KR101385658B1 - Composition Comprising Extract of Alpiniae Semen for Treatment of Prostate Cancer and Functional Food Comprising This - Google Patents
Composition Comprising Extract of Alpiniae Semen for Treatment of Prostate Cancer and Functional Food Comprising This Download PDFInfo
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- KR101385658B1 KR101385658B1 KR1020110087449A KR20110087449A KR101385658B1 KR 101385658 B1 KR101385658 B1 KR 101385658B1 KR 1020110087449 A KR1020110087449 A KR 1020110087449A KR 20110087449 A KR20110087449 A KR 20110087449A KR 101385658 B1 KR101385658 B1 KR 101385658B1
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- prostate cancer
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- A—HUMAN NECESSITIES
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- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
Abstract
본 발명은 익지인 추출물의 신규한 용도에 관한 것에 관한 것으로서, 보다 상세하게는 익지인의 유기용매 추출물을 유효성분으로 함유하는 전립선암 예방 및 치료용 조성물 및 식품학적으로 허용 가능한 식품보조 첨가제를 포함하는 익지인의 유기용매 추출물을 유효성분으로 함유하는 전립선암 예방용 기능성 식품에 관한 것이다. 본 발명에 따른 전립선암 치료용 조성물 및 기능성 식품은 전립선암 세포의 성장을 억제하고 세포사멸을 유도하는 효과가 있어 전립선암 치료 및 예방에 효과적으로 사용할 수 있다.The present invention relates to a novel use of the extract of ripen, and more particularly includes a composition for preventing and treating prostate cancer and a food acceptable additive for food containing the organic solvent extract of the ripen as an active ingredient. The present invention relates to a functional food for preventing prostate cancer containing an organic solvent extract of a ripe. The composition and the functional food for treating prostate cancer according to the present invention have an effect of inhibiting the growth of prostate cancer cells and inducing apoptosis, and thus can be effectively used for the treatment and prevention of prostate cancer.
Description
본 발명은 익지인 추출물의 신규한 용도에 관한 것이다. 구체적으로, 본 발명은 전립선암에 대해 탁월한 예방 또는 치료 효능을 나타내는 익지인 추출물을 유효성분으로 함유하는 치료용 조성물 및 기능성 식품에 관한 것이다.
The present invention relates to a novel use of the raw extract. Specifically, the present invention relates to a therapeutic composition and a functional food containing a raw extract that shows excellent preventive or therapeutic efficacy against prostate cancer as an active ingredient.
전립선은 남성에게만 있는 장기로서 정액의 일부를 만들고, 방광 아래 측에 있으면서 직장에 인접해 있는 장기이다. 전립선암은 전립선에서 발생하는 악성 종양으로, 서양의 경우 남성암 중 가장 흔한 암 중 하나이며, 우리나라에서도 최근 식이습관 등의 영향으로 남성에서 가장 빠르게 증가하고 있는 암으로, 대부분 50세 이상의 노년층에서 발생한다. 북미나 서구 유럽 등의 선진국에서는 남성암 중 약 20%를 차지하는 가장 흔한 암으로 미국의 경우 연간 발생하는 남성암 중에서 빈도가 가장 높으며, 암으로 인한 사망 원인 중 폐암에 이어 2위를 차지하고 있다. 우리나라의 경우에도 평균 수명의 증가, 노인층의 증가, 식생활 양식의 서구화, 진단 기술의 발달 및 전립선암에 대한 인식의 증가로 병원을 찾는 환자가 증가하여 최근 들어 전립선암의 빈도가 크게 증가하고 있다. 중앙 암등록자료에 의하면 2001년에는 전립선암의 암발생 등록분율이 남성암의 2.7%, 2002년에는 3.0%로 6위였으며, 최근에 가장 빠르게 증가하고 있어 향후 발생률이 더욱 증가될 것으로 예측되는 암이다. 전립선암은 유전적 소인 외에도 호르몬, 식이습관, 화학약품 등에 의해서도 발병하는 것으로 알려져 있다.The prostate is an organ that exists only in males that makes up part of the semen and is located below the bladder and adjacent to the rectum. Prostate cancer is a malignant tumor that occurs in the prostate gland, and is one of the most common cancers among men in the West, and it is the fastest growing cancer in men due to recent dietary habits in Korea. do. In developed countries such as North America and Western Europe, it is the most common cancer that accounts for about 20% of male cancers, and the United States has the highest frequency of male cancers occurring annually, and ranks second after lung cancer among cancer deaths. In Korea, the incidence of prostate cancer has increased significantly in recent years due to an increase in life expectancy, an increase in the elderly, westernization of a diet, development of diagnostic technology, and increased awareness of prostate cancer. According to the central cancer registration data, the cancer incidence fraction of prostate cancer was 6th in 2001, 2.7% of male cancers and 3.0% in 2002, and it is the fastest growing in recent years and is expected to increase further. to be. Prostate cancer is known to be caused by hormones, dietary habits, and chemicals in addition to genetic predisposition.
전립선암은 대부분 전립선 속의 선세포(gland cell)가 암화된 것으로 림프절과 뼈에 잘 전이된다. 전립선암의 약 90%는 자신의 몸에서 만들어지는 남성호르몬에 의해 증식한다. 그 때문에 남성호르몬의 작용을 억제함으로써 암 증식을 막고 암세포의 일부를 사멸시키는 호르몬 치료법이 전립선암의 치료에 가장 보편적으로 사용된다(Greenlee, R. T et al., Cancer statistics. CA Cancer J. Clin. 50:7 (2000)).Most prostate cancers are cancers of gland cells in the prostate, which spread well to lymph nodes and bones. About 90% of prostate cancers are proliferated by male hormones that are produced in your body. For this reason, hormonal therapies that inhibit cancer growth and kill some of the cancer cells by inhibiting the action of male hormones are most commonly used in the treatment of prostate cancer (Greenlee, R. T et al., Cancer statistics.CA Cancer J. Clin 50: 7 (2000).
전립선암의 치료방법으로는 (a) 근치적 전립선 적출술 (b) 방사선 조사 (c) 화학요법 (d) 호르몬치료 등이 있다. 가장 널리 이용되는 치료방법은 호르몬 치료로서, 이는 전립선암세포의 상당 부분이 남성호르몬-의존적으로 증식하므로 남성호르몬 분비를 억제하거나 수술로 호르몬 생성을 차단하는 이른바 안드로젠(androgen) 제거방법이다. 이 방법은 80% 이상의 환자에서 암 증식억제 혹은 병변 축소 등 일시적인 치료효과를 보인다. 하지만 일시적인 호르몬 치료법에 좋은 반응을 보인 환자라도 일정 시간이 지나면 대부분 호르몬 저항성 전립선암(hormone-refractory prostate cancer: HRPC)으로 진전되며 이러한 HRPC 환자의 경우 평균 진단 후 1년 이내에 사망하게 된다. HRPC의 경우 기존의 항암제, 화학요법 또는 방사선 요법도 큰 효과를 나타내지 못하므로 새로운 치료방법이 요구되고 있다(Fong, L. et al., Induction of tissue-specific autoimmune prostatitis with prostatic acid phosphatase immunization: implications for immunotherapy of prostate cancer. J. Immunol. 159:3113.(1997)).Treatments for prostate cancer include (a) radical prostatectomy (b) radiation (c) chemotherapy (d) hormonal therapy. The most widely used treatment is hormonal therapy, which is a so-called androgen removal method that inhibits male hormone secretion or blocks hormone production by surgery, since a significant portion of prostate cancer cells multiply androgen-dependently. This method has a temporary therapeutic effect in more than 80% of patients, such as cancer suppression or lesion reduction. However, even patients who responded well to transient hormonal therapy progressed to hormone-refractory prostate cancer (HRPC) after a certain period of time, and those who die within one year of the mean diagnosis. In the case of HRPC, conventional anticancer drugs, chemotherapy, or radiation therapy do not show a great effect, so a new treatment method is required (Fong, L. et al., Induction of tissue-specific autoimmune prostatitis with prostatic acid phosphatase immunization: implications for immunotherapy of prostate cancer.J. Immunol. 159: 3113. (1997).
최근 사이토카인과 수지상세포를 이용한 면역치료 가능성이 제시되면서 수지상세포치료제 (DC 백신)를 이용한 면역치료가 HRPC 환자의 차세대 치료법으로 대두되고 있다 (Fong, L. et al., Dendritic cells in cancer immunotherapy. Annu. Rev. Immunol. 18:245.(2000); Xue BH. et al., Induction of human cytotoxic T lymphocytes specific for prostatespecific antigen. Prostate. 30:73.78.(1997)). 이러한 수지상세포를 이용한 면역치료의 임상시험을 위해서는 우선 동물 모델에서 효과성과 안전성이 확인되어야 하지만, 현재까지 사람 전립선암에 대한 수지상세포 백신의 효능을 평가할 만한 전립선암 동물모델이 없는 실정이다.
Recently, with the possibility of immunotherapy using cytokines and dendritic cells, immunotherapy using dendritic cell therapy (DC vaccine) has emerged as the next generation treatment for HRPC patients (Fong, L. et al., Dendritic cells in cancer immunotherapy. Annu. Rev. Immunol. 18: 245. (2000); Xue BH. Et al., Induction of human cytotoxic T lymphocytes specific for prostate specific antigen.Prostate. 30: 73.78. (1997)). For the clinical trial of immunotherapy using dendritic cells, the effectiveness and safety of the animal model should be confirmed first. However, there is no animal model for prostate cancer to evaluate the efficacy of dendritic cell vaccine against human prostate cancer.
한편, 익지인(Alpiniae Semen ; Alpinia oxyphylla Miquel)은 생강과 다년생 식물인 익지의 과실을 건조한 것으로 방향성 정유성분인 테르펜, 세스쿠이테르펜알콜 등이 주성분이다. 익지인은 생강과의 익지의 열매를 말한다. 또한, 익지인은 방향성 건위약, 정장약으로 사용되어 온 생약이다. 익지인의 매운맛 성분으로는 일반식(Ⅳ)의 야쿠치논 A와 일반식(Ⅴ)의 야쿠치논 B가 알려져 있다. 익지인은 비위의 허약으로 인한 복부팽만감, 신장기능 허약으로 소변이 잦고 대변을 힘없이 보는 증상, 소아야뇨증, 임신 중 자궁출혈, 비장 수렴기능이 떨어져 콧물이 흐를 때 쓰인다. 약리작용으로 심장수축력증가, 복수암세포억제, 회장(回腸) 수축력 증가 등이 보고되었다. 또한, 구토를 다스리고, 유정, 유뇨 등에 효과가 있으며, 항알레르기 작용 및 티로시나아제(tyrosinase) 활성 억제작용 등이 보고되어 있다. 기타 신경쇠약, 건망증, 불면증, 야뇨증, 요실금, 만성적 설사 등의 치료에 사용되어 왔다(신민교 외 1명 ,영림사, 한약대사전, pp251-252, 1990),On the other hand, Alpiniae Semen ( Alpinia oxyphylla Miquel) is dried fruit of ginger and perennial plant, the main ingredients are aromatic essential ingredients such as terpene, sesquiterpene alcohol. The ripe person refers to the ripe fruit of the ginger family. In addition, the acquaintance is a herbal medicine that has been used as a fragrance or placebo medicine. Yakchinnon A of general formula (IV) and yakuchinone B of general formula (V) are known as a spicy taste of a ripe. It is used when a runny nose flows due to abdominal bloating due to weakness of the stomach, weakness of the kidney due to weakness of the kidney function, frequent urination and weakness of feces, microurea, uterine bleeding during pregnancy, and spleen convergence. Pharmacological actions have been reported to increase cardiac contractility, multiple cancer cell suppression, and ileal contractility. In addition, it is effective in controlling vomiting, oil well, urination, and the like, and anti-allergic action and tyrosinase activity inhibitory action have been reported. It has been used to treat other nervous breakdowns, forgetfulness, insomnia, nocturnal enuresis, urinary incontinence, chronic diarrhea, etc. (Shin Min Kyo et al., Younglimsa, Chinese Medicine Dictionary, pp251-252, 1990),
그러나, 아직까지 익지인의 전립선암 관련 질환과 관련하여 상기 문헌 어디에도 개시되거나 공개된 바가 없다.
However, nothing has been disclosed or disclosed in the literature in relation to the prostate cancer-related diseases of the acquaintance.
이에, 본 발명자들은 익지인에 대한 생약 연구를 하던 중, 익지인 추출물이 전립선암 세포를 효과적으로 사멸시킬 수 있음을 확인함으로써 본 발명을 완성하였다.
Accordingly, the present inventors completed the present invention by confirming that the extract of the ripen can effectively kill the prostate cancer cells while studying the herbal medicine for the ripen.
본 발명의 목적은 익지인 추출물을 유효성분으로 함유하는 전립선암 치료용 조성물 및 기능성 식품을 제공하는 것이다.
It is an object of the present invention to provide a composition for treating prostate cancer and a functional food containing a raw extract as an active ingredient.
상기의 목적을 달성하기 위하여, 본 발명은 익지인(Alpiniae Semen)의 유기용매 추출물을 유효성분으로 함유하는 전립선암 예방 및 치료용 조성물을 제공한다.In order to achieve the above object, the present invention provides a composition for preventing and treating prostate cancer containing an organic solvent extract of Alpiniae Semen as an active ingredient.
또한, 본 발명은 식품학적으로 허용 가능한 식품보조 첨가제를 포함하는 익지인(Alpiniae Semen)의 유기용매 추출물을 유효성분으로 함유하는 전립선암 예방용 기능성 식품을 제공한다.
In another aspect, the present invention provides a functional food for preventing prostate cancer containing an organic solvent extract of Alpiniae Semen containing an acceptable food supplement additive as an active ingredient.
이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
본 발명은 익지인(Alpiniae Semen)의 유기용매 추출물을 유효성분으로 함유하는 전립선암 예방 및 치료용 조성물을 제공한다. 본 발명의 조성물은 활성성분으로서 익지인 추출물을 포함하며, 추가적으로 약제학적으로 허용가능한 담체 또는 희석제를 포함할 수 있다. 한편 익지인이란, 배경기술에서도 설명한 바와 같이 생강과 다년생 식물인 익지의 열매를 말하는 것이다. 즉, 본 발명에서 Alpiniae Semen은 익지(Alpinia oxyphylla Miquel:益智)의 열매를 말하며, 한자적 표현은 익지인(益智仁)이고 당업자들에게 있어 이와 같이 이해된다. The present invention provides a composition for preventing and treating prostate cancer, comprising an organic solvent extract of Alpiniae Semen as an active ingredient. The composition of the present invention includes a raw extract as an active ingredient, and may further include a pharmaceutically acceptable carrier or diluent. On the other hand, ripen, as described in the background art refers to the fruit of ripe, ginger and perennial plant. That is, in the present invention, Alpiniae Semen refers to the fruit of Alpinia oxyphylla Miquel (益智), and the Chinese character expression is Ikjiin (益智仁) and is understood as such by those skilled in the art.
본 발명의 전립선암 예방 및 치료용 조성물에 있어서, 상기 유기용매는 에탄올인 것이 바람직하고, 이때 상기 에탄올 추출물은 50℃에서 24시간 동안 추출되거나 45℃ 감압 조건에서 건조 및 농축되는 보다 바람직하고, 또한 상기 에탄올은 95%인 것이 가장 바람직하다.
In the composition for preventing and treating prostate cancer of the present invention, the organic solvent is preferably ethanol, wherein the ethanol extract is more preferably extracted at 50 ° C. for 24 hours or dried and concentrated at 45 ° C. under reduced pressure, and also Most preferably, the ethanol is 95%.
본 발명의 익지인 추출물은 익지인의 어느 부위에서도 가능하지만, 바람직하게는 과피로부터 추출되는 것이 바람직하다. 그리고 추출용액은 물 또는 유기용매로 추출하여 얻을 수 있는데, 유기용매로는 저급 알콜, 아세톤, 클로로포름, 메틸렌클로라이드, 에테르, 에틸아세테이트, 헥산 등을 예시할 수 있다. 저급알콜로는 메탄올, 에탄올, 프로판올 및 부탄올을 예시할 수 있으며, 에탄올이 가장 바람직하다.The ripe extract of the present invention is possible at any part of the ripe, but is preferably extracted from the skin. The extraction solution may be obtained by extraction with water or an organic solvent, and examples of the organic solvent may include lower alcohols, acetone, chloroform, methylene chloride, ether, ethyl acetate, and hexane. As the lower alcohol, methanol, ethanol, propanol and butanol can be mentioned, and ethanol is most preferable.
구체적으로, 익지인 건조물 또는 분말에 1 내지 5 배, 바람직하게는 3배의 95% 에탄올을 첨가하고 20 내지 100℃, 바람직하게는 40 내지 60℃의 온도에서 10 내지 100시간, 바람직하게는 15 내지 40시간, 더욱 바람직하게는 24시간 동안 추출한 후 여과하여 익지인의 에탄올 추출물을 제조할 수 있다. 바람직하게는 상기 추출액을 여과하여 얻어진 여액을 감압농축하여 제조할 수 있다. 상기 추출방법들에서 추출 공정은 필요에 따라 2회 이상 반복하여 실시할 수 있으며, 여과 후 얻어진 추출물을 동결 건조 또는 감압건조시켜 분말 형태로 만들 수도 있다.
Specifically, 1 to 5 times, preferably 3 times, 95% ethanol is added to the raw dry matter or powder and 10 to 100 hours, preferably 15, at a temperature of 20 to 100 ° C., preferably 40 to 60 ° C. To 40 hours, more preferably, 24 hours after extraction can be filtered to prepare the ethanol extract of the ripe. Preferably, the filtrate obtained by filtering the extract may be concentrated under reduced pressure. In the above extraction methods, the extraction process may be repeated two or more times as necessary, and the extract obtained after filtration may be lyophilized or dried under reduced pressure to obtain a powder form.
상기 "약제학적으로 허용가능한 담체"는 신체의 한 기관 또는 부분으로부터 신체의 다른 기관 또는 부분으로 활성 성분을 수송하는 역할을 하는 액체 또는 고체 충진제, 희석제, 부형제 또는 용매와 같은 약제학적으로 허용되는 물질, 조성물 또는 운반체(vehicle)를 의미한다.The "pharmaceutically acceptable carrier" is a pharmaceutically acceptable substance such as a liquid or solid filler, diluent, excipient or solvent which serves to transport the active ingredient from one organ or part of the body to another organ or part of the body. , Composition or vehicle.
본 발명의 전립선암 치료용 조성물은 유효성분과 함께 추가로 약제학적으로 허용되는 1종 이상의 담체를 첨가하여 약제로 제조할 수 있다. 상기 담체로는 식염수, 완충 식염수, 물, 글리세롤 및 에탄올 등이 있으나 이에 한정되지 않으며, 당해 기술 분야에 알려진 적합한 제제(Remingtons's Pharmaceutical Science(최근판), Mack Publishing Company, Easton PA)를 모두 사용 가능하다.The composition for treating prostate cancer of the present invention may be prepared as a medicament by adding one or more pharmaceutically acceptable carriers together with the active ingredient. The carrier may include, but is not limited to, saline, buffered saline, water, glycerol and ethanol, and any suitable agent known in the art (Remingtons's Pharmaceutical Science (Recent Edition), Mack Publishing Company, Easton PA) may be used. .
본 발명의 익지인 추출물을 약제화하기 위한 제제는 임상 투여시에 경구로 투여가 가능하며 일반적인 의약품 제제의 형태로 사용될 수 있으며, 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, 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.Formulations for medicating the extract of the ripen of the present invention can be administered orally during clinical administration and can be used in the form of general pharmaceutical formulations, and when formulated, commonly used fillers, extenders, binders, wetting agents, disintegrants And diluents such as surfactants or excipients. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and liquid preparations for oral use include suspensions, solvents, emulsions, and syrups. In addition to liquids and paraffins, various excipients may be included, such as wetting sweeteners, fragrances, preservatives and the like.
또한, 본 발명의 조성물에 추가될 수 있는 생약재는 약학적으로 허용되는 임의의 생약재일 수 있으며, 예를 들면, 고본(Angelicae tenuissimae Radix), 천마(Gastrodiae Rhizoma), 시호(Bapleuri Radix), 당귀(Angelicae gigantis Radix), 도인(Persicae Semen), 계지(Cinnamomi Ramulus), 대황(Rhei Rhizoma), 감초(Glycyrrhizae Radix), 천궁(Cnidii Rhizoma), 진피(Aurantii nobilis Pericarpium), 택사(Alismatis Rhizoma), 황련(Coptidis Rhizoma), 황금(Scutellariae Radix), 복령(Hoelen), 작약(Paeoniae Radix), 백출(Atractylodis Rhizoma alba), 황백(Phellodendri Cortex), 치자(Gardeniae Fructus), 반하(Pinelliae Tuber), 조구등(Uncaria Ramuluset Uncus), 지실(Ponciri Fructus), 인삼(Gingseng), 맥문동(Liriopis Tuber), 원지(Polygalae Radix), 석창포(Acori graminei Rhizoma), 창출(Atractylodis Rhizoma alba), 감국(Chrysanthemi Flos), 방풍(Ledebouriellae Radix), 생강(Alpiniae Semen crudus), 망초(Natrii sulfas), 대조(Zizyphi Fructus), 단삼(Salviae Radix), 목단피(Mautan Radicis Cortex), 지황(Rehmanniae Radix), 박하(Menthae Herba), 산약(Dioscoreae Rhizoma), 저령(Polyporus), 하수오(Polygonimultiflori Radix), 구자(Allii tuberosi Semen), 결명자(Cassiae Semen), 구기자(Lycii Fructus), 독활(Araliae cordatae Radix), 두충(Eucommiae Cortex), 백화사설초(Hedyotis Herba), 삼백초(Saururus Herba), 인진(Artemisiaecapillaris Herba), 지모(Anemarrhenae Rhizoma), 홍화(Carthami Flos), 황기(Astragali Radix), 석송자(Lycopodium), 은행잎(Ginkgonis Folium), 황정(Polygonati Rhizoma), 연자육(Nelumbinis Semen), 용골(Fossilia ossis Mastodi), 지골피(Lycii radicis Cortex), 우슬(Achyranthis Radix), 숙지황(Rehmanniae Radix preparata), 흑임자(Perillae Semen), 백자인(Thujae Semen), 맥아(Hordei Fructus germinatus), 토사자(Cuscutae Semen), 파극천(Morindae Radix), 해송(Pini koraiensis Radix) 등을 단독으로 또는 배합하여 사용할 수 있다.
In addition, the herbal medicine that may be added to the composition of the present invention may be any pharmaceutically acceptable herbal medicine, for example, Angelica tenuissimae Radix, Gastrodiae Rhizoma, Bapleuri Radix, Angelica ( Angelicae gigantis Radix, Persicae Semen, Cinnamomi Ramulus, Rhubarb (Rhei Rhizoma), Licorice (Glycyrrhizae Radix), Cnidii Rhizoma, Aurantii nobilis Pericarpium, Taxa (Alismatis Rhizoma) Coptidis Rhizoma, Scutellariae Radix, Hoelen, Peeoniae Radix, Atractylodis Rhizoma alba, Phellodendri Cortex, Gardeniae Fructus, Pinelliae Tuber, Ramulu Set (Uncaria) Uncus, Ponciri Fructus, Ginseng (Gingseng), Liriopis Tuber, Polygalae Radix, Acori graminei Rhizoma, Atractylodis Rhizoma alba, Chrysanthemi Flos, Windproof (Ledebouri) ), Ginger (Alpiniae Semen crudus), forget-me-not (Natrii sulfas), control (Zizyphi) Fructus, Salviae Radix, Mautan Radicis Cortex, Rehmanniae Radix, Minthae Herba, Dioscoreae Rhizoma, Polyporus, Polygoni multiflori Radix, Gumen (Allii tuberosi Se) ), Cassiae Semen, Lycii Fructus, Araliae cordatae Radix, Eucommiae Cortex, Hedyotis Herba, Saururus Herba, Artemisiaecapillaris Herba, Jimo Rhiemarrhenae ), Safflower (Carthami Flos), Astragali Radix, Lycopodium, Ginkgois Folium, Polygonati Rhizoma, Nelumbinis Semen, Fossilia ossis Mastodi, Lycoii radicis Cortex , Achyranthis Radix, Rehmanniae Radix preparata, Perillae Semen, Thujae Semen, Malt (Hordei Fructus germinatus), Cuscutae Semen, Morindae Radix, Pear koraiensis ) May be used alone or in combination.
본 발명의 조성물은 실제 임상 투여시에 비경구의 여러 가지 제형으로 투여될 수 있는데, 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 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. 구체적으로, 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 포함된다. 비수성용제, 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, 글리세로제라틴 등이 사용될 수 있다. 또한 치료제의 효능 증진을 위해 칼슘이나 비타민 D3를 첨가할 수 있다. 이러한 조성물은 단위-용량(1회분) 또는 다중-용량(수 회분) 용기, 예를 들면, 밀봉된 앰풀 및 바이알에 제시될 수 있고, 사용 직전에 멸균성 액상 담체, 예를 들면, 주사용 수의 부가 만을 요구하는 동결-건조 조건 하에 저장할 수 있다. 즉석의 주사 용제 및 현탁제는 멸균성 산제, 과립제 및 정제로부터 제조할 수 있다.The composition of the present invention may be administered in various parenteral formulations during actual clinical administration, and solid preparations include tablets, pills, powders, granules, capsules, and the like. In addition to water, liquid, and paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. Specifically, preparations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. Propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used as the non-aqueous solvent and suspension agent. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like. In addition, calcium or vitamin D 3 may be added to enhance the efficacy of the treatment. Such compositions may be presented in unit-dose (single) or multi-dose (several) containers, such as sealed ampoules and vials, and immediately before use, sterile liquid carriers such as injectable water. Can be stored under freeze-drying conditions requiring only the addition of. Immediate injection solutions and suspensions can be prepared from sterile powders, granules and tablets.
본 발명의 제제는 대상의 연령, 성별, 상태, 체내에서 활성 성분의 흡수도, 불활성율 및 배설속도, 병용되는 약물에 따라 달리 적용될 수 있다. 본 발명은 또한 투약 단위의 제형들을 포함한다. 제형은 개별 투약 형태, 예를 들면 정제, 피복 정제, 캡슐제, 환제, 좌약 및 앰플제로 존재하고, 약제 중 유효 화합물의 함량은 개별 투약량의 분율 또는 배수에 해당한다. 투약 단위는, 예를 들면 개별 투여량의 1, 2, 3 또는 4배로, 또는 1/2, 1/3 또는 1/4배를 함유할 수 있다. 개별 투여량은 바람직하기로는 유효 화합물이 1회에 투여되는 양을 함유하며, 이는 통상 1일 투여량의 전부, 1/2, 1/3 또는 1/4배에 해당한다.
The formulations of the present invention can be applied differently depending on the age, sex, condition of the subject, the absorption of the active ingredient in the body, the inactivation rate and excretion rate, the drug used in combination. The invention also includes formulations of dosage units. The formulations are present in individual dosage forms, such as tablets, coated tablets, capsules, pills, suppositories, and ampoules, wherein the amount of active compound in the drug corresponds to the fraction or multiple of the individual dosage. Dosage units may contain, for example, one, two, three or four times the individual dosage, or 1/2, 1/3 or 1/4 times. The individual dosages preferably contain an amount in which the active compound is administered at one time, which usually corresponds to all, 1/2, 1/3 or 1/4 times the daily dosage.
본 발명에서 용어, "추출물(extract)"은 천연물로부터 분리된 활성성분을 의미한다. 추출물은 물, 유기용매, 또는 이의 혼합용매를 이용하는 추출과정으로 획득할 수 있으며, 추출액, 이의 건조 분말 또는 이를 이용하여 제형화된 모든 형태를 포함한다.
As used herein, the term "extract" refers to an active ingredient isolated from natural products. The extract may be obtained by an extraction process using water, an organic solvent, or a mixed solvent thereof, and includes an extract, a dry powder thereof, or any form formulated using the same.
본 발명의 구체적인 실시에서, 익지인의 에탄올 추출물은 PC-3 또는 DU 145 전립선암 세포를 100 ㎍/㎖에서 각각 80% 및 96% 사멸시킨다. 상기 결과는 본 발명의 익지인 추출물이 우수한 PC-3 또는 DU 145 전립선암 세포의 사멸 활성을 가지며, 나아가 전립선암 치료 및 예방 활성을 가진다는 것을 입증하는 것이다.
In a specific embodiment of the present invention, the ethanol extract of the ripen kills 80% and 96% of PC-3 or DU 145 prostate cancer cells at 100 μg / ml, respectively. The above results demonstrate that the raw extract of the present invention has excellent killing activity of PC-3 or DU 145 prostate cancer cells, and further has prostate cancer treatment and prophylactic activity.
본 발명에서 용어, "예방"이란 조성물의 투여로 전립선암 발병을 억제 또는 지연시키는 모든 행위를 의미한다.As used herein, the term "prevention" means any action that inhibits or delays the development of prostate cancer by administration of the composition.
본 발명에서 용어, "치료"란 조성물의 투여로 전립선암의 증세가 호전되거나 이롭게 변경하는 모든 행위를 의미한다.As used herein, the term "treatment" means any action that improves or advantageously changes the symptoms of prostate cancer by administration of the composition.
본 발명에서 익지인 추출물은 물, 유기 용매, 또는 이의 혼합 용매를 사용하여 추출하여 사용할 수 있다. 바람직하게는 유기 용매, 특히 에탄올을 사용하여 추출한다. 추출한 액은 바로 사용하거나 또는 농축 및/또는 건조하여 사용할 수 있다. 유기용매를 사용하여 추출하는 경우, 메탄올, 에탄올, 이소프로판올, 부탄올, 에틸렌, 아세톤, 헥산, 에테르, 클로로포름, 에틸아세테이트, 부틸아세테이트, 디클로로메탄, N, N-디메틸포름아미드(DMF), 디메틸설폭사이드(DMSO), 1,3-부틸렌글리콜, 프로필렌글리콜 또는 이들의 혼합용매인 유기용매를 사용하며 생약의 유효 성분이 파괴되지 않거나 최소화된 조건에서 실온 또는 가온하여 추출할 수 있다. 추출하는 유기용매에 따라 약제의 유효성분의 추출정도와 손실정도가 차이가 날 수 있으므로, 알맞은 유기용매를 선택하여 사용하도록 한다. 추출 방법은 특별히 제한되지 않고, 예를 들어 냉침 추출, 초음파 추출, 환류 냉각 추출 등이 있다. 여과는 추출액으로부터 부유하는 고체 입자를 제거하는 과정으로, 면, 나일론 등을 이용하여 입자를 걸러내거나 한외여과, 냉동여과법, 원심분리법 등을 사용할 수 있으나 이에 제한되지 않는다.The extracts ripe in the present invention can be extracted and used using water, an organic solvent, or a mixed solvent thereof. Preferably it is extracted using an organic solvent, in particular ethanol. The extracted liquid can be used directly or by concentrating and / or drying. When extracted with an organic solvent, methanol, ethanol, isopropanol, butanol, ethylene, acetone, hexane, ether, chloroform, ethyl acetate, butyl acetate, dichloromethane, N, N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), 1,3-butylene glycol, propylene glycol, or a mixed solvent thereof may be used and extracted by room temperature or warming under conditions where the active ingredient of the herbal medicine is not destroyed or minimized. Depending on the organic solvent to be extracted, the degree of extraction and loss of the active ingredient of the drug may vary, so select an appropriate organic solvent. The extraction method is not particularly limited, and examples thereof include cold extraction, ultrasonic extraction, and reflux cooling extraction. Filtration is a process of removing the suspended solid particles from the extract, it may be used to filter the particles using cotton, nylon or the like, or may be used, such as ultrafiltration, cryofiltration, centrifugal separation, but is not limited thereto.
추출액의 농축에는 감압농축, 역삼투압 농축 등의 방법이 사용될 수 있다. 농축 후 건조 단계는 동결건조, 진공건조, 열풍건조, 분무건조, 감압건조, 포말건조, 고주파건조, 적외선건조 등을 포함하나 이에 제한되지 않는다. 경우에 따라, 최종 건조된 추출물을 분쇄하는 공정을 추가할 수 있다.Concentration of the extract may be used, such as concentrated under reduced pressure, reverse osmosis concentration. The post-concentration drying step includes, but is not limited to, freeze drying, vacuum drying, hot air drying, spray drying, vacuum drying, foam drying, high frequency drying, infrared drying and the like. If desired, a process of grinding the final dried extract may be added.
또한, 상기 추출물은 추가의 분획 공정을 수행할 수 있다. 바람직하게는 상기 추출물을 증류수에 현탁시켜 비극성 유기 용매, 예를 들어, 헥산, 에테로, 디클로로메탄, 클로로포름, 에틸아세테이드 또는 이들의 혼합 용매로 비극성용매 가용층을 추출, 분리하여 수득하도록 하고, 이를 농축 및/또는 건조하여 사용할 수 있다.In addition, the extract can perform an additional fractionation process. Preferably, the extract is suspended in distilled water to obtain a nonpolar solvent soluble layer by extraction and separation with a nonpolar organic solvent such as hexane, ether, dichloromethane, chloroform, ethyl acetate, or a mixed solvent thereof. It can be used by concentrating and / or drying it.
본 발명에서, 용어 "약제학적으로 허용가능한 염"이란 약리학적 또는 생리학적으로 허용되는 무기산, 유기산 및 염기로부터 유도된 염을 의미한다. 적합산 산의 예로는 염산, 브롬산, 황산, 질산, 과염소산, 푸마르산, 말레산, 인산, 글리콜산, 락트산, 살리실산, 숙신산, 톨루엔-p-설폰산, 타르타르산, 아세트산, 시트르산, 메탄설폰산, 포름산, 벤조산, 말론산, 나프탈렌-2-설폰산, 벤젠설폰산 등을 포함할 수 있다. 적합한 염기로부터 유도된 염은 알칼리 금속, 예들 들어, 나트륨, 알칼리토금속, 예들 들어, 마그네슘, 암모늄 등을 포함할 수 있다.
In the present invention, the term "pharmaceutically acceptable salts" means salts derived from pharmacologically or physiologically acceptable inorganic acids, organic acids and bases. Examples of suitable acid include hydrochloric acid, bromic acid, sulfuric acid, nitric acid, perchloric acid, fumaric acid, maleic acid, phosphoric acid, glycolic acid, lactic acid, salicylic acid, succinic acid, toluene-p-sulfonic acid, tartaric acid, acetic acid, citric acid, methanesulfonic acid, Formic acid, benzoic acid, malonic acid, naphthalene-2-sulfonic acid, benzenesulfonic acid, and the like. Salts derived from suitable bases may include alkali metals such as sodium, alkaline earth metals such as magnesium, ammonium and the like.
본 발명의 전립선암 질환 예방 및 치료용 약학조성물은 조성물 총 중량에 대하여 상기 추출물 또는 화합물을 0.1 내지 50 중량%로 포함한다. 또한, 상기 조성물은 약효를 증가시키지는 않으나 약재 조성물에 통상 사용되어 냄새, 맛, 시각 등을 향상시킬 수 있는 추가성분을 포함할 수 있다. 또한, 상기 조성물은 비타민 B1, B2, B6, C, E, 니아신, 카르니친, 베타인, 엽산 판토텐산, 비오틴, 아연, 철, 칼슘, 크롬, 마그네슘, 이들의 혼합물 등의 무기, 유기 첨가물들을 추가로 포함할 수 있다. 또한, 상기 조성물은 단독 사용하거나 기존 사용되어진 전립선암에 대한 치료 활성을 가지는 물질을 포함할 수 있다.
The pharmaceutical composition for preventing and treating prostate cancer diseases of the present invention comprises 0.1 to 50% by weight of the extract or compound based on the total weight of the composition. In addition, the composition does not increase the efficacy, but may include additional ingredients that are commonly used in the pharmaceutical composition to improve the smell, taste, time and the like. In addition, the composition adds inorganic and organic additives such as vitamins B1, B2, B6, C, E, niacin, carnitine, betaine, folate pantothenic acid, biotin, zinc, iron, calcium, chromium, magnesium, and mixtures thereof. It can be included as. In addition, the composition may include a substance having a therapeutic activity against prostate cancer, used alone or previously used.
본 발명에서 용어, "환자"는 전립선암 및 이의 직, 간접적 원인에 의해 유발된 질환을 가지고, 본 발명의 조성물을 투여에 의하여 증상이 호전될 수 있는 인간과 말, 양, 돼지, 염소, 낙타, 영양, 개 등의 동물을 의미한다. 본 발명의 익지인 추출물을 포함하는 조성물을 환자에게 투여함으로써, 상기에서 언급한 전립선암을 효과적으로 예방 및 치료할 수 있다. 본 발명의 조성물을 기존의 전립선암 치료제와 병행하여 투여할 수 있다.As used herein, the term "patient" refers to humans and horses, sheep, pigs, goats, and camels that have a disease caused by prostate cancer and its direct and indirect causes, and whose symptoms may be improved by administering the composition of the present invention. Means animals such as nutrition, dogs. By administering to the patient a composition comprising the extract of the present invention, it is possible to effectively prevent and treat the above-mentioned prostate cancer. The composition of the present invention can be administered in parallel with existing prostate cancer therapies.
본 발명에서 용어, "투여"는 어떠한 적절한 방법으로 환자에게 소정의 물질을 도입하는 것을 의미하며, 본 발명의 조성물의 투여 경로는 목적 조직에 도달할 수 있는 한 어떠한 일반적인 경로를 통하여 경구 또는 비경구 투여될 수 있다. 또한, 조성물은 활성 물질이 표적 세포로 이동할 수 있는 임의의 장치에 의해 투여될 수 있다.As used herein, the term "administration" means introducing a predetermined substance into a patient by any suitable method, and the route of administration of the composition of the present invention is oral or parenteral via any general route as long as the target tissue can be reached. May be administered. In addition, the composition may be administered by any device in which the active agent may migrate to the target cell.
본 발명의 조성물은 약제학적으로 유효한 양으로 투여한다. 본 발명에서 용어, "약제학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 유효 용량 수준은 환자의 성병, 연령, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출 비율, 치료 기간, 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 있다. 단일 또는 다중 투여될 수 있다. 상기 요소를 모두 고려하여 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 당업자에 의해 용이하게 결정될 수 있다. 본 발명의 제조 방법에 따라 제조된 추출물 또는 화합물을 포함하는 조성물의 투여방법은 경구투여 또는 정맥투여가 바람직하고, 일반적으로 그 유효 용량은 경구투여인 경우에는 보통 성인을 기준으로 1회에 1 내지 500 ㎎/㎏이 바람직하며, 정맥투여인 경우에는 1 내지 100 ㎎/㎏이 바람직하며, 하루 2-3 회 투여될 수 있다. 특정 환자에 대한 투여용량 수준은 성별, 연령, 익지인상태, 식이, 투여시간, 투여방법, 약제혼합, 환자의 상태 및 신경 질환의 발병 정도에 따라 변화될 수 있다.
The composition of the present invention is administered in a pharmaceutically effective amount. As used herein, the term “pharmaceutically effective amount” means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and an effective dose level refers to a patient's sexually transmitted disease, age, severity, and drug activity. , Drug sensitivity, time of administration, route of administration and rate of release, duration of treatment, factors including concurrently used drugs, and other factors well known in the medical arts. The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. It may be single or 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 adverse effect, and can be easily determined by those skilled in the art. The method of administering the composition comprising the extract or compound prepared according to the preparation method of the present invention is preferably oral administration or intravenous administration. In general, when the effective dose is oral administration, it is usually 1 to 1 time per adult. 500 mg / kg is preferred, and in the case of intravenous administration, 1 to 100 mg / kg is preferred, and may be administered 2-3 times a day. Dosage levels for a particular patient may vary depending on sex, age, ripening status, diet, time of administration, method of administration, drug mixture, the condition of the patient and the extent of the development of neurological disease.
또한, 본 발명은 식품학적으로 허용 가능한 식품보조 첨가제를 포함하는 익지인(Alpiniae Semen)의 유기용매 추출물을 유효성분으로 함유하는 전립선암 예방용 기능성 식품을 제공한다.In addition, the present invention Alpiniae containing a food supplement acceptable food supplement ( Alpiniae Semen ) provides a functional food for the prevention of prostate cancer containing the organic solvent extract as an active ingredient.
본 발명의 기능성 식품은 익지인의 유기용매 추출물을 총중량에 대해 0.1 내지 5중량% 포함하는 것이 바람직하며, 1중량%로 포함하는 것이 더욱 바람직하다. 본 발명의 기능성 식품은 그 제형에 있어서 특별히 한정되는 바는 없으며, 예를 들어 육류, 소세지, 빵, 쵸코렛, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알코올음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강식품을 모두 포함한다.The functional food of the present invention preferably comprises 0.1 to 5% by weight, more preferably 1% by weight of the organic solvent extracts of the ripe. Functional food of the present invention is not particularly limited in the formulation, for example, dairy products including meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, ice cream, Various soups, beverages, tea, drinks, alcoholic beverages and vitamin complexes, etc., and includes all of the health food in the usual sense.
본 발명에 있어서 "기능성 식품"은 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 invention, "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 "functional" refers to the structure of the human body And ingestion for the purpose of obtaining nutrients for function or for obtaining useful effects in health uses such as physiological actions.
본 발명에서는 PC-3 또는 DU 145 전립선암 세포에 본 발명의 익지인 추출물을 투입한 결과, PC-3 또는 DU 145 전립선암 세포가 사멸하는 것을 확인하였다(도 1 및 도 2 참조). 또한, 유세포 분석 및 웨스턴 블럿에 의한 결과, 익지인 추출물은 인간 전립선암 세포주인 PC-3 및 DU 145 세포의 전립선암 세포를 특정 세포 주기에서 세포분열이 정지상태로 유지시켜 세포 자멸 과정인 아포토시스(apoptosis) 과정을 유도한다(도 3, 도 4 및 도 8 참조). 또한, 익지인 추출물은 전립선암 세포의 Myc, AP-1 세포신호 및 NF-κB 세포신호에 영향을 미친다(도 5, 도 6 및 도 7 참조). 따라서, 익지인 추출물이 전립선암 치료 효과가 있다는 것을 새롭게 알 수 있다. 이에, 본 발명에서는 익지인 추출물을 유효성분으로 함유하는 전립선암 예방용 기능성 식품을 제조함으로써 본 발명을 완성하였다(제조예 2 참조)
In the present invention, it was confirmed that the PC-3 or DU 145 prostate cancer cells were killed, as a result of injecting the raw extract of the present invention into PC-3 or DU 145 prostate cancer cells (see FIGS . 1 and 2 ). In addition, as a result of flow cytometry and Western blotting, the ripe extract extracts prostate cancer cells of human prostate cancer cell lines PC-3 and DU 145 cells in a specific cell cycle to stop cell division in apoptosis process (apoptosis). apoptosis) process (see FIGS. 3, 4 and 8 ). In addition, the ripe extracts affect the Myc, AP-1 and NF-κB cell signals of prostate cancer cells (see FIGS. 5, 6 and 7 ). Thus, it can be seen that the raw extract has a prostate cancer treatment effect. Thus, in the present invention, the present invention was completed by preparing a functional food for preventing prostate cancer containing a raw extract as an active ingredient (see Preparation Example 2 ).
상기에서 살펴본 바와 같이, 본 발명의 익지인 추출물은 전립선암 세포의 성장을 억제하고 세포사멸을 유도한다. 따라서 본 발명에 따른 전립선암 치료용 조성물은 전립선암 환자의 치료에 매우 효과적일 것이다.
As discussed above, the extract of the present invention inhibits the growth of prostate cancer cells and induces apoptosis. Therefore, the composition for treating prostate cancer according to the present invention will be very effective for the treatment of patients with prostate cancer.
도 1은 인간 전립선암 세포주인 PC-3 세포에서 실시예 1에서 얻어진 익지인 추출물의 도입이 전립선암 세포의 성장에 미치는 영향을 알아보기 위한 Alamar Blue 분석 결과이고, 이때 X축은 익지인 추출물의 농도이고, Y축은 생존한 인간 전립선암 PC-3 세포의 생존율을 나타낸다.
도 2는 인간 전립선암 세포주인 DU 145 세포에서 실시예 1에서 얻어진 익지인 추출물의 도입이 전립선암 세포의 성장에 미치는 영향을 알아보기 위한 Alamar Blue 분석 결과이고, 이때 X축은 익지인 추출물의 농도이고, Y축은 생존한 인간 전립선암 DU 145 세포의 생존율을 나타낸다.
도 3은 인간 전립선암 세포주인 PC-3 세포에서 실시예 1에서 얻어진 익지인 추출물의 도입이 전립선암 세포의 세포주기를 정지시키고 세포자멸에 미치는 영향을 알아보기 위한 유세포 분석 결과이다.
도 4는 인간 전립선암 세포주인 DU 145에서 실시예 1에서 얻어진 익지인 추출물의 도입이 전립선암 세포의 세포주기를 정지시키고 세포자멸에 미치는 영향을 알아보기 위한 유세포 분석 결과이다.
도 5는 인간 전립선암 세포주인 PC-3에서 익지인 추출물의 도입이 전립선암 세포의 Myc 세포신호에 미치는 영향을 알아보기 위한 Myc 리포터 어세이 방법으로 루시페라아제 활성을 분석한 결과이다.
도 6은 인간 전립선암 세포주인 PC-3에서 익지인 추출물의 도입이 전립선암 세포의 AP-1 세포신호에 미치는 영향을 알아보기 위한 AP-1 리포터 어세이 방법으로 루시페라아제 활성을 분석한 결과이다.
도 7은 인간 전립선암 세포주인 PC-3에서 익지인 추출물의 도입이 전립선암 세포의 NF-κB 세포신호에 미치는 영향을 알아보기 위한 NF-κB 리포터 어세이 방법으로 루시페라아제 활성을 분석한 결과이다.
도 8은 인간 전립선암 세포주인 PC-3에서 익지인 추출물의 도입이 전립선암세포의 NF-κB 세포신호에 미치는 영향을 알아보기 위한 I-κBβ 단백질의 양적 변화와 아포토시스를 유발하는 Caspase 3의 활성화를 Western blotting 방법으로 분석한 결과이다. 1 is a result of Alamar Blue analysis to determine the effect of the introduction of the raw extract obtained in Example 1 on the growth of prostate cancer cells in PC-3 cells, a human prostate cancer cell line, wherein the X-axis is the concentration of the extract And the Y axis represents the survival rate of surviving human prostate cancer PC-3 cells.
2 is a result of Alamar Blue analysis to determine the effect of the introduction of the raw extract of Example 1 obtained in Example 1 in the growth of prostate cancer cells in the human prostate cancer cell line DU 145 cells, wherein the X-axis is the concentration of the extract of the raw egg , Y axis shows survival rate of surviving human prostate cancer DU 145 cells.
Figure 3 is a flow cytometry result to determine the effect of the introduction of the raw extract obtained in Example 1 in PC-3 cells, a human prostate cancer cell line to stop the cell cycle and apoptosis of prostate cancer cells.
Figure 4 is a flow cytometry result to determine the effect of the introduction of the raw extract obtained in Example 1 in the human prostate cancer cell line DU 145 to stop the prostate cancer cells cell cycle and apoptosis.
5 is a result of analyzing luciferase activity by the Myc reporter assay method to determine the effect of the introduction of the raw extract in PC-3 human prostate cancer cell line Myc cell signal of prostate cancer cells.
Figure 6 shows the results of analyzing luciferase activity by the AP-1 reporter assay to determine the effect of the introduction of the raw extract in PC-3 human prostate cancer cell line AP-1 cell signal of prostate cancer cells.
Figure 7 is the result of analyzing luciferase activity in the NF-κB reporter assay to determine the effect of the introduction of the raw extract in PC-3 human prostate cancer cell line NF-κB cell signal of prostate cancer cells.
FIG. 8 shows the activation of
이하, 본 발명을 실시예를 통하여 보다 상세하게 설명한다. 그러나, 이들 실시예는 본 발명을 예시적으로 설명하기 위한 것으로 본 발명의 범위가 이들 실시예에 의해 제한되는 것은 아니다.
Hereinafter, the present invention will be described in more detail with reference to examples. However, these examples are for illustrative purposes only, and the scope of the present invention is not limited by these examples.
<실시예 1> 익지인 추출물의 제조<Example 1> Preparation of ripe raw extract
서울 약재상에서 구입한 익지인(중국산) 3 ㎏을 음지 및 실온에서 5일간 건조하고 분쇄하였다. 상기 분쇄된 익지인을 95% 에탄올(ethanol) 30 ℓ에 침지시키고 50℃에서 24시간 동안 추출하였다. 이것을 여과지를 통하여 여과한 후 45℃ 감압 조건에서 건조 및 농축하여 총 추출물 289 g을 수득하고, -20℃에서 보관하였다.
3 kg of ripen (Chinese) purchased from Seoul medicinal herb was dried and ground for 5 days at the shade and room temperature. The ground ripen was soaked in 30 L of 95% ethanol and extracted at 50 ° C. for 24 hours. This was filtered through filter paper, dried and concentrated under reduced pressure at 45 ° C. to obtain 289 g of the total extract, which was stored at −20 ° C.
<실시예 2> 인간 전립선암 세포주의 준비 및 처리Example 2 Preparation and Treatment of Human Prostate Cancer Cell Line
본 발명에 사용된 인간 전립선암 세포주인 PC-3와 DU 145를 ATCC(American Type Culture Collection, Manassas, VA, USA)로부터 입수하여 실험에 이용하였다. 구체적으로, PC-3와 DU 145 세포주를 10%의 소태아혈청(fetal bovine serum ; FBS)(Welgene)이 첨가된 DMEM(Dulbeco's Modified Eagle's Medium) 배지에서 37℃, 5% CO2의 수분이 있는 상태로 유지하고, 2-3 일 정도 계대배양하였다.
The human prostate cancer cell lines PC-3 and DU 145 used in the present invention were obtained from ATCC (American Type Culture Collection, Manassas, VA, USA) and used for experiments. Specifically, PC-3 and DU 145 cell lines were treated with DMEM (Dulbeco's Modified Eagle's Medium) medium containing 10% fetal bovine serum (FBS) (Welgene) at 37 ° C. and 5% CO 2 . It was kept in the state and it was passaged for 2-3 days.
<실시예 3> 익지인 추출물이 전립선암 세포의 성장에 미치는 영향<Example 3> Effect of the ripe Korean extract on the growth of prostate cancer cells
상기 실시예 1에서 추출한 익지인 추출물이 전립선암 세포의 성장에 미치는 영향을 알아보기 위하여, 인간 전립선암 세포인 PC-3와 DU 145 세포에 익지인의 에탄올 추출물을 48시간 처리하고 Alamar Blue 분석을 시행하였다. Alamar Blue 분석은 MTT 분석의 변형된 형태인데, 특정 효소에 의해서 분해되는 화합물을 살아있는 세포에 처리한 후 화합물이 분해되면서 나오는 생성물의 형광 세기를 측정함으로써 약물을 처리한 후 살아있는 세포의 상대적인 숫자를 알아내는 실험방법이다. 하기에서 보다 상세히 설명한다.In order to determine the effect of the extract of the ripen extracted in Example 1 on the growth of prostate cancer cells, the ethanol extract of the ripen was treated for 48 hours in PC-3 and DU 145 cells, which are human prostate cancer cells, and Alamar Blue analysis was performed. Was implemented. The Alamar Blue assay is a modified form of the MTT assay, in which a specific enzyme degrades a living cell and then measures the fluorescence intensity of the product as the compound breaks down to determine the relative number of living cells after treatment. I am an experimental method. It will be described in more detail below.
96 웰 플레이트에 각 웰 당 4 X 103 개의 PC-3와 DU 145 세포를 각각 주입(seeding)하고 24시간 배양하였다. DMSO(Dimethyl sulfoxide)에 녹인 상기 실시예 1의 익지인 에탄올 추출물을 각각 0 내지 100 ㎍/㎖ 농도(구체적으로, 각각 0, 3.125, 6.25, 12.5, 25, 50 및 100 ㎍/㎖ 농도)로 48시간 동안 처리하였을 때, 세포 성장을 저해하는 정도를 확인하였다(표 1 및 표 2). 각 농도의 추출물을 처리한 후, 96-웰 플레이트에서 각 웰에 채워진 0.2 ㎖의 세포 배양액에 20 ㎕의 Alamar Blue 시약을 첨가한 후 플레이트를 인큐베이터에서 2시간 동안 배양하였다. 각 웰의 세포를 고르게 반응시키기 위하여 플레이트를 천천히 흔들고, 544 ㎚의 파장에서 조사광을 조사하면서 590 ㎚에서 형광의 세기를 형광광도계(Fluorescence Microplate Reader; Molecular Devices Corp.)로 흡광도를 측정하였고, PC-3와 DU 145 인간 전립선암세포의 생존율을 또한 도 1 및 도 2에 나타내었다.
96 well plates were seeded with 4 × 10 3 PC-3 and DU 145 cells per well and incubated for 24 hours. Well-known of Example 1 dissolved in DMSO (dimethyl sulfoxide) When the ethanol extract was treated at concentrations of 0 to 100 μg / ml (specifically, concentrations of 0, 3.125, 6.25, 12.5, 25, 50, and 100 μg / ml, respectively) for 48 hours, the degree of inhibition of cell growth was confirmed. (Table 1 and Table 2). After treatment with each concentration of extract, 20 μl of Alamar Blue reagent was added to 0.2 ml of cell culture filled in each well in a 96-well plate, and the plates were incubated for 2 hours in an incubator. The plate was slowly shaken to evenly react the cells of each well, and the intensity of fluorescence was measured by a Fluorescence Microplate Reader (Molecular Devices Corp.) at 590 nm while irradiating irradiated light at a wavelength of 544 nm. Survival rates of -3 and DU 145 human prostate cancer cells are also shown in FIGS. 1 and 2.
그 결과, 표 1 및 표 2에서 나타난 바와 같이, 익지인의 처리 농도가 높을수록 전립선암 세포의 성장이 감소하였으며, 이로부터 익지인이 전립선암 치료 효과를 가짐을 알 수 있었다. 즉, 표 1에서는 25 ㎍/㎖에서 21%, 50 ㎍/㎖에서 49%, 100 ㎍/㎖에서 80%로 전립선암 세포를 사멸시켰다. 또한, 표 2에서는 25 ㎍/㎖에서 16%, 50 ㎍/㎖에서 77%, 100 ㎍/㎖에서 96%로 전립선암 세포를 사멸시켰다. 따라서, 실시예 1에서 추출된 익지인의 치료 효과가 보다 우수한 것으로 판단된다. 상기 표 1 및 표 2에서 익지인을 처리하지 않은 대조군의 전립선암 세포의 생존율 수를 1을 기준으로 하여 각각의 익지인 처리 농도에 따른 48시간 후의 전립선암 세포의 상대적 세포수를 기재하였다. 이와 같이, 본 발명의 익지인 추출물은 우수한 PC-3와 DU 145 전립선암 세포 사멸 활성을 가지며, 나아가 전립선암 치료 및 예방 활성을 가진다는 것을 입증한다.
As a result, as shown in Table 1 and Table 2, the higher the concentration of the acquaintance, the growth of prostate cancer cells decreased, from which the acquaintance was found to have a prostate cancer treatment effect. That is, in Table 1, prostate cancer cells were killed at 21% at 25 μg / ml, 49% at 50 μg / ml, and 80% at 100 μg / ml. In Table 2, prostate cancer cells were killed at 16% at 25 μg / ml, 77% at 50 μg / ml, and 96% at 100 μg / ml. Therefore, it is judged that the therapeutic effect of the ripen extract extracted in Example 1 is more excellent. Table 1 and Table 2 describe the relative cell numbers of prostate cancer cells after 48 hours according to the concentration of each of the ripen, based on the number of survival rate of the prostate cancer cells of the control group without the acquaintance. As such, the ripe extract of the present invention demonstrates excellent PC-3 and DU 145 prostate cancer cell killing activity and further has prostate cancer treatment and prophylactic activity.
<실시예 4> 익지인 추출물이 전립선암 세포의 세포분열 주기에 미치는 영향<Example 4> Effect of the ripe extract on the cell division cycle of prostate cancer cells
익지인 추출물이 암세포의 세포분열 주기에 미치는 영향을 알아보기 위하여, 유세포분석(Flow Cytometry)을 시행하였다. 유세포분석은 유액 상태의 세포가 감지지역을 통과할 때 세포의 특징을 신속하게 특정하는 방법으로 세포의 핵을 형광물질로 염색한 후 분석할 경우 세포분열 주기 분포의 정도를 확인할 수 있는 실험방법이다.Flow Cytometry was performed to determine the effects of the extracts on the cell division of cancer cells. Flow cytometry is a method to quickly identify the characteristics of a cell as it passes through the detection zone. When staining the cell nucleus with a fluorescent material, the flow cytometry can be determined. .
구체적으로, PC-3와 DU 145 세포를 웰당 2.4 x 105개 정도로 6-웰 플레이트에 주입(seeding)하고 24시간 배양하였다. 세포에 100 ㎍/㎖의 익지인 추출물을 투여하고 24시간을 두었다. 6-웰 플레이트에서 각 웰에 채워진 배양액을 제거하고 PBS(phosphate-buffered saline, 인산완충염수)로 2회 세척하였다. 트립신-EDTA 용액으로 처리하여 부착된 세포를 부유시킨 후 마이크로튜브에 옮기고 원심분리하여 세포를 회수하였다. 회수한 세포를 PBS로 세척하고 원심분리한 후 차가운 에탄올에 부유시켰다. 에탄올에 부유시킨 세포을 4℃에 보관하여 세포를 고정시킨 후 원심분리하고 PBS로 세척하였다. 세척한 세포를 500 ㎕의 PI 용액(50 ㎍/㎖의 Propidium Iodide, 10 ㎍/㎖의 RNase A)에 부유시킨 후 37℃에서 30분 보관하여 핵을 염색시킨 후 2 ㎖의 PBS를 첨가하였다. 용액에 부유된 세포를 유세포분석기(FACS; BD biosciences)로 분석하였고, PC-3와 DU 145 인간 전립선암 세포의 세포 주기 및 자멸을 각각 도 3과 도4에 나타내었다.Specifically, PC-3 and DU 145 cells were seeded in 6-well plates at about 2.4 × 10 5 cells per well and incubated for 24 hours. Cells were dosed with 100 μg / ml of raw extract and left for 24 hours. The culture medium in each well was removed from the 6-well plate and washed twice with PBS (phosphate-buffered saline). The attached cells were suspended by treatment with trypsin-EDTA solution, transferred to microtubes and centrifuged to recover the cells. The recovered cells were washed with PBS, centrifuged and suspended in cold ethanol. Cells suspended in ethanol were stored at 4 ° C to fix the cells, centrifuged and washed with PBS. The washed cells were suspended in 500 μl of PI solution (50 μg / ml of Propidium Iodide, 10 μg / ml of RNase A) and stored at 37 ° C. for 30 minutes to stain nuclei, and 2 ml of PBS was added thereto. Cells suspended in solution were analyzed by flow cytometry (FACS; BD biosciences), and cell cycles and apoptosis of PC-3 and DU 145 human prostate cancer cells were shown in FIGS. 3 and 4, respectively.
그 결과, 도 3 및 도 4에 나타난 바와 같이 익지인 추출물을 처리한 암세포는 대조군에 비하여 특정 세포 주기에서 세포분열이 정지상태에 있음을 확인하였고 세포 자멸 과정인 아포토시스(apoptosis) 과정이 진행 중이었으며, 이로부터 익지인 출물물이 암세포의 분열을 정지시키고 자멸에 이르게 함을 알 수 있다.
As a result, as shown in Figs. 3 and 4, the cancer cells treated with the raw extracts were found to have cell division in a stationary state in a specific cell cycle compared to the control group, and the apoptosis process, which is an apoptosis process, was in progress. From this, it can be seen that the raw extract stops the division of cancer cells and leads to apoptosis.
<실시예 5> 익지인 추출물이 전립선암 세포의 세포신호에 미치는 영향<Example 5> Effects of the ripe extracts on the cell signal of prostate cancer cells
익지인 추출물이 암세포의 성장을 주도하는 세포신호에 미치는 영향을 알아보기 위하여, 실제 세포 내에서 세포신호 저해 활성을 리포터 어세이(reporter assay)를 이용하여 확인하였다.In order to examine the effect of the extracts of the ripe on the cell signal leading to the growth of cancer cells, cell signal inhibition activity in the actual cells was confirmed using a reporter assay (reporter assay).
구체적으로, 상기 리포터 어세이는 암세포의 성장에 주요한 영향을 미치는 Myc과 AP-1, NF-κB의 전사활성을 측정할 수 있도록 고안된 각각의 루시페라아제 벡터(luciferase vector)를 인간 전립선암 세포 PC-3에 형질주입(transfection)한 후, 6시간 뒤 0 내지 100 ㎍/㎖ 농도의 익지인 추출물을 처리하고 24 시간이 지나 루시페라아제(luciferase)의 활성을 측정함으로써 진행하였다. 그 결과, 익지인 추출물이 인간 전립선암 세포 내에서 나타내는 Myc과 AP-1, NF-κB의 세포신호를 저해하는 정도를 하기 표 3에 기재하였다.
Specifically, the reporter assay is a human luciferase cell PC-3 luciferase vector (luciferase vector) designed to measure the transcriptional activities of Myc, AP-1, and NF-κB, which have a major effect on the growth of cancer cells. After transfection at 6 hours, the extract was treated with raw extract at a concentration of 0 to 100 μg / ml and after 24 hours, luciferase activity was measured. As a result, the degree of inhibition of cellular signals of Myc, AP-1, and NF-κB expressed in human prostate cancer cells is shown in Table 3 below.
또한, 도 5, 도 6 및 도 7에 나타난 바와 같이 익지인을 처리한 암세포는 대조군에 비하여 암세포의 성장을 주도하는 Myc, AP-1과 NF-κB의 전사활성을 저하시킴을 확인하였으며, 이로부터 익지인 추출물이 암세포의 성장을 억제함을 알 수 있었다.
In addition, as shown in Figures 5, 6 and 7, it was confirmed that the cancer cells treated with acquaintances lowered the transcriptional activities of Myc, AP-1, and NF-κB leading the growth of cancer cells compared to the control group. From the ripe extract was found to inhibit the growth of cancer cells.
<실시예 6> 익지인 추출물이 전립선암 세포의 NF-κB 세포신호에 미치는 영향<Example 6> Effect of the raw extract on the NF-κB cell signal of prostate cancer cells
익지인 추출물이 암세포의 성장을 주도하는 NF-κB 세포신호에 미치는 영향을 알아보기 위하여, 익지인 추출물을 인간 전립선암 세포에 처리한 후, NF-κB 활성을 저해하는 I-κBβ 단백질의 양적 변화를 Western blotting 방법으로 확인하였다.Quantitative Changes of I-κBβ Protein Inhibiting NF-κB Activity after Treatment of Ripe Extracts on Human Prostate Cancer Cells in order to Investigate the Effects of the Extracts on the NF-κB Cell Signals that Drive Cancer Cell Growth Was confirmed by Western blotting method.
구체적으로, PC-3 세포를 60 ㎜ dish에 60 내지 70% 자라도록 배양한 후 익지인 추출물을 0 내지 100 ㎍/㎖ 농도로 처리하였다. 24시간 후 배양 중이던 세포에서 배양액을 제거하고 PBS로 세척한 후 NP-40 용액으로 처리하여 세포용해액(cell lysate)을 얻었다. 세포용해액을 원심분리하여 세포 단백질이 녹아있는 상층액을 회수하고 농도를 측정한 후 전기영동을 위해 시료를 준비하였다. 준비한 시료를 전기영동하고 Western blotting을 진행하여 I-κBβ 항체로 I-κBβ 단백질의 양을 분석하였으며, 그 결과는 도 8과 같다.Specifically, PC-3 cells were cultured to grow 60-70% in a 60 mm dish, and then the raw extracts were treated with a concentration of 0-100 μg / ml. After 24 hours, the culture medium was removed from the cells in culture, washed with PBS, and treated with NP-40 solution to obtain cell lysate. The cell lysate was centrifuged to recover the supernatant in which cellular proteins were dissolved, and the sample was prepared for electrophoresis after measuring the concentration. The prepared samples were electrophoresed and Western blotting was performed to analyze the amount of I-κBβ protein with I-κBβ antibody, and the results are shown in FIG. 8.
도 8에서 나타난 바와 같이 익지인 추출물은 I-κBβ 단백질의 양을 증가시키고 NF-κB 활성을 저해하여 전립선암세포의 분열을 억제함을 알 수 있다.
As shown in Figure 8 ripen extract can be seen to increase the amount of I-κBβ protein and inhibit the proliferation of prostate cancer cells by inhibiting NF-κB activity.
<실시예 7> 익지인 추출물이 전립선암 세포의 세포자멸에 미치는 영향<Example 7> Effect of the ripe extract on apoptosis of prostate cancer cells
익지인 추출물이 암세포의 세포자멸(apoptosis)에 미치는 영향을 알아보기 위하여, 익지인 추출물을 인간 전립선암 세포에 처리한 후, 세포자멸 과정을 유도하는 Caspase 3의 활성화를 Western blotting 방법으로 확인하였다.In order to investigate the effect of the extracts on apoptosis of cancer cells, the extracts were treated on human prostate cancer cells, and then activation of
구체적으로, PC-3 세포를 60 ㎜ dish에 60 내지 70% 자라도록 배양한 후 익지인 추출물을 0 내지 100 ㎍/㎖ 농도로 처리하였다. 24시간 후 배양 중이던 세포에서 배양액을 제거하고 PBS로 세척한 후 NP-40 용액으로 처리하여 세포용해액(cell lysate)을 얻었다. 세포용해액을 원심분리하여 세포 단백질이 녹아있는 상층액을 회수하고 농도를 측정한 후 전기영동을 위해 시료를 준비하였다. 준비한 시료를 전기영동하고 Western blotting을 진행하여 Caspase 3 항체로 Caspase 3 활성화 정도를 분석하였으며, 그 결과는 도 8과 같다.Specifically, PC-3 cells were cultured to grow 60-70% in a 60 mm dish, and then the raw extracts were treated with a concentration of 0-100 μg / ml. After 24 hours, the culture medium was removed from the cells in culture, washed with PBS, and treated with NP-40 solution to obtain cell lysate. The cell lysate was centrifuged to recover the supernatant in which cellular proteins were dissolved, and the sample was prepared for electrophoresis after measuring the concentration. The prepared sample was electrophoresed and Western blotting was performed to analyze the degree of
도 8에 나타난 바와 같이 익지인 추출물은 암세포의 아포토시스를 주도하는 Caspase 3가 활성화되었음을 확인하였으며, 이를 통해 익지인이 암세포를 효과적으로 아포토시스에 이르게 하여 항암 효과를 나타냄을 알 수 있다.
As shown in FIG. 8, the extracts of the ripen confirmed that
<실시예 8> 익지인 추출물에 의한 급성독성 시험Example 8 Acute Toxicity Test with Ripen Extracts
본 발명에 이용된 익지인은 널리 약재로 이용되고 있어서 안정성에 문제가 없을 것으로 판단하였으나, 경구 투여시 및 복강내 투여시의 독성 실험을 수행하여 이를 확인하고자 하였다.The acquaintance used in the present invention was widely used as a medicinal herb, so it was determined that there was no problem in stability, but the oral administration and the intraperitoneal administration were performed by conducting toxicological tests.
6주령의 특정병원부재(SPF) SD계 랫트를 사용하여 급성독성실험을 실시하였다. 군당 2 마리씩의 동물에 본 발명의 실시예 1의 익지인 추출물을 각각 0.5% 메틸셀룰로즈 용액에 현탁하여 5 g/㎏의 용량으로 단회 경구투여하였다. 시험물질 투여후 동물의 폐사여부, 임상증상, 체중변화를 관찰하고 혈액학적 검사와 혈액생화학적검사를 실시하였으며, 부검하여 육안으로 복강장기와 흉강장기의 이상여부를 관찰하였다.Acute toxicity test was performed using 6-week-old SPF SD rats. To two animals per group, the raw extract of Example 1 of the present invention was suspended in 0.5% methylcellulose solution and administered once orally at a dose of 5 g / kg. After administration of the test substance, mortality, clinical symptoms, and changes in body weight were observed. Hematological and hematological examinations were performed. Necropsy was performed to observe abdominal and thoracic organ abnormalities.
시험결과, 시험물질을 투여한 모든 동물에서 특기할 만한 임상증상이나 폐사된 동물은 없었으며, 체중변화, 혈액검사, 혈액생화학 검사, 부검소견 등에서도 독성변화는 관찰되지 않았다. 이상의 결과 익지인 추출물은 모두 랫트에서 5 g/㎏까지 독성변화를 나타내지 않으며 경구 투여 최소치사량 (LD50)은 5 g/㎏이상인 안전한 물질로 판단되었다.
As a result of the test, there were no clinically symptomatic or dead animals in all the animals to which the test substance was administered, and no toxic change was observed in weight change, blood test, blood biochemical test, and autopsy findings. As a result, all of the raw extracts showed no change in toxicity in rats up to 5 g / kg and the minimum lethal dose (LD 50 ) was determined to be a safe substance of 5 g / kg or more.
<제조예 1> 익지인 추출물을 유효성분으로 함유하는 전립선암 치료제의 제조<Preparation Example 1> Preparation of a prostate cancer therapeutic agent containing the raw extract as an active ingredient
본 발명자들은 상기 실시예를 통해 익지인 추출물의 전립선암 치료 효능이 뛰어남을 확인하여 익지인 추출물을 유효성분으로 함유하는 전립선암 치료제를 하기와 같이 제조하였다. 또한, 하기 치료제의 제조예는 치료제 뿐만 아니라 기능성 식품의 제조에도 응용하여 사용될 수 있다.
The present inventors have confirmed that the prostate cancer treatment efficacy of the ripen extract through the above-mentioned examples to prepare a prostate cancer therapeutic agent containing the ripen extract as an active ingredient as follows. In addition, the preparation of the following therapeutic agents can be used for the application of not only therapeutic agents but also functional foods.
<1-1> 익지인 추출물을 함유하는 연질캅셀(soft gelatin capsules)<1-1> Soft gelatin capsules containing raw extract
익지인 추출물 20%
비타민 C 4.5%Vitamin C 4.5%
비타민 D3 0.001%Vitamin D 3 0.001%
황산망간 0.1%Manganese sulfate 0.1%
밀납 10%
팜유 25%Palm oil 25%
홍화씨유 30.399%
Safflower oil 30.399%
<1-2> 익지인 추출물을 함유하는 정맥주사용 제제의 제조 <1-2> Preparation of Intravenous Formulation Containing Ripe Raw Extract
익지인 추출물 0.2%Ripe Extract 0.2%
만니톨 0.3%Mannitol 0.3%
생리식염수 9.5%
Physiological saline 9.5%
<1-3> 익지인 추출물을 함유하는 정제(tablet)<1-3> tablets containing raw extracts
익지인 추출물 35%Ripe Extract 35%
비타민 C 10%
비타민 D3 0.001%Vitamin D 3 0.001%
황산망간 0.1%Manganese sulfate 0.1%
결정셀룰로오즈 25.0%Crystalline cellulose 25.0%
유당 17.999%Lactose 17.999%
스테아린산마그네슘 2%
Magnesium stearate 2%
<제조예 2> 익지인 추출물을 유효성분으로 함유하는 기능성 식품의 제조Preparation Example 2 Preparation of Functional Foods Containing Raw Extract as Active Ingredient
본 발명자들은 상기 실시예를 통해 익지인 추출물이 전립선암 치료 활성이 뛰어남을 확인하여 이를 유효성분으로 함유하는 기능성 식품을 하기와 같이 제조하였다.
The present inventors confirmed that the raw extract through the above-mentioned prostate cancer treatment activity was excellent and prepared a functional food containing it as an active ingredient as follows.
<2-1> 음료의 제조<2-1> Production of beverage
꿀 522 ㎎Honey 522 mg
치옥토산아미드 5 ㎎5 mg < RTI ID = 0.0 >
니코틴산아미드 10 ㎎
염산리보플라빈나트륨 3 ㎎3 mg of sodium riboflavin hydrochloride
염산피리독신 2 ㎎Pyridoxine hydrochloride 2 mg
이노시톨 30 ㎎Inositol 30 mg
오르트산 50 ㎎Orthoic acid 50 mg
익지인 추출물 0.48 ~ 1.28 ㎎Ripe Extract 0.48 ~ 1.28 mg
물 200 ㎖200 ml of water
상기 조성 및 함량으로 하여 통상적인 방법을 사용하여 음료를 제조하였다.
A beverage was prepared using the above-mentioned composition and content by a conventional method.
<2-2> 츄잉껌의 제조<2-2> Production of chewing gum
껌베이스 20 %
설탕 76.36 ~ 76.76 %Sugar 76.36 ~ 76.76%
익지인 추출물 0.24 ~ 0.64 %Ripe extract 0.24 ~ 0.64%
후르츠향 1 %Fruit flavor 1%
물 2 %Water 2%
상기 조성 및 함량으로 하여 통상적인 방법을 사용하여 츄잉껌을 제조하였다.
Chewing gum was prepared using the above-mentioned composition and content by a conventional method.
<2-3> 캔디의 제조<2-3> Manufacture of candy
설탕 50 ~ 60 %Sugar 50 to 60%
물엿 39.26 ~ 49.66 %Syrup 39.26 ~ 49.66%
익지인 추출물 0.24 ~ 0.64 %Ripe extract 0.24 ~ 0.64%
오렌지향 0.1 %Orange fragrance 0.1%
상기 조성 및 함량으로 하여 통상적인 방법을 사용하여 캔디를 제조하였다.
The composition and the content of the candy were prepared using a conventional method.
<2-4> 비스켓의 제조<2-4> Production of biscuit
박력1급 88 ㎏First class 88 ㎏ power
중력1급 76.4 ㎏Gravity Class 1 76.4 kg
정백당 16.5 ㎏16.5 kg
식염 2.5 ㎏Salt 2.5 ㎏
포도당 2.7 ㎏Glucose 2.7 kg
팜쇼트닝 40.5 ㎏Palm shortening 40.5 kg
암모 5.3 ㎏Ammonium 5.3 kg
중조 0.6 ㎏0.6 kg
중아황산나트륨 0.55 ㎏Sodium bisulfite 0.55 kg
쌀가루 5.0 ㎏Rice powder 5.0 kg
비타민 B1 0.003 ㎏Vitamin B1 0.003 kg
비타민 B2 0.003 ㎏Vitamin B2 0.003 kg
밀크향 0.16 ㎏Milk flavor 0.16 kg
물 71.1 ㎏Water 71.1 kg
전지분유 4 ㎏Whole milk powder 4 ㎏
대용분유 1 ㎏1 kg of substitute milk powder
제일인산칼슘 0.1 ㎏Calcium phosphate 0.1 kg
살포염 1 ㎏Spray salt 1 kg
분무유 25 ㎏Spray oil 25 kg
익지인 추출물 0.2 ~ 0.5 ㎏Ripe extract 0.2 ~ 0.5 ㎏
상기 조성 및 함량으로 하여 통상적인 방법을 사용하여 비스켓을 제조하였다.
The biscuits were prepared using the above-mentioned composition and content by a conventional method.
<2-5> 아이스크림의 제조<2-5> Production of ice cream
유지방 10.0 %Fat milk 10.0%
무지유고형분 10.8 %Solid oil content 10.8%
설탕 12.0 %Sugar 12.0%
물엿 3.0 %Starch syrup 3.0%
유화안정제(스팬, span) 0.5 %Emulsion stabilizer (span) 0.5%
향료(스트로베리) 0.15 %Perfume (Strawberry) 0.15%
물 63.31 ~ 62.91 %Water 63.31 ~ 62.91%
익지인 추출물 0.24 ~ 0.64 %Ripe extract 0.24 ~ 0.64%
상기 조성 및 함량으로 하여 통상적인 방법을 사용하여 아이스크림을 제조하였다.
Ice cream was prepared using conventional methods using the above composition and content.
<2-6> 쵸코렛의 제조<2-6> Manufacture of Chocolate
설탕 34.36 ~ 34.76 %Sugar 34.36 ~ 34.76%
코코아 버터 34 %Cocoa Butter 34%
코코아 매스 15 %
코코아 파우다 15 %
레시틴 0.5 %Lecithin 0.5%
바닐라향 0.5 %Vanilla flavor 0.5%
익지인 추출물 0.24 ~ 0.64 %Ripe extract 0.24 ~ 0.64%
상기 조성 및 함량으로 하여 통상적인 방법을 사용하여 초코렛을 제조하였다.
With the above composition and content, chocolate was prepared using conventional methods.
한편, 본 발명의 구체적 범위는 상기 기술한 실시예 보다는 특허청구범위에 의하여 한정지어지며, 특허청구 범위의 의미와 범위 및 그 등가적 개념으로 도출되는 모든 변경 및 변형된 형태를 본 발명의 범위로 포함하여 해석하여야 한다.It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory and are intended to provide further explanation of the invention, and are not intended to limit the scope of the invention. .
Claims (7)
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Non-Patent Citations (4)
| Title |
|---|
| E. Lee et al. Carcinogenesis. vol.19, no.8, pp.1377-1381 (1998) * |
| E. Lee et al. Carcinogenesis. vol.19, no.8, pp.1377-1381 (1998)* |
| S. Suja et al. Ancient science of life. vol.27, No.4, pp.33-40 (2008) * |
| 박상용 등. 대한침구학회지. 제18권, 제3호, 페이지 79-93 (2001) * |
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