types according to the mechanism. That is, a blocking agent having a mechanism for inhibiting the carcinogen reacting with the intracellular target or reaching the target and a suppressing agent for suppressing the process in which the cells exposed to the carcinogen appear as neoplasia. (suppressing agent) (Surh YJ, Nature Rev Cancer , 3, 768-780, 2003). Blocking agents include: 1) diallyl sulfide, isothiocyanate, and ellagic acid, which are inhibitors of the cytochrome P-450 enzyme. And 2) phenylethyl isothiocyanate, sulfoaphane, oltipraz, and the like, which are derivatives of a two-phase detoxification enzyme. Suppressing agents include: 1) DFMO as a polyamine metabolism inhibitor; 2) a retinoid family as a cell differentiation promoter; 3) a genistein as a protein kinase C inhibitor; 4) oxidative EGCG and the like are known as DNA damage inhibitors.
해독효소계의 활성을 조절하는 기전을 가진 블록킹 에이전트는 기능에 따라 단일기능 유도제(monofunctional inducer)와 이중기능 유도제(bifunctional inducer)의 두 개 군으로 나눌 수 있다. 단일기능 유도제는 퀴논 리덕타아제와 글루타치온-S-트랜스퍼라아제(glutathione-S-transferase) 등과 같은 2상 해독효소계의 활성을 유도하는 반면 이중기능 유도제는 단일기능 유도제에 의하여 유도되는 2상 해독효소계의 활성을 유도하는 동시에 사이토크롬 P-450 계열의 1상 해독효소계의 활성도 함께 유도한다. 일반적으로 2상 해독효소계의 활성증가는 발암성 또는 전발암성 물질의 체외 배출을 촉진시킴으로써 화학적 발암에 대한 예방효과와 관련이 있는 것으로 알려져 있으나, 1상 해독효소계의 활성증가는 전발암성 물질을 대 사하여 발암성을 부여 또는 증가시키는 것으로 알려져 있다. 따라서 화학적 암 예방에서는 단일기능 유도제가 이중기능 유도제보다 더 효과적이라 할 수 있다(Prochaska HJ and Talalay P, Cancer Res, 48, 4776-4782, 1988).Blocking agents having a mechanism for regulating the activity of the detoxifying enzyme system can be divided into two groups, monofunctional inducers and bifunctional inducers, depending on their function. Monofunctional inducers induce the activity of biphasic detoxifying enzymes such as quinone reductase and glutathione-S-transferase, while bifunctional inducers are biphasic detoxifying enzymes induced by monofunctional inducers. In addition to inducing the activity of the cytochrome P-450 family of
화학적 암 예방에 의한 해독효소계의 유전자 조절에는 안티옥시던트 레스폰스 엘리먼트(Antioxidant response element;ARE)와 제노바이오틱스 레스폰시브 엘리먼트(Xenobiotics-responsive element;XRE)의 두 개 조절인자가 관여하는 것으로 보고되었다(Okey AB et al ., Toxicol Lett, 70, 1-22). ARE는 2상 해독효소계의 활성유도를 조절하기 때문에 단일기능 유도제의 효과 검정에 이용될 수 있고 XRE는 1상과 2상 해독효소계의 활성증가를 동시에 조절하는 것으로 알려져 있어 이중기능 유도제의 효과 검정에 이용될 수 있다.Gene regulation of the detoxification enzyme system by chemical cancer prevention has been reported to involve two regulators, an antioxidant response element (ARE) and a Xenobiotics-responsive element (XRE). Okey AB et al . , Toxicol Lett , 70, 1-22). Since ARE modulates the activity induction of biphasic detoxification enzymes, it can be used to test the effects of monofunctional inducers. Can be used.
본 발명의 채찍말(Cutleria cylindrica)은 녹갈색을 띠고 유성체는 높이 30∼50cm, 기부에 갈색 털이 나고 원주상으로 길게 뻗으며, 굵기 2∼3mm, 차상으로 넓게 분기하고 상부는 가늘게 되고 끝은 털로 변한다. 노성하면 이 털은 없어진다. 속도 썩어서 중공(中空)으로 된다. 자웅의 배우자낭은 군(群)을 이루고 불규칙한 원형의 혹 모양으로 된다. 이것은 배게 가지의 전면에 산재하게 된다. 조간대의 조용한 곳의 암석 위에 있고 특히 봄에 타이드풀에서 흔히 볼 수 있다. 주로 일본에 분포되고 우리 나라에서는 대진, 삼척, 후포, 기성, 부산, 오동도에 분포한다(강제원, 한국동식물도감 식물편, 삼화출판사, 1968년).The whip of the present invention ( Cutleria cylindrica ) is greenish brown, the oily body is 30-50cm in height, brown hairs on the base, long circumferentially elongated, 2-3mm thick, broadly branched in the car phase, the top is thin and the ends are changed to hair. . This hair is lost when aging. The speed decays and becomes hollow. Her spouses form a group and become irregular circular humps. This is scattered all over the pillow. It is located on a rock in a quiet area of intertidal zone, especially in tide pools in spring. It is mainly distributed in Japan, and is distributed in Daejin, Samcheok, Fupo, Kiseong, Busan, and Odongdo in Korea (Gangjewon, Korean flora and fauna book, Samhwa Publisher, 1968).
본 발명자들은 인체 독성이 없거나 미약한 화학적 암 예방제를 개발하기 위하여 식용 가능한 천연물에서 단일기능 유도제의 활성을 검색하던 중, 채찍말 추출 물이 암 예방 지표효소인 퀴논 리덕타아제의 활성을 유도하며 세포독성이 없고, 1상 해독효소계의 활성은 유도하지 않지만 2상 해독효소계의 활성을 유도함으로서 화학적 암 예방 효과를 나타내어 이를 유효성분으로 함유하는 조성물은 암 예방을 위한 의약품으로 사용될 수 있음을 밝힘으로써 본 발명을 완성하였다.The inventors of the present invention, while searching for the activity of a monofunctional inducer in edible natural products to develop a chemical cancer preventive agent that is not toxic or weak in humans, the whip extract induces the activity of quinone reductase, a cancer prevention marker, It is not toxic and does not induce the activity of single-phase detoxifying enzyme system, but it shows chemical cancer prevention effect by inducing activity of two-phase detoxifying enzyme system, and thus the composition containing it as an active ingredient can be used as medicine for cancer prevention. The invention was completed.
본 발명의 목적은 인체 독성이 없으면서 탁월한 화학적 암 예방 효과를 가지는 채찍말 추출물을 유효성분으로 함유하는 의약품을 위한 조성물을 제공하는 것이다.It is an object of the present invention to provide a composition for a medicament containing a whip extract as an active ingredient having excellent chemical cancer prevention effect without human toxicity.
본 발명은 유효성분으로서 채찍말 추출물을 함유하는 암 예방용 약학 조성물에 관한 것이다.The present invention relates to a pharmaceutical composition for preventing cancer, comprising a whip extract as an active ingredient.
본 발명의 채찍말 추출물은 암 예방 지표효소인 퀴논 리덕타아제의 활성을 유도하며 세포독성이 없고, 1상 해독효소계의 활성은 유도하지 않지만 2상 해독효소계의 활성을 유도함으로서 체내 대사를 통한 전발암성 물질의 발암성 부여 또는 증가를 억제하고 발암성 또는 전발암성 물질의 체외 배출을 촉진시킴으로써 화학적 발암에 대한 예방 효과를 나타내므로, 이를 유효성분으로 함유하는 조성물은 암 예방을 위한 의약품으로 유용하게 이용될 수 있다.The whip extract of the present invention induces the activity of quinone reductase, a cancer prevention indicator enzyme, has no cytotoxicity, and does not induce the activity of the
상기 목적을 달성하기 위하여, 본 발명에 따른 약학 조성물은 유효성분으로서 채찍말 추출물을 함유하는 것을 특징으로 한다. In order to achieve the above object, the pharmaceutical composition according to the present invention is characterized by containing a whip extract as an active ingredient.
본 발명의 일실시예에 따른 약학 조성물은 화학적 암 예방을 위한 용도를 갖는 것을 특징으로 한다.The pharmaceutical composition according to one embodiment of the present invention is characterized by having a use for chemical cancer prevention.
본 발명의 일실시예에 따른 약학 조성물에 있어서, 상기 채찍말 추출물은 에탄올 추출물인 것이 바람직하다.In the pharmaceutical composition according to an embodiment of the present invention, the whip extract is preferably an ethanol extract.
본 발명의 일실시예에 따른 약학 조성물에 있어서, 상기 채찍말 추출물은 퀴논 리덕타아제의 활성을 증진시키는 것을 특징으로 한다. In the pharmaceutical composition according to an embodiment of the present invention, the whip extract is characterized in that to enhance the activity of quinone reductase.
본 발명의 일실시예에 따른 약학 조성물에 있어서, 상기 채찍말 추출물은 2상 해독효소계의 활성을 유도하는 것을 특징으로 한다.In the pharmaceutical composition according to an embodiment of the present invention, the whip extract is characterized by inducing activity of a biphasic detoxifying enzyme system.
이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
본 명세서에서 "항암"이라 함은, 암의 예방, 치료, 증상의 경감 및 완화 등을 모두 포괄하는 최광의의 의미이다. As used herein, the term "anticancer" is the broadest meaning encompassing all of the prevention, treatment, alleviation and alleviation of symptoms.
본 명세서에서 "화학적 암 예방"이라 함은, 암의 개시단계, 촉진단계, 진행단계 및 전이단계 중 어느 하나 이상을 억제하는 것을 포함하는 최광의의 의미이다. 그 중 특히 암의 개시단계 및 촉진단계에서 암 발생을 억제하는 것을 가리킨다. 또한, 발암물질이 세포내 표적물과 반응하거나 목적물에 도달하는 것을 억제하는 블록킹(blocking) 기전을 통해 암을 예방하는 것을 포함한다. 또한, 발암물질에 노출된 세포가 신생물(neoplasia)로 나타나는 과정을 억제하는 서프레싱(suppressing) 기전을 통해 암을 예방하는 것도 포함한다. 또한, 발암성 또는 전발암성 물질의 체외 배출을 촉진시킴으로써 암을 예방하는 것을 포함한다. 또한 전발암성 물질을 대사하여 암을 예방하는 것도 포함한다. As used herein, the term "chemical cancer prevention" is the broadest meaning including inhibiting any one or more of the initiation stage, promotion stage, progression stage, and metastasis stage of cancer. Among them, it refers to inhibiting cancer development at the onset and promotion stage of cancer. It also includes preventing cancer through a blocking mechanism that inhibits the carcinogen from reacting with or reaching the target within the cell. It also includes preventing cancer through a suppressing mechanism that inhibits the processes in which cells exposed to carcinogens appear as neoplasia. It also includes preventing cancer by facilitating ex vivo release of carcinogenic or precarcinogenic substances. It also includes metabolizing precancerous substances to prevent cancer.
본 명세서에서 "채찍말 추출물"이라 함은, 천연물인 채찍말로부터 유효성분 을 추출하여 얻어진 것이라면 특별히 한정하지 않고 모두 포함한다. 예컨대, 채찍말을 물이나 유기용매에 넣고 정치, 교반, 가압 또는 가열 등의 수단을 통해 유효성분을 용출함으로써 얻어진 결과물을 들 수 있다. 또한, 그와 같이 하여 얻어진 액상 추출물을 동결건조함으로써 얻어진 동결건조물을 포함한다. 또한, 그러한 동결건조물을 분쇄한 분말을 포함한다. 그 외에도 유효성분을 추출하기 위해 가능한 수단이 무엇이든지 가리지 않고 추출된 모든 추출물을 포함하며, 추출된 후 동결 건조 등의 가공을 거친 것까지도 모두 포함된다. 기타, 중탕이나 상온에 의한 추출법과 같이 예로부터 전해 내려오거나, 한의서 또는 교과서에 기재되어 있는 통상적인 추출법에 의한 추출물을 포함한다. 또한, 특정 활성 화합물들을 분리하기 위한 특별한 추출방법인 Stass Otto 추출법이나 각종 칼럼 크로마토그래피 방법 등을 통하여 얻어진 분획 추출물을 포함한다. As used herein, the term "whipped horse extract" includes all of them, without particular limitation, as long as they are obtained by extracting an active ingredient from a natural whip. For example, the result obtained by putting a whip into water or an organic solvent and eluting an effective component through means, such as standing, stirring, pressurization, or heating, is mentioned. It also includes a lyophilized product obtained by lyophilizing the liquid extract thus obtained. It also includes a powder obtained by grinding such lyophilisate. In addition, any possible means for extracting the active ingredient includes all the extracted extracts, including all the processed after extraction and freeze-drying. Others include extracts obtained by conventional extraction methods such as extraction by baths or room temperature, or by conventional extraction methods described in Chinese medicine or textbooks. In addition, it includes a fraction extract obtained through the Stass Otto extraction method, various column chromatography methods, etc., which is a special extraction method for separating specific active compounds.
본 발명은 화학적 암 예방용 채찍말 추출물을 제공한다.The present invention provides a whip extract for chemical cancer prevention.
상기 채찍말은 채취한 것, 양식한 것 또는 시판되는 것 등 제한 없이 사용할 수 있으며, 추출을 위한 용매는 에탄올이다. 본 발명자들은 채찍말을 물로 씻어 이물질 및 염분을 제거한 후 건조하여 추출한 뒤, 여과액을 감압농축 및 건조하여 채찍말 추출물을 수득하였다.The whip may be used without limitation, such as harvested, cultured or commercially available, the solvent for extraction is ethanol. The present inventors washed the whip with water to remove foreign substances and salt, and then dried and extracted, and the filtrate was concentrated under reduced pressure and dried to obtain a whip extract.
또한, 본 발명은 채찍말 추출물을 유효성분으로 함유하는 화학적 암 예방용 약학적 조성물을 제공한다.The present invention also provides a chemical cancer prevention pharmaceutical composition containing the lash extract as an active ingredient.
본 발명에 따른 약제학적 조성물은 약제학적 조성물의 제조에 통상적으로 사 용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다.The pharmaceutical compositions according to the invention may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.
본 발명의 조성물의 약학적 투여 형태는 이들의 약학적 허용가능한 염의 형태로도 사용될 수 있고, 또한 단독으로 또는 타 약학적 활성 화합물과 결합뿐만 아니라 적당한 집합으로 사용될 수 있다. 상기 염으로는 약학적으로 허용되는 것이면 특별히 한정되지 않으며, 예를 들어 염산, 황산, 질산, 인산, 불화수소산, 브롬화수소산, 포름산 아세트산, 타르타르산, 젖산, 시트르산, 푸마르산, 말레산, 숙신산, 메탄술폰산, 벤젠술폰산, 톨루엔술폰산, 나프탈렌술폰산 등을 사용할 수 있다. The pharmaceutical dosage forms of the compositions of the present invention may be used in the form of their pharmaceutically acceptable salts, and may be used alone or in combination with other pharmaceutically active compounds as well as in a suitable collection. The salt is not particularly limited as long as it is pharmaceutically acceptable, and for example, hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrofluoric acid, hydrobromic acid, formic acid acetic acid, tartaric acid, lactic acid, citric acid, fumaric acid, maleic acid, succinic acid, methanesulfonic acid , Benzene sulfonic acid, toluene sulfonic acid, naphthalene sulfonic acid and the like can be used.
본 발명에 따른 약제학적 조성물은, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 연고, 크림 등의 외용제, 좌제 및 멸균 주사용액 등을 비롯하여 약제학적 제제에 적합한 어떠한 형태로든 제형화하여 사용될 수 있다. The pharmaceutical compositions according to the present invention may be used in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, oral formulations, ointments, creams, external preparations, suppositories, and sterile injectable solutions. It may be used in formulated in any form suitable for pharmaceutical formulations.
본 발명에 따른 조성물에 있어서, 채찍말 추출물의 바람직한 투여량은 대상자의 연령, 성별, 체중, 증상, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 그러나, 바람직한 효과를 위해서, 본 발명의 채찍말 추출물은 1일 0.001 내지 1000 mg/kg으로 투여하는 것이 좋다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다. 또한, 그 투여량은 연령, 성별, 체중, 질병의 정도, 투여경로 등에 따라서 증감될 수 있다. 따라서, 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.In the composition according to the present invention, the preferred dosage of the whip extract depends on the subject's age, sex, weight, symptoms, degree of disease, drug form, route of administration, and duration, and may be appropriately selected by those skilled in the art. . However, for the desired effect, the whip extract of the present invention is preferably administered at 0.001 to 1000 mg / kg per day. Administration may be administered once a day or may be divided several times. In addition, the dosage may be increased or decreased depending on age, sex, weight, degree of disease, route of administration, and the like. Therefore, the above dosage does not limit the scope of the present invention in any aspect.
본 발명에 따른 조성물은, 쥐, 생쥐, 가축, 인간 등의 포유동물에 비경구, 경구 등의 다양한 경로로 투여될 수 있으며, 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁내 경막 또는 뇌혈관내(intracerebroventricular) 주사에 의해 투여될 수 있다. The composition according to the present invention can be administered to mammals such as rats, mice, livestock, humans by various routes, such as parenteral, oral, and all modes of administration can be expected, for example, oral, rectal Or by intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.
한편, 본 발명에 따른 조성물은, 그다지 심각한 독성 및 부작용은 없으므로 예방 목적으로 장기간 사용 시에도 안심하고 사용할 수 있다.On the other hand, the composition according to the present invention, there is no serious toxicity and side effects can be used with confidence even for long-term use for the purpose of prevention.
본 발명에 의한 조성물은, 유효성분으로서 채찍말 추출물을 전체 조성물 중량 중 0.001 내지 99.9중량% 함유할 수 있다. 0.001중량% 이상이어야 효과를 기대할 수 있고, 불순물의 존재 등으로 인해 99.9중량%를 넘기 어렵기 때문이다. The composition according to the present invention may contain 0.001 to 99.9% by weight of the whip extract as the active ingredient in the total weight of the composition. This is because the effect can be expected to be 0.001% by weight or more, it is difficult to exceed 99.9% by weight due to the presence of impurities.
한편, 경구 투여의 목적으로 본 발명의 채찍말 추출물을 정제, 캡슐, 츄잉정, 작은 봉지, 과립, 분말, 액체 용액, 현탁액, 분산액, 에멀젼, 시럽 등의 제제로 제형화하는 경우에 있어서는, 아라비아 고무, 옥수수 전분, 미세 결정질 셀룰로오스 또는 젤라틴과 같은 결합제, 인산 이칼슘 또는 락토오즈와 같은 부형제, 알긴산, 옥수수 전분 또는 감자 전분과 같은 붕해제, 스테아르산 마그네슘과 같은 윤활제, 슈크로오즈 또는 사카린과 같은 감미제 및 페퍼민트, 메틸 살리실산염 또는 과일향과 같은 향미제가 포함될 수 있으며, 투여 단위 형이 캡슐제인 경우에는 상기 성분 외에도 폴리에틸렌 글리콜 또는 지방유와 같은 액상 담체가 포함될 수 있다.On the other hand, in the case of formulating a whip extract of the present invention into tablets, capsules, chewing tablets, small bags, granules, powders, liquid solutions, suspensions, dispersions, emulsions, syrups and the like for the purpose of oral administration, Arabia Rubber, corn starch, binders such as microcrystalline cellulose or gelatin, excipients such as dicalcium phosphate or lactose, disintegrants such as alginic acid, corn starch or potato starch, lubricants such as magnesium stearate, sucrose or saccharin Sweetening agents and flavoring agents such as peppermint, methyl salicylate or fruit flavors may be included, and in the case of the dosage unit form of capsules, liquid carriers such as polyethylene glycol or fatty oils may be included in addition to the above components.
또한, 본 발명은 상기 채찍말 추출물 및 식품학적으로 허용 가능한 식품보조 첨가제를 포함하는 건강 기능성 식품 조성물을 제공한다. 본 발명에 따른 식품 조성물은, 예를 들어, 츄잉껌, 캐러멜 제품, 캔디류, 빙과류, 과자류 등의 각종 식품류, 청량 음료, 미네랄 워터, 알코올 음료 등의 음료 제품, 비타민이나 미네랄 등 을 포함한 건강기능성 식품류일 수 있다.The present invention also provides a health functional food composition comprising the whip extract and a food supplement acceptable food supplement. The food composition according to the present invention may be, for example, a health functional food product including chewing gum, caramel products, candy, ice cream, confectionery, various food products such as soft drinks, mineral water, alcoholic beverages, vitamins and minerals, and the like. Can be.
이 때, 상기 식품 중의 상기 채찍말 추출물의 양은 전체 식품 중량의 0.001 내지 99.9 중량%로 가할 수 있으며, 음료 중에는 100 ㎖를 기준으로 0.001 내지 0.1 g, 더 바람직하게는 0.05 내지 0.1 g의 비율로 가할 수 있다. At this time, the amount of the whip extract in the food can be added to 0.001 to 99.9% by weight of the total food weight, in the beverage in the ratio of 0.001 to 0.1 g, more preferably 0.05 to 0.1 g based on 100 ml Can be.
본 발명의 채찍말 추출물을 함유하는 음료는 지시된 비율로 필수 성분으로서 상기 채찍말 추출물을 함유하는 외에는 다른 성분에는 특별한 제한이 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. The beverage containing the whip extract of the present invention is an essential ingredient in the ratio indicated, and there are no special limitations on the other ingredients except the whip extract, and various flavors or natural carbohydrates, such as ordinary drinks, may be added as additional ingredients. It may contain.
상기 외에 본 발명의 건강기능성 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, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 기능성 식품 조성물들은 천연 과일 쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다. In addition to the above, the functional food composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), synthetic flavors such as synthetic and natural flavors, colorants and enhancers (such as cheese and chocolate), pectic acid and salts thereof, alginic acid And salts thereof, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. In addition, the functional food compositions of the present invention may contain fruit flesh for the production of natural fruit juices and fruit juice beverages and vegetable beverages. These components can be used independently or in combination. The proportion of such additives is not so critical but is generally selected from the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.
본 발명자들은 채찍말 추출물의 암 예방 지표효소인 퀴논 리덕타아제 활성 유도 효과를 측정하기 위하여 흰쥐의 간암세포주(Hepa1c1c7)를 대상으로 하는 실험 을 수행하였다. 본 발명의 채찍말 추출물은 50, 100 μg/ml의 농도에서 무처리의 대조구에 비하여 퀴논 리덕타아제 활성을 각각 2배, 2.7배 증가시킴을 확인하였다.The present inventors conducted an experiment in rat liver cancer cell line (Hepa1c1c7) in order to determine the effect of quinone reductase activity, a cancer prevention indicator enzyme of the whip extract. The whip extract of the present invention was confirmed to increase the quinone reductase activity by two-fold and 2.7-fold, respectively, at a concentration of 50 and 100 μg / ml.
또한, 본 발명의 채찍말 추출물은 세포 증식의 50% 저해농도인 IC50가 705 μg/ml로 계산되어 세포독성이 없거나 미약한 것으로 나타났다.In addition, the whip end of the present invention extracts the 50% inhibitory concentration of IC 50 of cell growth is calculated as 705 μg / ml showed a cytotoxic or weak.
또한, 본 발명의 채찍말 추출물의 1상 및 2상 해독효소계 활성에 대한 효과를 측정하기 위하여 인간의 간암세포주(HepG2)를 대상으로 하는 실험을 수행하였다. 본 발명의 채찍말 추출물은 1, 10, 100 μg/ml 의 농도에서 1상과 2상 해독효소계 활성을 모두 유도하는 XRE 활성에는 영향을 주지 않았으며, 2상 해독효소계 활성을 유도하는 ARE 활성에는 농도 의존적으로 영향을 주는 것으로 확인하였다. 이는 본 발명의 채찍말 추출물이 선택적으로 2상 해독효소계의 활성을 증가시키는 효과적인 화학적 암 예방 효과를 설명하는 것이다.In addition, experiments were conducted on human liver cancer cell lines (HepG2) to determine the effect on the
이하, 본 발명을 하기의 실시예 및 실험예에 의해 상세히 설명한다.Hereinafter, the present invention will be described in detail by the following Examples and Experimental Examples.
단, 하기 실시예 및 실험예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실시예 및 실험예에 의해 한정되는 것은 아니다.However, the following Examples and Experimental Examples are merely illustrative of the present invention, and the content of the present invention is not limited by the following Examples and Experimental Examples.
<< 실시예Example 1> 1> 채찍말Whip 추출물의 제조 Preparation of Extract
강원도 강릉시 금진 지역에서 채취한 채찍말을 물로 씻어 이물질 및 염분을 제거한 후 건조하여, 적당한 크기로 분쇄하여 추출용기에 채찍말 20 g과 에탄올 수 용액 총 500 ml를 가하여 환류 냉각하였고, 거름종이로 여과하여 추출물을 얻었다. 추출과정은 4회 반복하였고, 이후 용매를 감압 농축 및 건조하여 880 mg의 에탄올 추출물을 수득하였다.Wash the whip collected in Geumjin, Gangneung-si, Gangwon-do with water, remove foreign substances and salt, dry it, grind it to a suitable size, add 20 g of whip and 500 ml of ethanol water solution to the extraction container, and cool it under reflux. To obtain an extract. The extraction process was repeated four times, after which the solvent was concentrated under reduced pressure and dried to obtain 880 mg of ethanol extract.
<< 실험예Experimental Example 1> 1> 채찍말Whip 추출물의 퀴논 Quinones in Extract 리덕타아제Reductase 활성 유도 효과 측정 Activity Induction Effect Measurement
본 발명자들은 본 발명의 채찍말 추출물의 암 예방 지표효소인 퀴논 리덕타아제 활성 유도 효과를 측정하기 위하여 흰쥐의 간암세포주(Hepa1c1c7)를 대상으로 하는 실험을 수행하였다. 먼저, a-MEM(minimum essential medium)/10% FBS(fetal bovine serum) 용액을 간암세포배양액과 혼합하여 세포의 수를 1X105 cells/ml로 조제한 후에 96well plate에 100 μl씩 처리하여 24시간동안 5% CO2/37℃의 조건에서 배양하였다. 세포가 안정화 된 후에 상기 <실시예 1>에서 수득한 채찍말의 추출물을 25, 50, 100 μg/ml의 농도로 처리하고 24시간 동안 5% CO2/37℃의 조건에서 배양하였다. 배양 종료 후 세포를 PBS(phosphate buffered saline) 용액으로 씻어낸 후 0.08% 디지토닌(digitonin)과 2 mM EDTA를 포함한 용액 80 μl로 세포막을 용해시키고 단백질 용액을 얻었다. 단백질 용액 50 μl와 반응용액A(49 ml의 25 mM Tris buffer, 34 mg의 BSA, 0.34 ml 의 1.5% Tween-20 용액, 0.34 ml의 조효소용액, 100 유닛의 글루코우즈-6-포스테이트 디하이드로게나아제, 15 mg MTT, 50 μl의 50 mM 메나디온) 200 ul를 혼합하여 마이크로플레이트 리더로 610 nm에서 흡광도 증가율을 측정하였으며, 단백질의 양은 브래드포드(Bradford) 용액을 사용하여 595 nm에서 측정하여 구하였다. 상기의 반응용액A 중 조효소용액은 150 mM 글루코우즈-6-포스테이트(glucose-6-phosphate), 4.5 mM NADP, 0.75 mM FAD로 구성되었으며 상기의 MTT는 3-(4,5-dimethylthiazo-2-yl)-2,5-diphenyltetrazolium bromide의 약어이다. 퀴논 리덕타아제의 활성은 수학식 1에 의해 계산하였다.The present inventors conducted an experiment in the rat liver cancer cell line (Hepa1c1c7) in order to determine the effect of quinone reductase activity, a cancer prevention indicator enzyme of the whip extract of the present invention. First, mix the a-MEM (minimum essential medium) / 10% FBS (fetal bovine serum) solution with the liver cancer cell culture medium to determine the number of cells 1X10 5 After adjusted to cells / ml treated in 100 μl in 96well plate and incubated under the conditions of 5% CO 2/37 ℃ for 24 hours. After the cells are stabilized the <Example 1> an extract of the whip end obtained in 25, 50, and cultured under the conditions of 5% CO 2/37 ℃ during treatment with 100 μg / ml concentration in 24 hours. After incubation, the cells were washed with PBS (phosphate buffered saline) solution, and the cell membrane was lysed with 80 μl of a solution containing 0.08% digitonin and 2 mM EDTA to obtain a protein solution. 50 μl of protein solution and reaction solution A (49 ml of 25 mM Tris buffer, 34 mg of BSA, 0.34 ml of 1.5% Tween-20 solution, 0.34 ml of coenzyme solution, 100 units of glucose-6-postate dehydro) 200 ul of genease, 15 mg MTT, 50 μl of 50 mM menadione) was mixed and the absorbance increase was measured at 610 nm using a microplate reader, and the amount of protein was measured at 595 nm using a Bradford solution. Obtained. The crude enzyme solution in the reaction solution A was composed of 150 mM glucose-6-phosphate, 4.5 mM NADP, 0.75 mM FAD, and the MTT was 3- (4,5-dimethylthiazo-2. -yl) -2,5-diphenyltetrazolium bromide. The quinone reductase activity was calculated by the following equation.
(수학식 1)(Equation 1)
퀴논 리덕타아제의 활성 = A/BQuinone reductase activity = A / B
A : nmol MTT/min (채찍말 추출물을 처리한 세포내 퀴논 리덕타아제의 610 nm에서의 흡광도 증가율)A: nmol MTT / min (increase in absorbance at 610 nm of intracellular quinone reductase treated with whip extract)
B : mg protein (채찍말 추출물을 처리한 세포 전체의 단백질 양)B: mg protein (amount of protein in cells treated with whip extract)
그 결과, 도 1에 나타난 바와 같이 본 발명의 채찍말 추출물은 50, 100 μg/ml의 농도에서 무처리의 대조구에 비하여 퀴논 리덕타아제 활성을 각각 2배, 2.7배 증가시킴을 확인하였다.As a result, as shown in Figure 1, the whip extract of the present invention was confirmed to increase the quinone reductase activity by two-fold, 2.7-fold, respectively, compared to the untreated control at the concentration of 50, 100 μg / ml.
<< 실험예Experimental Example 2> 2> 채찍말Whip 추출물의 세포독성 측정 Cytotoxicity of Extracts
본 발명자들은 본 발명의 채찍말 추출물의 세포독성을 측정하기 위하여 흰쥐의 간암세포주(Hepa1c1c7)를 대상으로 하는 실험을 수행하였다. 먼저, a-MEM/10% FBS 용액을 간암세포배양액과 혼합하여 세포의 수를 5X104 cells/ml로 조제한 후에 96well plate에 100 μl씩 처리하여 24시간동안 5% CO2/37℃의 조건에서 배양하였다. 세포가 안정화 된 후에 상기 <실시예 1>에서 수득한 채찍말의 추출물을 2배 농도구배로 12.5-200 μg/ml 사이의 5개의 농도로 처리하고 24시간 동안 5% CO2/37℃의 조건에서 배양하였다. 배양 종료 후 10 μl의 Cell Counting Kit(CCK-8, Dojindo Laboratories)를 3시간 동안 처리한 후 마이크로플레이트 리더로 450 nm에서 흡광도를 측정하였다. 세포증식율은 무처리 세포의 흡광도를 100%로 하였을 때 상기 <실시예 1>에서 수득한 채찍말의 추출물을 처리한 세포의 흡광도를 %로 나타내었다.The present inventors conducted an experiment in the rat liver cancer cell line (Hepa1c1c7) to measure the cytotoxicity of the whip extract of the present invention. First, mix the a-MEM / 10% FBS solution with the hepatocellular cell culture medium to obtain 5 × 10 4 cells. After adjusted to cells / ml treated in 100 μl in 96well plate and incubated under the conditions of 5% CO 2/37 ℃ for 24 hours. After the cells are stabilized the <Example 1> an extract of the whip end obtained in a two-fold concentration gradient treated with five concentrations between 12.5-200 μg / ml and 5% CO 2 for 24 hours / the conditions of 37 ℃ Incubated at. After incubation, 10 μl of Cell Counting Kit (CCK-8, Dojindo Laboratories) was treated for 3 hours, and the absorbance was measured at 450 nm with a microplate reader. The cell proliferation rate represents the absorbance of the cells treated with the extract of the whip obtained in <Example 1> in% when the absorbance of the untreated cells was 100%.
그 결과, 도 2에 나타난 바와 같이, 상기 <실시예 1>에서 수득한 채찍말 추출물은 세포 증식의 50% 저해농도인 IC50가 705 μg/ml로 계산되어 세포독성이 없거나 미약한 것으로 나타났다.As a result, as shown in Figure 2, the whip extract obtained in Example 1 was calculated as IC 50 of 50% inhibitory concentration of cell proliferation was 705 μg / ml, it was shown that there is no cytotoxic or weak.
<< 실험예Experimental Example 3> 3> 채찍말Whip 추출물의 Of extract XREXRE 에 대한 효과 측정The effect on
본 발명자들은 본 발명의 채찍말 추출물의 1상 및 2상 해독효소계의 활성을 유도하는 XRE에 대한 효과를 측정하기 위하여 인간의 간암세포주(HepG2)를 대상으로 XRE의 리포터 진 어세이(Reporter gene assay)를 수행하였다. 먼저, DMEM(Dulbeco's minimum essential medium)/10% FBS 용액을 간암세포배양액과 혼합하여 세포의 수를 1X105 cells/ml로 조제한 후에 48well plate에 500 μl씩 처리하 여 5% CO2/37℃의 조건에서 배양하였다. 세포가 안정화 된 후에 XRE를 포함한 프로모터와 클로르암페니콜 아세틸 트랜스퍼라아제(Chloramphenicol acetyl transferase;CAT) 단백질 발현 유전자가 삽입된 벡터를 Fugene6(Roche Biochemicals)를 이용하여 형질전환 시켰다. 세포가 안정화 된 후에 상기 <실시예 1>에서 수득한 채찍말의 추출물을 1, 10, 100 μg/ml 의 농도로 처리하고 24시간 동안 5% CO2/37℃의 조건에서 배양하였다. 배양 종료 후 CAT-ELISA Kit(Roche Biochemicals)를 사용하여 CAT 단백질의 발현양을 측정하였다. CAT 단백질의 발현율은 무처리 세포에서의 CAT 단백질의 발현율을 1로 하였을 때 채찍말 추출물을 처리한 세포에서의 발현율 비로 나타내었다. 양성대조구로서 XRE의 활성을 증가시킨다고 알려진 발암물질인 3-MC(3-methylcolanthrene, Sigma)을 사용하여 함께 실험하였다.The present inventors report the reporter gene assay of XRE in human liver cancer cell line (HepG2) in order to measure the effect on the XRE that induces the activity of the
도 3에 나타난 바와 같이, 상기 <실시예 1>의 채찍말 추출물은 1상 및 2상 해독효소계의 활성을 유도하는 XRE에 대하여 농도 의존적인 영향이 없음을 확인하였다.As shown in Figure 3, the whip extract of <Example 1> was confirmed that there is no concentration-dependent effect on the XRE to induce the activities of the
<< 실험예Experimental Example 4> 4> 채찍말Whip 추출물의 Of extract AREARE 에 대한 효과 측정The effect on
본 발명자들은 본 발명의 채찍말 추출물의 2상 해독효소계의 활성을 유도하는 ARE에 대한 효과를 측정하기 위하여 인간의 간암세포주(HepG2)를 대상으로 ARE의 리포터 진 어세이를 수행하였다. 먼저, DMEM/10% FBS 용액을 간암세포배양액과 혼합하여 세포의 수를 1X105 cells/ml로 조제한 후에 48well plate에 500 μl씩 처리하여 5% CO2/37℃의 조건에서 배양하였다. 세포가 안정화 된 후에 ARE를 포함한 프로모터와 CAT 단백질 발현 유전자가 삽입된 벡터를 Fugene6(Roche Biochemicals)를 이용하여 형질전환 시켰다. 세포가 안정화 된 후에 상기 <실시예 1>에서 수득한 채찍말의 추출물을 1, 10, 100 μg/ml 의 농도로 처리하고 24시간 동안 5% CO2/37℃의 조건에서 배양하였다. 배양 종료 후 CAT-ELISA Kit(Roche Biochemicals)를 사용하여 CAT 단백질의 발현양을 측정하였다. CAT 단백질의 발현율은 무처리 세포에서의 CAT 단백질의 발현율을 1로 하였을 때 채찍말 추출물을 처리한 세포의 발현율 비로 나타내었다.The present inventors performed a reporter assay of ARE in human liver cancer cell line (HepG2) in order to measure the effect on the ARE inducing the activity of the two-phase detoxification enzyme system of the whip extract of the present invention. First, mix the DMEM / 10% FBS solution with the liver cancer cell culture medium and change the number of cells to 1 × 10 5. After adjusted to cells / ml and treated in 500 μl in 48well plate and incubated under the conditions of 5% CO 2/37 ℃. After the cells were stabilized, the promoter containing the ARE and the vector into which the CAT protein expression gene was inserted were transformed using Fugene6 (Roche Biochemicals). After the cells were cultured in the stabilized <Example 1> under the conditions of the whip extract treated with the 1, 10, 100 μg / ml concentration of a horse and 5% CO 2 for 24 hours / 37 ℃ obtained in. After the incubation, CAT-ELISA Kit (Roche Biochemicals) was used to measure the expression level of CAT protein. The expression rate of the CAT protein was expressed as the ratio of the expression rate of the cells treated with the whip extract when the expression rate of the CAT protein in the untreated cells was 1.
도 4에 나타난 바와 같이, 상기 <실시예 1>의 채찍말 추출물의 처리 농도가 증가할수록 ARE의 활성이 농도 의존적으로 증가함을 확인하였다.As shown in Figure 4, it was confirmed that as the treatment concentration of the whip extract of <Example 1> increased the activity of the ARE concentration-dependently.
상기 <실험예 3>과 <실험예 4>로부터 본 발명의 채찍말 추출물은 선택적으로 2상 해독효소계의 활성을 증가시키는 효과적인 화학적 암 예방 효과를 가지는 것으로 판명되었다.From Experimental Example 3 and Experimental Example 4, the whip extract of the present invention was found to have an effective chemical cancer prevention effect to selectively increase the activity of the biphasic detoxifying enzyme system.
하기에 본 발명의 일실시예에 따른 조성물의 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아니라 단지 구체적으로 설명하고자 함이다. Hereinafter, the preparation examples of the composition according to an embodiment of the present invention will be described, but the present invention is not intended to be limited thereto but merely to be described in detail.
제제예Formulation example 1. 정제의 제조 1. Preparation of Tablets
실시예 1의 채찍말 추출물………….100 mgWhip extract of Example 1. … … … .100 mg
옥수수 전분……………………………………….68 mgCorn Starch ... … … … … … … … … … … … … … … .68 mg
락토오즈……………………………………………90 mgLactose ... … … … … … … … … … … … … … … … … 90 mg
미세결정질 셀룰로즈……………………………..40 mgMicrocrystalline cellulose… … … … … … … … … … … ..40 mg
마그네슘 스테아레이트……………………………2 mgMagnesium stearate … … … … … … … … … … 2 mg
통상적인 정제의 제조 방법에 따라, 상기 성분들을 제시된 함량으로 첨가하여 균일하게 혼합하고, 교반한 후, 과립화하였다. 건조 후 타정기를사용하여 1 정당 유효 성분인 채찍말 추출물이 100 mg씩 포함되어 있는 목적하는 정제를 제조하였다.According to the conventional method of preparing tablets, the above ingredients were added to the indicated contents, mixed uniformly, stirred and granulated. After drying, using a tableting machine, a desired tablet containing 100 mg of a whip extract as an active ingredient was prepared.
제제예Formulation example 2. 캅셀제의 제조 2. Preparation of capsule
실시예 1의 채찍말 추출물……………100 mgWhip extract of Example 1. … … … … 100 mg
옥수수 전분…………………………………………..68 mgCorn Starch ... … … … … … … … … … … … … … … … ..68 mg
락토오즈……………………………………………….90 mgLactose ... … … … … … … … … … … … … … … … … … .90 mg
미세결정질 셀룰로즈…………………………………40 mgMicrocrystalline cellulose… … … … … … … … … … … … … 40 mg
*마그네슘 스테아레이트………………………………2 mgMagnesium Stearate … … … … … … … … … … … 2 mg
통상적인 캅셀제의 제조 방법에 따라, 상기 성분들을 제시된 함량으로 첨가하여 균일하게 혼합한 후, 1 캅셀 당 100 mg의 채찍말 추출물이 포함되도록 적절한 크기의 젤라틴 캅셀에 충진하여 목적하는 캅셀제를 제조하였다.According to the conventional method for preparing the capsules, the above-mentioned ingredients were added and mixed uniformly, and then the desired capsules were prepared by filling into gelatin capsules of an appropriate size such that 100 mg of whiplash extract was contained per capsule.
제제예Formulation example 3. 3. 츄잉정의Chewing Definition 제조 Produce
실시예 1의 채찍말 추출물………………100 mgWhip extract of Example 1. … … … … … 100 mg
과립당 시럽…………………………………………….240 mgGranulated sugar syrup … … … … … … … … … … … … … … … … .240 mg
향료………………………………………………………2 mgSpices… … … … … … … … … … … … … … … … … … … … … 2 mg
옥수수 전분……………………………………………60 mgCorn Starch ... … … … … … … … … … … … … … … … … 60 mg
만니톨………………………………………………….100 mgMannitol… … … … … … … … … … … … … … … … … … … .100 mg
마그네슘 스테아레이트………………………………..20 mgMagnesium stearate … … … … … … … … … … … ..20 mg
정제수…………………………………………………..적당량Purified water… … … … … … … … … … … … … … … … … … … ..Appropriate
통상적인 츄잉정의 제조 방법에 따라, 상기 성분들을 적당량의 물에 혼합하고, 가열하면서 용해시킨 후, 냉각시키고 성형기에 넣어 목적하는 형상의 츄잉정을, 1개 당 100 mg의 채찍말 추출물이 포함되도록 제조하였다.According to a conventional method of preparing chewing tablets, the above ingredients are mixed in an appropriate amount of water, dissolved while heating, cooled and placed in a molding machine so that 100 mg of whiplash extract per one is included. Prepared.
제제예Formulation example 4. 캔디의 제조 4. Manufacture of Candy
실시예 1의 채찍말 추출물……………100 mgWhip extract of Example 1. … … … … 100 mg
과립당 시럽………………………………………….640 mgGranulated sugar syrup … … … … … … … … … … … … … … … .640 mg
향료……………………………………………………2 mgSpices… … … … … … … … … … … … … … … … … … … … 2 mg
물엿……………………………………………………230 mgcorn syrup… … … … … … … … … … … … … … … … … … … … 230 mg
50% 타르타르산……………………………………….20 mg50% tartaric acid… … … … … … … … … … … … … … … .20 mg
정제수………………………………………………….적당량Purified water… … … … … … … … … … … … … … … … … … … Appropriate amount
과립당 시럽을 소량의 물에 완전히 용해하면서 110℃까지 가열한 후, 채찍말 추출물을 용해한 나머지의 물과 물엿을 첨가하여, 145℃까지 온도를 올렸다. 불을 끄고, 향료와 타르타르산을 첨가하여 혼합하고, 75~80 ℃로 냉각시킨 후, 성형 롤러로 성형하여 채찍말 추출물을 함유한 캔디를 제조하였다.The granulated sugar syrup was heated to 110 ° C. while completely dissolving in a small amount of water, and then the remaining water and starch syrup was dissolved, and the temperature was raised to 145 ° C. The fire was turned off, the fragrance and tartaric acid were added, mixed, cooled to 75-80 ° C., and molded with a forming roller to prepare a candy containing whip extract.
제제예Formulation example 5. 음료의 제조 5. Manufacture of drinks
실시예 1의 채찍말 추출물……………100 mgWhip extract of Example 1. … … … … 100 mg
농축 과즙….………………………………………….2 gConcentrated Juicer… .… … … … … … … … … … … … … … … … .2 g
슈크로즈………………………………………………12 gSucrose… … … … … … … … … … … … … … … … … … 12 g
시트르산 나트륨…………………………………….100 mgSodium citrate… … … … … … … … … … … … … … .100 mg
향료…………………………………………………….70 mgSpices… … … … … … … … … … … … … … … … … … … … .70 mg
물…………………………………………………….적당량water… … … … … … … … … … … … … … … … … … … … Appropriate amount
통상적인 음료의 제조 방법에 따라, 상기 성분들을 제시 된 함량으로 적당량의 물에 혼합하고, 가열하여 용해시킨 후, 냉각시키고 용기에 충전하여 200 ml 용 량의 음료 1병당 100 mg의 채찍말 추출물을 포함하는 음료를 제조하였다.According to the conventional method for preparing a beverage, the above ingredients are mixed in an appropriate amount of water in a given content, heated to dissolve, cooled, and filled into a container to obtain 100 mg of whiplash extract per bottle of 200 ml of beverage. A beverage containing was prepared.
도 1은 본 발명의 채찍말(Cutleria cylindrica) 추출물의 퀴논 리덕타아제(Quinone reductase) 활성 유도 효과를 나타낸 도이며,1 is a whip of the present invention ( Cutleria) cylindrica ) extract shows the effect of quinone reductase activity inducing,
도 2는 본 발명의 채찍말 추출물의 세포독성 평가를 나타낸 도이며,Figure 2 is a diagram showing the cytotoxicity evaluation of the whip extract of the present invention,
도 3은 본 발명의 채찍말 추출물의 제노바이오틱스 레스폰시브 엘리먼트(Xenobiotics-responsive element;XRE)에 대한 영향을 나타낸 도이며(* 3-메틸콜란트린(3-methylcolanthrene) 처리 대조구),Figure 3 is a diagram showing the effect on the Xenobiotics-responsive element (XRE) of the whip extract of the present invention (3-methylcolanthrene treatment control),
도 4는 본 발명의 채찍말 추출물의 안티옥시던트 레스폰스 엘리먼트(Antioxidant response element;ARE)에 대한 효과를 나타낸 도이다.Figure 4 is a view showing the effect on the antioxidant response element (ARE) of the whip extract of the present invention.
Claims (5)
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