KR20220143281A - Composition for preventing and treating liver cancer containing ginsenoside Rh2 and ginsenoside Rg5 as active ingredients - Google Patents
Composition for preventing and treating liver cancer containing ginsenoside Rh2 and ginsenoside Rg5 as active ingredients Download PDFInfo
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- KR20220143281A KR20220143281A KR1020210049598A KR20210049598A KR20220143281A KR 20220143281 A KR20220143281 A KR 20220143281A KR 1020210049598 A KR1020210049598 A KR 1020210049598A KR 20210049598 A KR20210049598 A KR 20210049598A KR 20220143281 A KR20220143281 A KR 20220143281A
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- South Korea
- Prior art keywords
- ginsenoside
- cancer
- mixture
- pharmaceutical composition
- liver cancer
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- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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- A—HUMAN NECESSITIES
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Abstract
Description
본 발명은 진세노사이드(Ginsenoside) Rh2 및 진세노사이드 Rg5의 혼합물, 또는 이들의 약학적으로 허용 가능한 염을 유효성분으로 함유하는 간암 예방 및 치료용 약학적 조성물에 관한 것이다.The present invention relates to a pharmaceutical composition for preventing and treating liver cancer comprising a mixture of ginsenoside Rh2 and ginsenoside Rg5, or a pharmaceutically acceptable salt thereof, as an active ingredient.
일반적인 원발성 간암인 간세포암종(Hepatocellular carcinoma; HCC)은 난치암 중 사망률이 5번째로 매년 발병률이 지속적으로 증가하고 있으며, 주변 장기나 림프절로 급속 전이되는 특징을 가지고 있어 심각한 이환율과 사망률을 보이는 악성 종양이다. 간암의 조기 진단을 위한 여러 가지 노력에도 불구하고, 초기에 뚜렷한 증상이 없어 대부분의 간암 환자는 간암 중기 혹은 말기에 발견되어 치료 및 완치가 어려우며, 소수의 환자만이 간이식 혹은 수술을 받을 수 있기 때문에 예후가 좋지 않다. 또한, 간암은 재발 위험이 높아 환자의 5년 생존율이 50%에 정도에 못 미치는 것으로 알려져 있다. Hepatocellular carcinoma (HCC), a common primary liver cancer, has the fifth highest mortality rate among intractable cancers, and the incidence continues to increase every year. to be. Despite various efforts for early diagnosis of liver cancer, most patients with liver cancer are found in the middle or late stage of liver cancer because there are no clear symptoms in the early stages, making treatment and cure difficult. Therefore, the prognosis is not good. In addition, it is known that liver cancer has a high risk of recurrence, and the 5-year survival rate of patients is less than 50%.
현재 간암을 치료하기 위한 요법으로 화학 요법 및 방사선 요법 등이 실시되고 있으나 치료에 한계가 있고, 여러 가지 부작용을 유발하기 때문에 치료를 받은 간암 환자의 평균 생존율은 11 내지 20개월밖에 되지 않는다. 간암에서 가장 많이 사용되는 표적 치료제인 소라페닙(sorafenib)은 단독 혹은 다른 항암제와 병행 투여에도 치료 효과가 매우 낮을 뿐만 아니라 약물 내성을 야기하여 치료가 불가능해질 수 있다. 따라서 간암을 치료할 수 있는 새로운 치료 방법 및 전략이 필요한 실정이다.Chemotherapy and radiation therapy are currently being used as therapies to treat liver cancer, but the treatment has limitations and causes various side effects, so the average survival rate of liver cancer patients who received treatment is only 11 to 20 months. Sorafenib, the most frequently used targeted treatment for liver cancer, has very low therapeutic effect even when administered alone or in combination with other anticancer drugs, and may cause drug resistance, making treatment impossible. Therefore, there is a need for a new treatment method and strategy to treat liver cancer.
인삼 및 인삼을 가공한 홍삼에는 인삼 속 식물에만 존재하는 특유의 사포닌들이 들어 있어 특유의 약리 활성을 나타내는데, 이러한 사포닌은 지금까지 30여 종이 알려져 있다. 인삼 사포닌은 아글리콘의 구조에 따라 크게 프로토파낙사다이올계 진세노사이드, 프로토파낙사트라이올계 진세노사이드 및 올레아놀린산계 진세노사이드로 분류되며, 아글리콘에 결합되어 있는 당의 종류나 결합된 당의 수 또는 결합위치에 따라 약리 효능이 다르다. 특히 담마란계의 트리테르페노이드인 프로토파낙사다이올과 프로토파낙사트라이올에 글루코오스, 람노오스, 아라비노오스 또는 자일로오스 같은 당류가 결합된 화합물들이 특유의 약리 활성을 나타낸다. Ginseng and ginseng-processed red ginseng contain unique saponins that exist only in plants of the genus ginseng and exhibit unique pharmacological activity. About 30 types of these saponins are known so far. Ginseng saponins are largely classified into protopanaxadiol-based ginsenosides, protopanaxatriol-based ginsenosides and oleanoic acid-based ginsenosides according to the structure of aglycone, and The pharmacological efficacy is different depending on the number or binding position. In particular, compounds in which saccharides such as glucose, rhamnose, arabinose or xylose are combined with protopanaxadiol and protopanaxatriol, which are triterpenoids of the dammaran family, exhibit unique pharmacological activity.
상기 30 여종의 인삼 사포닌 중 진세노사이드 Rh2가 항암 효과를 나타낸다는 여러 가지 연구들이 발표되었다. 예를 들어, 진세노사이드 Rh2는 F9 teratocarcinoma(기형암세포)의 재분화를 유도하며(Lee등, Proc. 6th Intl. Ginseng symp., 127, 1993), Morris 간암세포(Odashiam 등, Europ. J. Cancer, 15, 885, 1979)와 B16 melanoma(흑색 종양세포), MK-1(위암세포) (Matsunaga 등, Chem. Pharm. Bull., 38, 3480, 1990) 및 HRA(난소암세포) (Kikuchi 등, Anticancer Drugs. England, 2, 63, 1991) 등 여러 가지의 암세포에 대한 증식억제 효과를 나타내는 것으로 보고되었다. 또한 난소암세포을 이식한 생체내 시험에서 항암제인 시스플라틴과 병용투여했을 때나 단독투여했을 때 독성이나 부작용이 거의 없는 것으로 알려져 있으며(Tode 등, J. Cancer Res, Clin. Oncol., 120, 24, 1993), 난소암 발생억제와 생존기간 연장효과가 시스플라틴과 유사하였다(Kikuchi 등, Anticancer Drugs, England, 2, 63, 1991). Several studies have been published that the ginsenoside Rh2 among the 30 types of ginseng saponins exhibits anticancer effects. For example, the ginsenoside Rh2 induces redifferentiation of F9 teratocarcinoma (teratocarcinoma cells) (Lee et al., Proc. 6th Intl. Ginseng symp., 127, 1993), and Morris liver cancer cells (Odashiam et al., Europ. J. Cancer). , 15, 885, 1979) and B16 melanoma (melanoma cells), MK-1 (gastric cancer cells) (Matsunaga et al., Chem. Pharm. Bull., 38, 3480, 1990) and HRA (ovarian cancer cells) (Kikuchi et al., Anticancer Drugs. England, 2, 63, 1991) have been reported to exhibit antiproliferative effects on various cancer cells. Also, it is known that there is almost no toxicity or side effects when administered in combination with the anticancer drug cisplatin or when administered alone in an in vivo test in which ovarian cancer cells are transplanted (Tode et al., J. Cancer Res, Clin. Oncol., 120, 24, 1993). , The effects of ovarian cancer suppression and survival time extension were similar to those of cisplatin (Kikuchi et al., Anticancer Drugs, England, 2, 63, 1991).
그러나, 진세노사이드 Rh2는 그 항암 효과가 현저하지 못하여 단독으로 암치료에 사용할 때에 암 치료효과가 미비하다는 문제점을 갖고 있다. 더구나 진세노사이드 Rh2가 백삼에는 존재하지 않으며(Kitagawa 등, 일본약학잡지, 103, 612, 1983), 홍삼에는 0.001%, 산삼에는 0.004%으로 극미량만 함유되어 있어 진세노사이드 Rh2를 대량으로 섭취하여 부족한 항암 효과를 높이는 것에도 한계가 있다.However, ginsenoside Rh2 has a problem in that its anticancer effect is not remarkable, and when used alone for cancer treatment, the cancer treatment effect is insufficient. Moreover, ginsenoside Rh2 does not exist in white ginseng (Kitagawa et al., Japanese Pharmacopoeia, 103, 612, 1983), red ginseng contains only a very trace amount of 0.001% and wild ginseng 0.004%. There is also a limit to enhancing the insufficient anticancer effect.
이에, 본 발명자들은 부작용이 없는 천연물 유래 항암제를 개발하기 위해 노력한 결과, 진세노사이드 Rh2 및 진세노사이드 Rg5의 혼합물이 진세노사이드 Rh2, 진세노사이드 Rg5 단독뿐만 아니라, 간암에서 가장 많이 사용되는 표적 치료제인 소라페닙(sorafenib)보다 우수한 항암 효과를 나타내므로, 간암 예방 및 치료용 약학적 조성물로 유용하게 사용될 수 있음을 밝힘으로써, 본 발명을 완성하였다.Accordingly, as a result of the present inventors' efforts to develop a natural anticancer agent without side effects, a mixture of ginsenoside Rh2 and ginsenoside Rg5 is the most used target in liver cancer, as well as ginsenoside Rh2 and ginsenoside Rg5 alone. The present invention was completed by revealing that it can be usefully used as a pharmaceutical composition for the prevention and treatment of liver cancer because it exhibits a superior anticancer effect than the therapeutic agent sorafenib.
본 발명의 목적은 진세노사이드(Ginsenoside) Rh2 및 진세노사이드 Rg5의 혼합물, 또는 이들의 약학적으로 허용가능한 염을 유효성분으로 함유하는 간암 예방 및 치료용 약학적 조성물을 제공하기 위한 것이다.It is an object of the present invention to provide a pharmaceutical composition for preventing and treating liver cancer containing a mixture of ginsenoside Rh2 and ginsenoside Rg5, or a pharmaceutically acceptable salt thereof, as an active ingredient.
상기 목적을 달성하기 위하여, 본 발명은 진세노사이드(Ginsenoside) Rh2 및 진세노사이드 Rg5의 혼합물, 또는 이들의 약학적으로 허용가능한 염을 유효성분으로 함유하는 간암 예방 및 치료용 약학적 조성물을 제공한다.In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing and treating liver cancer containing a mixture of ginsenoside Rh2 and ginsenoside Rg5, or a pharmaceutically acceptable salt thereof, as an active ingredient. do.
또한, 본 발명은 진세노사이드 Rh2 및 진세노사이드 Rg5의 혼합물, 또는 이들의 약학적으로 허용가능한 염을 유효성분으로 함유하는 간암 예방 및 개선용 건강식품용 조성물을 제공한다.In addition, the present invention provides a composition for health food for preventing and improving liver cancer containing a mixture of ginsenoside Rh2 and ginsenoside Rg5, or a pharmaceutically acceptable salt thereof, as an active ingredient.
본 발명의 진세노사이드(Ginsenoside) Rh2 및 진세노사이드 Rg5 혼합물은 진세노사이드 Rh2, 진세노사이드 Rg5 단독으로 처리한 군과 비교하여 간암세포에 대한 현저한 세포독성을 나타내고, 간암세포 이종 이식 동물모델에서 간암 표적 치료제인 소라페닙(sorafenib)보다 우수한 항암 효과를 나타내므로, 인체에 안전하고 부작용이 적은 간암 예방 및 치료용 약학적 조성물의 유효성분으로 유용하게 사용될 수 있다. The ginsenoside Rh2 and ginsenoside Rg5 mixture of the present invention exhibits significant cytotoxicity against liver cancer cells compared to the group treated with ginsenoside Rh2 and ginsenoside Rg5 alone, and hepatocellular xenograft animal model Since it exhibits a superior anticancer effect than sorafenib, a liver cancer-targeted therapeutic agent, it can be usefully used as an active ingredient in a pharmaceutical composition for preventing and treating liver cancer that is safe for the human body and has fewer side effects.
도 1은 이종이식 마우스 모델(xenograft mouse model)에서 진세노사이드(Ginsenoside) Rh2 및 진세노사이드 Rg5의 항암 효과를 확인한 도이다.
도 2는 H&E staining 염색을 통한 조직학적 분석 결과를 나타낸 도이다.
도 3은 진세노사이드 Rh2 및 진세노사이드 Rg5 처리시 괴사 마커인 c-PARP 발현 변화를 웨스턴 블랏을 통한 확인한 결과를 나타낸 도이다:
con: 무처리 대조군;
Rh2: 진세노사이드 Rh2 단독 처리군;
Rg5: 진세노사이드 Rg5 단독 처리군;
Combi: 진세노사이드 Rh2 및 진세노사이드 Rg5 혼합물 처리군; 및
S: 소라페닙 단독 처리군.1 is a diagram confirming the anticancer effect of ginsenoside Rh2 and ginsenoside Rg5 in a xenograft mouse model.
2 is a view showing the histological analysis results through H&E staining staining.
3 is a diagram showing the results of confirming the change in the expression of c-PARP, a necrosis marker, through western blot during treatment with ginsenoside Rh2 and ginsenoside Rg5:
con: untreated control;
Rh2: ginsenoside Rh2 alone treatment group;
Rg5: ginsenoside Rg5 alone treatment group;
Combi: ginsenoside Rh2 and ginsenoside Rg5 mixture treatment group; and
S: Sorafenib alone treatment group.
이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
본 발명은 진세노사이드(Ginsenoside) Rh2 및 진세노사이드 Rg5의 혼합물, 또는 이들의 약학적으로 허용가능한 염을 유효성분으로 함유하는 암 예방 및 치료용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for preventing and treating cancer comprising a mixture of ginsenoside Rh2 and ginsenoside Rg5, or a pharmaceutically acceptable salt thereof, as an active ingredient.
상기 진세노사이드는 인삼, 수삼, 백삼 및 홍삼으로 구성된 군으로부터 선택된 어느 하나에서 분리된 것 또는 인공적으로 합성된 어느 것을 사용하여도 무방하나 인체에 안전하고 부작용이 적은 인삼 등에서 분리된 것을 이용하는 것이 보다 바람직하다.As the ginsenoside, one isolated from any one selected from the group consisting of ginseng, fresh ginseng, white ginseng and red ginseng or artificially synthesized may be used. desirable.
상기 진세노사이드 Rh2는 하기 [화학식 1]로 표시되는 것이 바람직하고,The ginsenoside Rh2 is preferably represented by the following [Formula 1],
[화학식 1][Formula 1]
상기 진세노사이드 Rg5는 하기 [화학식 2]로 표시되는 것이 바람직하나 이에 한정되지 않는다:The ginsenoside Rg5 is preferably represented by the following [Formula 2], but is not limited thereto:
[화학식 2][Formula 2]
상기 혼합물은 간세포암종(Hepatocellular carcinoma)에 우수한 항암 효과를 가지기 위하여, 진세노사이드 Rh2 및 진세노사이드 Rg5를 각각 4:1 ~ 1:4 중량비, 바람직하게는 2:1 내지 1:2 중량비, 가장 바람직하게는 2:3 중량비로 혼합되어야 한다.The mixture contains ginsenoside Rh2 and ginsenoside Rg5 in a weight ratio of 4:1 to 1:4, preferably 2:1 to 1:2 by weight, most in order to have an excellent anticancer effect on hepatocellular carcinoma. Preferably, it should be mixed in a 2:3 weight ratio.
또한, 상기 혼합물은 간암, 위암, 췌장암, 대장암, 자궁경부암, 유방암, 폐암, 전립선암, 난소암, 신장암, 피부암 및 갑상선암, 특히 간세포암종에 암세포 괴사(necrosis)를 통한 우수한 항암 효과를 나타낸다.In addition, the mixture shows an excellent anticancer effect through cancer cell necrosis in liver cancer, stomach cancer, pancreatic cancer, colorectal cancer, cervical cancer, breast cancer, lung cancer, prostate cancer, ovarian cancer, kidney cancer, skin cancer and thyroid cancer, especially hepatocellular carcinoma .
본 발명의 구체적인 실시예에서, 본 발명자들은 진세노사이드 Rh2와 Rg5의 암세포 사멸 효과를 간세포암종 세포주를 이용하여 확인한 결과, 진세노사이드 Rh2와 Rg5를 2:3 중량비로 혼합한 혼합물이 진세노사이드 Rh2, 진세노사이드 Rg5 단독으로 처리한 군과 비교하여 현저한 간암세포에 대한 세포독성을 나타냄을 확인하였다.In a specific embodiment of the present invention, the present inventors confirmed the cancer cell killing effect of ginsenosides Rh2 and Rg5 using a hepatocellular carcinoma cell line. As a result, a mixture of ginsenosides Rh2 and Rg5 in a 2:3 weight ratio is ginsenoside. It was confirmed that Rh2 and ginsenoside Rg5 showed significant cytotoxicity against hepatocellular carcinoma compared to the group treated alone.
또한, 본 발명자들은 간세포암종 이종이식 마우스 모델을 통해 항암 효과를 확인한 결과, 양성대조군인 소라페닙(sorafenib)과 비교하여 진세노사이드 Rh2와 Rg5를 2:3 중량비로 혼합한 혼합물이 우수한 항암 효과를 나타내는 것을 확인하였다(도 1 참조).In addition, the present inventors confirmed the anticancer effect through a hepatocellular carcinoma xenograft mouse model. As a result, a mixture of ginsenosides Rh2 and Rg5 in a 2:3 weight ratio showed excellent anticancer effect compared to sorafenib, a positive control. It was confirmed that it was shown (see FIG. 1).
아울러, 본 발명자들은 본 발명의 혼합물을 처리한 종양의 조직학적 분석 및 괴사 마커인 c-PARP 발현 분석을 수행한 결과, 본 발명의 혼합물은 진세노사이드 Rh2, 진세노사이드 Rg5 단독으로 처리한 군뿐만 아니라, 소라페닙과 비교하여 현저한 항암 효과를 나타냄을 확인하였다(도 2 및 도 3 참조).In addition, the present inventors performed histological analysis of tumors treated with the mixture of the present invention and c-PARP expression analysis, a necrosis marker, as a result, the mixture of the present invention was treated with ginsenoside Rh2, ginsenoside Rg5 alone In addition, it was confirmed that it exhibits a significant anticancer effect compared to sorafenib (see FIGS. 2 and 3).
따라서, 본 발명의 진세노사이드 Rh2 및 진세노사이드 Rg5 혼합물은 진세노사이드 Rh2, 진세노사이드 Rg5 단독으로 처리한 군과 비교하여 현저한 간암세포에 대한 세포독성을 나타내고, 간암세포 이종 이식 동물모델에서 간암 표적 치료제인 소라페닙(sorafenib)보다 우수한 항암 효과를 나타내므로, 인체에 안전하고 부작용이 적은 간암 예방 및 치료용 약학적 조성물의 유효성분으로 유용하게 사용될 수 있다. Therefore, the ginsenoside Rh2 and ginsenoside Rg5 mixture of the present invention exhibits significant cytotoxicity to liver cancer cells compared to the group treated with ginsenoside Rh2 and ginsenoside Rg5 alone, and in the liver cancer cell xenograft animal model Since it exhibits a superior anticancer effect than sorafenib, a target treatment for liver cancer, it can be usefully used as an active ingredient in a pharmaceutical composition for preventing and treating liver cancer that is safe for the human body and has fewer side effects.
한편, 본 발명의 진세노사이드 Rh2 및 진세노사이드 Rg5는 이들의 약학적으로 허용 가능한 염의 형태로 사용할 수 있으며, 염으로는 약학적으로 허용가능한 알칼리 부가염이 유용하다. '약학적으로 허용가능한 염'이란 표현은 처리 대상에 비교적 비독성이고 무해한 유효작용을 갖는 농도로서 이 염에 기인한 부작용이 화학식 1 또는 화학식 2의 염기 화합물의 이로운 효능을 떨어뜨리지 않는 화학식 1 또는 화학식 2의 염기 화합물의 어떠한 유기 또는 무기 부가염을 의미한다. 이들 염은 알칼리 금속염(나트륨염, 칼륨염 등) 및 알칼리 토금속염(칼슘염, 마그네슘염 등) 등을 포함한다. 예를 들면, 알루미늄, 알기닌, 벤자틴, 칼슘, 콜린, 디에틸아민, 디올아민, 글라이신, 라이신, 마그네슘, 메글루민, 올아민, 칼륨, 나트륨, 트로메타민, 아연염 등이 포함될 수 있다.On the other hand, ginsenoside Rh2 and ginsenoside Rg5 of the present invention may be used in the form of their pharmaceutically acceptable salts, and pharmaceutically acceptable alkali addition salts are useful as salts. The expression 'pharmaceutically acceptable salt' refers to a concentration having an effective action that is relatively non-toxic and harmless to the subject to be treated, and the side effects caused by the salt do not reduce the beneficial efficacy of the basic compound of Formula 1 or
또한, 본 발명의 진세노사이드 Rh2 및 진세노사이드 Rg5는 약학적으로 허용되는 염뿐만 아니라, 통상의 방법에 의해 제조될 수 있는 모든 염, 이성질체, 수화물 및 용매화물을 모두 포함한다.In addition, ginsenoside Rh2 and ginsenoside Rg5 of the present invention include all salts, isomers, hydrates and solvates that can be prepared by conventional methods as well as pharmaceutically acceptable salts.
본 발명에 따른 부가염은 통상의 방법으로 제조할 수 있으며, 예를 들면 화학식 1 또는 화학식 2의 화합물을 수혼화성 유기용매, 예를 들면 아세톤, 메탄올, 에탄올, 또는 아세토니트릴 등에 녹이고 과량의 염기를 가한 후 침전시키거나 결정화시켜서 제조할 수 있다. 이어서 이 혼합물에서 용매를 증발시킨 후 건조시켜서 부가염을 얻거나 또는 석출된 염을 흡인 여과시켜 제조할 수 있다.The addition salt according to the present invention can be prepared by a conventional method, for example, by dissolving the compound of Formula 1 or
본 발명의 조성물을 의약품으로 사용하는 경우, 상기 진세노사이드 Rh2 및 진세노사이드 Rg5의 혼합물 또는, 이들의 약학적으로 허용가능한 염을 유효성분으로 함유하는 약학적 조성물은 임상투여 시에 다양한 하기의 경구 또는 비경구 투여 형태로 제제화되어 투여될 수 있으나, 이에 한정되는 것은 아니다.When the composition of the present invention is used as a pharmaceutical, a pharmaceutical composition containing a mixture of the ginsenoside Rh2 and ginsenoside Rg5 or a pharmaceutically acceptable salt thereof as an active ingredient may be administered in various It may be formulated and administered in an oral or parenteral dosage form, but is not limited thereto.
경구 투여용 제형으로는 예를 들면 정제, 환제, 경/연질 캅셀제, 주사제, 액제, 현탁제, 시럽제, 과립제, 엘릭시르제 등이 있는데, 이들 제형은 유효성분 이외에 희석제(예: 락토즈, 덱스트로즈, 수크로즈, 만니톨, 솔비톨, 셀룰로즈 및/ 또는 글리신), 활택제(예: 실리카, 탈크, 스테아르산 및 그의 마그네슘 또는 칼슘염 및/또는 폴리에틸렌 글리콜)를 함유하고 있다. 정제는 또한 마그네슘 알루미늄 실리케이트, 전분 페이스트, 젤라틴, 메틸셀룰로즈, 나트륨 카복시메틸셀룰로즈 및/또는 폴리비닐피롤리딘과 같은 결합제를 함유할 수 있으며, 경우에 따라 전분, 한천, 알긴산 또는 그의 나트륨 염과 같은 붕해제 또는 비등 혼합물 및/또는 흡수제, 착색제, 향미제, 및 감미제를 함유할 수 있다.Formulations for oral administration include, for example, tablets, pills, hard/soft capsules, injections, solutions, suspensions, syrups, granules, elixirs, and the like. rose, sucrose, mannitol, sorbitol, cellulose and/or glycine), lubricants (eg silica, talc, stearic acid and its magnesium or calcium salts and/or polyethylene glycol). Tablets may also contain binders such as magnesium aluminum silicate, starch paste, gelatin, methylcellulose, sodium carboxymethylcellulose and/or polyvinylpyrrolidine, optionally starch, agar, alginic acid or its sodium salt. disintegrants or effervescent mixtures and/or absorbents, colorants, flavoring agents, and sweetening agents.
상기 약학적 조성물은 비경구 투여할 수 있으며, 비경구 투여는 피하주사, 정맥주사, 근육 내 주사 또는 흉부내 주사를 주입하는 방법에 의한다.The pharmaceutical composition may be administered parenterally, and parenteral administration is performed by subcutaneous injection, intravenous injection, intramuscular injection or intrathoracic injection.
이때, 비경구 투여용 제형으로 제제화하기 위하여 상기 진세노사이드 Rh2 및 진세노사이드 Rg5의 혼합물 또는, 이들의 약학적으로 허용가능한 염을 안정제 또는 완충제와 함께 물에 혼합하여 용액 또는 현탁액으로 제조하고, 이를 앰플 또는 바이알 단위 투여형으로 제조할 수 있다. 상기 조성물은 멸균되고/되거나 방부제, 안정화제, 수화제 또는 유화 촉진제, 삼투압 조절을 위한 염 및/또는 완충제 등의 보조제, 및 기타 치료적으로 유용한 물질을 함유할 수 있으며, 통상적인 방법인 혼합, 과립화 또는 코팅 방법에 따라 제제화할 수 있다.At this time, in order to formulate a formulation for parenteral administration, a mixture of the ginsenoside Rh2 and ginsenoside Rg5 or a pharmaceutically acceptable salt thereof is mixed in water with a stabilizer or buffer to prepare a solution or suspension, It can be prepared in ampoules or vial unit dosage form. The composition may be sterilized and/or contain adjuvants such as preservatives, stabilizers, wetting agents or emulsification accelerators, salts and/or buffers for regulating osmotic pressure, and other therapeutically useful substances, and mixing, granulation, in a conventional manner. It can be formulated according to the method of formulation or coating.
또한, 본 발명의 화합물의 인체에 대한 투여량은 환자의 나이, 몸무게, 성별, 투여형태, 건강상태 및 질환 정도에 따라 달라질 수 있으며, 몸무게가 70 ㎏인 성인 환자를 기준으로 할 때, 일반적으로 0.1 ~ 1,000 ㎎/일이며, 구체적으로 1 ~ 500 ㎎/일, 보다 구체적으로 1 ~ 400mg, 1 ~ 300mg, 1 ~ 200mg, 1 ~ 100mg, 이며, 의사 또는 약사의 판단에 따라 일정시간 간격으로 1일 1회 내지 수회로 분할 투여할 수도 있다.In addition, the dosage of the compound of the present invention to the human body may vary depending on the patient's age, weight, sex, dosage form, health status and disease level, and is generally based on an adult patient weighing 70 kg. 0.1 to 1,000 mg/day, specifically 1 to 500 mg/day, more specifically 1 to 400 mg, 1 to 300 mg, 1 to 200 mg, 1 to 100 mg, and 1 at regular time intervals according to the judgment of a doctor or pharmacist It may be administered in divided doses from once a day to several times a day.
또한, 본 발명은 진세노사이드 Rh2 및 진세노사이드 Rg5의 혼합물, 또는 이들의 약학적으로 허용가능한 염을 유효성분으로 함유하는 암 예방 및 개선용 건강식품용 조성물을 제공한다.In addition, the present invention provides a composition for health food for preventing and improving cancer containing a mixture of ginsenoside Rh2 and ginsenoside Rg5, or a pharmaceutically acceptable salt thereof, as an active ingredient.
상기 진세노사이드 Rh2 및 진세노사이드 Rg5 혼합물은 인삼, 수삼, 백삼 및 홍삼으로 구성된 군으로부터 선택된 어느 하나에서 분리된 것이 바람직하고, 진세노사이드 Rh2는 하기 [화학식 1]로 표시되는 것이 바람직하고,The ginsenoside Rh2 and ginsenoside Rg5 mixture is preferably isolated from any one selected from the group consisting of ginseng, fresh ginseng, white ginseng and red ginseng, and ginsenoside Rh2 is preferably represented by the following [Formula 1],
[화학식 1][Formula 1]
상기 진세노사이드 Rg5는 하기 [화학식 2]로 표시되는 것이 바람직하나 이에 한정되지 않는다:The ginsenoside Rg5 is preferably represented by the following [Formula 2], but is not limited thereto:
[화학식 2][Formula 2]
본 발명의 진세노사이드 Rh2 및 진세노사이드 Rg5의 혼합물은 진세노사이드 Rh2, 진세노사이드 Rg5 단독으로 처리한 군과 비교하여 현저한 간암세포에 대한 세포독성을 나타내고, 간암세포 이종 이식 동물모델에서 간암 표적 치료제인 소라페닙(sorafenib)보다 우수한 항암 효과를 나타내므로, 인체에 안전하고 부작용이 적은 간암 예방 및 개선용 건강식품용 조성물의 유효성분으로 유용하게 사용될 수 있다. The mixture of ginsenoside Rh2 and ginsenoside Rg5 of the present invention exhibits significant cytotoxicity to liver cancer cells compared to the group treated with ginsenoside Rh2 and ginsenoside Rg5 alone, and liver cancer in liver cancer cell xenograft animal model Since it exhibits a superior anticancer effect than sorafenib, a target treatment, it can be usefully used as an active ingredient in a composition for health food for preventing and improving liver cancer, which is safe for the human body and has fewer side effects.
상기 식품의 종류에는 특별한 제한은 없다. 상기 물질을 첨가할 수 있는 식품의 예로는 드링크제, 육류, 소세지, 빵, 비스켓, 떡, 쵸코렛, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 알콜 음료 및 비타민 복합제 등이 있으며, 통상적인 의미에서의 건강 식품을 모두 포함한다.There is no particular limitation on the type of the food. Examples of foods to which the above substances can be added include drinks, meat, sausage, bread, biscuits, rice cakes, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, There are beverages, alcoholic beverages, and vitamin complexes, and includes all health foods in a conventional sense.
본 발명의 진세노사이드 Rh2 및 진세노사이드 Rg5의 혼합물 또는, 이들의 약학적으로 허용가능한 염은 식품에 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용될 수 있고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효 성분의 혼합양은 그의 사용 목적(예방 또는 개선용)에 따라 적합하게 결정될 수 있다. 일반적으로, 건강식품 중의 상기 진세노사이드 Rh2 및 진세노사이드 Rg5의 혼합물 또는, 이들의 약학적으로 허용가능한 염의 양은 전체 식품 중량의 0.01 내지 15 중량%로 가할 수 있으며, 건강 음료 조성물은 100 ㎖를 기준으로 0.02 내지 5 g, 바람직하게는 0.3 내지 1 g의 비율로 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 mixture of ginsenoside Rh2 and ginsenoside Rg5 of the present invention, or a pharmaceutically acceptable salt thereof, can be added to food as it is or used together with other foods or food ingredients, and can be appropriately used according to a conventional method. have. The mixing amount of the active ingredient may be appropriately determined depending on the purpose of its use (for prevention or improvement). In general, the amount of the mixture of the ginsenoside Rh2 and the ginsenoside Rg5 or a pharmaceutically acceptable salt thereof in the health food can be added in an amount of 0.01 to 15% by weight of the total food weight, and the health beverage composition is 100 ml It can be added in a ratio of 0.02 to 5 g, preferably 0.3 to 1 g, based on the standard. However, in the case of long-term ingestion for health and hygiene purposes or for health control, the above 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 above the above range.
본 발명의 건강 기능성 음료 조성물은 지시된 비율로 필수 성분으로서 상기 진세노사이드 Rh2 및 진세노사이드 Rg5의 혼합물 또는, 이들의 약학적으로 허용가능한 염을 함유하는 외에는 다른 성분에는 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 20g, 바람직하게는 약 5 내지 12 g이다.The health functional beverage composition of the present invention is not particularly limited in other ingredients except for containing a mixture of the ginsenoside Rh2 and ginsenoside Rg5 or a pharmaceutically acceptable salt thereof as an essential ingredient in the indicated ratio. It may contain various flavoring agents or natural carbohydrates as additional ingredients, such as beverages. 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 such as conventional sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those described above, natural flavoring agents (taumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.
상기 외에 본 발명의 진세노사이드 Rh2 및 진세노사이드 Rg5의 혼합물 또는, 이들의 약학적으로 허용가능한 염은 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. 그밖에 본 발명의 진세노사이드 Rh2 및 진세노사이드 Rg5의 혼합물 또는, 이들의 약학적으로 허용 가능한 염은 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 진세노사이드 Rh2 및 진세노사이드 Rg5의 혼합물 또는, 이들의 약학적으로 허용가능한 염 100 중량부 당 0 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, a mixture of ginsenoside Rh2 and ginsenoside Rg5 of the present invention, or a pharmaceutically acceptable salt thereof, is a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, Colorants and thickeners (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, etc. may contain. In addition, the mixture of ginsenoside Rh2 and ginsenoside Rg5 of the present invention, or a pharmaceutically acceptable salt thereof, may contain natural fruit juice and pulp for the production of fruit juice beverages and vegetable beverages. These components may be used independently or in combination. The proportion of these additives is not so important, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the mixture of the ginsenoside Rh2 and the ginsenoside Rg5 of the present invention, or a pharmaceutically acceptable salt thereof. .
이하, 본 발명을 실시예에 의하여 상세히 설명한다.Hereinafter, the present invention will be described in detail by way of Examples.
단, 하기 실시예는 본 발명을 구체적으로 예시하는 것이며, 본 발명의 내용이 실시예 및 제조예에 의해 한정되는 것은 아니다.However, the following Examples specifically illustrate the present invention, and the content of the present invention is not limited by the Examples and Preparation Examples.
<실시예 1> 진세노사이드(Ginsenoside) Rh2와 Rg5의 분리<Example 1> Separation of ginsenoside Rh2 and Rg5
본 발명에서 사용한 진세노사이드 Rh2와 Rg5는 앰보연구소(대한민국, 대전)에서 구입하여 사용하였다.Ginsenosides Rh2 and Rg5 used in the present invention were purchased from Ambo Research Institute (Daejeon, Korea) and used.
구체적으로, HPLC를 통한 purity 측정 결과, Rh2는 98.2%, Rg5는 93.47%로 나타났으며, 세포 실험하기에 이상 없는 수치임을 확인하였다. 한편, 각각의 진세노사이드는 DMSO에 녹여 50 mM의 stock solution으로 만들어 -20℃에 보관하며, 실험 직전에 계획한 농도에 맞게 희석하여 사용하였다.Specifically, as a result of purity measurement through HPLC, Rh2 was 98.2% and Rg5 was 93.47%, and it was confirmed that the values were not abnormal for cell experiments. On the other hand, each ginsenoside was dissolved in DMSO to make a 50 mM stock solution, stored at -20°C, and diluted according to the concentration planned just before the experiment.
<실시예 2> 진세노사이드 Rh2와 Rg5의 암세포 사멸 효과 확인<Example 2> Confirmation of cancer cell killing effect of ginsenosides Rh2 and Rg5
<2-1> 간암세포의 배양 및 계대<2-1> Culture and passage of liver cancer cells
간세포암종 세포주인 Hep3B은 일반 부착 세포 성장 배지에 넣고 37℃, 5% CO2 인큐베이터에서 배양시켰다. 상기 성장 배지는 DMEM high glucose를 사용하였고 100 mm plate의 ratio가 70%일 때 trypsin 1 ml 처리 후 20 ~ 30%를 다음 plate로 옮겨주었다.Hep3B, a hepatocellular carcinoma cell line, was placed in a normal adherent cell growth medium and cultured at 37° C., 5% CO 2 in an incubator. DMEM high glucose was used as the growth medium, and when the ratio of 100 mm plate was 70%, after treatment with 1 ml of trypsin, 20-30% was transferred to the next plate.
<2-2> 간암세포에 대한 세포 독성 확인<2-2> Confirmation of cytotoxicity to liver cancer cells
세포 생존율(cell viability)을 확인하기 위해 96-well cell culture plate(SPL Lifesciences)에 상기 <2-1>에서 배양한 Hep3B 세포를 배지 100 μL에 2×105 cells/well의 농도로 각 well에 분주하여 CO2 인큐베이터에서 24시간 배양하였다. 그런 다음, 진세노사이드 Rh2와 Rg5를 각각 1:0, 4:1, 3:2, 2:3, 1:4, 0:1 중량비로 혼합한 후, 30 μM 농도로 각각의 well에 처리하여 반응시킨 후, EZ-Cytox 시약 10 μL를 넣고 4시간 동안 배양한 후 microplate reader(Bio-Rad)를 이용하여 480 nm에서 흡광도를 측정하여 분석하였다.To check cell viability, the Hep3B cells cultured in <2-1> above were placed in a 96-well cell culture plate (SPL Lifesciences) in 100 μL of medium at a concentration of 2×10 5 cells/well in each well. It was aliquoted and cultured for 24 hours in a CO 2 incubator. Then, ginsenosides Rh2 and Rg5 were mixed in a weight ratio of 1:0, 4:1, 3:2, 2:3, 1:4, 0:1, respectively, and then treated at a concentration of 30 μM in each well. After the reaction, 10 μL of EZ-Cytox reagent was added, and after incubation for 4 hours, absorbance was measured at 480 nm using a microplate reader (Bio-Rad) and analyzed.
그 결과, 진세노사이드 Rh2와 Rg5를 혼합한 혼합물이 진세노사이드 Rh2, 진세노사이드 Rg5 단독으로 처리한 군과 비교하여 유의적인 항암 활성을 나타내고, 특히 진세노사이드 Rh2와 Rg5를 2:3 중량비로 혼합한 혼합물이 다른 혼합비율 군과 비교하여 현저히 우수한 항암 활성을 나타내는 것을 확인하였다.As a result, the mixture of ginsenosides Rh2 and Rg5 showed significant anticancer activity compared to the group treated with ginsenoside Rh2 and ginsenoside Rg5 alone. It was confirmed that the mixture mixed with this showed significantly superior anticancer activity compared to other mixing ratio groups.
<실시예 3> 이종이식 마우스 모델(xenograft mouse model)을 이용한 항암 효과 확인<Example 3> Confirmation of anticancer effect using a xenograft mouse model
6주령 수컷 누드 마우스(balb/c nude)에 식염수에 섞은 간세포암종 세포주 Hep3B 세포(1×107개)을 마트리겔(matrigel)과 1:1로 섞은 뒤, avertin으로 마취된 마우스의 오른쪽 등 피하에 26G needle을 끼운 주사기로 조심히 투여하였다.In 6-week-old male nude mice (balb/c nude), hepatocellular carcinoma cell line Hep3B cells (1×10 7 cells) mixed with saline were mixed 1:1 with matrigel, and then subcutaneously on the right back of a mouse anesthetized with avertin. Carefully administered with a syringe fitted with a 26G needle.
진세노사이드 물질 투여는 ip injection(복강 주사)을 통해 이루어졌으며 해당 농도는 세포독성 실험을 통해 정해진 농도(Rh2:Rg5=2:3)이다. 해당 진세노사이드 물질은 DMSO에 녹인 후 이를 다시 식염수(pbs)와 섞어 주고 500 ul volume으로 매회 복강 투여 처리하였다. 처리 농도는 100 μM이고 처리 시기는 일주일에 2회이며 일정한 날과 시간에 처리하는 것으로 마우스의 스트레스를 최소화하였고, 총 8주간 처리하였다. 또한, 상기 동일한 조건으로 진세노사이드 Rh2, 진세노사이드 Rg5 단독, 및 양성대조군으로 소라페닙(sorafenib)을 이용하여 실험을 수행하였다.The ginsenoside substance was administered through ip injection (intraperitoneal injection), and the concentration was determined through a cytotoxicity test (Rh2:Rg5=2:3). The ginsenoside material was dissolved in DMSO, mixed with saline (pbs) again, and administered intraperitoneally at 500 ul volume each time. The treatment concentration was 100 μM, the treatment period was twice a week, and the stress of the mice was minimized by treatment on a fixed day and time, and treated for a total of 8 weeks. In addition, experiments were performed using ginsenoside Rh2, ginsenoside Rg5 alone, and sorafenib as a positive control under the same conditions.
그 결과, 도 1에 나타낸 바와 같이 8주간 투여가 진행되는 동안 Tumor 차이를 육안으로 관찰한 결과, 양성대조군인 소라페닙과 비교하여 진세노사이드 Rh2와 Rg5를 2:3 중량비로 혼합한 혼합물이 유의적인 항암 효과를 나타냄을 확인하였다(도 1).As a result, as shown in FIG. 1, as a result of visually observing the tumor difference during the 8-week administration, the mixture of ginsenosides Rh2 and Rg5 in a 2:3 weight ratio was significant compared to the positive control sorafenib. It was confirmed that it exhibits an anticancer effect (FIG. 1).
<실시예 4> H&E staining 염색을 통한 조직학적 분석<Example 4> Histological analysis through H&E staining staining
상기 <실시예 3>에서 8주간 진세노사이드 물질 및 소라페닙을 마우스에 처리한 후, 마우스를 희생시켜 종양을 적출한 후, 적출한 종양을 10% formaldehyde에 고정시킨 후 H&E staining을 수행하였다.In <Example 3>, mice were treated with ginsenoside substances and sorafenib for 8 weeks, the mice were sacrificed and tumors were excised, and then the extracted tumors were fixed in 10% formaldehyde, followed by H&E staining.
그런 다음, image j 프로그램을 이용했으며 전체 부분 중 괴사(necrosis) 부분을 범위로 계산하였고, 이를 그래프로 나타내었다.Then, the image j program was used and the necrosis part of the whole part was calculated as a range, and this was shown as a graph.
그 결과, 도 2에 나타낸 바와 같이, 진세노사이드 Rh2와 Rg5를 2:3 중량비로 혼합한 혼합물은 진세노사이드 Rh2, 진세노사이드 Rg5 단독으로 처리한 군과 비교하여 간세포암종에 대한 현저한 항암 효과를 나타낼 뿐 아니라, 양성대조군인 소라페닙과 비교해도 유의적인 항암효과를 나타냄을 확인하였다(도 2).As a result, as shown in Figure 2, a mixture of ginsenosides Rh2 and Rg5 in a 2:3 weight ratio had a significant anticancer effect on hepatocellular carcinoma compared to the group treated with ginsenosides Rh2 and Rg5 alone. It was confirmed that not only showed a significant anticancer effect, but also compared with the positive control, sorafenib (Fig. 2).
<실시예 5> 괴사 마커인 c-PARP 발현 확인<Example 5> Confirmation of expression of c-PARP, a marker of necrosis
상기 <실시예 4>와 동일한 방법으로 종양을 적출한 후, tumor에서 추출한 protein으로 western blot을 진행 하였다. House keeping gene으로 GAPDH를 선택했으며, necrosis factor로 잘 알려진 cleaved-PARP를 사용하였다.After the tumor was extracted in the same manner as in <Example 4>, western blot was performed with the protein extracted from the tumor. GAPDH was selected as the house keeping gene, and cleaved-PARP, which is well known as a necrosis factor, was used.
구체적으로 western blot은 종양 조직을 protein lysis buffer에 처리한 뒤, 이를 통해 얻은 단백질을 웨스턴 블럿을 하기 위해 정량을 한 뒤 SDS PAGE gel에 넣고 전기영동으로 이를 분자크기별로 분리시켜주었다. 이후 gel을 PVDF membrane으로 전기영동을 이용해 240 mA 2시간 동안 옮겨주고 이를 1차 항체를 4℃에서 Over night 시켜준다. 이후 1차 항체별로 발광 처리(HRP conjugated) 된 2차 항체를 상온에서 1시간 처리 한뒤 HRP 발광 처리 약물로 이를 암실에서 필름을 통해 발광 시켰다.Specifically, for western blot, the tumor tissue was treated with protein lysis buffer, and the protein obtained through this was quantified for western blotting, and then put into SDS PAGE gel and separated by molecular size by electrophoresis. After that, the gel is transferred to a PVDF membrane using electrophoresis at 240 mA for 2 hours, and the primary antibody is over night at 4°C. Thereafter, the secondary antibody luminescence-treated (HRP-conjugated) for each primary antibody was treated at room temperature for 1 hour and then luminescent with HRP luminescence-treated drug through the film in a dark room.
그 결과, 도 3에 나타낸 바와 같이 진세노사이드 Rh2와 Rg5를 2:3 중량비로 혼합한 혼합물은 진세노사이드 Rh2, 진세노사이드 Rg5 단독으로 처리한 군과 비교하여 cleaved-PARP가 높고 나타났으며, 소라페닙과 비교할때도 진세노사이드 Rh2와 Rg5를 2:3 중량비로 혼합한 혼합물에서 cleaved-PARP 발현이 높게 나타나는 것을 확인하였다(도 3). As a result, as shown in FIG. 3, the mixture of ginsenoside Rh2 and Rg5 in a 2:3 weight ratio showed high cleaved-PARP compared to the group treated with ginsenoside Rh2 and ginsenoside Rg5 alone. , it was confirmed that cleaved-PARP expression was high in a mixture of ginsenosides Rh2 and Rg5 in a 2:3 weight ratio even when compared with sorafenib ( FIG. 3 ).
따라서, 본 발명의 진세노사이드 Rh2와 Rg5를 2:3 중량비로 혼합한 혼합물은 진세노사이드 Rh2, 진세노사이드 Rg5 단독 처리군 뿐만 아니라, 양상대조군인 소라페닙보다 우수한 항암 효과를 나타냄을 확인하였다.Therefore, it was confirmed that the mixture of ginsenoside Rh2 and Rg5 of the present invention in a 2:3 weight ratio exhibited superior anticancer effect than sorafenib, a side control group, as well as the ginsenoside Rh2 and ginsenoside Rg5 alone treatment group. .
Claims (10)
A pharmaceutical composition for preventing and treating cancer comprising a mixture of ginsenoside Rh2 and ginsenoside Rg5, or a pharmaceutically acceptable salt thereof, as an active ingredient.
The pharmaceutical composition according to claim 1, wherein the ginsenoside is isolated from any one selected from the group consisting of ginseng, fresh ginseng, white ginseng and red ginseng.
[화학식 1]
The pharmaceutical composition according to claim 1, wherein the ginsenoside Rh2 is represented by the following [Formula 1]:
[Formula 1]
[화학식 2]
The pharmaceutical composition according to claim 1, wherein the ginsenoside Rg5 is represented by the following [Formula 2]:
[Formula 2]
The pharmaceutical composition according to claim 1, wherein the mixture is a mixture of ginsenoside Rh2 and ginsenoside Rg5 in a weight ratio of 4:1 to 1:4, respectively.
The pharmaceutical composition according to claim 1, wherein the mixture is a mixture of ginsenoside Rh2 and ginsenoside Rg5 in a weight ratio of 2:3, respectively.
According to claim 1, wherein the cancer is liver cancer, stomach cancer, pancreatic cancer, colorectal cancer, cervical cancer, breast cancer, lung cancer, prostate cancer, ovarian cancer, kidney cancer, characterized in that any one selected from the group consisting of skin cancer and thyroid cancer pharmaceutical composition.
The pharmaceutical composition according to claim 1, wherein the cancer is hepatocellular carcinoma.
The pharmaceutical composition according to claim 1, wherein the mixture causes necrosis of hepatocellular carcinoma.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020210049598A KR20220143281A (en) | 2021-04-16 | 2021-04-16 | Composition for preventing and treating liver cancer containing ginsenoside Rh2 and ginsenoside Rg5 as active ingredients |
| KR1020230124305A KR20230136105A (en) | 2021-04-16 | 2023-09-18 | Composition for preventing and treating liver cancer containing ginsenoside Rh2 and ginsenoside Rg5 as active ingredients |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020210049598A KR20220143281A (en) | 2021-04-16 | 2021-04-16 | Composition for preventing and treating liver cancer containing ginsenoside Rh2 and ginsenoside Rg5 as active ingredients |
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| KR1020230124305A Division KR20230136105A (en) | 2021-04-16 | 2023-09-18 | Composition for preventing and treating liver cancer containing ginsenoside Rh2 and ginsenoside Rg5 as active ingredients |
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| KR20220143281A true KR20220143281A (en) | 2022-10-25 |
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| Application Number | Title | Priority Date | Filing Date |
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| KR1020210049598A KR20220143281A (en) | 2021-04-16 | 2021-04-16 | Composition for preventing and treating liver cancer containing ginsenoside Rh2 and ginsenoside Rg5 as active ingredients |
| KR1020230124305A KR20230136105A (en) | 2021-04-16 | 2023-09-18 | Composition for preventing and treating liver cancer containing ginsenoside Rh2 and ginsenoside Rg5 as active ingredients |
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| KR (2) | KR20220143281A (en) |
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