KR101971986B1 - Composition comprising Silverberry like taxillus extract for preventing or treating cancer - Google Patents
Composition comprising Silverberry like taxillus extract for preventing or treating cancer Download PDFInfo
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- KR101971986B1 KR101971986B1 KR1020170136406A KR20170136406A KR101971986B1 KR 101971986 B1 KR101971986 B1 KR 101971986B1 KR 1020170136406 A KR1020170136406 A KR 1020170136406A KR 20170136406 A KR20170136406 A KR 20170136406A KR 101971986 B1 KR101971986 B1 KR 101971986B1
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- South Korea
- Prior art keywords
- mistletoe
- extract
- cancer
- oak
- taxillus
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Abstract
Description
참나무겨우살이( Taxillus yadoriki ( Siebold ) Danser ) 추출물을 유효성분으로 포함하는 항암용 조성물 관한 것이다. Oakill mistlet ( Taxillus yadoriki ( Siebold ) Danser ) extract as an active ingredient.
통계청이 발표한 2012년 사망 및 사망원인 통계자료에 따르면 우리나라의 사망률 순위는 암, 심장질환, 뇌혈관 질환 등으로 나타났다(National Statical Office, 2012). 그 중에서 암은 현재 전 세계적으로 가장 높은 사망률 1위의 질병이며, 의학의 발전 및 여러 가지 노력에도 불구하고 사망률이 개선되지 않아 그 중요성이 부각되고 있다. 특히 현재 사용되고 있는 항암약물의 독성 및 부작용이 문제점으로 대두되고 있어, 천연물에서 항암제를 찾고자 하는 노력이 증가하고 있다.According to statistics released by the National Statistical Office (NSO) in 2012, death rates ranked in Korea as cancer, heart disease, and cerebrovascular disease (National Statical Office, 2012). Among them, cancer is now the world's highest disease with the highest mortality rate, and despite the development of medical science and various efforts, the mortality rate has not improved and its importance has been highlighted. Especially, toxic and side effects of currently used anticancer drugs are becoming a problem, and efforts to find anticancer drugs in natural products are increasing.
겨우살이(mistletoe)는 유럽과 동양에서 오랜 세월 동안 고혈압, 당뇨, 류마티즘, 종양 등을 치유하기 위해 민간요법상의 약재로 사용되어 왔으며, 유럽에서는 건강과 축복을 가져다주는 신비의 식물로 추앙 받고 있다. 세계 전역에는 30속 1,500종의 식물이 있는 것으로 알려져 있으며, 유럽지역에 서식하는 겨우살이 중에서 민간 약재로 사용되었던 것은 주로 비스쿰 알붐 로란테시아(Viscum album loranthacea)이며, 한국 지역에서 서식하는 것과 분류학상 구별된다(Khwaja TA 등, 1986, Oncology 43 Suppl 1:42-50; Khawaja T.A. 등, 1980. Experimentia, 36: 599-600). Mistletoe has long been used as a medicinal herb to cure hypertension, diabetes, rheumatism, and tumors in Europe and the Orient, and is regarded as a mysterious plant that brings health and blessings in Europe. It is known that there are 1,500 species of plants in 30 genera throughout the world. Viscum album loranthacea, which was used as a private medicinal herb among European mistletoe, (Khwaja TA et al., 1986, Oncology 43 Suppl 1: 42-50; Khawaja TA et al., 1980. Experimentia, 36: 599-600).
유럽지역에 서식하는 겨우살이는 체액성 및 세포성 면역체계를 자극하는 면역 증강 효과가 있는 것이 인정되었고, 동물 및 인간에 대한 임상 실험 결과, 종양세포에 대하여 직ㆍ간접적으로 대응하는 대식세포 및 자연 살해 세포의 활성을 증가시킴으로써 종양세포의 성장을 억제하고, 암환자의 생존율을 증진시키는 효과가 있는 것으로 보고되었다. In Europe, the mistletoe has been recognized to have an immune-enhancing effect to stimulate the humoral and cellular immune system, and as a result of clinical trials on animals and humans, it has been found that the mistletoe, which directly or indirectly responds to tumor cells, It has been reported that by increasing the activity of the cells, it inhibits the growth of tumor cells and enhances the survival rate of cancer patients.
국내에 자생하는 겨우살이류는 단향과에 속하는 겨우살이(Viscum album var. coloratum), 붉은겨우살이(V. album for. rubroauranticum)와 꼬리겨우살이과에 속하는 참나무겨우살이(Taxillus yadoriki), 꼬리겨우살이(Loranthus tanakae) 및 동백나무겨우살이(Korthalsella japonica) 등 이다. 이들은 자생지가 구별되므로 서로 상이한 종 임은 분명하다. 국내에서 주로 약재로 이용 및 연구되는 겨우살이는 겨우살이(Viscum album var. coloratum )이며, 그 외 종에 대해서는 그 항암을 비롯한 여러 효과에 대한 연구가 미비한 실정이다. 특히, 참나무겨우살이( Taxillus yadoriki ( Siebold ) Danser ) 추출물을 유효성분으로 포함하는 항암용 조성물에 대하여는 현재까지 연구되거나 보고된 바가 없다. Mistletoe sprouts domesticated in Korea are Viscum album var. Coloratum , V. album for rubroauranticum and Taxillus spp. Belonging to the tail mistletoe, yadoriki ), tail mistletoe ( Loranthus tanakae ) and camphor tree mistletoe ( Korthalsella japonica ). It is clear that these are different species because their native regions are distinct. Viscum album var. Coloratum , which is mainly used as a medicinal product in Korea, is studied and studies on various effects such as anticancer effect on other species are insufficient. In particular, no anticancer composition containing an extract of oak mistletoe ( Taxillus yadoriki ( Siebold ) Danser ) as an active ingredient has been studied or reported to date.
따라서, 부작용이 없는 천연물 유래 항암제 개발에 대한 요구가 높아짐에 따라, 본 발명자들은 국내 자생 겨우살이들 중에서 부작용이 없고 효과가 우수한 항암 효과를 위한 천연물질을 선별하기 위해 예의 노력한 결과, 참나무겨우살이( Taxillus yadoriki ( Siebold ) Danser ) 추출물을 유효성분으로 포함하는 항암용 조성물에 대한 본 발명을 완성하였다. Thus, the higher the demand for natural products derived from cancer drug development no side effects, the present inventors have found that the domestic indigenous mistletoe example for screening natural substances for anti-cancer effect without the side effect that excellent effects result from efforts, oak mistletoe (Taxillus yadoriki ( Siebold ) Danser ) extract as an active ingredient.
이에 본 발명자들은 국내 자생 겨우살이들 중에서 부작용이 없고 효과가 우수한 항암 효과를 위한 천연물질을 선별하기 위해 예의 노력한 결과, 참나무겨우살이(Taxillus yadoriki ( Siebold ) Danser ) 추출물을 유효성분으로 포함하는 항암용 조성물에 대한 본 발명을 완성하였다. Accordingly, the present inventors have made intensive efforts to select natural substances for the anticancer effect without side effects among the domestic wild mistletoe, and as a result, they have found that an anticancer composition comprising an extract of oak mistletoe (Taxillus yadoriki ( Siebold ) Danser ) Thereby completing the present invention.
따라서, 본 발명의 목적은 암 예방 또는 치료용 약학적 조성물을 제공하는 것이다. Accordingly, an object of the present invention is to provide a pharmaceutical composition for preventing or treating cancer.
또한, 본 발명의 또 다른 목적은 암 예방 또는 개선용 건강기능식품을 제공하는 것이다. Still another object of the present invention is to provide a health functional food for cancer prevention or improvement.
상기 목적을 달성하기 위해, 본 발명은 참나무겨우살이(Taxillus yadoriki (Siebold) Danser) 추출물을 유효성분으로 포함하는 항암용 조성물을 제공한다. In order to achieve the above object, the present invention provides an anticancer composition comprising an extract of oak mistletoe (Taxillus yadoriki (Siebold) Danser) as an active ingredient.
본 발명의 바람직한 실시예에서, 상기 참나무겨우살이의 기주나무는 녹나무(Cinnamomum camphora), 상수리나무(Quercus acutissima Carruth), 삼나무(Cryptomeria japonica), 참식나무(Neolitsea sericea) 및 벗나무(Prunus serrulata)일 수 있다.In a preferred embodiment of the present invention, the host tree of the oak mist mistake is selected from the group consisting of Cinnamomum camphora , Quercus acutissima Carruth , Cryptomeria japonica , Neolitsea sericea ) and chrysanthemum ( Prunus serrulata) .
본 발명의 바람직한 실시예에서, 상기 참나무겨우살이 추출물은 물, C1 내지 C2의 저급 알코올 또는 이들의 혼합물을 용매로 하여 추출하는 것일 수 있다. In a preferred embodiment of the present invention, the oak mistletoe extract may be extracted with water, a C 1 to C 2 lower alcohol or a mixture thereof as a solvent.
본 발명의 바람직한 실시예에서, 상기 저급 알코올은 에탄올 또는 메탄올인 것일 수 있다.In a preferred embodiment of the present invention, the lower alcohol may be ethanol or methanol.
본 발명의 바람직한 실시예에서, 상기 암은 대장암, 폐암, 간암, 위암, 췌장암, 담도암, 유방암, 자궁경부암 및 전립선암으로 구성된 군으로부터 선택되는 것 일 수 있다. In a preferred embodiment of the present invention, the cancer may be selected from the group consisting of colon cancer, lung cancer, liver cancer, stomach cancer, pancreatic cancer, biliary cancer, breast cancer, cervical cancer and prostate cancer.
또한, 본 발명은 참나무겨우살이( Taxillus yadoriki ( Siebold ) Danser ) 추출물을 유효성분으로 포함하는 암 예방 또는 개선용 건강기능식품을 제공한다. The invention also oak mistletoe (Taxillus yorgaki ( Siebold ) Danser ) extract as an active ingredient.
본 발명의 바람직한 실시예에서, 상기 참나무겨우살이의 기주나무는 녹나무(Cinnamomum camphora), 상수리나무(Quercus acutissima Carruth), 삼나무(Cryptomeria japonica), 참식나무(Neolitsea sericea) 및 벗나무(Prunus serrulata)일 수 있다. In a preferred embodiment of the present invention, the host tree of the oak mist mistake is selected from the group consisting of Cinnamomum camphora , Quercus acutissima Carruth , Cryptomeria japonica , Neolitsea sericea ) and chrysanthemum ( Prunus serrulata) .
본 발명의 바람직한 실시예에서, 상기 암은 대장암, 폐암, 간암, 위암, 췌장암, 담도암, 유방암, 자궁경부암 및 전립선암으로 구성된 군으로부터 선택되는 것 일 수 있다. In a preferred embodiment of the present invention, the cancer may be selected from the group consisting of colon cancer, lung cancer, liver cancer, stomach cancer, pancreatic cancer, biliary cancer, breast cancer, cervical cancer and prostate cancer.
따라서, 본 발명은 참나무겨우살이( Taxillus yadoriki ( Siebold ) Danser ) 추출물을 유효성분으로 포함하는 암 예방 또는 치료용 약학적 조성물을 제공한다.Accordingly, the present invention oak mistletoe (Taxillus It provides yadoriki (Siebold) Danser) A pharmaceutical composition for preventing or treating cancer comprising the extract as an active ingredient.
본 발명의 참나무겨우살이 추출물은 암세포 증식을 억제하는 효과가 다른 겨우살이 종에 비해 뛰어나므로, 암 예방 또는 치료용 약학적 조성물로 제공할 수 있다. The oak mistletoe extract of the present invention is superior to other mistletoe species in inhibiting cancer cell proliferation, and thus can be provided as a pharmaceutical composition for preventing or treating cancer.
도 1은 참나무겨우살이의 암세포 증식 억제 효과를 확인하였다 :
도 1a는 본 실험에 사용된 겨우살이 시료를 나타내며 ; 및
도 1b는 참나무겨우살이 시료의 추출 부위별 암세포 증식 억제 효과를 나타낸다.
도 2는 참나무겨우살이 외의 다른 겨우살이 종들의 암세포 증식 억제 효과를 확인하였다 :
도 2a는 붉은겨우살이의 암세포 증식 억제 효과를 나타내며 ; 및
도 2b는 동백살이의 암세포 증식 억제 효과를 나타내며 ; 및
도 2c는 지리산에서 수집한 겨우살이로부터 추출한 시료의 암세포 증식 억제 효과를 나타내며 ; 및
도 2d는 덕유산 및 홍천에서 수집한 겨우살이로부터 추출한 시료의 암세포 증식 억제 효과를 나타내며 ; 및
도 2e는 꼬리겨우살이의 암세포 증식 억제 효과를 나타낸다.
도 3은 참나무겨우살이의 기주목별 암세포 증식 억제 효과를 나타낸다.1 shows the inhibitory effect of oak mistletoe on cancer cell proliferation:
Figure 1a shows the mistletoe sample used in this experiment; And
FIG. 1B shows the effect of inhibiting cancer cell proliferation at the extraction site of oak seedlings.
FIG. 2 shows the inhibitory effect of other mistletoe species other than oak mistletoe on cancer cell proliferation:
2A shows the inhibitory effect of red mistletoe on cancer cell proliferation; And
Figure 2b shows the cancer cell proliferation inhibitory effect of Camellia sinensis; And
FIG. 2c shows the cancer cell proliferation inhibitory effect of the sample extracted from the mistletoe collected in Jiri acid; And
FIG. 2d shows the inhibitory effect of a sample extracted from mistletoe collected from Deogyusan and Hongcheon on cancer cell proliferation; And
Fig. 2E shows the effect of suppressing cancer cell proliferation of the tail mistletoe.
Fig. 3 shows the effect of inhibiting proliferation of cancer cells in the early stage of oak mistletoe.
이하, 본 발명을 보다 상세히 설명한다. Hereinafter, the present invention will be described in more detail.
상술한 바와 같이, 국내에서 주로 약재로 이용 및 연구되는 겨우살이는 겨우살이(Viscum album var. coloratum )이며, 그 외 종에 대해서는 그 항암을 비롯한 여러 효과에 대한 연구가 미비한 실정이다. 특히, 참나무겨우살이( Taxillus yadoriki ( Siebold ) Danser ) 추출물을 유효성분으로 포함하는 항암용 조성물에 대하여는 현재까지 연구되거나 보고된 바가 없다. As mentioned above, the mistletoe used and medicinally studied in Korea is mistletoe ( Viscum album var. Coloratum ) , and the other effects on other species are not studied. In particular, no anticancer composition containing an extract of oak mistletoe ( Taxillus yadoriki ( Siebold ) Danser ) as an active ingredient has been studied or reported to date.
본 발명에 따른 참나무겨우살이 추출물은 암세포 증식을 억제하는 효과가 다른 겨우살이 종에 비해 뛰어나므로, 암 예방 또는 치료용 조성물로 활용할 수 있다. The oak mistletoe extract according to the present invention is superior to other mistletoe species in inhibiting cancer cell proliferation and thus can be used as a composition for preventing or treating cancer.
본 발명에 있어서 '예방'은 조성물의 투여로 발병을 억제시키거나 발병을 지연시키는 모든 행위를 의미한다. In the present invention, " prevention " means all actions that inhibit the onset or delay the onset of the administration of the composition.
본 발명에 있어서, '개선' 또는 '치료'란 조성물의 투여로 상기 질환의 증세가 호전되거나 이롭게 변경되는 모든 행위를 의미한다.In the present invention, 'improvement' or 'treatment' means all the actions that improve or ameliorate symptoms of the disease upon administration of the composition.
본 발명에 있어서 '투여'는 임의의 적절한 방법으로 환자에게 소정의 물질을 제공하는 것을 의미하며, 본 발명의 조성물의 투여 경로는 목적 조직에 도달할 수 있는 한 일반적인 모든 경로를 통하여 경구 또는 비경구 투여될 수 있다. 또한, 조성물은 활성물질이 표적 세포로 이동할 수 있는 임의의 장치에 의해 투여될 수 있다.In the present invention, " administering " means providing a predetermined substance to a patient by any appropriate method, and the administration route of the composition of the present invention is oral or parenteral ≪ / RTI > The composition may also be administered by any device capable of transferring the active agent to the target cell.
따라서, 본 발명은 참나무겨우살이( Taxillus yadoriki ( Siebold ) Danser ) 추출물을 유효성분으로 포함하는 암 예방 또는 치료용 약학적 조성물을 제공할 수 있다.Accordingly, the present invention oak mistletoe (Taxillus yadoriki (Siebold) Danser) it is possible to provide a pharmaceutical composition for preventing or treating cancer comprising the extract as an active ingredient.
본 발명의 참나무겨우살이는 주로 제주도 낮은 지대의 상록수에 기생하는데, 제주도 서귀포 인근 지역에서는 가로수나 정원수에 기생하기도 한다. 또한, 기주나무는 녹나무(Cinnamomum camphora), 상수리나무(Quercus acutissima Carruth), 삼나무(Cryptomeria japonica), 참식나무(Neolitsea sericea) 및 벗나무(Prunus serrulata)인 것이 바람직하나, 이에 한정되지 않는다. The oak mistletoe of the present invention is mainly parasitized in evergreen trees in the lower part of Jeju Island. In addition, the host wood is camphor tree ( Cinnamomum camphora , Quercus acutissima Carruth , Cryptomeria japonica , Neolitsea sericea ) and chrysanthemum ( Prunus serrulata) , but are not limited thereto.
본 발명의 참나무겨우살이 추출물은 하기의 단계들을 포함하는 제조방법에 의해 제조되는 것이 바람직하나 이에 한정되지 않는다:The oak mistletoe extract of the present invention is preferably but not limited to be produced by a manufacturing method comprising the following steps:
1) 참나무겨우살이에 추출용매를 가하여 추출하는 단계;1) extracting oak mistletoe with an extraction solvent;
2) 단계 1)의 추출물을 여과하는 단계; 및2) filtering the extract of step 1); And
3) 단계 2)의 여과한 추출물을 감압 농축한 후 건조하는 단계.3) Concentrating the filtered extract of step 2) under reduced pressure and drying.
상기 방법에 있어서, 단계 1)의 참나무겨우살이는 재배한 것 또는 시판되는 것 등 제한 없이 사용할 수 있다. 상기 참나무겨우살이는 참나무겨우살이의 뿌리, 꽃, 줄기, 잎 또는 열매가 모두 이용 가능하며, 이에 한정되지 않는다.In the above method, the oak mistletoe of step 1) may be used without limitation such as grown or commercially available. The oak mistletoe may be any of roots, flowers, stems, leaves or fruits of oak mistletoe, but is not limited thereto.
본 발명의 참나무겨우살이 추출물은 물, C1 내지 C2의 저급 알코올 또는 이들의 혼합물을 용매로 하여 추출하는 것이 바람직하며, 상기 저급 알코올은 에탄올 또는 메탄올인 것이 바람직하나 이에 한정되지 않는다.The oak mistletoe extract of the present invention is preferably extracted with water, a C 1 to C 2 lower alcohol or a mixture thereof, and the lower alcohol is preferably ethanol or methanol, but is not limited thereto.
상기 방법에 있어서, 참나무겨우살이 추출물의 추출 방법으로는 여과법, 열수 추출, 침지 추출, 환류냉각 추출 및 초음파추출 등 당업계의 통상적인 방법을 이용할 수 있다. 상기 추출용매는 건조된 참나무겨우살이 분량의 2 내지 20 배 첨가하여 추출하는 것이 바람직하다. 추출온도는 20 내지 80 인 것이 바람직하나 이에 한정하지 않는다. 또한, 추출시간은 10 내지 100 시간인 것이 바람직하며, 구체적으로 24 내지 96 시간이 더욱 바람직하고, 보다 구체적으로 72 시간이 가장 바람직하나 이에 한정하지 않는다.In the above method, the oak mistletoe extract may be extracted by a conventional method such as filtration, hot water extraction, immersion extraction, reflux cooling extraction, and ultrasonic extraction. Preferably, the extraction solvent is added by 2 to 20 times the amount of the dried oak mistletoe. The extraction temperature is preferably 20 to 80, but is not limited thereto. The extraction time is preferably 10 to 100 hours, more preferably 24 to 96 hours, and most preferably 72 hours, but not always limited thereto.
상기 방법에 있어서, 단계 3)의 감압농축은 진공감압농축기 또는 진공회전증발기를 이용하는 것이 바람직하나 이에 한정하지 않는다. 또한, 건조는 감압건조, 진공건조, 비등건조, 분무건조 또는 동결건조하는 것이 바람직하나 이에 한정하지 않는다.In the above method, it is preferable to use a vacuum decompression concentrator or a vacuum rotary evaporator for the decompression concentration in step 3), but it is not limited thereto. The drying is preferably performed under reduced pressure, vacuum drying, boiling, spray drying or freeze drying, but not always limited thereto.
본 발명에서 상기 암은 대장암, 폐암, 간암, 위암, 췌장암, 담도암, 유방암, 자궁경부암 및 전립선암으로 구성된 군으로부터 선택되는 것이 바람직하나, 이에 한정되지 않는다.In the present invention, the cancer is preferably selected from the group consisting of colon cancer, lung cancer, liver cancer, stomach cancer, pancreatic cancer, biliary cancer, breast cancer, cervical cancer and prostate cancer.
본 발명의 구체적인 실시예에 있어서, 본 발명자들은 겨우살이 시료별로 암세포 증식 억제 효능을 측정한 결과, 참나무겨우살이 추출물에 암세포 증식 억제 효능이 있음을 확인하였다(도 1 및 도 2).In a specific example of the present invention, the present inventors measured cancer cell proliferation inhibitory effect for each of the mistletoe samples, and found that the oak seed mistletoe extract has cancer cell proliferation inhibitory effect (FIGS. 1 and 2).
또한, 본 발명자들은 참나무겨우살이의 기주목별로 암세포 증식 억제 효능을 비교하기 위하여 측정한 결과, 상수리나무 외에도 참식나무가 기주목인 경우 암세포 증식 억제 효능이 뛰어남을 확인하였다(도 3).In addition, the inventors of the present invention measured the effect of inhibiting proliferation of cancer cells on the growth of oak seedlings, and found that, in addition to the oak tree, it was excellent in inhibiting cancer cell proliferation when the oak tree attracted attention.
따라서, 본 발명의 참나무겨우살이 추출물은 암세포의 증식을 억제하는 효능이 있으므로, 참나무겨우살이 추출물을 유효성분으로 포함하는 암 예방 또는 치료용 약학적 조성물로서 사용할 수 있다. Therefore, the oak mistletoe extract of the present invention has an effect of inhibiting the proliferation of cancer cells, and thus can be used as a pharmaceutical composition for preventing or treating cancer comprising oak seed mistletoe extract as an active ingredient.
본 발명의 조성물은 경구 또는 비경구의 여러 가지 제형일 수 있다. 상기 조성물을 제형화할 경우에는 하나 이상의 완충제(예를 들어, 식염수 또는 PBS), 항산화제, 정균제, 킬레이트화제(예를 들어, EDTA 또는 글루타치온), 충진제, 증량제, 결합제, 아쥬반트(예를 들어, 알루미늄 하이드록사이드), 현탁제, 농후제 습윤제, 붕해제 또는 계면활성제, 희석제 또는 부형제를 사용하여 조제될 수 있다. The compositions of the present invention may be of various oral or parenteral formulations. When formulating the composition, one or more buffers (e.g., saline or PBS), antioxidants, bacteriostats, chelating agents (e.g., EDTA or glutathione), fillers, extenders, binders, adjuvants Aluminum hydroxide), suspending agents, thickening agents, disintegrating agents or surfactants, diluents or excipients.
경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 하나 이상의 화합물에 적어도 하나 이상의 부형제 예를 들면, 전분(옥수수 전분, 밀 전분, 쌀 전분, 감자 전분 등 포함), 칼슘카보네이트(calcium carbonate), 수크로스(sucrose), 락토오스(lactose), 덱스트로오스, 솔비톨, 만니톨, 자일리톨, 에리스리톨 말티톨, 셀룰로즈, 메틸 셀룰로즈, 나트륨 카르복시메틸셀룰로오즈 및 하이드록시프로필메틸-셀룰로즈 또는 젤라틴 등을 섞어 조제된다. 예컨대, 활성성분을 고체 부형제와 배합한 다음 이를 분쇄하고 적합한 보조제를 첨가한 후 과립 혼합물로 가공함으로써 정제 또는 당의정제를 수득할 수 있다. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient, such as starch (cornstarch, wheat starch, rice starch, potatoes Starch and the like), calcium carbonate, sucrose, lactose, dextrose, sorbitol, mannitol, xylitol, erythritol maltitol, cellulose, methylcellulose, sodium carboxymethylcellulose and hydroxypropylmethylcellulose - It is prepared by mixing cellulose or gelatin. For example, tablets or tablets may be obtained by combining the active ingredient with a solid excipient, then milling it, adding suitable auxiliaries, and processing the mixture into granules.
또한, 단순한 부형제 이외에 스테아린산 마그네슘, 탈크 등과 같은 윤활제들도 사용된다. 경구투여를 위한 액상 제제로는 현탁제, 내용액제, 유제 또는 시럽제 등이 해당되는데, 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제 또는 보존제 등이 포함될 수 있다. 또한, 경우에 따라 가교결합 폴리비닐피롤리돈, 한천, 알긴산 또는 나트륨 알기네이트 등을 붕해제로 첨가할 수 있으며, 항응집제, 윤활제, 습윤제, 향료, 유화제 및 방부제 등을 추가로 포함할 수 있다.In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like may also be used. Liquid preparations for oral administration include suspensions, solutions, emulsions or syrups. In addition to water and liquid paraffin which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, fragrances or preservatives are included . In addition, crosslinked polyvinylpyrrolidone, agar, alginic acid, or sodium alginate may optionally be added as a disintegrant, and may further include an anticoagulant, a lubricant, a wetting agent, a flavoring agent, an emulsifying agent and an antiseptic agent .
비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁용제, 유제, 동결건조제제 또는 좌제 등이 포함된다. 비수성용제 및 현탁용제로는 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, 글리세롤, 젤라틴 등이 사용될 수 있다.Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations or suppositories. Examples of non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate, and the like. As a base for suppositories, witepsol, macrogol, tween 61, cacao paper, laurin, glycerol, gelatin and the like can be used.
본 발명의 조성물은 경구 또는 비경구로 투여될 수 있으며, 비경구 투여시 피부외용; 복강내, 직장, 정맥, 근육, 피하, 자궁내 경막 또는 뇌혈관내 주사하는 주사제; 경피 투여제; 또는 비강 흡입제의 형태로 당업계에 공지된 방법에 따라 제형화할 수 있다.The composition of the present invention may be administered orally or parenterally, and may be administered externally for parenteral administration; Intraperitoneal, rectal, intravenous, intramuscular, subcutaneous, intrauterine, or intracerebral injection; Percutaneous administration agents; Or in the form of a nasal inhaler, according to methods known in the art.
상기 주사제의 경우에는 반드시 멸균되어야 하며 박테리아 및 진균과 같은 미생물의 오염으로부터 보호되어야 한다. 주사제의 경우 적합한 담체의 예로는 이에 한정되지는 않으나, 물, 에탄올, 폴리올(예를 들어, 글리세롤, 프로필렌 글리콜 및 액체 폴리에틸렌 글리콜 등), 이들의 혼합물 및/또는 식물유를 포함하는 용매 또는 분산매질일 수 있다. 보다 바람직하게는, 적합한 담체로는 행크스 용액, 링거 용액, 트리에탄올 아민이 함유된 PBS (phosphate buffered saline) 또는 주사용 멸균수, 10% 에탄올, 40% 프로필렌 글리콜 및 5% 덱스트로즈와 같은 등장 용액 등을 사용할 수 있다. 상기 주사제를 미생물 오염으로부터 보호하기 위해서는 파라벤, 클로로부탄올, 페놀, 소르빈산, 티메로살 등과 같은 다양한 항균제 및 항진균제를 추가로 포함할 수 있다. 또한, 상기 주사제는 대부분의 경우 당 또는 나트륨 클로라이드와 같은 등장화제를 추가로 포함할 수 있다.In the case of such injections, they must be sterilized and protected against contamination of microorganisms such as bacteria and fungi. Examples of suitable carriers for injectables include, but are not limited to, solvents or dispersion media containing water, ethanol, polyols (e.g., glycerol, propylene glycol and liquid polyethylene glycol, etc.), mixtures thereof and / or vegetable oils . More preferably, suitable carriers include isotonic solutions such as Hanks' solution, Ringer's solution, phosphate buffered saline (PBS) containing triethanolamine, or sterile water for injection, 10% ethanol, 40% propylene glycol and 5% dextrose Etc. may be used. In order to protect the injection from microbial contamination, various antibacterial and antifungal agents such as parabens, chlorobutanol, phenol, sorbic acid, thimerosal and the like may be further included. In addition, the injections may in most cases additionally include isotonic agents, such as sugars or sodium chloride.
경피 투여제의 경우 연고제, 크림제, 로션제, 겔제, 외용액제, 파스타제, 리니멘트제, 에어롤제 등의 형태가 포함된다. 상기에서 경피 투여는 약학 조성물을 국소적으로 피부에 투여하여 약학 조성물에 함유된 유효한 양의 활성성분이 피부 내로 전달되는 것을 의미한다. Examples of transdermal dosage forms include ointments, creams, lotions, gels, solutions for external use, pastes, liniments, and air lozenges. In the above, transdermal administration means that the pharmaceutical composition is locally administered to the skin, so that an effective amount of the active ingredient contained in the pharmaceutical composition is delivered into the skin.
흡입 투여제의 경우, 본 발명에 따라 사용되는 추출물은 적합한 추진제, 예를 들면, 디클로로플루오로메탄, 트리클로로플루오로메탄, 디클로로테트라플루오로에탄, 이산화탄소 또는 다른 적합한 기체를 사용하여, 가압 팩 또는 연무기로부터 에어로졸 스프레이 형태로 편리하게 전달 할 수 있다. 가압 에어로졸의 경우, 투약 단위는 계량된 양을 전달하는 밸브를 제공하여 결정할 수 있다. 예를 들면, 흡입기 또는 취입기에 사용되는 젤라틴 캡슐 및 카트리지는 화합물, 및 락토즈 또는 전분과 같은 적합한 분말 기제의 분말 혼합물을 함유하도록 제형화할 수 있다. 비경구 투여용 제형은 모든 제약 화학에 일반적으로 공지된 처방서인 문헌(Remington's Pharmaceutical Science, 15th Edition, 1975. Mack Publishing Company, Easton, Pennsylvania 18042, Chapter 87: Blaug, Seymour)에 기재되어 있다.In the case of inhalation dosage forms, the extracts used in accordance with the present invention may be formulated in a pressurized pack or a pressurized pack using a suitable propellant, for example, dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide, It can be conveniently delivered in the form of an aerosol spray from a nebulizer. In the case of a pressurized aerosol, the dosage unit may be determined by providing a valve that delivers a metered amount. For example, gelatin capsules and cartridges for use in an inhaler or insufflator may be formulated to contain a compound, and a powder mixture of a suitable powder base such as lactose or starch. Formulations for parenteral administration are described in Remington's Pharmaceutical Science, 15th Edition, 1975. Mack Publishing Company, Easton, Pennsylvania 18042, Chapter 87: Blaug, Seymour, commonly known in all pharmaceutical chemistries.
본 발명의 조성물은 약제학적으로 유효한 양으로 투여한다. 본 발명에 있어서, "약제학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 유효용량 수준은 환자의 질환의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출 비율, 치료기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 본 발명의 조성물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고 종래의 치료제와는 순차적 또는 동시에 투여될 수 있으며, 단일 또는 다중 투여될 수 있다. 즉, 본 발명의 조성물의 총 유효량은 단일 투여량(single dose)으로 환자에게 투여될 수 있으며, 다중 투여량(multiple dose)으로 장기간 투여되는 분할 치료 방법(fractionated treatment protocol)에 의해 투여될 수 있다. 상기한 요소들을 모두 고려하여 부작용없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 이는 당업자에 의해 용이하게 결정될 수 있다.The composition of the present invention is administered in a pharmaceutically effective amount. In the present invention, " pharmaceutically effective amount " means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level will depend on the type of disease, severity, , Sensitivity to the drug, time of administration, route of administration and rate of release, duration of treatment, factors including co-administered drugs, and other factors well known in the medical arts. The composition of the present invention can be administered as an individual therapeutic agent or in combination with other therapeutic agents, and can be administered sequentially or simultaneously with conventional therapeutic agents, and can be administered singly or in multiple doses. That is, the total effective amount of the composition of the present invention may be administered to a patient in a single dose and administered by a fractionated treatment protocol administered over a long period in multiple doses . It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without side effects, which can be easily determined by those skilled in the art.
본 발명의 약학적 조성물의 투여량은 환자의 체중, 연령, 성별, 건강상태, 식이, 투여시간, 투여방법, 배설율 및 질환의 중증도에 따라 그 범위가 다양하다. 일일 투여량으로는, 비경구 투여 시 참나무겨우살이 추출물을 기준으로 하루에 체중 1 ㎏당 바람직하게 0.01 내지 50 ㎎, 더 바람직하게는 0.1 내지 30 ㎎의 양으로 투여되도록, 그리고 경구 투여 시는 본 발명의 참나무겨우살이 추출물을 기준으로 하루에 체중 1 ㎏당 바람직하게 0.01 내지 100 ㎎, 더 바람직하게는 0.01 내지 10 ㎎의 양으로 투여되도록 1 내지 수회에 나누어 투여할 수 있다. 그러나 투여 경로, 비만의 중증도, 성별, 체중, 연령 등에 따라서 증감될 수 있으므로 상기 투여량이 어떠한 방법으로도 본 발명의 범위를 한정하는 것은 아니다.The dosage of the pharmaceutical composition of the present invention varies depending on the patient's body weight, age, sex, health condition, diet, administration time, administration method, excretion rate, and disease severity. The daily dose is preferably in the range of 0.01 to 50 mg, more preferably 0.1 to 30 mg per kg of body weight per day on the basis of oak seed mist extract in the case of parenteral administration, and when administered orally, May be administered in an amount of 1 to several times, preferably in an amount of 0.01 to 100 mg, more preferably 0.01 to 10 mg per kg of body weight per day on the basis of the oak seed mistletoe extract of the present invention. However, the dosage may be varied depending on the route of administration, the severity of obesity, sex, weight, age, etc. Therefore, the dosage is not limited to the scope of the present invention by any means.
본 발명의 조성물은 단독으로, 또는 수술, 방사선 치료, 호르몬 치료, 화학 치료 및 생물학적 반응 조절제를 사용하는 방법들과 병용하여 사용할 수 있다.The composition of the present invention may be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy, and biological response modifiers.
본 발명의 약학 조성물은 또한 참나무겨우살이 추출물을 유효성분으로 포함하는 외용제의 제형으로 제공할 수 있다. 본 발명의 암 예방 및 치료용 약학 조성물을 피부외용제로 사용하는 경우, 추가로 지방 물질, 유기 용매, 용해제, 농축제 및 겔화제, 연화제, 항산화제, 현탁화제, 안정화제, 발포제(foaming agent), 방향제, 계면활성제, 물, 이온형 유화제, 비이온형 유화제, 충전제, 금속이온봉쇄제, 킬레이트화제, 보존제, 비타민, 차단제, 습윤화제, 필수 오일, 염료, 안료, 친수성 활성제, 친유성 활성제 또는 지질 소낭 등 피부 외용제에 통상적으로 사용되는 임의의 다른 성분과 같은 피부 과학 분야에서 통상적으로 사용되는 보조제를 함유할 수 있다. 또한 상기 성분들은 피부 과학 분야에서 일반적으로 사용되는 양으로 도입될 수 있다.The pharmaceutical composition of the present invention can also be provided as a formulation of an external preparation containing oak mistletoe extract as an active ingredient. When the pharmaceutical composition for preventing and treating cancer according to the present invention is used as an external preparation for skin, it may further contain a fatty substance, an organic solvent, a solubilizing agent, a thickening agent and a gelling agent, a softening agent, an antioxidant, a suspending agent, a stabilizer, Surfactants, water, ionic emulsifiers, nonionic emulsifiers, fillers, sequestering agents, chelating agents, preservatives, vitamins, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic active agents, Such as lipid vesicles, and any other ingredients conventionally used in dermatologic external preparations. The components can also be introduced in amounts commonly used in the field of dermatology.
본 발명의 암 예방 및 치료용 약학 조성물이 피부 외용제로 제공될 경우, 이에 제한되는 것은 아니나, 연고, 패취, 겔, 크림 또는 분무제 등의 제형일 수 있다.When the pharmaceutical composition for cancer prevention and treatment of the present invention is provided as an external preparation for skin, it may be a formulation such as, but not limited to, an ointment, a patch, a gel, a cream or a spray.
또한, 본 발명은 참나무겨우살이( Taxillus yadoriki ( Siebold ) Danser ) 추출물을 유효성분으로 포함하는 암 예방 또는 개선용 건강기능식품을 제공할 수 있다.The invention also oak mistletoe (Taxillus yorganiki ( Siebold ) Danser ) extract as an active ingredient.
본 발명의 참나무겨우살이의 기주나무는 녹나무(Cinnamomum camphora), 상수리나무(Quercus acutissima Carruth), 삼나무(Cryptomeria japonica), 참식나무(Neolitsea sericea) 및 벗나무(Prunus serrulata)로 하는 것이 바람직하나, 이에 한정되지 않는다. Host wood of oak mistletoe of the present invention is camphor (Cinnamomum camphora , Quercus acutissima Carruth , Cryptomeria japonica , Neolitsea sericea and Prunus serrulata. However , the present invention is not limited thereto.
본 발명에서 상기 암은 대장암, 폐암, 간암, 위암, 췌장암, 담도암, 유방암, 자궁경부암 및 전립선암으로 구성된 군으로부터 선택되는 것이 바람직하나, 이에 한정되지 않는다.In the present invention, the cancer is preferably selected from the group consisting of colon cancer, lung cancer, liver cancer, stomach cancer, pancreatic cancer, biliary cancer, breast cancer, cervical cancer and prostate cancer.
상기 식품의 종류에는 특별한 제한은 없다. 상기 참나무겨우살이( Taxillus yadoriki ( Siebold ) Danser) 추출물을 첨가할 수 있는 식품의 예로는 드링크제, 육류, 소시지, 빵, 비스킷, 떡, 초콜릿, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 알코올 음료 및 비타민 복합제, 유제품 및 유가공 제품 등이 있으며, 통상적인 의미에서의 건강기능식품을 모두 포함한다.There is no particular limitation on the kind of the food. The oak mistletoe ( Taxillus yadoriki (Siebold) Danser) Examples of foods that can be added to the extract, if drinks, meat, sausage, bread, biscuits, cakes, chocolates, candies, snacks, cookies, pizza, and other noodles, dairy, including gum, ice cream Products, various soups, beverages, alcoholic beverages and vitamin complexes, dairy products and dairy products, and includes health functional foods in a conventional sense.
본 발명의 참나무겨우살이( Taxillus yadoriki ( Siebold ) Danser ) 추출물은 식품에 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효 성분의 혼합량은 그의 사용 목적(예방 또는 개선용)에 따라 적합하게 결정될 수 있다. 일반적으로, 건강식품 중의 상기 화합물의 양은 전체 식품 중량의 0.1 내지 90 중량부로 가할 수 있다. 그러나 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하일 수 있으며, 안전성 면에서 아무런 문제가 없기 때문에 유효성분은 상기 범위 이상의 양으로도 사용될 수 있다.The oak mistletoe of the present invention ( Taxillus yadoriki ( Siebold ) Danser ) extract may be added directly to the food or may be used with other food or food ingredients, and may be suitably used according to conventional methods. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (for prevention or improvement). Generally, the amount of the compound in the health food may be 0.1 to 90 parts by weight of the total food. However, in the case of long-term intake intended for health and hygiene purposes or for the purpose of controlling health, the amount may be less than the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount exceeding the above range.
본 발명의 건강 기능성 음료 조성물은 지시된 비율로 필수 성분으로서 본 발명의 화합물을 함유하는 것 외에는 다른 성분에 특별한 제한이 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연 향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 당 일반적으로 약 1 내지 20 g, 바람직하게는 약 5 내지 12 g이다.The health functional beverage composition of the present invention is not particularly limited to the other ingredients except that it contains the compound of the present invention as an essential ingredient in the indicated ratios and may contain various flavors or natural carbohydrates as an additional ingredient . Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. Natural flavors (tau martin, stevia extracts (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavors other than those described above The ratio of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 of the composition of the present invention.
상기 외에 본 발명의 참나무겨우살이( Taxillus yadoriki ( Siebold ) Danser ) 추출물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 본 발명의 참나무겨우살이(Taxillus yadoriki ( Siebold ) Danser ) 추출물은 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 참나무겨우살이( Taxillus yadoriki ( Siebold ) Danser ) 추출물 100 중량부 당 0.1 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the oak mistletoe ( Taxillus The extracts of yadoriki ( Siebold ) Danser ) can be used as flavorings such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and thickening agents (cheese, chocolate etc.), pectic acid and its salts, Salts thereof, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like. In addition, the Taxillus yadoriki ( Siebold ) Danser extract of the present invention may contain natural fruit juice and pulp for the production of fruit juice drinks and vegetable drinks. These components may be used independently or in combination. Although the ratio of these additives is not so important, the oak mistletoe of the present invention ( Taxillus is generally selected from yadoriki (Siebold) range Danser) extract 100 parts by weight of 0.1 to about 20 parts by weight per.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시 예는 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 Examples. 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 .
겨우살이 추출물 제조 Manufacture of mistletoe extract
<1-1> 참나무겨우살이<1-1> Oak tree mistletoe (( TaxillusTaxillus yadorikiyadoriki ( ( SieboldSiebold ) ) DanserDance )) 추출물 제조 Extract preparation
본 발명의 참나무겨우살이( Taxillus yadoriki ( Siebold ) Danser ) 추출물을 제조하기 위하여 에탄올을 추출용매로 사용하여 참나무겨우살이( Taxillus yadoriki (Siebold) Danser ) 에탄올 추출물을 제조하였다. The oak mistletoe of the present invention ( Taxillus yadoriki ( Siebold ) Danser ) extract was prepared by using ethanol as an extraction solvent to prepare oak mistletoe ( Taxillus yadoriki (Siebold) Danser ) ethanol extract.
구체적으로, 본 연구에 사용된 참나무겨우살이( Taxillus yadoriki ( Siebold ) Danser)는 녹나무(Cinnamomum camphora), 상수리나무(Quercus acutissima Carruth), 삼나무(Cryptomeria japonica), 참식나무(Neolitsea sericea) 또는 벗나무(Prunus serrulata)를 기주나무로 하여 서식하며, 제주도에서 수집하였다. 국립산림과학원 산림약용자원 연구소에서 동정한 파쇄된 시료 10 g에 70% 에탄올 200 ㎖을 각각 첨가하여 상온에서 48 시간 교반한 후 추출하였다. 추출 후 여과지(filter paper;Whatman NO. 2, Maidstone, UK)로 여과하여 40 ℃ 이하의 중탕에서 감압 환류 냉각장치(N-1110S, EYELA, Tokyo, JAPAN)로 농축한 후 동결건조하였다. 모든 시료는 실험 전까지 80 ℃ 냉동 보관하였으며, 디메틸설폭사이드(dimethyl sulfoxide, DMSO)에 용해하여 실험에 사용하였다. 회수율은 10.1 ~ 21.45%이며, 구체적으로는 하기 [표 1]와 같다. Specifically, the oak mistletoe used in this study ( Taxillus yadoriki (Siebold) Danser) is Camphor (Cinnamomum camphora , Quercus acutissima Carruth ), Cryptomeria japonica , Neolitsea sericea ) or chrysanthemum ( Prunus serrulata ) as host trees and collected from Jeju Island. To 10 g of the crushed samples identified in the Forestry and Forestry Research Institute, 200 ml of 70% ethanol were added, and the mixture was stirred at room temperature for 48 hours and then extracted. After extraction, the mixture was filtered with a filter paper (Whatman NO. 2, Maidstone, UK), concentrated by a reduced pressure reflux condenser (N-1110S, EYELA, Tokyo, Japan) at a temperature of 40 ° C or lower and freeze-dried. All samples were stored frozen at 80 ° C until the experiment and dissolved in dimethyl sulfoxide (DMSO). The recovery rate is 10.1 to 21.45%, specifically, as shown in Table 1 below.
<1-2> 겨우살이 추출물 제조 <1-2> Preparation of mistletoe extract
본 발명의 겨우살이 추출물을 제조하기 위하여 에탄올을 추출용매로 사용하여 겨우살이 에탄올 추출물을 제조하였다. In order to prepare the mistletoe extract of the present invention, ethanol was used as an extracting solvent to prepare an ethanol extract of mistletoe.
구체적으로 도 1a에 나타난 바와 같이, 본 연구에 사용된 겨우살이 시료는 제주도, 덕유산, 지리산에서 수집한 붉은겨우살이(Viscum album for rubroaurantiacum ), 겨우살이(Viscum album var. coloratum ), 동백나무겨우살이(Korthalsella japonica ( Thunb .) Engl) 및 꼬리겨우살이(Loranthus tanakae Franch . & Sav .)이며, 기주나무는 각각 서어나무(Carpinus laxiflora), 졸참나무(Quercus serrata), 상수리나무(Quercus acutissima Carruth), 감탕나무(Ilex integra Thunb .), 생달나무(Cinnamomum yabunikkei H. Ohba), 동백나무(Camellia japonica L.), 신갈나무(Quercus mongolica), 굴참나무(Quercus cariabilis Blume) 및 사방오리나무(Alnus firma Siebold et Zucc) 로 하여 서식한다. 상기 실시예<1-1>과 동일한 과정으로 겨우살이 에탄올 추출물을 제조하였다. As specifically shown in Figure 1a, the mistletoe sample is a red mistletoe collected in Jeju Island, Deogyusan, Jiri (Viscum album for rubroaurantiacum), mistletoe (Viscum album var. Coloratum), camellia mistletoe (Korthalsella japonica used in this study ( Thunb .) Engl ) and tail mistletoe (Loranthus tanakae Franch . & Sav .) , And the host trees are Carpinus laxiflora , Quercus ( Quercus) serrata , Quercus acutissima Carruth , Ilex integra Thunb . ), Bony trees ( Cinnamomum yabunikkei H. Ohba ), Camellia japonica L. , Quercus mongolica , Quercus cariabilis Blume and Alnus firm Siebold et Zucc . The ethanol extract of mistletoe was prepared in the same manner as in Example <1-1>.
겨우살이 추출물의 암세포 증식 억제 측정Inhibition of cancer cell proliferation by mistletoe extract
본 발명의 참나무겨우살이(Taxillus yadoriki (Siebold) Danser) 및 겨우살이의 암세포 증식 억제를 측정하기 위하여 MTT 분석(methylthiazolyldiphenyl tetrazolium bromide assay)을 실시하였다. MTT assay (methylthiazolyldiphenyl tetrazolium bromide assay) was performed to measure inhibition of cancer cell proliferation of oak mistletoe ( Taxillus yadoriki (Siebold) Danser) and mistletoe of the present invention.
구체적으로, 대장암 세포주 HCT116을 1x105 세포/웰(well)의 농도로 접종하고 96-웰에 10% fatal bovine serum(FBS)를 첨가한 DMEM/F-12배지에 대장암 세포주 HCT116을 1x105 세포/웰(well)의 농도로 96-웰에 각각 100 ㎕씩 첨가 후 24시간 세포배양하여 24 시간 동안 5% CO2, 37 ℃의 인큐베이터( incubator)에서 배양한 후, 상기 [실시예 1]에서 제조한 겨우살이 추출물 100 mg/㎖로 DMSO에 녹여진 샘플을 DMEM/F-12배지에 1:1000으로 희석해서 세포에 최종 100 ㎍/㎖ 주입하였다. 첨가 후 24 시간 동안 추가 배양한 후 각 웰에 인산완충식염수(posphate buffered saline, PBS)에 녹인 MTT (1 ㎎/㎖) 용액 50 ㎕씩 첨가하여 2 시간 동안 다시 배양했다. 그 후 웰 바닥에 형성된 포르마잔(formazan)이 흩어지지 않게 상등액을 제거하고, 디메틸설폭사이드(dimethyl sulfoxide, DMSO)를 100 ㎕ 첨가하여 천천히 녹인 후, 자외선/가시광선 분광광도계(UV/Visible spectrophotometer;Human Cop., Xma-3000PC, Seoul, Korea)를 이용하여 540 ㎚에서 흡광도를 측정하였다.Specifically, a colorectal cancer cell line HCT116 1x10 5 cells / well (well) 1x10 colon cancer cell line HCT116 concentration DMEM / F-12 culture medium was inoculated, and the addition of 10% fatal bovine serum (FBS) in 96-well 5 as The cells were cultured for 24 hours in an incubator of 5% CO 2 and 37 ° C for 24 hours, and then cultured in the same manner as in Example 1, Was diluted 1: 1000 in DMEM / F-12 medium and the final 100 μg / ml was injected into the cells. After the addition, the cells were further incubated for 24 hours. Then, 50 μl of MTT (1 mg / ml) solution dissolved in phosphate-buffered saline (PBS) was added to each well, followed by further incubation for 2 hours. Thereafter, the supernatant was removed and 100 μl of dimethyl sulfoxide (DMSO) was added thereto to slowly dissolve the formazan formed on the bottom of the well, and the resultant was immersed in a UV / Visible spectrophotometer (UV / Visible spectrophotometer). Human Cop., Xma-3000PC, Seoul, Korea) was used to measure the absorbance at 540 nm.
그 결과, 도 1b에서 나타나는 바와 같이 참나무겨우살이(Taxillus yadoriki (Siebold) Danser) 추출물을 첨가한 대장암세포(HCT116)의 생존률이 감소하는 것을 확인하였다. 이때 기주나무가 상수리나무인 참나무겨우살이(Taxillus yadoriki (Siebold) Danser)의 줄기로부터 제조한 추출물의 경우 암세포 증식 억제 효능이 가장 뛰어남을 확인하였다. 이는 도 2의 다른 겨우살이들과 비교하여 참나무겨우살이(Taxillus yadoriki (Siebold) Danser)의 암세포 증식 억제 효능이 뛰어남을 알 수 있다. 명확히는, 각각 붉은겨우살이(도 2a), 동백나무겨우살이(도 2b), 지리산 자생 겨우살이(도 2c), 신갈나무 기주 겨우살이(도 2d) 및 신갈나무 기주 꼬리겨우살이(도 2e)의 추출물이다. 이때, 도 2e의 SW480은 대장암 세포이다. As a result, it was confirmed that the survival rate of colorectal cancer cells (HCT116) supplemented with oak mistletoe ( Taxillus yadoriki (Siebold) Danser) extract was decreased as shown in Fig. 1B. At this time, it was confirmed that the extract prepared from the stem of the oak mistletoe ( Taxillus yadoriki (Siebold) Danser), which is an oak tree, has the best inhibitory effect on cancer cell proliferation. This shows that the oak mistletoe ( Taxillus yadoriki (Siebold) Danser) is superior in inhibiting cancer cell proliferation as compared with the other mistletes of Fig. Specifically, it is an extract of red mugwort (Fig. 2a), camellia mist mistake (Fig. 2b), Jiri mugwort mistletoe (Fig. 2c), mongolian mistletoe mistletoe (Fig. 2d) and Quercus mongolica tails mistletoe (Fig. 2e). At this time, SW480 of FIG. 2E is a colon cancer cell.
참나무겨우살이Oak mistletoe (( TaxillusTaxillus yadorikiyadoriki ( ( SieboldSiebold ) ) DanserDance )) 의 of 기주목별By period 암세포 증식 억제 측정 Cancer cell proliferation inhibition assay
본 발명의 참나무겨우살이( Taxillus yadoriki ( Siebold ) Danser )의 추출물의 증식 억제 효능을 기주목별로 비교하기 위하여 녹나무(Cinnamomum camphora), 상수리나무(Quercus acutissima Carruth), 삼나무(Cryptomeria japonica), 참식나무(Neolitsea sericea) 및 벗나무(Prunus serrulata)의 기주목에 따른 추출물 시료를 대상으로 MTT 분석을 실시하였다. The oak mistletoe of the present invention ( Taxillus yadoriki ( Siebold ) Danser ) in order to compare the growth inhibitory effect of camphor ( Cinnamomum camphora , Quercus acutissima MTT analysis was performed on the extracts of Carruth , Cryptomeria japonica , Neolitsea sericea and Prunus serrulata .
구체적으로, [실시예 2]와 동일한 방법으로 MTT 분석을 실시하였다. 이때 각 추출물을 50 ㎕씩 첨가하였다. Specifically, MTT analysis was carried out in the same manner as in [Example 2]. At this time, 50 μl of each extract was added.
그 결과, 도 3b에서 나타나는 바와 같이 상수리나무 외에도 참식나무가 기주목인 경우 암세포 증식 억제 효능이 뛰어남을 확인하였다. As a result, as shown in Fig. 3 (b), it was confirmed that, in addition to the oak tree, the effect of inhibiting cancer cell proliferation was excellent when the sesame tree was the main target.
Claims (8)
상기 참나무겨우살이의 기주나무는 녹나무(Cinnamomum camphora), 상수리나무(Quercus acutissima Carruth), 삼나무(Cryptomeria japonica), 참식나무(Neolitsea sericea) 및 벗나무(Prunus serrulata)로 이루어진 군에서 선택되는 어느 하나인 것을 특징으로 하는 대장암 예방 또는 치료용 약학적 조성물.
A pharmaceutical composition for prevention or treatment of colorectal cancer comprising leaf or stem extract of Oakill mistletoe (Taxillus yadoriki (Siebold) Danser) as an active ingredient,
The host tree of the oak mistletoe is any one selected from the group consisting of Cinnamomum camphora, Quercus acutissima Carruth, Cryptomeria japonica, Neolitsea sericea and Prunus serrulata. Or a pharmaceutically acceptable salt thereof.
The pharmaceutical composition for preventing or treating colon cancer according to claim 1, wherein the oak mistletoe extract is extracted with water, C 1 to C 2 lower alcohol or a mixture thereof as a solvent.
The pharmaceutical composition according to claim 3, wherein the lower alcohol is ethanol or methanol.
상기 참나무겨우살이의 기주나무는 녹나무(Cinnamomum camphora), 상수리나무(Quercus acutissima Carruth), 삼나무(Cryptomeria japonica), 참식나무(Neolitsea sericea) 및 벗나무(Prunus serrulata)로 이루어진 군에서 선택되는 어느 하나인 것을 특징으로 하는 대장암 예방 또는 개선용 건강기능식품.A health functional food for prevention or improvement of colorectal cancer comprising leaf or stem extract of Oakill mistletoe (Taxillus yadoriki (Siebold) Danser) as an active ingredient,
The host tree of the oak mistletoe is any one selected from the group consisting of Cinnamomum camphora, Quercus acutissima Carruth, Cryptomeria japonica, Neolitsea sericea and Prunus serrulata. To prevent or improve colorectal cancer.
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