KR101158203B1 - Composition comprising the extract of Opuntia humifusa for preventing or treating uterine cervical cancer - Google Patents
Composition comprising the extract of Opuntia humifusa for preventing or treating uterine cervical cancer Download PDFInfo
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- KR101158203B1 KR101158203B1 KR1020100065026A KR20100065026A KR101158203B1 KR 101158203 B1 KR101158203 B1 KR 101158203B1 KR 1020100065026 A KR1020100065026 A KR 1020100065026A KR 20100065026 A KR20100065026 A KR 20100065026A KR 101158203 B1 KR101158203 B1 KR 101158203B1
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- extract
- cervical cancer
- cactus
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- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
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- A61K2236/30—Extraction of the material
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Abstract
본 발명은 천년초선인장 유기용매 추출물을 유효성분으로 함유하는 자궁경부암의 예방 또는 치료를 위한 약제학적 조성물 및 건강기능성 식품 조성물에 관한 것이다. 상기 본 발명에 의한 천년초선인장 유기용매 추출물은 상대적으로 부작용 및 독성 발현율이 적고 생체 친화적이며 자궁경부암 세포의 성장억제, 세포주기의 지연 및 세포사멸의 유도 효과가 있어 자궁경부암의 예방 또는 치료에 유용하게 이용될 수 있다. The present invention relates to a pharmaceutical composition and a health functional food composition for the prevention or treatment of cervical cancer, which contains an extract of the millennial cactus organic solvent as an active ingredient. The millennial cactus organic solvent extract according to the present invention has relatively low side effects and toxic expression rate, is bio-friendly, and has an effect of inhibiting the growth of cervical cancer cells, delaying cell cycle and apoptosis, and thus useful for preventing or treating cervical cancer. Can be used.
Description
본 발명은 천년초선인장 (Opuntia humifusa) 유기용매 추출물을 유효성분으로 함유하는 자궁경부암의 예방 또는 치료를 위한 조성물에 관한 것이다. 더욱 상세하게는 자궁경부암 세포의 생장억제, 세포주기의 지연 및 세포사멸의 유도로 자궁경부암을 예방하거나 치료할 수 있는 천년초선인장 유기용매 추출물을 유효성분으로 함유하는 자궁경부암의 예방 또는 치료를 위한 약제학적 조성물 및 건강기능성 식품 조성물에 관한 것이다.
The present invention relates to a composition for the prevention or treatment of cervical cancer containing Opuntia humifusa organic solvent extract as an active ingredient. More specifically, the pharmaceutical composition for the prevention or treatment of cervical cancer containing the millennial cactus organic solvent extract, which can prevent or treat cervical cancer as an active ingredient, by inhibiting the growth of cervical cancer cells, delaying cell cycle and inducing apoptosis. A composition and a nutraceutical composition.
과학기술의 발전은 많은 질병의 치료를 가능하게 하였다. 그럼에도 불구하고 식습관 등의 환경적 요인에 의한 만성퇴행성 질환은 증가하고 있으며, 암은 그 대표적인 질병으로 현대사회에서 인류복지에 큰 위협이 되고 있다. 특히 자궁경부암의 경우에 있어 조기 진단으로 인하여 유병율이 감소되고는 있지만 여전히 여성에서 유방암 다음으로 높은 암 사망률의 원인이 되고 있다.Advances in technology have made it possible to treat many diseases. Nevertheless, chronic degenerative diseases caused by environmental factors such as eating habits are increasing, and cancer is a representative disease and is a great threat to human welfare in modern society. In the case of cervical cancer, in particular, the prevalence decreases due to early diagnosis, but it is still the cause of cancer mortality in women after breast cancer.
현재 암 환자의 치료제 개발은 계속 연구되고 있으나 현재 일상에서 널리 사용되고 있는 항암제의 대부분은 합성물질들로 부작용이 매우 심하여 자주 그 문제점이 대두되고 있다. 최근에는 부작용이 적으면서 유효한 항암제를 개발하기 위해 천연 식물 자원으로부터 생리활성을 가진 물질 검색이 많이 이루어지고 있다. 따라서 암의 발생 후 치료뿐만 아니라, 암의 발생을 예방하기 위한 독성이 적고 효과적인 천연물 유래의 항암제 개발이 필요하다.Currently, the development of treatment for cancer patients has been continuously studied, but most of the anti-cancer drugs widely used in everyday life are synthetic materials, and the side effects are very serious, and the problem is frequently raised. Recently, in order to develop effective anti-cancer drugs with few side effects, a lot of biologically active substances are searched from natural plant sources. Therefore, it is necessary to develop anti-cancer agents derived from natural products with low toxicity and effective to prevent cancer after developing cancer.
한편, 손바닥 선인장은 전 세계적으로 알려진 약 4,000여 종의 선인장 가운데 한 종류이며, 대부분 열대 및 아열대성으로 국내에는 도입종인 백년초(Opuntia ficus-indica)가 온난한 제주도 지방을 중심으로 재배 생산되고 있고, 이미 국내외적으로 많은 연구가 이루어지고 건강식품의 형태로 상품화되어 있다. On the other hand, palm cactus is one of the 4,000 species of cactus known all over the world. Mostly tropical and subtropical, Opuntia ficus-indica , an introduced species in Korea, is cultivated and produced mainly in the warm province of Jeju Island. Many studies have already been made at home and abroad and commercialized in the form of health food.
이와 대조적으로 천년초선인장(Opuntia humifusa)은 손바닥 선인장류의 일종이지만 사계절이 뚜렷한 온대지역에 자생하며 월동이 가능한 다년생이고, 우리나라 토종 선인장으로, 한반도 전역에서 노지재배에 의한 생산이 가능하며, 현재 경기 및 충남 지역에서 주로 생산되고 있다(한승호, 김길수, 김복현 등, 천연초 선인장의 안전 생산기술 개발 및 접촉성 피부염 치료제 개발, 2008). In contrast, Opuntia humifusa is a kind of palm cactus, but it is a perennial plant that grows in the temperate zone with four distinct seasons and can be overwintered. It is a native cactus of Korea, and it can be produced by open field cultivation throughout the Korean peninsula. It is mainly produced in the region (Han Seung-ho, Kim Gil-su, Kim Bok-hyun, etc., development of safe production technology for natural cactus and development of treatment for contact dermatitis, 2008).
천년초선인장은 백년초에 비하여 덜 알려져 있을 뿐만 아니라, 연구를 통하여 밝혀진 정보가 적은 실정이다. 천년초선인장은 초기연구단계로서 토종선인장으로 주로 국내에서만 연구가 이루어지고 있으며, 골다공증 방지, 유방암 세포 성장 억제 효과에 대한 연구(Korean J. Food & Nutr. Vol.22. No. 4, 485-491. 2009) 및 발효액을 이용한 자궁경부암 세포주에 대한 항암작용에 대한 연구가 알려진 정도이다. 특히 대한민국 특허 제10-0698533호에는 월동선인장의 발효액을 이용한 항균 감염증 및 항암 작용에 대한 예방 및 치료용 조성물의 제조방법이 공개되어 있으나, 물, 메탄올 및 에탄올 추출물은 항암활성이 없어, 효모균이나 유산균을 첨가하여 발효하는 단계를 거쳐야 한다고 기재되어 있다. 따라서 상기 특허의 경우 효모균이나 유산균을 첨가하여 발효하는 단계를 거쳐야 하므로 공정이 복잡한 단점이 있었다.
Millennial cactus is not only less known than early centennial, but little information is revealed through research. Millennial cactus is an early research stage, and it is a native cactus, which has been studied mainly in Korea, and studies on the effects of osteoporosis prevention and breast cancer cell growth inhibition (Korean J. Food & Nutr. Vol. 2009) and anticancer activity of cervical cancer cell line using fermentation is known. In particular, Korean Patent No. 10-0698533 discloses a method for preparing a composition for the prevention and treatment of antimicrobial infections and anticancer activity using fermentation broth of wintering cactus, but water, methanol and ethanol extracts do not have anticancer activity. It is described that it should go through the step of adding fermentation. Therefore, in the case of the patent, the process has to be complicated by adding a yeast or a lactic acid bacterium.
천연초선인장이 백년초에 비하여 페놀(phenol)과 플라보노이드(flavonoid) 성분 함량이 높다고 밝혀진 점 등으로 보아 인체건강에 미치는 기능성은 더욱 다양하고 뛰어날 수 있을 것으로 기대되는 바, 본 발명자들은 천년초선인장(Opuntia humifusa)의 헥산 및 에틸아세테이트 추출물에 의한 자궁경부암 예방 또는 치료 효과에 대해서 지속적인 연구를 한 결과, 자궁경부암 세포인 HeLa 세포에서 MTT assay를 통하여 세포 증식 억제를 확인하였을 뿐만 아니라, 유세포분석(flow cytometry)을 통해 세포분열의 지연 및 세포사멸 유도를 확인하여 본 발명을 완성하게 되었다.
Natural second cactus compared to baeknyeoncho phenol (phenol) and flavonoids (flavonoid) component content is higher functionality seen by periods, such as on the human health identified as bar is expected to excel and more varied, the present inventors have cheonnyeoncho Cactus (Opuntia humifusa As a result of continuous studies on the prevention or treatment of cervical cancer by the hexane and ethyl acetate extract of), it was confirmed that the inhibition of cell proliferation by MTT assay in HeLa cells, cervical cancer cells, and flow cytometry. Through the confirmation of the delay of cell division and induction of apoptosis, the present invention was completed.
따라서 본 발명의 목적은 천년초선인장 유기용매 추출물을 유효성분으로 함유하는 자궁경부암의 예방 또는 치료를 위한 약제학적 조성물을 제공하는 것이다.Therefore, it is an object of the present invention to provide a pharmaceutical composition for the prevention or treatment of cervical cancer, which contains the cheonnyeoncho cactus organic solvent extract as an active ingredient.
본 발명의 다른 목적은 천년초선인장 유기용매 추출물을 유효성분으로 함유하는 자궁경부암의 예방 또는 개선을 위한 건강기능성 식품 조성물을 제공하는 것이다.Another object of the present invention is to provide a health functional food composition for the prevention or improvement of cervical cancer, which contains the cheonnyeoncho cactus organic solvent extract as an active ingredient.
본 발명의 다른 목적 및 이점은 하기의 발명의 상세한 설명, 청구범위 및 도면에 의해 더욱 명확하게 된다.
Other objects and advantages of the present invention will become more apparent from the following detailed description of the invention, claims and drawings.
상기한 목적을 달성하기 위해, 본 발명은 천년초선인장 유기용매 추출물을 유효성분으로 함유하는 자궁경부암의 예방 또는 치료를 위한 약제학적 조성물을 제공한다.In order to achieve the above object, the present invention provides a pharmaceutical composition for the prevention or treatment of cervical cancer, containing the cheonnyeoncho cactus organic solvent extract as an active ingredient.
또한, 본 발명은 천년초선인장 유기용매 추출물을 유효성분으로 함유하는 자궁경부암의 예방 또는 개선을 위한 건강기능성 식품 조성물을 제공한다.In addition, the present invention provides a health functional food composition for the prevention or improvement of cervical cancer, containing the cheonnyeoncho cactus organic solvent extract as an active ingredient.
상기 조성물은 자궁경부암 세포의 세포주기의 지연 및 세포사멸의 유도하는 것을 특징으로 한다.The composition is characterized in that the induction of cell cycle delay and apoptosis of cervical cancer cells.
또한, 상기 유기용매는 헥산 또는 에틸아세테이트인 것을 특징으로 한다.
In addition, the organic solvent is characterized in that the hexane or ethyl acetate.
이하, 본 발명을 보다 구체적으로 설명한다.Hereinafter, the present invention will be described more specifically.
본 발명은 천년초선인장 유기용매 추출물을 유효성분으로 함유하는 자궁경부암의 예방 또는 치료를 위한 조성물을 제공한다. The present invention provides a composition for the prevention or treatment of cervical cancer, containing the cheonnyeoncho cactus organic solvent extract as an active ingredient.
본 발명에 있어서 상기 조성물을 자궁경부암세포(HeLa)에 처리하여 천년초 선인장 헥산 및 에틸아세테이트 추출물이 자궁경부암세포 성장억제 및 세포주기에 미치는 영향을 평가하였다. 이를 통하여 천년초선인장 추출물의 자궁경부암 예방 또는 개선 내지 치료 가능성을 확인하고자 하였다. In the present invention, the composition was treated to cervical cancer cells (HeLa) to evaluate the effect of the cheonnyeoncho cactus hexane and ethyl acetate extract on cervical cancer cell growth inhibition and cell cycle. The aim of this study was to determine the possibility of preventing or improving cervical cancer of Chun-Yang Cactus Extract.
그 결과, 본 발명에 의한 천년초선인장 유기용매 추출물을 함유하는 조성물은 자궁경부암세포 성장억제 및 세포주기 진행 지연에 효과가 있는 것으로 나타났다. 보다 구체적으로 본 발명에 의한 천년초선인장 유기용매 추출물의 자궁경부암 세포인 HeLa 세포에 대한 암세포 증식 억제 효과는 다음과 같다. 헥산 추출물을 100, 500, 1000 ㎍/ml의 농도로 처리하였을 경우 모두 유의적으로 HeLa 세포의 증식을 억제하였고, 추출물의 농도를 500 ㎍/ml로 첨가했을 때 50% 이상의 높은 억제효과를 나타내었다(도 1). 그리고 HeLa 세포에 대한 에틸아세테이트 추출물의 암세포 성장억제 효과는 OHF-E와 OHR-E에서 40% 이상의 증식 억제효과를 보였다(도 2). 또한 헥산 또는 에틸아세테이트 추출물을 100 ㎍/ml로 처리하고 24, 72, 120 시간동안 배양하였을 경우 시간-의존적으로 자궁경부암 세포를 억제하는 것으로 나타났다(도 3 및 도 4).
As a result, the composition containing the millennial cactus organic solvent extract according to the present invention has been shown to be effective in inhibiting cervical cancer cell growth and cell cycle progression. More specifically, the effect of inhibiting cancer cell proliferation of HeLa cells, which are cervical cancer cells, of the millennial cactus organic solvent extract according to the present invention is as follows. When hexane extracts were treated at concentrations of 100, 500, and 1000 ㎍ / ml, all proliferation of HeLa cells was significantly inhibited. When the concentration of extract was added at 500 ㎍ / ml, the inhibitory effect was higher than 50%. (FIG. 1). And cancer cell growth inhibitory effect of ethyl acetate extract on HeLa cells showed more than 40% proliferation inhibitory effect in OHF-E and OHR-E (Fig. 2). In addition, when hexane or ethyl acetate extract was treated with 100 ㎍ / ml and incubated for 24, 72, 120 hours it was shown to inhibit the cervical cancer cells in a time-dependent manner (Fig. 3 and 4).
한편, 조직의 항상성은 세포 증식과 아폽토시스(apoptosis) 사이의 균형에 의해 조절되고, 세포증식, 세포주기의 진행과 아폽토시스(apoptosis)의 균형이 비정상적으로 이루어지면 암이 유발된다. 그러므로 암세포의 세포증식을 억제하고 세포주기 진행을 지연하며 아폽토시스(apoptosis)를 유도하는 것은 암을 억제하는 효과적인 방법이다. 본 발명에서는 선행된 세포독성(cytotoxicity) 실험에서 효과 있는 천년초선인장의 부위 추출물을 선정하여 각 암세포의 세포주기 진행에 미치는 영향을 조사하였다. 세포 배양액에 추출물 100 ㎍/ml을 첨가하여 24시간 배양한 후 세포 DNA (cellular DNA)를 프로피디움 요오드화물(propidium iodide)로 염색하여 유세포분석 (flow cytometry) 방법으로 세포주기를 분석하였다. On the other hand, tissue homeostasis is regulated by the balance between cell proliferation and apoptosis, and cancer is caused when cell proliferation, cell cycle progression, and apoptosis have an unbalanced balance. Therefore, inhibiting cell proliferation of cancer cells, delaying cell cycle progression and inducing apoptosis are effective methods of inhibiting cancer. In the present invention, by selecting the extract of the millennial cactus effective in the above cytotoxicity experiments and investigated the effect on the cell cycle progression of each cancer cell. After incubating for 24 hours by adding 100 ㎍ / ml of the extract to the cell culture, the cell cycle was analyzed by flow cytometry by staining cellular DNA with propidium iodide.
그 결과, 도 5에 나타난 바와 같이, 천년초선인장 OHF-E와 OHS-H, OHSt-H를 처리한 HeLa세포에서 G1기의 세포가 대조군에 비해 유의적으로 증가하였다(P<.05). 반면 S기와 G2/M기의 세포는 천년초추출물에 의해 유의적으로 감소하였는데(P<.05), 이는 천년초추출물이 HeLa 세포의 G1 arrest를 유도함을 나타내는 것이다. OHF-E 와 OHR-E를 처리하였을 경우 sub-G1기의 세포가 증가함을 보여주고 있다. 이는 아폽토시스(apoptosis)가 일어난 세포가 증가한 것으로 해석할 수 있다. HeLa 세포에 OHF-E, OHSt-E와 OHS-H를 100 ㎍/ml 농도로 처리한 후 24시간 배양한 결과, 처리한 추출물에서 non-apoptotic cell death가 일어난 세포수는 대조군에 비해 유의적으로 증가하는 것으로 나타났으며(P<.05), 특히 줄기의 에틸아세테이트 추출물은 가장 높은 세포사멸 효과를 보여주었다 (도 6).
As a result, as shown in Figure 5, in the HeLa cells treated with millennial cactus OHF-E, OHS-H, OHSt-H significantly increased G1 cells compared to the control group (P <.05). On the other hand, cells of S and G2 / M phases were significantly decreased by P. C. extract (P <.05), indicating that C. C. extract induced G1 arrest of HeLa cells. Treatment with OHF-E and OHR-E showed an increase in sub-G1 cells. This can be interpreted as an increase in cells in which apoptosis has occurred. HeLa cells were treated with OHF-E, OHSt-E and OHS-H at 100 ㎍ / ml for 24 hours, and the number of non-apoptotic cell deaths in the treated extracts was significantly higher than that of the control. It was found to increase (P <.05), especially the ethyl acetate extract of the stem showed the highest apoptosis effect (Fig. 6).
따라서 본 발명에 의한 천년초선인장 유기용매 추출물을 유효성분으로 함유하는 조성물은 천연추출물을 기반으로 한 자궁경부암의 예방 또는 치료를 위한 약제학적 조성물로 이용될 수 있다.
Therefore, the composition containing the cheonnyeoncho cactus organic solvent extract according to the present invention as an active ingredient can be used as a pharmaceutical composition for the prevention or treatment of cervical cancer based on natural extracts.
본 발명의 조성물에 있어서, 상기 천년초선인장 추출물은 종래 천연물 추출에 널리 알려진 추출용매인 물, 유기용매 또는 이들의 혼합용매를 이용하여 추출될 수 있으나, 바람직하게는 천년초선인장의 헥산(hexane) 또는 에틸아세테이트(ethyl acetate) 추출물로 상기 추출물이 항암효과가 우수한 것으로 나타났다. 헥산 추출은 미량성분들까지 폭 넓게 추출가능하며 주로 기름을 추출할 때 이용하는 방법이다. 상기 헥산 및 에틸아세테이트의 농도는 특별히 제한이 있는 것은 아니나, 80% 이상의 헥산 또는 에틸아세테이트인 경우 추출 효율을 높일 수 있다. 상기 헥산 추출물은 극성이 다른 유기용매를 이용하여 더욱 분획할 수 있으며, 각종 크로마토그래피를 이용하여 더욱 정제할 수도 있다.In the composition of the present invention, the millennial cactus extract may be extracted using water, an organic solvent or a mixed solvent thereof, which is a well-known extractant for extracting natural products, but preferably hexane or ethyl of cactus millet cactus. As the acetate (ethyl acetate) extract, the extract was shown to have an excellent anticancer effect. Hexane extraction is widely applicable to trace components and is mainly used for oil extraction. The concentration of hexane and ethyl acetate is not particularly limited, but when the hexane or ethyl acetate of 80% or more can increase the extraction efficiency. The hexane extract may be further fractionated using an organic solvent having a different polarity, and may be further purified using various chromatography.
본 발명의 조성물에 있어서, 상기 천년초선인장 추출물은 추출 부위에 특별히 제한이 있는 것은 아니며, 열매(열매에서 종자를 분리하고 남은 과육), 종자, 줄기 및 뿌리의 유기용매 추출물로서 발효액이 아닌 그 자체를 이용하여 추출한 것이다. 다만 천년초 종자의 헥산 추출물, 열매 또는 줄기의 에틸아세테이트 추출물이 세포주기의 지연 및 세포사멸 유도의 항암효과가 높아 바람직하다. In the composition of the present invention, the cheonnyeoncho cactus extract is not particularly limited in the extraction site, and is an organic solvent extract of fruit (seeds left after separating the seeds from the fruit), seeds, stems and roots, not the fermentation broth itself. It is extracted using. However, hexane extracts of cheonnyeoncho seeds, ethyl acetate extracts of fruits or stems are preferred because they have a high anticancer effect of delaying cell cycle and inducing apoptosis.
본 발명에 있어서, 추출물에는, 추출, 분획 및 정제 처리의 각 단계에서 얻어지는 모든 추출액, 분획 및 정제물, 그 희석액 또는 농축액, 또는 그 건조물 중 어느 하나라도 포함하는 것으로 한다.
In the present invention, the extract should include any of the extracts, fractions and purified products obtained in each step of extraction, fractionation and purification, any dilution or concentrate thereof, or dried products thereof.
본 발명의 조성물에서, 바람직하게는 조성물 총중량에 대하여 상기 천년초선인장 추출물은 0.0001 내지 90 중량%로 포함할 수 있다. 본 발명의 조성물에서, 당업계에 알려진 통상의 방법에 의해 산제, 과립제, 정제, 캡슐제, 주사제, 크림, 젤, 패취, 분무제 또는 연고제 등의 형태로 제제화될 수 있다. In the composition of the present invention, preferably the cheonnyeoncho cactus extract based on the total weight of the composition may comprise 0.0001 to 90% by weight. In the compositions of the present invention, they may be formulated in the form of powders, granules, tablets, capsules, injections, creams, gels, patches, sprays or ointments by conventional methods known in the art.
또한, 본 발명의 천년초선인장 유기용매 추출물을 유효성분으로 함유하는 약제학적 조성물은, 약제학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다. 상기 천년초선인장 추출물을 유효성분으로 함유하는 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 올리고당, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. In addition, the pharmaceutical composition containing the millennial cactus organic solvent extract of the present invention as an active ingredient may further include appropriate carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions. Carriers, excipients and diluents that may be included in the composition containing the millennial cactus extract as an active ingredient include lactose, dextrose, sucrose, oligosaccharide, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate , Gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 추출물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(calcium carbonate), 수크로오스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제된다. 또한, 단순한 부형제 이외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 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, 동결건조제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.
When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and the solid preparations may include at least one excipient such as starch, calcium carbonate, sucrose, or the like in the extract. Or lactose, gelatin, or the like is mixed. In addition to simple excipients, lubricants such as magnesium styrate talc are also used. Oral liquid preparations include suspending agents, liquid solutions, 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. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.
본 발명의 추출물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 바람직한 효과를 위해서, 본 발명의 추출물은 1일 기준으로 0.0001 내지 1000 mg/kg으로, 보다 효과적이기 위해 0.01 내지 l50 mg/kg으로 투여하는 것이 좋다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다. Preferred dosages of the extracts of the present invention vary depending on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. For the desired effect, the extract of the present invention is preferably administered at 0.0001 to 1000 mg / kg on a daily basis, 0.01 to l50 mg / kg to be more effective. The administration may be carried out once a day or divided into several times. The dose is not intended to limit the scope of the invention in any way.
본 발명의 추출물은 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁내 경막 또는 뇌혈관내(intracerebroventricular) 주사에 의해 투여될 수 있다.
Extracts of the invention can be administered by a variety of routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebroventricular injections.
본 발명에 의한 다른 양태에 따르면, 본 발명은 천년초선인장 유기용매 추출물을 유효성분으로 함유하는 자궁경부암의 예방 또는 개선을 위한 건강기능성 식품 조성물을 제공하는 것이다.According to another aspect of the present invention, the present invention is to provide a health functional food composition for the prevention or improvement of cervical cancer containing an extract of millennial cactus organic solvent as an active ingredient.
상기 조성물은 자궁경부암 세포의 생장억제, 세포주기의 지연 및 세포사멸을 유도하는 것을 특징으로 한다. 따라서 본 발명에 의한 천년초선인장 추출물을 함유하는 식품 조성물은, 자궁경부암의 예방 또는 개선을 위한 건강기능성 식품 조성물로 이용될 수 있다.The composition is characterized by inducing growth inhibition of cervical cancer cells, cell cycle delay and apoptosis. Therefore, the food composition containing millennial cactus extract according to the present invention can be used as a health functional food composition for the prevention or improvement of cervical cancer.
본 명세서에서 식품이란 함은 영양소를 한 가지 또는 그 이상 함유하고 있는 천연물 또는 가공품을 의미하며, 바람직하게는 어느 정도의 가공 공정을 거쳐 직접 먹을 수 있는 상태가 된 것을 의미하며, 통상적인 의미로서, 식품, 식품 첨가제, 건강 기능성 식품 및 음료를 모두 포함한다. 본 명세서에서 건강기능성 식품이란, 건강기능식품에 관한 법률 제6727호에 따른 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 제조 및 가공한 식품을 의미하며, "기능성"이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건 용도에 유용한 효과를 얻을 목적으로 섭취하는 것을 의미한다.In the present specification, the term "food" means a natural product or processed product containing one or more nutrients, and preferably means a state in which it can be directly eaten through some processing process. Includes food, food additives, nutraceuticals and beverages. In the present specification, the health functional food means a food manufactured and processed using raw materials or ingredients having functional properties useful for the human body according to Act No. 6767 of the Health Functional Food Act, and the term "functionality" refers to the structure of the human body and It means ingestion for the purpose of obtaining useful effects on health use such as nutrient control or physiological action with respect to function.
본 발명의 식품 조성물에서, 바람직하게는 상기 추출물은 조성물 총중량에 대하여 0.0001 내지 90 중량%로 포함될 수 있다. 본 발명의 식품은, 식품학적으로 허용 가능한 식품보조첨가제를 더 포함할 수도 있으며, 환제, 분말, 과립, 침제, 정제, 캡슐 또는 음료 형태로 제제화될 수 있다.In the food composition of the present invention, preferably the extract may be included in 0.0001 to 90% by weight relative to the total weight of the composition. The food of the present invention may further comprise a food acceptable food supplement, and may be formulated in the form of pills, powders, granules, acupuncture, tablets, capsules or beverages.
예를 들어, 상기 정제 형태의 건강기능성 식품은 그대로 또는 부형제, 결합제, 붕해제 또는 다른 첨가제를 넣어 고르게 섞은 것을 적당한 방법으로 과립상으로 한 다음 활택제 등을 넣어 압축성형하여 조제하거나 정제 형태의 건강기능식품을 그대로 또는 부형제, 결합제, 붕해제 또는 다른 적당한 첨가제를 넣어 고르게 섞은 것을 직접 압축성형하여 만들거나 또는 미리 만든 과립에 건강기능식품을 그대로 혹은 적당한 첨가제를 넣어 고르게 섞은 다음 압축성형하여 조제하거나 건강기능식품에 부형제, 결합제 또는 다른 적당한 첨가제를 넣어 고르게 섞은 분말을 용매로 습윤시키고, 습윤된 분말을 저압으로 틀에 넣어서 성형한 후, 적당한 방법으로 건조하여 조제한다. 또한, 상기 정제 형태의 건강기능식품에 필요에 따라 교미제 등을 넣을 수 있으며, 적당한 제피제로 제피 가능하다.For example, the health functional food in the form of tablets may be prepared as it is or by adding an excipient, a binder, a disintegrating agent or other additives to make a granular form in a suitable manner, and then compressing by adding a lubricant or the like or preparing a health in a tablet form. It is made by directly compressing the functional food as it is or by mixing it evenly with an excipient, binder, disintegrant or other suitable additives, or mixing the health functional food as it is or evenly adding the appropriate additive to the prepared granules, The excipient, binder or other suitable additives are added to the functional food, and the powder mixed evenly is wetted with a solvent, the wet powder is molded into a mold at low pressure, and then dried and prepared by a suitable method. In addition, the nutraceutical can be added to the health functional food in the form of tablets, if necessary, can be avoided with a suitable epidermis.
상기 캅셀 형태의 건강기능성 식품 중 경질캅셀제는 보통 캅셀에 건강기능식품 또는 건강기능식품에 적당한 부형제 등을 고르게 섞은 것 또는 적당한 방법으로 입상으로 한 것 또는 입상으로 한 것에 적당한 제피제로 제피한 것을 그대로 또는 가볍게 성형하여 충전하여 조제하며, 연질캅셀제는 보통 캅셀에 건강기능식품 또는 건강기능식품에 적당한 부형제 등을 넣은 것을 젤라틴 등 적당한 캅셀기제에 글리세린 또는 소르비톨 등을 넣어 소성을 높인 캅셀기제로 피포하여 일정한 형상으로 성형하여 조제하며, 필요에 따라 상기 캅셀기제에 착색료 보존료 등을 첨가할 수 있다.Among the health functional foods in the form of capsules, the hard capsules are usually prepared by mixing the capsules evenly with the health functional foods or the excipients suitable for the health functional foods, granulated by a suitable method or granulated with a suitable epidermal agent as it is or Soft capsules are prepared by filling them, and soft capsules are usually filled with capsules containing glycerin or sorbitol in a capsule form containing gelatin or appropriate excipients suitable for health functional foods or health functional foods. It is molded and prepared, and a coloring agent preservative etc. can be added to the said capsule base as needed.
상기 환형태의 건강기능성 식품은 보통 건강기능식품에 부형제, 결합제, 붕해제 등을 고르게 섞은 다음 적당한 방법으로 구상으로 성형하여 조제하며, 필요에 따라 백당이나 다른 적당한 제피제로 제피를, 또는 전분, 탈크 또는 적당한 물질로 환의를 입힐 수도 있다.
The health functional food in the form of a cyclic form is usually prepared by mixing excipients, binders, disintegrants and the like evenly in the health functional foods and forming them into spherical forms in a suitable manner. Or they may be greeted with a suitable substance.
또한, 본 발명의 조성물은, 관련 질환의 예방을 위한 건강보조식품의 식품보조첨가제로서 사용될 수 있다. 본 발명의 추출물을 첨가할 수 있는 식품으로는, 각종 식품류, 예를 들어, 음료, 껌, 차, 비타민 복합제, 건강보조 식품류 등이 있으며, 환제, 분말, 과립, 침제, 정제, 캡슐 또는 음료인 형태로 사용할 수 있다. In addition, the composition of the present invention can be used as a food supplement of health supplements for the prevention of related diseases. Foods to which the extract of the present invention may be added include various foods, for example, beverages, gums, teas, vitamin complexes, dietary supplements, and the like, which are pills, powders, granules, tablets, tablets, capsules or beverages. Available in form.
이때, 식품 또는 음료 중의 상기 추출물의 양은, 일반적으로 본 발명의 식품 조성물의 경우 전체식품 중량의 0.0001 내지 90 중량%로 가할 수 있으며, 건강 음료 조성물의 경우 100㎖를 기준으로 0.0001 내지 20 중량%로 가할 수 있다. At this time, the amount of the extract in the food or beverage, in general, can be added to 0.0001 to 90% by weight of the total food weight of the food composition of the present invention, 0.0001 to 20% by weight based on 100ml for the health beverage composition Can be added.
본 발명에서 정의되는 추출물 이외의 식품보조첨가제는 당업계에 통상적인 식품첨가제, 예를 들어 향미제, 풍미제, 착색제, 충진제, 안정화제 등을 포함하며 하기에 예시한다. Food additives other than the extracts defined in the present invention include food additives customary in the art, such as flavors, flavors, colorants, fillers, stabilizers and the like, and are exemplified below.
상기 음료 조성물의 경우, 지시된 비율로 필수 성분으로서 상기 추출물 이외 함유하는 액체 성분에는 특별한 제한점은 없으며, 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상기 천연 탄수화물의 예로는 예를 들어, 포도당, 과당 등의 모노사카라이드 예를 들어, 말토오스, 수크로오스 등의 디사카라이드 예를 들어, 덱스트린, 사이클로 덱스트린 등의 폴리사카라이드 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마틴, 스테비아 추출물(예를 들어, 레바우디오시드 A, 글리시르히진 등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100㎖당 일반적으로 약 1 내지 20g, 바람직하게는 약 5 내지 12g이다.In the case of the beverage composition, there are no particular limitations on the liquid components contained in the indicated ratios other than the extract as essential components, and may contain various flavors or natural carbohydrates, etc. as additional components, as in general beverages. Examples of the natural carbohydrates include, for example, monosaccharides such as glucose and fructose, for example, disaccharides such as maltose and sucrose, for example, conventional sugars such as polysaccharides such as dextrin and cyclodextrin, and xylitol. Sugar alcohols such as sorbitol and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin, stevia extract (e.g., Rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of natural carbohydrates is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.
상기 외에 본 발명의 조성물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명의 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 0.001 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.
In addition to the above, the composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof, alginic acid and its Salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks, and the like. In addition, the compositions of the present invention may contain flesh for the production of natural fruit juices and fruit juice drinks and vegetable drinks. These components can be used independently or in combination. The proportion of such additives is not so critical but is generally selected in the range of 0.001 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.
이상에서 설명한 바와 같이, 본 발명에 의한 천년초선인장 유기용매 추출물은 자궁경부암 세포의 성장억제, 세포주기의 지연 및 세포사멸의 유도 효과가 있으므로 자궁경부암의 예방 또는 치료 내지 개선에 효과적으로 이용될 수 있다. 또한, 본 발명에 의한 천년초선인장 추출물은 천연물 추출물로서 상대적으로 부작용 및 독성 발현율이 낮고 생체 친화적으로 자궁경부암을 예방, 치료 또는 개선할 수 있는 효과를 도모할 수 있다. As described above, the millennial cactus organic solvent extract according to the present invention has an effect of inhibiting the growth of cervical cancer cells, delaying cell cycle and apoptosis, and thus can be effectively used for the prevention or treatment or improvement of cervical cancer. In addition, the cheonnyeoncho cactus extract according to the present invention as a natural extract can relatively low side effects and toxic expression rate and can promote the effect of preventing, treating or improving cervical cancer biocompatible.
나아가, 본 발명은 천년초선인장 추출물의 활용범위를 단순한 식품에서 예방용 혹은 치료용 약물로까지 확대시킴으로써 천년초선인장의 가치를 높이고 관련 업종 종사자의 수입증대로 까지 이어질 것으로 예상된다.
Furthermore, the present invention is expected to increase the value of millennial cactus extract and to increase the income of workers in related industries by expanding the application range of millennial cactus extract from simple foods to preventive or therapeutic drugs.
도 1은 본 발명에 의한 천년초선인장 헥산 추출물의 자궁경부암세포 성장 억제 효과를 나타낸 도면이다. 평균±표준오차(n=3), 서로 다른 윗첨자는 통계적으로 유의차가 있음을 의미함(p<0.05).
도 2는 본 발명에 의한 천년초선인장 에틸아세테이트 추출물의 자궁경부암세포 성장 억제 효과를 나타낸 도면이다. 평균±표준오차(n=3), 서로 다른 윗첨자는 통계적으로 유의차가 있음을 의미함(p<0.05).
도 3은 본 발명에 의한 천년초선인장 헥산 추출물의 장시간 처리 시 자궁경부암세포의 성장 억제 효과를 나타낸 도면이다. 평균±표준오차(n=3), 서로 다른 윗첨자는 통계적으로 유의차가 있음을 의미함(p<0.05).
도 4는 본 발명에 의한 천년초선인장 에틸아세테이트 추출물의 장시간 처리 시 자궁경부암세포의 성장 억제 효과를 나타낸 도면이다. 평균±표준오차(n=3), 서로 다른 윗첨자는 통계적으로 유의차가 있음을 의미함(p<0.05).
도 5는 본 발명에 의한 천년초선인장 추출물 처리 시 자궁경부암세포의 세포주기 지연 효과를 나타낸 도면이다.
도 6은 본 발명에 의한 천년초선인장 추출물 처리 시 자궁경부암세포의 세포사멸 효과를 나타낸 도면이다.1 is a view showing the effect of inhibiting the growth of cervical cancer cells of cheonnyeoncho cactus hexane extract according to the present invention. Mean ± standard error (n = 3), different superscripts indicate statistically significant difference (p <0.05).
Figure 2 is a diagram showing the effect of inhibiting the growth of cervical cancer cells of cheonnyeoncho cactus ethyl acetate extract according to the present invention. Mean ± standard error (n = 3), different superscripts indicate statistically significant difference (p <0.05).
Figure 3 is a view showing the growth inhibitory effect of cervical cancer cells during prolonged treatment of cheonnyeoncho cactus hexane extract according to the present invention. Mean ± standard error (n = 3), different superscripts indicate statistically significant difference (p <0.05).
Figure 4 is a view showing the growth inhibitory effect of cervical cancer cells during prolonged treatment of the millennial cactus ethyl acetate extract according to the present invention. Mean ± standard error (n = 3), different superscripts indicate statistically significant difference (p <0.05).
Figure 5 is a view showing the cell cycle delay effect of cervical cancer cells during the millennial cactus extract treatment according to the present invention.
Figure 6 is a view showing the apoptosis effect of cervical cancer cells during the treatment of millennial cactus extract according to the present invention.
이하, 첨부된 도면을 참조하여 실시예를 통하여 본 발명을 더욱 상세하게 설명하고자 한다. 이들 실시예는 오로지 본 발명을 보다 구체적으로 설명하기 위한 것으로, 본 발명의 요지에 따라 본 발명의 범위가 이들 실시예에 의해 제한되지 않는다는 것은 당업계에서 통상의 지식을 가진 자에 있어서 자명할 것이다.
Hereinafter, the present invention will be described in more detail with reference to the accompanying drawings. It is to be understood by those skilled in the art that these embodiments are only for describing the present invention in more detail and that the scope of the present invention is not limited by these embodiments in accordance with the gist of the present invention .
실시예 1. 천년초선인장 추출물 제조Example 1. Preparation of Millennial Cactus Extract
1-1. 천년초선인장 열매 추출물 제조1-1. Manufacture of Millennial Cactus Fruit Extract
천년초선인장(Opuntia humifusa)의 열매(종자를 분리한 과육) 1.36kg을 동결건조 및 분쇄하여 메탄올 8L을 첨가하고 실온에서 48 내지 72시간씩 3회 상온추출한 후, 여과지(Whatman No.2, Maidstone, England)로 여과하고 회전 진공 농축기(rotary vacuum evaporator; R-210 Rotavapor, BUCHI Co.)로 농축하여 천년초 선인장 열매 추출물 230g을 수득하여 하기 실험예의 시료로 사용하였다(이하, “OHF-M”이라 명명함). After lyophilization and pulverization of 1.36 kg of the fruit (pulp from which seeds were isolated) of Opuntia humifusa , 8 L of methanol was added and extracted at room temperature three times at room temperature for 48 to 72 hours, and then filter paper (Whatman No. 2, Maidstone, England) and concentrated with a rotary vacuum evaporator (R-210 Rotavapor, BUCHI Co.) to obtain 230g Cactus fruit extract was used as a sample of the following experimental example (hereinafter referred to as "OHF-M" Business card).
상기 천년초선인장 열매 추출물(OHF-M) 230g을 헥산 2L, 에틸아세테이트 2L 및 물 2L로 순차 분획한 후, 농축 및 동결 건조하여 천년초선인장 열매의 헥산가용성 분획물(OHF-H) 25g, 에틸아세테이트가용성 분획물(OHF-E) 4g 및 수가용성 분획물(OHF-W) 201g을 각각 수득하여 하기 실험예의 시료로 사용하였다.
230 g of the millennial cactus fruit extract (OHF-M) was sequentially fractionated with 2 L of hexane, 2 L of ethyl acetate, and 2 L of water, and then concentrated and freeze-dried to obtain 25 g of hexane-soluble fraction (OHF-H) of the millennial cactus. 4 g of (OHF-E) and 201 g of water-soluble fraction (OHF-W) were each obtained and used as a sample for the following experimental example.
1-2. 천년초선인장 종자 추출물 제조1-2. Manufacture of Millennial Cactus Seed Extract
천년초선인장(Opuntia humifusa)의 종자 1.53kg을 사용하는 것을 제외하고는, 상기 실시예 1-1과 동일한 공정을 수행하여 천년초선인장 종자 추출물 80g을 수득하여 하기 실험예의 시료로 사용하였다(이하, “OHS-M”이라 명명함). Except for using 1.53 kg of the seed of Opuntia humifusa (Ountia humifusa ), the same process as in Example 1-1 was carried out to obtain 80 g of millennial cactus seed extract was used as a sample of the following experimental example (hereinafter, "OHS -M ”).
상기 천년초선인장 종자 추출물(OHS-M) 80g을 헥산 2L, 에틸아세테이트 2L 및 물 2L로 순차 분획한 후, 농축 및 동결 건조하여 천년초선인장 종자의 헥산가용성 분획물(OHS-H) 21g, 에틸아세테이트가용성 분획물(OHS-E) 3.1g 및 수가용성 분획물(OHS-W) 55.9g을 각각 수득하여 하기 실험예의 시료로 사용하였다.
80 g of the Millennial Cactus Seed Extract (OHS-M) was sequentially fractionated with 2L of hexane, 2L of ethyl acetate and 2L of water, and then concentrated and freeze-dried to obtain 21 g of hexane-soluble fraction (OHS-H) of the Millennial Cactus Seed (OHS-H) 3.1 g of (OHS-E) and 55.9 g of water-soluble fraction (OHS-W) were each obtained and used as samples in the following experimental example.
1-3. 천년초선인장 줄기 추출물 제조1-3. Manufacture of Millennial Cactus Stem Extract
천년초선인장(Opuntia humifusa)의 줄기 800g을 사용하는 것을 제외하고는, 상기 실시예 1-1과 동일한 공정을 수행하여 천년초선인장 줄기 추출물 80g을 수득하여 하기 실험예의 시료로 사용하였다(이하, “OHSt-M”이라 명명함). Except for using 800 g of the stem of Opuntia humifusa ( Ountia humifusa ), the same process as in Example 1-1 was obtained to obtain 80 g of the cheonnyeon cactus stem extract was used as a sample of the following experimental example (hereinafter, "OHSt- Named M ”).
상기 천년초선인장 줄기 추출물(OHSt-M) 80g을 헥산 2L, 에틸아세테이트 2L 및 물 2L로 순차 분획한 후, 농축 및 동결 건조하여 천년초선인장 줄기의 헥산가용성 분획물(OHSt-H) 20g, 에틸아세테이트가용성 분획물(OHSt-E) 1.7g 및 수가용성 분획물(OHSt-W) 58.3g을 각각 수득하여 하기 실험예의 시료로 사용하였다.
80 g of the cheonnyeon cactus stem extract (OHSt-M) was sequentially fractionated with 2L of hexane, 2L of ethyl acetate, and 2L of water, and then concentrated and freeze-dried to obtain 20 g of hexane-soluble fraction (OHSt-H) of cheonnyeon cactus stem, ethyl acetate-soluble fraction 1.7 g of (OHSt-E) and 58.3 g of water-soluble fraction (OHSt-W) were each obtained and used as samples in the following experimental example.
1-4. 천년초선인장 뿌리 추출물 제조1-4. Manufacture of Millennial Cactus Root Extract
천년초선인장(Opuntia humifusa)의 뿌리 16g을 사용하는 것을 제외하고는, 상기 실시예 1-1과 동일한 공정을 수행하여 천년초선인장 뿌리 추출물 2g을 수득하여 하기 실험예의 시료로 사용하였다(이하, “OHR-M”이라 명명함). Except for using 16 g of the root of Opuntia humifusa ( Ountia humifusa ), the same process as in Example 1-1 was carried out to obtain 2 g of millennial cactus root extract was used as a sample of the following experimental example (hereinafter, "OHR- Named M ”).
상기 천년초선인장 뿌리 추출물(OHR-M) 2g을 헥산 2L, 에틸아세테이트 2L 및 물 2L로 순차 분획한 후, 농축 및 동결 건조하여 천년초선인장 뿌리의 헥산가용성 분획물(OHR-H) 0.35g, 에틸아세테이트가용성 분획물(OHR-E) 0.24g 및 수가용성 분획물(OHR-W) 1.41g을 각각 수득하여 하기 실험예의 시료로 사용하였다. 천년초선인장의 각 부위별 추출물의 수득율을 하기 표 1에 나타내었다.2 g of cheonnyeon's cactus root extract (OHR-M) was sequentially fractionated with 2L of hexane, 2L of ethyl acetate and 2L of water, and then concentrated and freeze-dried to hexane soluble fraction (OHR-H) of 0.35g, ethyl acetate soluble. 0.24 g of fraction (OHR-E) and 1.41 g of water-soluble fraction (OHR-W) were each obtained and used as samples in the following experimental example. The yield of the extract for each part of the millennial cactus is shown in Table 1 below.
실시예 2. 세포 배양Example 2. Cell Culture
본 발명에 사용한 암세포주는 자궁 경부암 세포인 HeLa(human cervix adenocarcinoma)는 한국세포주은행(Korean Cell Line Bank, KCLB)에서 구입하였다. HeLa 세포주는 Dulbecco's modified Eagle's medium(DMEM, Caisson, USA)에 10% 우태혈청(fetal bovine serum, Gemcell, Gemini, USA)과 1% L-글루타민(Caisson, USA)과 1% 페니실린 및 스트렙토마이신(Caisson, USA)이 함유된 배지를 사용하여, 37℃ 5% CO2 배양기에서 배양하였다.
Cancer cell line used in the present invention, HeLa (human cervix adenocarcinoma), which is a cervical cancer cell, was purchased from Korean Cell Line Bank (KCLB). HeLa cell lines in Dulbecco's modified Eagle's medium (DMEM, Caisson, USA) with 10% fetal bovine serum (Gemcell, Gemini, USA) and 1% L-glutamine (Caisson, USA) and 1% penicillin and streptomycin (Caisson). , USA) was used to culture in a 37 °
실시예 3. 자궁경부암세포 증식 억제효과 측정(Cytotoxicity)Example 3. Measurement of cervical cancer cell proliferation inhibitory effect (Cytotoxicity)
천년초선인장 추출물의 암세포 증식억제 효과는 3-(4,5-dimethylthiazol-2-yl)-2,3 diphenyltetrazolium bromide(MTT) assay(Roche, Germany)를 사용하여 행하였다. 세포주를 1 x 104 cells/well의 밀도로 96-well plate에 분주하여 24시간 동안 37℃ 5% CO2 배양기에서 배양시킨 후 천년초선인장 부위별 추출물을 0, 100, 500, 1000 ㎍/ml의 농도로 첨가하여 24시간 배양하였다. 각 웰(well)에 MTT labeling reagent(Roche, Germany)를 10 μL씩 첨가하고 4시간 동안 배양(37oC, 5% CO2)한 후 solubilization solution(Roche, Germany)을 100 μL씩 첨가하여 인큐베이터(incubator)에 10시간 유치시키고, 550 nm에서 ELISA reader(PowerWaveXS, Bio-tek, Winooski, USA)로 흡광도를 측정하였다. 그 결과를 도 1 내지 도 4에 나타내었다.
Inhibition of cancer cell proliferation of millennial cactus extract was performed using 3- (4,5-dimethylthiazol-2-yl) -2,3 diphenyltetrazolium bromide (MTT) assay (Roche, Germany). Cell lines were dispensed in 96-well plates at a density of 1 x 10 4 cells / well and incubated in a 5% CO 2 incubator at 37 ° C for 24 hours, followed by extracting 0, 100, 500, 1000 ㎍ / ml It was added at the concentration and incubated for 24 hours. Add 10 μL of MTT labeling reagent (Roche, Germany) to each well, incubate for 4 hours (37 o C, 5% CO 2 ), and add 100 μL of solubilization solution (Roche, Germany) to the incubator. (incubator) was kept for 10 hours, and absorbance was measured at 550 nm with an ELISA reader (PowerWaveXS, Bio-tek, Winooski, USA). The results are shown in FIGS. 1 to 4.
실시예 4. 자궁경부암세포 주기 분석Example 4 Cervical Cancer Cell Cycle Analysis
HeLa 세포를 3 x 105 cells/well의 밀도로 6 well-plate에 분주하여 24시간 동안 배양(37℃, 5% CO2)시킨 후 천년초선인장 추출물을 100 μg/mL 씩 분주하여 24시간 동안 배양하였다. PBS로 세포 단층을 씻어낸 후 트립신-EDTA를 첨가하여 세포를 수집하였다. 수집한 세포를 차가운 70% 에탄올을 넣어 -20℃에서 1시간 보관한 다음 고정한 후 프로피디움 요오드화물(propidium iodide, Sigma)을 첨가하고 30분간 염색하여 FACSCalibur (Becton Dickinson, USA)를 사용해서 유세포분석(flow cytometry) 방법으로 세포주기를 분석하였다.
Dispense HeLa cells into 6 well-plates at a density of 3 x 10 5 cells / well and incubate for 24 hours (37 ° C, 5% CO 2 ), then incubate for 24 hours with 100 μg / mL aliquot It was. Cell monolayers were washed with PBS and then cells were collected by adding trypsin-EDTA. The collected cells were stored in cold 70% ethanol for 1 hour at -20 ° C, fixed, and then stained for 30 minutes with propidium iodide (Sigma), followed by flow cytometry using FACSCalibur (Becton Dickinson, USA). The cell cycle was analyzed by flow cytometry.
실시예 5. 자궁경부암세포 사멸 분석Example 5 Cervical Cancer Cell Death Analysis
세포를 6 well-plate에 분주한 후 위와 동일한 방법으로 천년초선인장 추출물을 100 μg/mL씩 분주하여 24시간 동안 배양하였으며, PBS로 세포 단층을 씻어낸 후 트립신-EDTA를 첨가하여 세포를 수집하였다. Annexin V-FITC(BD Pharmingen, USA)를 50 μg/mL 프로피디움 요오드(propidium iodide)와 1:100 비율로 혼합하여 세포를 암실에서 15분 염색한 후 FACSCalibur(Becton Dickinson)를 사용하여 유세포분석(flow cytometry) 방법으로 아폽토틱 셀(apoptotic cell) 수를 측정하였다.After dispensing the cells into 6 well-plates, 100 μg / mL of the 1000-million cactus extract was incubated for 24 hours in the same manner as above, and the cells were collected by washing the cell monolayer with PBS and adding trypsin-EDTA. Annexin V-FITC (BD Pharmingen, USA) was mixed with 50 μg / mL propidium iodide in a 1: 100 ratio and the cells were stained for 15 minutes in the dark, followed by flow cytometry using FACSCalibur (Becton Dickinson). Apoptotic cells were counted by flow cytometry.
본 발명에서는 100% 헥산(hexane)을 이용하여 천년초선인장의 유효성분을 추출하였다. 천년초선인장을 믹서기에 갈아서 균질화 시킨 후 헥산(hexane)을 첨가하여 24시간 동안 교반시켰다. 그리고 약 5시간을 기다려 상층액을 분리한 후, 유기용매 전용 필터에 거른 후 여과된 액체를 증기 추출기에 넣고 헥산(hexane) 성분을 분리하여 천년초선인장의 유효성분만을 추출 하였다.
In the present invention, 100% hexane (hexane) was used to extract the active ingredient of millennial cactus. The millennial cactus was ground into a mixer, homogenized, and then stirred for 24 hours by adding hexane (hexane). After waiting for about 5 hours, the supernatant was separated, filtered through an organic solvent-only filter, and the filtered liquid was placed in a steam extractor to separate hexane (hexane) component to extract only the active ingredient of millennial cactus.
제제예 1. 건강기능성 식품의 제조 Formulation Example 1 Preparation of Health Functional Food
천년초선인장 추출물 1000 ㎎ 1000 years Cactus Extract 1000 mg
(OHSt-E) (OHSt-E)
비타민 혼합물 적량 Vitamin mixture proper amount
비타민 A 아세테이트 70 ㎍70 μg of Vitamin A Acetate
비타민 E 1.0 ㎎ Vitamin E 1.0 mg
비타민 B1 0.13 ㎎ Vitamin B1 0.13 mg
비타민 B2 0.15 ㎎ Vitamin B2 0.15 mg
비타민 B6 0.5 ㎎ Vitamin B6 0.5 mg
비타민 B12 0.2 ㎍ 0.2 μg of vitamin B12
비타민 C 10 ㎎
비오틴 10 ㎍ 10 μg biotin
니코틴산아미드 1.7 ㎎ Nicotinic Acid 1.7 mg
엽산 50 ㎍ 50 μg folic acid
판토텐산 칼슘 0.5 ㎎ Calcium Pantothenate 0.5mg
무기질 혼합물 적량 Mineral mixture
황산제1철 1.75 ㎎ Ferrous Sulfate 1.75 mg
산화아연 0.82 ㎎ Zinc Oxide 0.82 mg
탄산마그네슘 25.3 ㎎ Magnesium carbonate 25.3 mg
제1인산칼륨 15 ㎎ Potassium monophosphate 15 mg
제2인산칼슘 55 ㎎ Dibasic calcium phosphate 55 mg
구연산칼륨 90 ㎎ Potassium Citrate 90 mg
탄산칼슘 100 ㎎
염화마그네슘 24.8 ㎎ Magnesium chloride 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강기능성 식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강기능성 식품 조성물 제조에 사용할 수 있다.
Although the composition ratio of the above-mentioned vitamin and mineral mixtures is mixed with a component suitable for a health food in a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients may be mixed according to a general health functional food manufacturing method. Next, the granules may be prepared and used for preparing the health functional food composition according to a conventional method.
제제예 2.Formulation Example 2. 건강기능성 음료의 제조Preparation of Health Functional Drink
천년초선인장 추출물 1000 ㎎ 1000 years Cactus Extract 1000 mg
(OHSt-E) (OHSt-E)
구연산 1000 ㎎Citric acid 1000 mg
올리고당 100 g100 g oligosaccharides
매실농축액 2 gPlum concentrate 2 g
타우린 1 g1 g of taurine
정제수를 가하여 전체 900 ㎖Add 900 ml of purified water
통상의 건강기능성 음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간 동안 85℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2ℓ 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강기능성 음료 조성물 제조에 사용한다. 상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 수요계층, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.After mixing the above components in accordance with the conventional method for preparing a health functional beverage, and stirring and heating at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed sterilization and refrigerated and then It is used for the manufacture of the health functional beverage composition of the invention. Although the composition ratio is a mixture of the components suitable for the preferred beverage as a preferred embodiment, the blending ratio may be arbitrarily varied according to the regional and national preferences such as the demand level, the demanding country, and the intended use.
이상으로 본 발명의 특정한 부분을 상세히 기술하였으나, 당업계의 통상의 지식을 가진 자에게 있어 이러한 구체적인 기술은 단지 바람직한 구현예일 뿐이며, 이에 본 발명의 범위가 제한되는 것이 아닌 점은 명백하다. 따라서 본 발명의 실질적인 범위는 첨부된 청구항과 그의 균등물에 의하여 정의된다고 할 것이다.Although specific portions of the present invention have been described in detail above, it will be apparent to those skilled in the art that these specific techniques are merely preferred embodiments, and thus the scope of the present invention is not limited thereto. It is therefore intended that the scope of the present invention be defined by the appended claims and their equivalents.
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