KR20200133968A - Composition comprising extracts of saw palmetto and rhodiola sachalinensis for preventing or treating benign prostatic hyperplasia - Google Patents
Composition comprising extracts of saw palmetto and rhodiola sachalinensis for preventing or treating benign prostatic hyperplasia Download PDFInfo
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- KR20200133968A KR20200133968A KR1020190059318A KR20190059318A KR20200133968A KR 20200133968 A KR20200133968 A KR 20200133968A KR 1020190059318 A KR1020190059318 A KR 1020190059318A KR 20190059318 A KR20190059318 A KR 20190059318A KR 20200133968 A KR20200133968 A KR 20200133968A
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- extract
- saw palmetto
- prostatic hyperplasia
- honggyeongcheon
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Abstract
Description
본 발명은 홍경천 추출물 또는 홍경천과 쏘팔메토 복합추출물의 전립선비대증 예방, 개선 또는 치료 용도에 관한 것이다.The present invention relates to the use of honggyeongcheon extract or honggyeongcheon and saw palmetto complex extract to prevent, improve or treat prostatic hypertrophy.
전립선비대증(Benign prostatic hyperplasia, BPH)은 그에 대한 임상적 정의가 규정된 후 전 세계적으로 40대 이후의 남성에게서 매우 흔하게 나타나는 질환으로 알려져 왔다. BPH의 증상으로는 소변 장해인 하부요로증상(lower urinary tract symptoms, LUTS)가 대표적인데 급뇨(urgency), 빈뇨(frequency), 약한 배뇨(weak stream), 야뇨증(nocturia)과 불충분한 배뇨로 인한 잔료감(incomplete emptying of urine) 등의 증상이 나타난다. BPH는 요도 주위를 둘러싸고 있는 전립선 상피 세포와 기질 세포의 과다 증식으로 인해 발생하는 것으로 알려져 있다. 이러한 원인은 나이가 들면서 테스토스테론이 감소하게 되는데 5α-환원효소(5-AR)에 의해 테스토스테론이 전환되어 생성되는 디하이드로테스토스테론(DHT)이 전립선 세포를 자극하여 이상 생장하는 것으로 알려져 있다. 전립선비대증으로 인한 가장 큰 불편함은 야간에 수면을 충분하게 유지할 수 없어 피로를 해소하기 어렵거나, 야외 활동 시 잦은 배뇨증상으로 인해 심한 심리적 스트레스를 받는 것이다.Benign prostatic hyperplasia (BPH) has been known as a very common disease in men after their 40s around the world after the clinical definition for it was established. Symptoms of BPH include lower urinary tract symptoms (LUTS), which are urinary disorders, including urgency, frequency, weak stream, nocturia, and cup due to insufficient urination. Symptoms such as incomplete emptying of urine appear. BPH is known to be caused by overproliferation of prostate epithelial cells and stromal cells surrounding the urethra. The cause of this is that testosterone decreases with age. Dihydrotestosterone (DHT), which is produced by conversion of testosterone by 5α-reductase (5-AR), is known to stimulate prostate cells to grow abnormally. The biggest discomfort caused by an enlarged prostate is that it is difficult to relieve fatigue due to the inability to maintain sufficient sleep at night, or to receive severe psychological stress due to frequent urination symptoms during outdoor activities.
전립선비대증의 개선을 위해 5-AR 저해제 혹은 α-adrenergic receptor blockers 등이 제약의 형태로 처방되어 왔다. 몇몇 연구들에서 DHT와 5-AR의 발현을 조절하여 전립선비대증을 예방하거나 치료하기 위해 토마토와 검정 복분자 추출물과 같은 식물 추출물들을 사용하였다. 이 중 소팔메토 열매추출물(Extract of Saw palmetto berry, SP)이 대표적인 천연물 소재로 전 세계적으로 전립선비대증 개선을 위한 건강보조식품으로 널리 이용되고 있다[1]. 국내에서도 전립선 건강에 유용한 건강기능식품 고시형 원료로 인정받아 30여 업체가 관련제품을 생산, 판매하고 있다. 쏘팔메토에 대한 초기의 임상 연구에서 쏘팔메토가 전립선비대증으로 인해 발생하는 하부요로증상에 효과적이라고 알려져 왔다[2]. 그러나, Avins와 Bent[3]는 그들의 연구를 통해 쏘팔메토가 전립선비대증을 개선한다는 어떠한 과학적 근거를 발견하지 못하였다고 보고한 이후, 쏘팔메토의 전립선비대증에 대한 효능 및 독성에 대한 문제가 지속적으로 대두되어 왔다[4, 5]. 특히 쏘팔메토 추출물은 널리 사용되고 있는 식이 보충제임에도 불구하고, 잠재적인 독성이나 부작용에 관한 연구가 대부분 1년 미만의 기간 동안 시행됨에 따라 다양한 인구 집단과 연구 기간을 기반으로 한 보다 명확한 독성연구의 필요성이 제기되었다[6]. 최근 Avins 등[7]은 쏘팔메토를 일일 최대 960 mg의 농도로 18개월간 섭취하였을 때에도 심각한 독성은 나타나지 않았다고 보고하였으나, 여전히 처방 의약품이나 다른 식이 보충제간의 상호작용에 관한 분석뿐만 아니라 무증상이 배제된 쏘팔메토 추출물을 장기간 섭취 시 나타날 수 있는 부작용에 대한 연구가 필요하다고 언급하였다. 국내에서도 2015년 대한배뇨장애요실금학회를 통해 전립선비대증 개선에 관한 쏘팔메토 추출물의 효능에 대한 문제가 제기된 이후[8], 건강기능식품에 관한 법률에 따라 2017년 식품의약안전처에서 건강기능식품 재평가 계획을 발표하였다. 이와 같이 국내외적으로 쏘팔메토에 대한 여러 부정적인 연구결과가 보고되고 있음에도 불구하고 쏘팔메토 추출물은 여전히 하부요로 증상을 갖는 남성들을 위한 해결책으로서 잘 팔리고 있기 때문에 쏘팔메토 추출물의 세포독성 및 전립선 건강 개선 효과 유무에 대한 과학적인 근거뿐만 아니라, 쏘팔메토 추출물 외에 안전성이 높은 천연물 유래 고기능성 전립선 건강 개선 관련 소재를 개발할 필요가 있다.To improve prostatic hyperplasia, 5-AR inhibitors or α-adrenergic receptor blockers have been prescribed in the form of pharmaceuticals. Several studies have used plant extracts such as tomato and black bokbunja extract to control the expression of DHT and 5-AR to prevent or treat prostatic hyperplasia. Among them, the extract of saw palmetto berry (SP) is a representative natural material and is widely used as a health supplement for improving prostatic hyperplasia [1] . In Korea, more than 30 companies are producing and selling related products as it has been recognized as a notified raw material for health functional food useful for prostate health. Early clinical studies on saw palmetto have shown that saw palmetto is effective for lower urinary tract symptoms caused by prostatic hyperplasia [2] . However, after Avins and Bent [3] reported that they did not find any scientific evidence that saw palmetto improves prostatic hyperplasia through their research, problems with the efficacy and toxicity of saw palmetto on prostatic hyperplasia have continued. Has emerged [4, 5] . In particular, although saw palmetto extract is a widely used dietary supplement, most studies on potential toxicity or side effects have been conducted for less than one year, so there is a need for more clear toxicity studies based on various population groups and study periods. Has been raised [6] . Recently, Avins et al. [7] reported that no serious toxicity was observed even when saw palmetto was ingested at a concentration of up to 960 mg per day for 18 months, but asymptomatic as well as analysis on the interaction between prescription drugs and other dietary supplements was still excluded. He mentioned that there is a need for research on side effects that may occur when taking saw palmetto extract for a long time. In Korea, since the issue of the efficacy of saw palmetto extract for improving prostatic hyperplasia was raised in 2015 through the Korean Society for Urinary Incontinence with Urination Disorders [8] , health functions were conducted by the Ministry of Food and Drug Safety in 2017 according to the Health Functional Food Act. Announced a food reevaluation plan. Despite the reports of negative research results on saw palmetto at home and abroad, saw palmetto extract is still sold well as a solution for men with lower urinary tract symptoms, so the cytotoxicity and prostate health of saw palmetto extract In addition to the scientific basis for the presence or absence of the improvement effect, there is a need to develop high-functional prostate health improvement-related materials derived from highly safe natural products in addition to saw palmetto extract.
한편 홍경천(Rhodiola sachalinensis)은 해발 2,000 m 이상의 고산지대에서 자라는 다년생식물로 그 뿌리를 잘 건조하여 대체의약품의 소재로 사용하고 있다. 홍경천에는 phenylpropanoids, flavonoids, tannins, 배당체들과 유기산들이 풍부하게 있다[9], 홍경천의 주요 성분으로는 salidroside, rosavins과 ρ-tyrosol 등이 있어 우울증, 피로감과 인지기능 장애 개선효과가 있고, 항산화, 항염증, 항암, 심혈관 보호 및 신경 보호 효과가 있다고 알려져 있다[10]. 현재 홍경천 추출물(Extracts of Rhodiola sachalinensis, RS)은 피로개선에 도움을 줄 수 있는 고시형 원료로, 다양한 제품들이 개발되고 있으나, 전립선 건강 개선에 관한 효능은 검증된 바가 없어 제품화 되지 못하고 있는 실정이다.On the other hand, Rhodiola sachalinensis is a perennial plant that grows in alpine regions over 2,000 m above sea level, and its roots are well dried and used as a material for alternative medicines. Honggyeongcheon is rich in phenylpropanoids, flavonoids, tannins, glycosides and organic acids [9] . The main ingredients of Honggyeongcheon include salidroside, rosavins and ρ-tyrosol, which are effective in improving depression, fatigue and cognitive dysfunction. It is known to have anti-inflammatory, anti-cancer, cardiovascular and neuroprotective effects [10] . Currently, extracts of Rhodiola sachalinensis (RS) is a noticeable raw material that can help improve fatigue, and various products are being developed, but the efficacy for improving prostate health has not been proven, so it has not been commercialized.
본 발명자들은 부작용이 적은 전립선비대증 치료제에 대해 연구하던 중 홍경천 추출물이 전립선비대증을 치료한다는 사실을 확인하였으며, 그 후 지속적인 연구를 통해 월등하게 우수한 전립선비대증 치료 효과를 나타내는 홍경천 추출물의 제조 조건을 확립하였다. 나아가 홍경천 추출물을 쏘팔메토 추출물과 혼합한 복합 추출물이 쏘팔메토 단독 추출물이 가지는 세포독성을 나타내지 않으면서 동시에 전립선비대증 치료 효과를 상승적으로 유도함을 확인하여 본 발명을 완성하였다.The inventors of the present invention confirmed that the extract of honggyeongcheon cures prostatic hyperplasia while researching the treatment for prostatic hyperplasia with less side effects, and after that, through continuous research, we established the manufacturing conditions for the extract of honggyeongcheon, which shows superior prostatic hypertrophy treatment effect. . Furthermore, the present invention was completed by confirming that the complex extract obtained by mixing the honggyeongcheon extract with the saw palmetto extract did not exhibit the cytotoxicity of the saw palmetto extract alone and at the same time synergistically induces the therapeutic effect of prostatic hyperplasia.
본 발명은 부작용 없이 전립선비대증을 치료할 수 있는 기술을 제공하는 것을 목적으로 한다.An object of the present invention is to provide a technology capable of treating an enlarged prostate without side effects.
그러나, 본 발명이 이루고자 하는 기술적 과제는 이상에서 언급한 과제에 제한되지 않으며, 언급되지 않은 또 다른 과제들은 아래의 기재로부터 당업자에게 명확하게 이해될 수 있을 것이다.However, the technical problem to be achieved by the present invention is not limited to the above-mentioned problems, and other problems that are not mentioned will be clearly understood by those skilled in the art from the following description.
상술한 과제를 해결하기 위하여, 본 발명은 홍경천(Rhodiola sachalinensis) 추출물을 유효성분으로 함유하는 전립선비대증의 예방 또는 치료용 약학적 조성물을 제공한다.In order to solve the above-described problems, the present invention provides a pharmaceutical composition for preventing or treating prostatic hyperplasia, containing an extract of Rhodiola sachalinensis as an active ingredient.
본 발명은 또한, 홍경천(Rhodiola sachalinensis) 추출물 및 쏘팔메토 추출물을 유효성분으로 함유하는 전립선비대증의 예방 또는 치료용 약학적 조성물을 제공한다.The present invention also provides a pharmaceutical composition for the prevention or treatment of prostatic hyperplasia, comprising honggyeongcheon ( Rhodiola sachalinensis ) extract and saw palmetto extract as active ingredients.
본 발명의 일 실시예에 따르면, 상기 홍경천 추출물은 홍경천 분말을 에탄올 용액에 침지한 후 초음파 추출하여 제조한 것일 수 있다.According to an embodiment of the present invention, the honggyeongcheon extract may be prepared by immersing the honggyeongcheon powder in an ethanol solution and then ultrasonically extracting.
본 발명의 일 실시예에 따르면, 상기 쏘팔메토 추출물은 쏘팔메토 열매 추출물일 수 있다.According to an embodiment of the present invention, the saw palmetto extract may be a saw palmetto fruit extract.
본 발명의 일 실시예에 따르면, 상기 홍경천 추출물 및 쏘팔메토 추출물은 1:2 내지 2:1의 중량비로 포함되는 것일 수 있다.According to an embodiment of the present invention, the honggyeongcheon extract and saw palmetto extract may be included in a weight ratio of 1:2 to 2:1.
본 발명은 또한, 홍경천(Rhodiola sachalinensis) 추출물 및 쏘팔메토 추출물을 유효성분으로 함유하는 전립선비대증의 예방 또는 개선용 건강기능식품 조성물을 제공한다.The present invention also provides a health functional food composition for preventing or improving prostatic hyperplasia, containing honggyeongcheon ( Rhodiola sachalinensis ) extract and saw palmetto extract as active ingredients.
이하, 본 발명을 보다 상세하게 설명한다.Hereinafter, the present invention will be described in more detail.
상술한 바와 같이, 소팔메토 추출물은 대표적인 천연물 소재로 전 세계적으로 전립선비대증 개선을 위한 건강보조식품으로 널리 이용되고 있으나, 쏘팔메토가 전립선비대증을 개선한다는 어떠한 과학적 근거를 발견하지 못하였다고 보고된 이후, 쏘팔메토의 전립선비대증에 대한 효능 및 독성에 대한 문제가 지속적으로 제기되고 있는 가운데, 쏘팔메토 추출물의 세포독성 및 전립선 건강 개선 효과 유무에 대한 과학적인 근거가 필요할 뿐만 아니라, 쏘팔메토 추출물 외에 안전성이 높은 천연물 유래 고기능성 전립선 건강 개선 관련 소재의 개발이 지속적으로 요구되고 있다.As described above, saw palmetto extract is a representative natural material and is widely used as a health supplement for improving prostatic hyperplasia worldwide, but it has been reported that no scientific evidence that saw palmetto improves prostatic hyperplasia has been found. Since then, while issues regarding the efficacy and toxicity of saw palmetto on prostatic hyperplasia have been continuously raised, scientific evidence for the presence or absence of the cytotoxic and prostate health improvement effect of saw palmetto extract is needed, as well as saw palmetto extract. In addition, development of materials related to high functional prostate health improvement derived from natural products with high safety is continuously required.
이에 본 발명자들은, 전립선비대증을 효과적으로 치료하면서 체내에 안전한 천연물 치료제를 탐색하던 중, 홍경천 단독 추출물이 정소세포 및 전립선 정상세포에는 독성을 나타내지 않으면서, 전립선비대증 세포만 특이적으로 사멸시킴으로써 전립선비대증을 예방 또는 치료하는 효과가 있는 것을 확인하고, 전립선비대증 치료 효과를 극대화 할 수 있는 홍경천 추출물의 제조 조건을 확립하였다.Therefore, the present inventors, while searching for a safe natural product therapeutic agent in the body while effectively treating prostatic hyperplasia, the extract of Hong Gyeong-cheon alone did not show toxicity to testicular cells and normal prostate cells, and specifically kills prostatic hyperplasia cells, thereby reducing prostatic hyperplasia. It was confirmed that there is a preventive or therapeutic effect, and the conditions for producing honggyeongcheon extract that can maximize the treatment effect of prostatic hyperplasia were established.
또한, 쏘팔메토 단독 추출물이 놀랍게도 전립선비대증 세포를 사멸시키는 효과가 크지 않으면서, 정소 세포 및 전립선 정상 세포에는 세포 독성이 있는 것을 확인하였다.In addition, it was confirmed that the extract of saw palmetto alone was surprisingly insignificant in killing prostatic hyperplasia cells, while having cytotoxicity to testis cells and normal prostate cells.
나아가, 전립선비대증 치료 효과가 미미한 농도의 쏘팔메토 추출물과 홍경천 추출물이 혼합된 복합 추출물이 각각의 단독 추출물 대비 상승된 전립선비대증 세포 사멸 효과를 나타내면서, 정상 세포에 대한 세포 독성은 현저하게 저하되는 것을 확인하고 본 발명을 완성하였다.Furthermore, it was found that the mixed extract of saw palmetto extract and honggyeongcheon extract at a concentration of insignificant treatment effect for prostatic hyperplasia showed an elevated prostatic hyperplasia cell killing effect compared to each single extract, while the cytotoxicity to normal cells was significantly reduced. And completed the present invention.
이에, 본 발명은 홍경천(Rhodiola sachalinensis) 추출물을 유효성분으로 함유하는 전립선비대증의 예방 또는 치료용 약학적 조성물을 제공한다.Accordingly, the present invention provides a pharmaceutical composition for the prevention or treatment of prostatic hyperplasia, comprising the extract of Rhodiola sachalinensis as an active ingredient.
또한, 본 발명은 홍경천(Rhodiola sachalinensis) 추출물 및 쏘팔메토 추출물을 유효성분으로 함유하는 전립선비대증의 예방 또는 치료용 약학적 조성물을 제공한다.In addition, the present invention provides a pharmaceutical composition for the prevention or treatment of prostatic hyperplasia, containing honggyeongcheon ( Rhodiola sachalinensis ) extract and saw palmetto extract as active ingredients.
본 발명에서 용어 “약학적 조성물”은 본 발명의 홍경천 및 쏘팔메토 추출물을 유효성분으로 포함하는 조성물에 희석제 또는 담체와 같은 다른 화학 성분들을 혼합한 혼합물을 의미한다.In the present invention, the term "pharmaceutical composition" refers to a mixture in which other chemical components such as a diluent or a carrier are mixed with a composition comprising the extract of Rhododendron and saw palmetto of the present invention as active ingredients.
본 발명에서 용어 “치료”는 이롭거나 바람직한 임상적 결과를 수득하기 위한 접근을 의미한다. 또한 치료를 받지 않았을 때 예상되는 생존율과 비교하여 생존율을 늘리는 것을 의미할 수도 있다. 본 발명에서 “치료”는 치료학적 치료 및 예방적 또는 예방조치 방법 모두를 가리킨다. 상기 치료들은 예방되는 장애뿐만 아니라 이미 발생한 장애에 있어서 요구되는 치료를 포함한다.In the present invention, the term "treatment" refers to an approach to obtain beneficial or desirable clinical results. It may also mean increasing the survival rate compared to the expected survival rate without treatment. In the present invention, "treatment" refers to both therapeutic treatment and prophylactic or preventative measures. Such treatments include the disorder to be prevented as well as the treatment required for a disorder that has already occurred.
본 발명에서 용어 “상승적인(synergistic)” 은 각 성분이 병용(조합) 투여될 때 발생되는 효과가, 단일 성분으로서 단독으로 투여될 때 발생되는 효과의 합 보다 더 큰 것을 의미한다 [Chou and Talalay, Adv. Enzyme. Regul., 22:27-55, 1984]. In the present invention, the term “synergistic” means that the effect generated when each ingredient is administered in combination (combination) is greater than the sum of the effects generated when administered alone as a single ingredient [Chou and Talalay , Adv. Enzyme. Regul., 22:27-55, 1984].
본 발명에서 용어 “홍경천”은 홍경천(Rhodiola sachalinensis) 뿌리를 건조한 것을 의미한다. 홍경천은 우울증, 피로감과 인지기능 장애 개선효과가 있고, 항산화, 항염증, 항암, 심혈관 보호 및 신경 보호 효과가 있다고 알려져 있다.In the present invention, the term "honggyeongcheon" means that the roots of honggyeongcheon ( Rhodiola sachalinensis ) are dried. Hong Gyeong-cheon is known to be effective in improving depression, fatigue and cognitive dysfunction, as well as antioxidant, anti-inflammatory, anti-cancer, cardiovascular and neuroprotective effects.
본 발명에서 용어 “쏘팔메토(Saw Palmetto)”는 쏘팔메토(Serenoa repens)의 열매를 건조한 것을 의미한다. In the present invention, the term “Saw Palmetto” means dried fruits of Saw Palmetto ( Serenoa repens ).
본 발명의 홍경천 및 쏘팔메토는 상업적으로 판매되는 것을 구입하여 사용하거나, 자연에서 직접 채취 또는 재배한 것을 사용할 수 있다.The honggyeongcheon and saw palmetto of the present invention may be purchased and used commercially, or may be directly harvested or cultivated in nature.
본 발명의 구체적인 일 실시예에서는 홍경천 분말을 에탄올 용액에 침지한 후 초음파로 추출한 추출물을 사용하였다.In a specific embodiment of the present invention, an extract extracted by ultrasonication after immersing honggyeongcheon powder in an ethanol solution was used.
본 발명에서의 용어, “추출물(extract)”은, 목적하는 물질을 다양한 용매에 침지한 다음, 상온, 저온 또는 가온 상태에서 일정시간 동안 추출하여 수득한 액상성분, 상기 액상성분으로부터 용매를 제거하여 수득한 고형분 등의 결과물을 의미한다. 뿐만 아니라, 상기 결과물에 더하여, 상기 결과물의 희석액, 이들의 농축액, 이들의 조정제물, 정제물 등을 모두 포함하는 것으로 포괄적으로 해석될 수 있다.In the present invention, the term "extract" refers to a liquid component obtained by immersing a target substance in various solvents and then extracting it at room temperature, low temperature, or warm state for a certain period of time, and removing the solvent from the liquid component. It means the result of obtained solid content etc. In addition, in addition to the resulting product, it can be comprehensively interpreted as including all of the diluted solution of the resultant, the concentrate thereof, the preparation thereof, and the purified product.
본 발명의 구체적인 일 실시예에서는 홍경천과 쏘팔메토 추출물을 각각 1:2, 1:1, 2:1의 중량비로 혼합한 복합 추출물을 전립선비대증 세포에 처리하여 전립선비대증 치료 효과를 확인하였다. 그 결과, 도 3에서 확인되는 바와 같이 홍경천과 쏘팔메토 추출물을 1:2 ~ 2:1 중량비로 혼합하여 투여하는 경우, 전립선비대증 세포 사멸에 대한 상승 효과를 나타냄을 알 수 있었다. 구체적으로, 전립선비대증 세포 사멸에 대한 상승 효과는 모든 복합 추출물 투여군에서 확인되었다.In a specific embodiment of the present invention, a complex extract obtained by mixing honggyeongcheon and saw palmetto extracts in a weight ratio of 1:2, 1:1, and 2:1, respectively, was treated on the prostatic hyperplasia cells to confirm the therapeutic effect of prostatic hyperplasia. As a result, as shown in FIG. 3, when the honggyeongcheon and saw palmetto extract were mixed and administered in a weight ratio of 1:2 to 2:1, it could be seen that a synergistic effect on prostatic hyperplasia cell death was exhibited. Specifically, the synergistic effect on prostatic hyperplasia cell death was confirmed in all complex extract administration groups.
본 발명의 조성물은 정소 세포 및 전립선 정상세포에 대한 독성이 없어 인체에 추가적인 이점을 갖는다. The composition of the present invention is not toxic to testicular cells and normal prostate cells and thus has an additional advantage to the human body.
본 발명의 구체적인 일실시예에서는 홍경천 및 쏘팔메토 추출물의 인체 안정성을 확인하기 위해, 이들 추출물을 정소 세포 및 전립선 정상세포에 처리한 후 세포생존율을 확인하였다. 그 결과, 치료적 유효농도에서 쏘팔메토에 의한 정상 세포의 생존율이 50~ 60%에 불과하여 세포 독성이 매우 큰 것을 확인하였고, 이에 비해 홍경천 추출물은 치료 효과가 있는 모든 범위에서 정상 세포에 대한 세포 독성을 나타내지 않는 것을 확인하였다. 또한 쏘팔메토 추출물과 홍경천 추출물을 4:1, 2:1, 1:1, 1:2의 중량비로 혼합하여 투여하는 경우, 정소 세포에서는 쏘팔메토 추출물과 홍경천 추출물을 1:2의 중량비로 혼합 투여한 군에서 유의적으로 세포독성을 억제하는 것을 확인하였고, 전립선 정상세포에서는 쏘팔메토 추출물과 홍경천 추출물을 1:1의 중량비로 혼합 투여한 군에서부터 유의적으로 세포독성을 억제하는 것을 확인하였다.In a specific embodiment of the present invention, in order to confirm the human stability of the extracts of honggyeongcheon and saw palmetto, the cell viability was confirmed after treatment with these extracts on testis cells and normal prostate cells. As a result, it was confirmed that the survival rate of normal cells by saw palmetto was only 50-60% at the therapeutically effective concentration, so that the cytotoxicity was very high.In contrast, Rhododendron extract was effective against normal cells in all ranges with therapeutic effects. It was confirmed that it did not show cytotoxicity. In addition, when the saw palmetto extract and the rhododendron extract are mixed in a weight ratio of 4:1, 2:1, 1:1, and 1:2, in the testis cells, the saw palmetto extract and the rhododendron extract are mixed in a weight ratio of 1:2. It was confirmed that cytotoxicity was significantly suppressed in the mixed administration group, and in the normal prostate cells, it was confirmed that the cytotoxicity was significantly suppressed from the group administration of the saw palmetto extract and the rhododendron extract at a weight ratio of 1:1. I did.
따라서, 본 발명에 따른 조성물은 전립선비대증 치료 효과를 상승시키면서도 인체에 부작용 없이 안전하게 사용될 수 있다.Therefore, the composition according to the present invention can be safely used without side effects to the human body while increasing the therapeutic effect of prostatic hyperplasia.
본 발명의 약학 조성물은 약학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다.The pharmaceutical composition of the present invention may further include suitable carriers, excipients, and diluents commonly used in the preparation of pharmaceutical compositions.
본 발명에 따른 약학 조성물은, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다.The pharmaceutical composition according to the present invention is formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., external preparations, suppositories, and sterile injectable solutions, respectively, according to conventional methods. I can.
본 발명의 약학 조성물에 함유될 수 있는 담체, 부형제 및 희석제로는 락토오즈(lactose), 덱스트로즈, 수크로스(sucrose), 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다.Carriers, excipients, and diluents that may be contained in the pharmaceutical composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, Gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oils.
제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다.In the case of formulation, it is prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, and surfactants that are usually used.
경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 화합물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(calcium carbonate), 수크로스 또는 락토오스, 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다.Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and such solid preparations include at least one excipient for the compound, such as starch, calcium carbonate, sucrose or lactose. , Gelatin, etc. are mixed to prepare it. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral use include suspensions, liquid solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweetening agents, fragrances, and preservatives may be included. .
비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories. As the non-aqueous solvent and suspension, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used. As a base for suppositories, witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin, and the like may be used.
상기 본 발명의 약학적 조성물은 약제학적으로 유효한 양으로 투여한다.The pharmaceutical composition of the present invention is administered in a pharmaceutically effective amount.
본 발명에서 용어 "약제학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 유효 용량 수준은 개체 종류 및 중증도, 연령, 성별, 감염된 바이러스 종류, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출 비율, 치료기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 본 발명의 조성물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여될 수 있고 종래의 치료제와는 순차적 또는 동시에 투여될 수 있다. 그리고 단일 또는 다중 투여될 수 있다. 상기 요소를 모두 고려하여 부작용없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 당업자에 의해 용이하게 결정될 수 있다.In the present invention, the term "pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level is the type and severity of the individual, age, sex, and type of infected virus. , Drug activity, sensitivity to drugs, time of administration, route of administration and rate of excretion, duration of treatment, factors including drugs used concurrently, and other factors well known in the medical field. The composition of the present invention may be administered as an individual therapeutic agent or administered in combination with other therapeutic agents, and may be administered sequentially or simultaneously with a conventional therapeutic agent. And can be administered single or multiple. It is important to administer an amount capable of obtaining the maximum effect in a minimum amount without side effects in consideration of all the above factors, and can be easily determined by a person skilled in the art.
본 발명의 약학적 조성물은 전립선비대증의 예방 또는 치료를 위하여 단독으로, 또는 수술, 호르몬 치료, 약물 치료 및 생물학적 반응 조절제를 사용하는 방법들과 병용하여 사용할 수 있다.The pharmaceutical composition of the present invention can be used alone or in combination with surgery, hormone therapy, drug therapy, and methods of using a biological response modifier for the prevention or treatment of prostatic hyperplasia.
상기 약학 조성물은 쥐, 생쥐, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁 내 경막 또는 뇌혈관 내 주사에 의해 투여될 수 있다.The pharmaceutical composition may be administered to mammals such as mice, mice, livestock, and humans by various routes. All modes of administration can be expected and can be administered, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or cerebrovascular injection.
다른 측면에서, 본 발명은 홍경천(Rhodiola sachalinensis) 추출물 및 쏘팔메토 추출물을 유효성분으로 함유하는 전립선비대증의 예방 또는 개선용 건강기능식품 조성물을 제공한다.In another aspect, the present invention provides a health functional food composition for preventing or improving prostatic hyperplasia, containing honggyeongcheon ( Rhodiola sachalinensis ) extract and saw palmetto extract as active ingredients.
상기 건강기능식품은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 그 밖에 천연 과일 주스 및 과일 주스 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 또한, 건강기능식품은 육류, 소세지, 빵, 초콜릿, 캔디류, 스넥류, 과자류, 피자, 라면, 껌류, 아이스크림류, 스프, 음료수, 차, 기능수, 드링크제, 알코올 및 비타민 복합제 중 어느 하나의 형태일 수 있다.The health functional foods include various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavoring agents and natural flavoring agents, coloring agents and thickeners (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid and salts thereof, It may contain organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. In addition, it may contain natural fruit juices and pulp for the production of fruit juices and vegetable beverages. These components may be used independently or in combination. In addition, health functional foods may be in the form of any one of meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, gum, ice cream, soup, beverage, tea, functional water, drink, alcohol and vitamin complex. I can.
본 발명의 건강 음료 조성물은 홍경천과 쏘팔메토 추출물의 혼합물을 함유하는 것 외에는 액체성분에는 특별한 제한은 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다.The health beverage composition of the present invention is not particularly limited to the liquid component, except that it contains a mixture of honggyeongcheon and saw palmetto extract, and may contain various flavoring agents or natural carbohydrates as an additional component, such as a conventional beverage.
또한, 상기 건강기능식품은 식품첨가물을 추가로 포함할 수 있으며, “식품첨가물”로서의 적합여부는 다른 규정이 없는 한 식품의약품안정청에 승인된 식품첨가물공전의 총칙 및 일반시험법 등에 따라 해당 품목에 관한 규격 및 기준에 의하여 판정한다.In addition, the above health functional food may additionally contain food additives, and the suitability as a “food additive” is determined by the general rules of the Food Additive Code approved by the Food and Drug Administration and the general test method, etc. It is judged according to the relevant standards and standards.
상기 “식품첨가물공전”에 수재된 품목으로 예를 들어, 케톤류, 글리신, 구연산 칼륨, 니코틴산, 계피산 등의 화학적 합성품, 감색소, 감초추출물, 결정셀룰로오스, 고랭색소, 구아검 등의 천연첨가물, L-글루타민산나트륨제제, 면류첨가알칼리제, 보존료제제, 타르색소제제 등의 혼합 제제류 등을 들 수 있다.Items listed in the "Food Additives Code", for example, chemical synthetic products such as ketones, glycine, potassium citrate, nicotinic acid, and cinnamic acid, natural additives such as reduced pigment, licorice extract, crystalline cellulose, high cooling pigment, guar gum, etc., L -Mixed preparations such as sodium glutamate preparations, noodle-added alkali preparations, preservative preparations, and tar coloring preparations, etc. are mentioned.
상기 전립선비대증 예방 또는 개선용 건강기능식품 조성물에서 홍경천 및 쏘팔메토 추출물에 대한 설명, 이의 효과 및 관련 모든 설명은 전술한 바와 동일하므로, 중복 기재에 따른 본 명세서의 과도한 복잡성을 피하기 위하여 그 기재를 생략한다.In the health functional food composition for preventing or improving prostatic hyperplasia, the description of honggyeongcheon and saw palmetto extract, its effects, and all related descriptions are the same as described above, so that the description is made to avoid excessive complexity of the present specification due to redundant description. Omit it.
본 발명의 조성물은 장기 투여시에도 부작용이 없을 뿐 아니라, 전립선비대증 치료 효과가 뛰어나고 안정적인 효능을 보이며, 특히 쏘팔메토 추출물과 병용하였을 때 상승효과를 나타내어, 전립선비대증 예방 또는 치료제, 의약외품, 건강기능식품 소재로 유용하게 이용될 수 있다.The composition of the present invention not only has no side effects even when administered for a long period of time, but also has excellent and stable efficacy for treating prostatic hyperplasia, and exhibits a synergistic effect, especially when used in combination with saw palmetto extract, to prevent or treat prostatic hyperplasia, quasi-drugs, health functions. It can be usefully used as a food material.
도 1은 홍경천 추출물 또는 쏘팔메토 추출물의 전립선비대증 치료 효과를 확인한 결과이다: A는 전립선비대증 세포에 홍경천 또는 쏘팔메토 단독 추출물을 농도별로 처리한 후 세포생존율을 측정한 결과, B는 LDH 활성을 분석한 결과.
도 2는 홍경천 및 쏘팔메토 복합 추출물의 전립선비대증 상승적 치료 효과를 확인한 결과이다.
도 3은 홍경천 추출물 농도 의존적인 전립선비대증의 상승적 치료 효과를 확인한 결과이다: A는 전립선비대증 세포에 쏘팔메토 추출물 및 홍경천 추출물을 농도비를 달리하여 처리한 후 세포생존율을 측정한 결과, B는 웨스턴 블랏 결과, C는 ELISA 측정 결과.
도 4는 홍경천 추출물 또는 쏘팔메토 추출물의 정소 세포에 대한 세포독성을 확인한 결과이다: A는 정소 세포에 홍경천 또는 쏘팔메토 단독 추출물을 농도별로 처리한 후 세포생존율을 측정한 결과, B는 LDH 활성을 분석한 결과.
도 5는 홍경천 추출물 또는 쏘팔메토 추출물의 전립선 정상 세포에 대한 세포독성을 확인한 결과이다: A는 전립선 정상 세포에 홍경천 또는 쏘팔메토 단독 추출물을 농도별로 처리한 후 세포생존율을 측정한 결과, B는 LDH 활성을 분석한 결과.
도 6은 홍경천 및 쏘팔메토 복합 추출물의 정소 세포에 대한 세포독성 감소 효과를 확인한 결과이다: A는 정소 세포에 복합 추출물을 처리한 후 세포생존율을 측정한 결과, B는 LDH 활성을 분석한 결과, C는 토스테스테론을 측정한 결과.
도 7은 홍경천 및 쏘팔메토 복합 추출물의 전립선 정상 세포에 대한 세포독성 감소 효과를 확인한 결과이다: A는 홍경천 추출물 농도 의존적인 세포생존율 증가를 확인한 결과, B는 홍경천 추출물 농도 의존적인 LDH 활성 감소를 확인한 결과.1 is a result of confirming the therapeutic effect of prostatic hyperplasia of rhododendron extract or saw palmetto extract: A is a result of measuring cell viability after treatment of rhododendron or saw palmetto alone extract by concentration on prostatic hyperplasia cells, B is LDH activity Analysis results.
Figure 2 is a result of confirming the synergistic treatment effect of prostatic hypertrophy of the composite extract of honggyeongcheon and saw palmetto.
Figure 3 is a result of confirming the synergistic treatment effect of prostatic hyperplasia concentration-dependent honggyeongcheon extract: A is a result of measuring the cell viability after treating prostatic hyperplasia cells at different concentration ratios, B is Western Blot result, C is the ELISA measurement result.
Figure 4 is a result of confirming the cytotoxicity of the testis cells of honggyeongcheon extract or saw palmetto extract: A is a result of measuring the cell viability after treatment of the testis cells with the extract of Rhododendron or saw palmetto alone, B is LDH As a result of analyzing activity.
Figure 5 is a result of confirming the cytotoxicity of the prostate normal cells of the rhododendron extract or saw palmetto extract: A is the result of measuring the cell viability after treating the prostate normal cells with the extract of Rhodiolaris or saw palmetto alone by concentration, B Is the result of analysis of LDH activity.
6 is a result of confirming the cytotoxicity reduction effect of the composite extract of honggyeongcheon and saw palmetto on testis cells: A is a result of measuring the cell viability after treating the testis cells with the complex extract, B is a result of analyzing LDH activity , C is the result of measuring tosterone.
Figure 7 is a result of confirming the cytotoxicity reduction effect of the honggyeongcheon and saw palmetto complex extract on normal prostate cells: A is a result of confirming the increase in cell viability dependent on the concentration of the honggyeongcheon extract concentration, B is a result of a decrease in LDH activity dependent on the concentration of the honggyeongcheon extract Confirmation result.
이하 본 발명을 실시예 및 시험예에 근거하여 더욱 상세히 설명한다. 그러나 본 발명이 하기의 실시예나 시험예에 의해 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail based on Examples and Test Examples. However, the present invention is not limited by the following Examples or Test Examples.
[실시예 1][Example 1]
홍경천 추출물의 제조조건 확립Establishment of manufacturing conditions for Honggyeongcheon extract
<1-1> 실험방법<1-1> Experimental method
홍경천으로부터 전립선비대증 개선에 효능을 갖는 유용물질들을 대량으로 추출하기 위한 추출법을 확립하기 위해 고온공압추출법과 초음파추출법을 비교하였다. 이때 추출을 위한 용매는 에탄올을 정제수에 희석하여 30 중량%와 50 중량%으로 따로 준비한 다음, 각각의 분말 100g씩을 1,000 mL의 에탄올 용액에 각각 침지하였다. 공압추출은 공압추출기(DH 700, 대한메디안, 한국)를 이용하여 100 Mpa의 압력으로 12시간 동안 50℃에서 가온 추출하고 10,000 rpm에서 원심분리하여 그 여액(1)을 따로 취하였다. 추출 후 잔류물에 다시 1,000 mL의 에탄올을 가하고, 50℃에서 24시간 동안 다시 공압 추출한 후 10,000 rpm에서 원심분리하여 새로운 여액(2)를 얻었다. 여액 (1)과 (2)를 혼합한 후 감압농축장치를 이용하여 에탄올을 제거한 후 동결건조하여 고압 추출물 분말을 획득하였다. 초음파 추출은 30 중량%와 50 중량% 에탄올 용액 1,000 mL에 각각의 분말 100g씩을 30분간 침지한 후 50℃로 고정한 초음파추출기(SJC-II-50L, GREENAPPLE사, 중국)에서 1시간 정치한 다음 1,000 W의 출력에서 20 KHz의 주파수로 30분 동안 추출하였다. 추출 후 추출물을 10,000 rpm에서 원심분리하여 그 여액(3)을 따로 취한 후 남겨진 잔류물을 같은 조건에서 초음파 추출하여 하고, 10,000 rpm에서 원심분리하여 새로운 여액(4)를 얻었다. 여액 (3)과 (4)를 혼합한 후 감압농축장치를 이용하여 에탄올을 제거한 후 동결건조하여 초음파 추출물 분말을 획득하였다.High-temperature pneumatic extraction and ultrasonic extraction were compared in order to establish an extraction method for mass extraction of useful substances effective in improving prostatic hyperplasia from Rhododendron. At this time, the solvent for extraction was prepared separately in 30% by weight and 50% by weight by diluting ethanol in purified water, and then 100 g of each powder was immersed in each of 1,000 mL of ethanol solution. Pneumatic extraction was performed using a pneumatic extractor (DH 700, Daehan Mediaan, Korea) at a pressure of 100 Mpa for 12 hours at 50°C, followed by centrifugation at 10,000 rpm to separate the filtrate (1). After extraction, 1,000 mL of ethanol was added to the residue again, followed by pneumatic extraction at 50° C. for 24 hours and centrifuged at 10,000 rpm to obtain a new filtrate (2). After mixing the filtrates (1) and (2), ethanol was removed using a vacuum concentrator, and then freeze-dried to obtain a high-pressure extract powder. For ultrasonic extraction, 100g of each powder was immersed in 1,000 mL of 30% by weight and 50% by weight ethanol solution for 30 minutes, and then allowed to stand for 1 hour in an ultrasonic extractor (SJC-II-50L, GREENAPPLE, China) fixed at 50°C. Extracted for 30 minutes at a frequency of 20 KHz at the output of W. After extraction, the extract was centrifuged at 10,000 rpm, the filtrate (3) was separately taken, and the remaining residue was ultrasonically extracted under the same conditions, and centrifuged at 10,000 rpm to obtain a new filtrate (4). After mixing the filtrates (3) and (4), ethanol was removed using a vacuum concentrator, and then freeze-dried to obtain an ultrasonic extract powder.
<1-2> 추출 수율 확인<1-2> Confirmation of extraction yield
홍경천으로부터 얻어진 30 중량% 에탄올 추출물과 50 중량% 에탄올 추출물의 무게를 측정하여 추출조건에 따라 분말시료 100 g에서 얻어진 고형분의 함량을 백분율(%)로 계산하여 추출 수율을 산출하였다.The 30% by weight ethanol extract and 50% by weight ethanol extract obtained from Honggyeongcheon were weighed, and the content of solids obtained from 100 g of the powder sample was calculated as a percentage (%) according to extraction conditions to calculate the extraction yield.
[표 1][Table 1]
추출방법에 따른 고형분 추출 수율 비교 (p<0.05)Comparison of solid content extraction yield according to extraction method (p<0.05)
같은 시료 중 같은 추출방법에 따라 에탄올 용액 농도 차이에서 얻어진 고형분 추출률 값의 다른 영문 어깨 글씨(a-b)는 통계적인 유의성이 있음을 나타낸다(p<0.05).In the same sample, different English superscripts (a-b) of the value of the solid content extraction rate obtained from the difference in ethanol solution concentration according to the same extraction method indicate that there is statistical significance (p<0.05).
같은 시료 중 같은 에탄올 용액의 조건에서 추출방법에 따라 얻어진 고형분 추출률 값의 다른 영문 어깨 글씨(X-Y)는 통계적인 유의성이 있음을 나타낸다(p<0.05).Other English superscripts (X-Y) of the solid content extraction rate values obtained according to the extraction method under the same ethanol solution conditions in the same sample indicate statistical significance (p<0.05).
에탄올 용매 조건에서 추출방법에 따른 고형분 추출률은 [표 1]에 나타냈다. 홍경천 추출물은 에탄올 함량이 높을수록, 고온공압추출보다는 초음파 추출조건에서 추출률이 높게 나타났다. 구체적으로, 공압추출에서는 통계적인 유의성은 없으나 다소 증가하는 것으로 나타났다. 반면에 초음파 추출에서는 에탄올 농도가 30 중량%일 때 추출률이 29.39%에서 에탄올 농도가 50 중량%일 때 37.53%로 나타나, 약 8.19% 더 많이 추출되는 것으로 나타났고 백분율로 다시 환산하면 약 21.68 중량%의 추출 증가 효율을 보였다. 에탄올 농도를 50 중량%로 고정하였을 경우, 공압추출에서는 26.24% 추출률을 나타내어 초음파 추출이 11.29% 더 높은 추출률을 나타냈고 백분율로 환산하면 약 30.08%의 추출률 증가를 보였다.The solid content extraction rate according to the extraction method in ethanol solvent conditions is shown in [Table 1]. The higher the ethanol content, the higher the extraction rate of the honggyeongcheon extract was under the ultrasonic extraction conditions than the high-temperature pneumatic extraction. Specifically, there was no statistical significance in pneumatic extraction, but it was found to slightly increase. On the other hand, in ultrasonic extraction, the extraction rate was 29.39% when the ethanol concentration was 30% by weight and 37.53% when the ethanol concentration was 50% by weight, indicating that about 8.19% more was extracted. When converted back to percentage, about 21.68% by weight Showed increased extraction efficiency. When the ethanol concentration was fixed at 50% by weight, the extraction rate of pneumatic extraction was 26.24%, and the extraction rate of ultrasonic extraction was 11.29% higher, and the extraction rate was increased by about 30.08% in terms of percentage.
<1-3> 총 폴리페놀 함량 확인<1-3> Confirmation of total polyphenol content
건조한 시료를 1.0 mg/mL의 농도로 준비한 후 용액 200 μL에 증류수 1.8 mL를 가하고, 1N Folin-Ciocalteu's phe- nol reagent 200 μL를 가한 뒤 5분간 실온에서 방치하였다. 이 혼합액에 7% Na2CO3 2 mL를 가하고, 다시 실온에서 1시간 방치한 후 760 nm에서 흡광도를 측정하였다. 표준곡선은 gallic acid를 사용하여 작성하였다. After preparing a dried sample at a concentration of 1.0 mg/mL, 1.8 mL of distilled water was added to 200 μL of the solution, 200 μL of 1N Folin-Ciocalteu's phe-nol reagent was added, and then left at room temperature for 5 minutes. 2 mL of 7% Na2CO3 was added to the mixture, and the mixture was allowed to stand at room temperature for 1 hour, and the absorbance was measured at 760 nm. The standard curve was prepared using gallic acid.
[표 2][Table 2]
추출방법에 따른 고형분에 함유된 총폴리페놀 함량 비교 (p<0.05)Comparison of total polyphenol content in solids according to extraction method (p<0.05)
추출방법에 따른 고형분에 함유된 총 폴리페놀 함량은 [표 2]에 나타냈다. 홍경천은 에탄올 함량이 높을수록, 공압추출보다는 초음파 추출 조건에서 총 폴리페놀 함량이 높게 나타났다.The total polyphenol content contained in the solid content according to the extraction method is shown in [Table 2]. The higher the ethanol content in Honggyeongcheon, the higher the total polyphenol content was in ultrasonic extraction conditions than in pneumatic extraction.
<1-4> DPPH 라디컬 소거능 <1-4> DPPH radical scavenging ability
DPPH 라디컬 소거능은 추출물 0.5mL (10.0μg/mL)에 0.2mM 2,2-diphenyl-2-picrylhydrazl (DPPH) 용액을 0.5mL 분주하여 30분간 방치시킨 후, 517 nm에서 흡광도(GENESYS 10 UV)를 측정하였다. 대조군은 시료 대신 용매를 가하여 동일한 방법으로 측정하였다. 양성대조군은 Vitamin C를 10.0 μg/mL로 준비하여 시험하였다. 또한 시료 자체의 색에 대한 흡광도 값을 보정하기 위해 0.2 nm DPPH 대신에 메탄올을 첨가하여 흡광도를 측정하였다. 이때 얻어진 값을 기준으로 추출물의 항산화 활성을 백분율로 표시하였고, 환산한 값이 100%에 가까울수록 항산화 활성이 높은 것으로 표현하였다.DPPH radical scavenging ability is obtained by dispensing 0.5 mL of 0.2
[표 3][Table 3]
추출방법에 따른 각각의 추출물의 동일 농도(10.0μg/mL)에서 DPPH 라디칼 소거능 (p<0.05)DPPH radical scavenging ability (p<0.05) at the same concentration (10.0μg/mL) of each extract according to the extraction method
에탄올 용매 조건에서 추출방법에 따른 DPPH 라디칼 소거능 값은 [표 3]에 나타냈다. 홍경천은 에탄올 함량이 높을수록, 공압추출보다는 초음파 추출에서 DPPH 라디칼 소거능이 높게 나타났다. 구체적으로, 홍경천 분말에 대한 에탄올 농도가 30 중량%일 때 공압추출은 57.28%, 초음파 추출은 72.32%로 15.04%(백분율 환산 20.79% 높게 나타났다.DPPH radical scavenging ability values according to the extraction method in ethanol solvent conditions are shown in [Table 3]. The higher the ethanol content of Rongkyungcheon, the higher the DPPH radical scavenging ability in ultrasonic extraction than in pneumatic extraction. Specifically, when the ethanol concentration of honggyeongcheon powder was 30% by weight, pneumatic extraction was 57.28% and ultrasonic extraction was 72.32%, which was 15.04% (20.79% as a percentage).
<1-5> 전립선 정상세포에 대한 독성 <1-5> Toxicity to normal prostate cells
추출방법에 따른 추출물의 전립선 정상세포에 대한 세포독성은 MTT assay로 시험하였다. 96 well plate에 well당 MRC-5 섬유아세포와 RWPE 전립선 정상세포를 접종하여 5% CO2, 37℃ 조건에서 24시간 배양하여 세포단층을 얻은 후, 세포접종용 배지로 희석한 추출물 6.25 ~ 100 ug/mL를 100 uL/well씩 접종하여 48시간 배양하였다. 48시간 후, 배양액 100 uL을 제거한 후, MTT 용액 10 uL씩을 각 well에 가하여 5% CO2, 37℃ 배양기에서 4시간 동안 정치하였다. MTT 용액을 완전히 제거한 다음, 100 μL dimethyl sulfoxide (DMSO)로 세포 내에 형성된 formazan 결정체를 용해하여 ELISA plate reader (BioTec Ex800, USA)로 490 nm에서 흡광도를 측정하였다. The cytotoxicity of the extract according to the extraction method to normal prostate cells was tested by MTT assay. MRC-5 fibroblasts per well and normal RWPE prostate cells were inoculated into a 96 well plate and cultured at 37°C for 24 hours to obtain a cell monolayer, and the extract diluted with a cell inoculation medium 6.25 ~ 100 ug/ mL was inoculated at 100 uL/well and cultured for 48 hours. After 48 hours, 100 uL of the culture solution was removed, 10 uL of MTT solution was added to each well, and the mixture was allowed to stand for 4 hours in an incubator at 37°C at 5% CO2. After the MTT solution was completely removed, formazan crystals formed in the cells were dissolved with 100 μL dimethyl sulfoxide (DMSO), and the absorbance was measured at 490 nm with an ELISA plate reader (BioTec Ex800, USA).
[표 4][Table 4]
추출방법에 따른 각각의 추출물(100 μg/mL)의 정상세포에 대한 독성 효과 (p<0.05)Toxic effect of each extract (100 μg/mL) on normal cells according to the extraction method (p<0.05)
[표 4]는 추출방법에 따른 2가지 추출물들의 정상세포에 대한 세포 독성 효과를 나타낸다. 정상 세포주 MRC-5 섬유아세포와 RWPE 전립선 정상세포에서 세포독성을 실시한 결과, 홍경천추출물은 추출용매인 에탄올 30 중량%와 50 중량% 모두에서 세포독성을 확인할 수 없었고, 초음파 추출법과 공압추출법으로 준비한 추출물에 대해서도 세포 사멸효과가 발견되지 않아 세포 독성은 없는 것으로 나타났다. [Table 4] shows the cytotoxic effects of the two extracts according to the extraction method on normal cells. As a result of cytotoxicity in normal cell lines MRC-5 fibroblasts and RWPE prostate normal cells, rhododendron extract was not able to confirm cytotoxicity in both 30% by weight and 50% by weight of ethanol, an extract prepared by ultrasonic and pneumatic extraction. It was also found that there was no cytotoxicity as no apoptosis effect was found.
<1-6> 전립선비대증 세포의 사멸 효과<1-6> Apoptosis effect of prostatic hyperplasia cells
추출조건에 따른 홍경천 추출물의 전립선비대증 세포에 대한 사멸효과는 MTT (3-(4,5-dimethylthiazol)-2, 5-diphenyltetrasolium bromide) 측정법으로 시험하였다. BPH-1 세포를 1×105 cells/well 밀도로 10% 소태아 혈청, 100 units/ml 페니실린 및 100 ug/ml 스트렙토마이신을 함유한 RPMI 1620 배지가 담긴 96 웰 배양플레이트에서 37℃, 5% CO2 환경으로 1일 배양한 후 혈청이 첨가되지 않은 RPMI 1640 배지로 교체하고, 각각의 추출물을 농도별로 첨가하여 24시간 배양하였다. MTT 용액 (5mg/ml, Sigma, 미국)을 웰당 20ul씩 첨가하여 37℃에서 4시간 반응 후 MTT 용액을 제거하고 DMSO를 웰당 100ul씩 첨가하였다. 실온에서 포르마잔 유도체를 녹인 후 490 nm에서 흡광도를 측정하였다. The killing effect of the extract of Rhododendron rhododendron according to the extraction conditions on prostatic hyperplasia cells was tested by MTT (3-(4,5-dimethylthiazol)-2, 5-diphenyltetrasolium bromide) assay. BPH-1 cells at 1×10 5 cells/well density in a 96-well culture plate containing 10% fetal bovine serum, 100 units/ml penicillin and 100 ug/ml streptomycin in RPMI 1620 medium at 37°C, 5% After 1 day incubation in a CO 2 environment, it was replaced with RPMI 1640 medium to which serum was not added, and each extract was added for each concentration and cultured for 24 hours. MTT solution (5mg/ml, Sigma, USA) was added at 20ul per well, reacted at 37°C for 4 hours, the MTT solution was removed, and DMSO was added at 100ul per well. After dissolving the formazan derivative at room temperature, absorbance was measured at 490 nm.
[표 5][Table 5]
추출방법에 따른 각각의 추출물의 동일 농도(100 μg/mL)에서 전립선비대증 표피세포(BPH-1)의 사멸 효과 (p<0.05)Killing effect of prostatic hyperplasia epidermal cells (BPH-1) at the same concentration (100 μg/mL) of each extract according to the extraction method (p<0.05)
추출방법에 따른 홍경천 추출물의 전립선비대증 세포에 대한 사멸 효과를 측정하였다. [표 5]에 나타난 바와 같이 PC3 전립선비대증 세포에서 세포독성을 실시한 결과, 양성대조군인 피네스테라이드 투여군은 세포 생존율이 66.25%로 나타났고 홍경천 추출물 시료에서도 세포 사멸효과가 있음을 확인할 수 있었다. 에탄올 농도가 높고 초음파 추출법을 사용하였을 때, 전립선비대증 세포의 사멸효과가 더 높게 나타났다. The killing effect of the extract of honggyeongcheon according to the extraction method on prostatic hyperplasia cells was measured. As shown in [Table 5], as a result of cytotoxicity in PC3 prostatic hyperplasia cells, the positive control group administered with finesteride showed a cell viability of 66.25%, and it could be confirmed that there was a cell apoptosis effect in the extract sample of Honggyeongcheon. When the ethanol concentration was high and the ultrasonic extraction method was used, the killing effect of prostatic hyperplasia cells was higher.
결론적으로 본 발명에 따른 홍경천 추출 조건을 개발하기 위한 시험에서 홍경천 추출물은 초음파 추출법이 공압추출법보다 전립선비대증 개선에 유용한 물질들을 좀 더 많이 추출하는 것으로 나타났다.In conclusion, in the test to develop the conditions for extracting honggyeongcheon according to the present invention, it was found that the ultrasonic extraction method extracts more substances useful for improving prostatic hyperplasia than the pneumatic extraction method.
[실시예 2][Example 2]
홍경천 및 쏘팔메토 복합 추출물의 제조Preparation of Rhododendron and Saw Palmetto Complex Extract
<2-1> 홍경천 추출물의 제조<2-1> Preparation of Honggyeongcheon extract
상기 실시예 1을 통해 확인한 홍경천 추출물의 최적 추출 조건을 적용하여 홍경천 추출물을 준비하였다. 구체적으로, 홍경천은 중국 티벳자치구산으로 중국 연변대학교로부터 제공받았다. 잘 건조된 홍경천을 분말로 만든 후 분말 100g을 50% 에탄올 용액 1 L에서 60분간 침지한 후 초음파 추출기(SJC-Ⅱ-50L, GREENAPPLE, Uhan, China)를 사용하여 30℃에서 30분간 2회 반복 추출한 후 5,000 rpm에서 20분간 4℃의 조건에서 원심분리하여 그 상등액을 취하여 동결건조하였다. 동결건조한 홍경천추출물 분말을 진공포장하여 냉장보관하면서 하기 실험에 사용하였다.The honggyeongcheon extract was prepared by applying the optimal extraction conditions of the honggyeongcheon extract identified in Example 1. Specifically, Hong Gyeongcheon was provided by Yanbian University in China as a product from Tibet Autonomous Region, China. After making a well-dried rhododendron into powder, 100g of the powder is immersed in 1 L of 50% ethanol solution for 60 minutes, and then repeated twice at 30℃ for 30 minutes using an ultrasonic extractor (SJC-Ⅱ-50L, GREENAPPLE, Uhan, China). After extraction, centrifugation was performed at 5,000 rpm for 20 minutes at 4°C, and the supernatant was taken and lyophilized. The freeze-dried rhododendron extract powder was vacuum-packed and stored in a refrigerator to be used in the following experiment.
<2-2> 쏘팔메토 추출물의 준비<2-2> Preparation of saw palmetto extract
본 발명에서 사용한 쏘팔메토 추출물은 K사로부터 구입하였다.The saw palmetto extract used in the present invention was purchased from K company.
<2-3> 복합 추출물의 제조<2-3> Preparation of complex extract
상기에서 제조한 홍경천 추출물과 쏘팔메토 추출물을 혼합하여 복합 추출물을 제조한 후 실험에 사용하였다.A composite extract was prepared by mixing the honggyeongcheon extract prepared above and the saw palmetto extract, and then used in the experiment.
[실험방법][Experiment method]
세포배양Cell culture
본 실험에 사용된 전립선 정상세포(RWPE)와 BPH 세포(BPH-1)는 한양대학교 의과대학으로부터 분양받았으며, TM3 정소세포는 한국세포주은행(KCLB, Seoul)으로부터 분양받아 사용하였다. 세포 배양은 DMEM(Dulbecco Modified Eagle Medium)과 RPMI-1640 배지에 10% fetal bovine serum(FBS) 100 unit/mL의 penicillin, 100 μg/mL의 streptomycin 을 첨가하여 사용하고, 95%의 습도가 유지되는 37℃, 5% CO2 incubator (MCO-170AIC-PK, Panasonic, Sakata, Japan)에서 배양하였다. 세포가 바닥 면적의 90% 정도까지 자란 상태에서 계대 배양을 실시하였다. Prostate normal cells (RWPE) and BPH cells (BPH-1) used in this experiment were distributed from Hanyang University College of Medicine, and TM3 testis cells were distributed from Korea Cell Line Bank (KCLB, Seoul). Cell culture was performed by adding 10% fetal bovine serum (FBS) 100 unit/mL penicillin and 100 μg/mL streptomycin to DMEM (Dulbecco Modified Eagle Medium) and RPMI-1640 medium, and maintaining 95% humidity. It was cultured in a 37°C, 5% CO 2 incubator (MCO-170AIC-PK, Panasonic, Sakata, Japan). Subculture was performed while the cells were grown to about 90% of the floor area.
MTT 분석MTT analysis
각 세포주에서 RS와 SP에 대한 세포생존율을 확인하기 위해 MTT(Tetrazolium, Sigma) 분석을 실시하였다. 각 세포주를 96-well plate에 1105 cells/mL의 농도로 100 μL씩 분주하여 24시간 동안 37℃, 5% CO2 incubator에서 배양한 후, 시료를 각각 6.25 ~ 100 μg/mL의 농도로 처리한 후, 24시간 동안 배양하였다. 각 well에 5 μg/mL로 PBS 완충용액에 녹인 MTT 용액을 10 μL씩 첨가하여 다시 1시간 동안 반응시켰다. Formazan 형성을 확인한 후, 배지를 완전히 제거하고, well 바닥에 형성된 formazan을 녹이기 위해 100 μL의 DMSO(Dimethyl Sulfoxide)를 첨가한 후, ELISA reader (SPECTRA MAX 190, Molecular Devices, Califonia, USA)를 이용하여 450 nm에서 흡광도를 측정하여 각 추출물들을 처리하지 않고 배양시킨 대조군 세포를 100%로 하였을 때의 세포생존율을 나타내었다.In each cell line, MTT (Tetrazolium, Sigma) analysis was performed to confirm the cell viability for RS and SP. Dispense 100 μL of each cell line into a 96-well plate at a concentration of 110 5 cells/mL, incubate in a 37°C, 5% CO 2 incubator for 24 hours, and treat the samples at a concentration of 6.25 ~ 100 μg/mL, respectively. Then, it was incubated for 24 hours. 10 μL of MTT solution dissolved in PBS buffer solution at 5 μg/mL to each well was added and reacted for 1 hour again. After confirming the formation of formazan, the medium was completely removed, and 100 μL of DMSO (Dimethyl Sulfoxide) was added to dissolve the formazan formed at the bottom of the well, and then, using an ELISA reader (SPECTRA MAX 190, Molecular Devices, Califonia, USA). Absorbance was measured at 450 nm to show the cell viability when the control cells cultured without treatment with each extract were 100%.
Lactate dehydrogenase (LDH) 활성 분석Lactate dehydrogenase (LDH) activity assay
LDH 측정은 CytoTox detection kit (Takara, Shuzo Co., Ltd, Otsu, Japan)를 사용하여 측정하였다. 양성대조군은 시료처리하지 않은 군으로, 음성대조군은 세포와 시료를 모두 처리하지 않은 것으로 정의하여 상대적인 LDH 생성 정도를 측정하였다. LDH was measured using a CytoTox detection kit (Takara, Shuzo Co., Ltd, Otsu, Japan). The positive control group was defined as the non-sampled group, and the negative control group was defined as not treated with both cells and samples, and the relative LDH production was measured.
DNA fragmentation 분석DNA fragmentation analysis
Apoptotic-specific DNA fragmentation을 정량하기 위해 Cell death detection ELISA plus kit(Roche Molecular Biochemicals, Mannheim, Germany)를 사용하였다. SP 및 RS을 얼마만큼 세포에 처리한 다음, lysate 상등액을 회수하였다. 상등액 20 uL를 streptavidin-coated plate에 옮긴 후, immune-reagent 80 uL를 각 microwell에 첨가하여 2시간동안 실온에서 반응시켰다. Incubation buffer로 각 웰을 세척하고, substrate solution을 첨가하여 20~30분간 반응시킨 후, 405 nm에서 흡광도를 측정하였다.Cell death detection ELISA plus kit (Roche Molecular Biochemicals, Mannheim, Germany) was used to quantify apoptotic-specific DNA fragmentation. After some amount of SP and RS were treated on the cells, the lysate supernatant was recovered. After transferring 20 uL of the supernatant to a streptavidin-coated plate, 80 uL of immune-reagent was added to each microwell and reacted at room temperature for 2 hours. Each well was washed with an incubation buffer, and after reacting for 20 to 30 minutes by adding a substrate solution, absorbance was measured at 405 nm.
세포 내 테스토스테론 농도 측정Measurement of testosterone concentration in cells
세포 내 테스토스테론 농도는 ELISA kit(Enzo, Farmingdale, NY, USA)를 사용하여 측정하였다. 배양이 끝난 후, 배지 100 uL를 goat anti-mouse IgG microtiter plate에 옮긴 다음, 테스토스테론 항체를 첨가 후 1시간 배양하였다. 세척 후 stop solution을 첨가한 후 반응을 중지하고 405 nm에서 흡광도를 측정하였다. Intracellular testosterone concentration was measured using an ELISA kit (Enzo, Farmingdale, NY, USA). After the cultivation was completed, 100 uL of the medium was transferred to a goat anti-mouse IgG microtiter plate, and then incubated for 1 hour after addition of a testosterone antibody. After washing, the reaction was stopped after adding a stop solution, and absorbance was measured at 405 nm.
Western blot 분석Western blot analysis
각 세포를 6-well plate에 세포수가 4×105 cells/well 이 되도록 분주하고 80% confluence로 배양한 후, SP와 RS를 처리하여 24시간 배양하였다. 배양 후 well을 pH 7.4인 PBS로 2회 세척한 후 세포를 채취하였다. Lysis buffer (50 mM Tris-HCl pH 7.5, 50 mM NaCl, 1% Triton X-100, 1 M DTT)를 사용하여 cell lysate를 준비하였고, 4℃의 조건에서 13,000 rpm으로 15분간 원심분리하여 얻은 상등액을 총단백질 추출액으로 사용하였다. Bio-Radprotein assay(Bio-Rad Laboratories, Hercules, CA, USA)로 단백질을 정량하였으며, 단백질 100 μg과 sample buffer(60 mM Tris-HCl; pH 6.8, 2% SDS, 25% glycerol, 14.4 mM 2-mercaptaethanol, 0.1% bromphenol blue)를 혼합하여 100℃에서 10분간 끓인 후 냉각하여 전기영동하였다. 분리된 단백질을 함유한 acrylamide gel을 nitrocellulose membrane(Schleicher and Schuell, Keene, NH, USA)으로 electroblotting에 의해 이전시킨 후, 5% skim milk를 함유한 PBS-T(0.1% Tween 20 in PBS)에 담구어 상온에서 1시간 정도 배양하여 비특이 단백질들에 대한 blocking을 실시하고 PBS-T로 15분 정도 세척하였다. 준비된 membrane에 1차 항체를 처리하여 상온에서 2시간 이상 또는 4℃에서 over night 시킨 다음 PBS-T로 세척하고 처리된 1차 항체에 맞는 2차 항체를 사용하여 상온에서 1시간 정도 반응시켰다. 다시 PBS-T로 세척하고 enhanced chemiluminescence(ECL) 용액(Amersham Life Science Corp, Arlington Heights, IL, USA)을 적용시킨 다음 특정 단백질의 발현 양을 확인하였다(Amersham Imager 680, GE Healthcare BioScience, Uppsala, Sweden). 본 실험에 사용된 항체들은 Santa Cruz Biotechnology Inc. (Santa Cruz, CA, USA)에서 구입하였으며, 2차 항체로 사용된 peroxidase- labeled donkey anti-rabbit immunoglobulin peroxidase-labeled sheep anti-mouse immunoglobulin은 Amersham Corp.에서 구입하였다. Each cell was dispensed into a 6-well plate so that the number of cells was 4×10 5 cells/well, cultured with 80% confluence, and then treated with SP and RS for 24 hours. After incubation, the wells were washed twice with PBS of pH 7.4, and cells were collected. Cell lysate was prepared using lysis buffer (50 mM Tris-HCl pH 7.5, 50 mM NaCl, 1% Triton X-100, 1 M DTT), and the supernatant obtained by centrifugation at 13,000 rpm for 15 minutes at 4°C. Was used as the total protein extract. Protein was quantified by Bio-Radprotein assay (Bio-Rad Laboratories, Hercules, CA, USA), and 100 μg of protein and sample buffer (60 mM Tris-HCl; pH 6.8, 2% SDS, 25% glycerol, 14.4 mM 2- mercaptaethanol, 0.1% bromphenol blue) was mixed, boiled at 100°C for 10 minutes, cooled, and electrophoresed. The acrylamide gel containing the separated protein was transferred to a nitrocellulose membrane (Schleicher and Schuell, Keene, NH, USA) by electroblotting, and then placed in PBS-T (0.1
통계처리Statistical processing
각 실험에서 얻어진 결과들은 평균±표준편차(standard deviation, SD)로 나타내었고, 데이터 간 유의차는 Student's t-test와 one-way analysis of variance(ANOVA)인 Duncan's multiple range test를 이용하여 p<0.05 수준에서 검증하였다.The results obtained in each experiment were expressed as mean ± standard deviation (SD), and the significant difference between the data was p<0.05 level using Student's t-test and Duncan's multiple range test, one-way analysis of variance (ANOVA). Verified in.
[실험결과][Experiment result]
1. 홍경천 또는 쏘팔메토 단독 추출물의 전립선비대증 개선 효과 확인1. Confirmation of the effect of improving prostatic hyperplasia by extract of honggyeongcheon or saw palmetto alone
<1-1> 홍경천 추출물의 전립선비대증 개선 효과 확인<1-1> Confirmation of the effect of honggyeongcheon extract on improving prostatic hyperplasia
본 발명에서 확립한 제조 조건으로 제조한 홍경천 단독 추출물의 전립선비대증 개선 효과를 전립선비대증 세포 BPH-1에서 홍경천 추출물에 대한 세포생존율을 MTT 분석을 통해 확인하였다.The effect of improving prostatic hypertrophy of honggyeongcheon alone extract prepared under the manufacturing conditions established in the present invention was confirmed through MTT analysis for the cell viability of the honggyeongcheon extract in prostatic hyperplasia cells BPH-1.
그 결과, [도 1]에 나타난 바와 같이 BPH-1 전립선비대증 세포에 홍경천 추출물을 처리한 결과, 전립선비대증 세포의 생존율이 농도 의존적으로 감소하여 홍경천 추출물의 전립선비대증 개선 효과를 확인할 수 있었다.As a result, as shown in [Fig. 1], as a result of treating BPH-1 prostatic hyperplasia cells with honggyeongcheon extract, the survival rate of prostatic hyperplasia cells decreased in a concentration-dependent manner, thereby confirming the effect of improving prostatic hypertrophy of the honggyeongcheon extract.
이는, 상기 실시예 <1-6>의 결과와도 일치하며, 상기 [표 5]를 참조하면, 본 발명의 제조 조건으로 제조한 홍경천 추출물을 처리한 전립선비대증 세포의 생존율이 55.52%로 나타나 양성대조군인 피네스테라이드 투여군의 세포 생존율이 66.25%인 것과 비교할 때 양성대조군 보다 월등하게 우수한 개선 효과가 있음을 알 수 있다. 또한 LDH 활성은 농도의존적으로 다소 증가하는 듯 보이나 유의성이 없으므로 홍경천 추출물에 의한 세포생존율 감소와는 무관한 것으로 생각된다.This is consistent with the results of Example <1-6>, and referring to [Table 5], the survival rate of prostatic hyperplasia cells treated with the honggyeongcheon extract prepared under the production conditions of the present invention was 55.52%, indicating that it was positive. It can be seen that the cell survival rate of the control group administered with finesteride is 66.25%, which is superior to that of the positive control group. In addition, LDH activity seems to increase somewhat in a concentration-dependent manner, but since it is not significant, it is thought to be irrelevant to the decrease in cell viability by the extract of honggyeongcheon.
<1-2> 쏘팔메토 추출물의 전립선비대증 치료 효과 확인<1-2> Confirmation of the effect of saw palmetto extract on the treatment of prostatic hyperplasia
쏘팔메토 단독 추출물의 전립선비대증 개선 효과를 확인하기 위하여 전립선비대증 세포 BPH-1에 쏘팔메토 단독 추출물을 6.25~100 ug/mL 의 농도로 처리한 후 MTT 분석을 통해 세포생존율을 확인하였다.In order to confirm the effect of improving prostatic hyperplasia of the extract of saw palmetto alone, the extract of saw palmetto alone was treated with BPH-1 in prostatic hyperplasia cells at a concentration of 6.25 to 100 ug/mL, and then the cell viability was confirmed through MTT analysis.
그 결과, [도 1]에 나타난 바와 같이 쏘팔메토 추출물의 처리 농도가 6.25 ug/mL에서 50 ug/mL 농도에 이르기까지 아무런 변화를 나타나지 않았으며, 100 ug/mL 농도에서는 약 41%의 세포생존율이 확인되었다. 그러나 홍경천 추출물과는 달리 100 ug/mL 농도에서 LDH 활성 또한 대조군에 비해 약 0.5배 감소한 것으로 보아, 이는 세포생존율 감소에 의한 LDH 활성의 감소로 사료된다. As a result, as shown in [Fig. 1], there was no change in the treatment concentration of saw palmetto extract from 6.25 ug/mL to 50 ug/mL concentration, and about 41% of cells at 100 ug/mL concentration The survival rate was confirmed. However, unlike the Rhododendron extract, the LDH activity at 100 ug/mL was also reduced by about 0.5 times compared to the control, which is thought to be a decrease in LDH activity due to a decrease in cell viability.
2. 홍경천 및 쏘팔메토 복합 추출물의 상승적 전립선비대증 치료 효과 확인2. Synergistic prostatic hyperplasia treatment effect of Rhododendron and saw palmetto extract
<2-1> 전립선비대증 세포에 대한 복합 추출물의 상승적 치료 효과 확인<2-1> Confirmation of the synergistic therapeutic effect of the complex extract on prostatic hyperplasia cells
본 실험에서는 쏘팔메토 추출물과 홍경천 추출물을 혼합한 복합 추출물의 전립선비대증 치료 효과를 확인하였다. 먼저, 상기 단독 추출물의 실험결과를 참고하여, 전립선 치료 효과가 없거나 효과가 미미한 것으로 확인된 농도로 쏘팔메토 추출물과 홍경천 추출물을 각각 준비한 후 이를 혼합하여 복합 추출물을 제조하였다. 그 후 전립선비대증 세포 BPH-1에 쏘팔메토 단독 추출물, 홍경천 단독 추출물 및 복합 추출물을 각각 처리한 후 MTT 분석을 통해 세포생존율을 측정하였다.In this experiment, the treatment effect of the complex extract obtained by mixing saw palmetto extract and rhododendron extract was confirmed. First, referring to the experimental results of the single extract, saw palmetto extract and rhododendron extract were prepared respectively at concentrations confirmed to have no or insignificant effect on prostate treatment, and then mixed to prepare a composite extract. Thereafter, the prostatic hyperplasia cells BPH-1 were treated with saw palmetto alone extract, honggyeongcheon alone extract, and complex extract, respectively, and then the cell viability was measured through MTT analysis.
그 결과 하기 [표 6] 및 [도 2]에 나타난 바와 같이, 50 ug/ml의 쏘팔메토 추출물을 단독으로 처리하였을 때는 전립선비대증 세포 생존율이 95%를 상회하여 치료 효과가 두드러지지 않았고, 25 ug/ml의 홍경천 추출물 단독 투여군은 대조군에 비해 약간 전립선비대증 세포 사멸효과가 있었으나 유의미한 정도는 아니었다. 반면, 쏘팔메토와 홍경천의 복합 추출물의 경우는 대조군 및 단독 투여군에 비해 전립선비대증 세포 생존율이 유의적으로 감소하여 전립선비대증 치료 효과가 현저하게 증가한 것을 확인할 수 있었다. As a result, as shown in the following [Table 6] and [FIG. 2], when 50 ug/ml of saw palmetto extract was treated alone, the prostatic hyperplasia cell survival rate exceeded 95%, and the treatment effect was not remarkable, 25 The group administered with ug/ml of honggyeongcheon extract alone had a slightly more prostatic hyperplasia cell killing effect than the control group, but this was not significant. On the other hand, in the case of the combined extract of saw palmetto and honggyeongcheon, it was confirmed that the prostatic hyperplasia cell survival rate was significantly decreased compared to the control group and the single administration group, and the treatment effect of prostatic hyperplasia was significantly increased.
[표 6][Table 6]
상기 실험에서 얻어진 결과를 바탕으로, 혼합 처리에 의한 시너지 효과를 추가적으로 검증하기 위하여 콜비식으로 계산된 이론값과 실측값을 비교한 결과를 하기 [표 7]에 나타내었다. 이때, 전립선비대증 치료 효과는 추출물 처리에 따라 사멸하는 전립선비대증 세포의 개수를 백분율로 환산한 값을 하기 [표 7]에 나타내었으며, 단독 추출물 투여군의 백분율 실측치를 하기 콜비 공식에 대입하여 계산된 복합 추출물의 백분율 예측치 또한 [표 7]에 나타내었다.Based on the results obtained in the above experiment, the results of comparing the theoretical value calculated by the Colby's equation and the measured value in order to additionally verify the synergy effect by the mixing treatment are shown in Table 7 below. At this time, the therapeutic effect of prostatic hyperplasia is shown in the following [Table 7] by converting the number of prostatic hyperplasia cells killed by the extract treatment into a percentage, and the calculated composite calculated by substituting the measured percentage of the single extract administration group into the following Colby formula The percentage predicted value of the extract is also shown in [Table 7].
E = (A + B) - (A×B / 100)E = (A + B)-(A×B / 100)
상기 식에서, A는 활성성분 A의 약효이고, B는 활성성분 B의 약효이며, E는 예측치로 성분 A와 성분 B (A+B)가 혼합되었을 경우의 예측되는 약효이다.In the above formula, A is the drug effect of the active ingredient A, B is the drug effect of the active ingredient B, and E is the predicted drug effect when ingredient A and ingredient B (A+B) are mixed as a predicted value.
[표 7][Table 7]
그 결과, 쏘팔메토 및 홍경천 복합 추출물의 경우 상기 [표 7]에 나타난 바와 같이 전립선비대증 치료 효과 이론값 23.65% 보다 실측값이 34.3%로 현저하게 높아 단독으로 적용된 유효 성분에 비해 상승적으로 향상된 효과를 나타냄을 확인할 수 있다.As a result, in the case of the combined extract of saw palmetto and rhododendron, as shown in [Table 7], the actual value of the prostatic hyperplasia treatment effect was significantly higher at 34.3% than the theoretical value of 23.65%, and the effect was synergistically improved compared to the active ingredient applied alone. It can be seen that it represents.
이러한 결과는 복합 추출물이 추출물 각각을 단독으로 사용한 경우보다 전립선비대증 치료 효과에 있어서 시너지 효과를 나타내어 홍경천 추출물 또는 소팔메토 추출물 각각의 사용량을 감소시킬 수 있음을 의미하며, 특히 하기 결과로부터 확인되는 부작용을 수반하는 쏘팔메토 추출물의 사용량을 감소시킬 수 있음을 제시한다.These results indicate that the composite extract exhibits a synergistic effect in the treatment effect of prostatic hyperplasia compared to the case of using each extract alone, so that the amount of use of each of the Rhododendron extract or the cow palmetto extract can be reduced. It is suggested that the amount of used saw palmetto extract can be reduced.
<2-2> 홍경천 추출물의 농도별 처리에 따른 상승적 전립선비대증 치료 효과 확인<2-2> Confirmation of synergistic prostatic hyperplasia treatment effect according to concentration treatment of honggyeongcheon extract
본 실험에서는 쏘팔메토 추출물과 홍경천 추출물을 병용 처리함에 있어서, 홍경천 추출물의 농도를 달리하여 상승적 전립선비대증 치료 효과를 확인하였다. 먼저, 전립선비대증 세포 BPH-1에 쏘팔메토 추출물은 50 ug/ml로 동일하게 처리하면서, 홍경천 추출물 25, 50, 100 ug/ml를 각각 처리한 후 MTT 분석을 통해 세포생존율을 측정하였다. 또한, 웨스턴 블랏을 통해 세포사멸에 관여하는 조절 단백질의 발현율을 측정하고, ELISA 키트를 이용하여 DNA fragmentation 농도를 측정하였다.In this experiment, in the combination treatment of saw palmetto extract and honggyeongcheon extract, the synergistic prostatic hyperplasia treatment effect was confirmed by varying the concentration of the honggyeongcheon extract. First, the Saw Palmetto extract was treated in the same manner as 50 ug/ml in prostatic hyperplasia cells BPH-1, and 25, 50, and 100 ug/ml of honggyeongcheon extract were treated, respectively, and then cell viability was measured through MTT analysis. In addition, the expression rate of the regulatory protein involved in apoptosis was measured through Western blot, and the DNA fragmentation concentration was measured using an ELISA kit.
그 결과, 쏘팔메토 추출물 단독처리에 비해 홍경천 추출물과 병용 처리하였을 때 농도 의존적으로 세포생존율이 감소하였으며, 쏘팔메토 추출물과 홍경천 추출물을 1:2의 비율로 병용처리 하였을 때 세포생존율이 약 57%로 가장 큰 폭으로 감소하는 것을 확인하였다(도 3A). As a result, cell viability decreased in a concentration-dependent manner when treated in combination with honggyeongcheon extract compared to treatment with saw palmetto extract alone, and cell viability was about 57 when combined treatment of saw palmetto extract and honggyeongcheon extract in a ratio of 1:2. It was confirmed that the largest decrease in% was observed (FIG. 3A).
다음으로, 세포사멸과 관련된 단백질의 발현을 살펴본 결과, 홍경천 추출물은 농도 의존적으로 세포사멸을 촉진하는 Bax 단백질의 발현을 증가시키고, 세포사멸을 억제하는 Bcl2 단백질의 발현을 감소시켜 세포사멸 마커 단백질인 PCNA 단백질의 발현이 감소되는 것을 확인할 수 있었다(도 3B). 이때 세포사멸의 전형적인 현상인 DNA fragmentation 농도 또한 유의적으로 증가하였다(도 3C).Next, as a result of examining the expression of proteins related to apoptosis, the extract of honggyeongcheon increased the expression of Bax protein, which promotes apoptosis in a concentration-dependent manner, and reduced the expression of Bcl2 protein, which inhibits apoptosis. It was confirmed that the expression of the PCNA protein was decreased (Fig. 3B). At this time, the DNA fragmentation concentration, which is a typical phenomenon of apoptosis, was also significantly increased (Fig. 3C).
3. 홍경천 또는 쏘팔메토 단독 추출물의 세포독성 확인3. Confirmation of cytotoxicity of extract of honggyeongcheon or saw palmetto alone
홍경천 추출물 또는 쏘팔메토 추출물이 정소세포와 전립선 정상세포에서 세포독성을 나타내는지 확인하기 위하여 TM3 정소세포 및 전립선 정상세포(RWPE)에 각각의 단독 추출물을 농도별로 처리한 후 MTT 분석을 통해 세포생존율을 확인하였다.In order to confirm whether the rhododendron extract or saw palmetto extract exhibits cytotoxicity in testis cells and normal prostate cells, TM3 testis cells and normal prostate cells (RWPE) were treated with each single extract by concentration, and then cell viability through MTT analysis. Was confirmed.
<3-1> 정소세포에 대한 세포사멸 효과 확인<3-1> Confirmation of apoptosis effect on testis cells
쏘팔메토 추출물의 정소세포에 대한 세포독성을 확인하기 위하여 쏘팔메토 추출물을 6.25, 12.5, 25, 50, 100 μg/mL의 농도로 처리 한 후 MTT assay를 실시하여 세포생존율을 측정하였다. In order to confirm the cytotoxicity of the saw palmetto extract to testis cells, the saw palmetto extract was treated at a concentration of 6.25, 12.5, 25, 50, and 100 μg/mL, and then MTT assay was performed to measure the cell viability.
그 결과, [도 4]에 나타난 바와 같이 쏘팔메토 추출물을 6.25, 12.5, 25, 50, 100 ug/mL 농도로 처리하는 경우 각각 91, 82, 74, 68, 61%의 세포생존율을 나타내어 농도 의존적으로 세포생존율이 감소함을 확인할 수 있었다(도 4A). 뿐만 아니라, 쏘팔메토 추출물 처리에 따른 세포 손상 증가에 따라 LDH 활성 증가가 확인되었다(도 4B). As a result, as shown in [Fig. 4], when the saw palmetto extract was treated at a concentration of 6.25, 12.5, 25, 50, and 100 ug/mL, the cell viability of 91, 82, 74, 68, and 61% were respectively shown. It was confirmed that the cell viability was dependently decreased (FIG. 4A). In addition, it was confirmed that the LDH activity increased according to the increase in cell damage caused by the saw palmetto extract treatment (Fig. 4B).
그러나, 홍경천 추출물을 처리하였을 때는 정소세포의 세포 생존율과 LDH 활성에 영향을 미치지 않았으므로 쏘팔메토 추출물 단독처리와는 달리 세포독성이 없음을 확인하였다. However, it was confirmed that there was no cytotoxicity unlike saw palmetto extract alone, since treatment with the extract of honggyeongcheon did not affect the cell viability and LDH activity of testis cells.
상기 결과로부터, 쏘팔메토 추출물의 세포 독성(15-17)을 확인할 수 있었고, 또한 홍경천 추출물이 쏘팔메토 추출물 유래 세포독성을 감소시키는 효과가 있음을 확인할 수 있었다.From the above results, it was possible to confirm the cytotoxicity (15-17) of the saw palmetto extract, and it was also confirmed that the honggyeongcheon extract has an effect of reducing the cytotoxicity derived from the saw palmetto extract.
<3-2> 전립선 정상세포에 대한 세포사멸 효과 확인<3-2> Confirmation of apoptosis effect on normal prostate cells
상기와 동일한 방법으로 쏘팔메토 및 홍경천 단독 추출물의 전립선 정상세포에 대한 세포독성 유무를 확인하였다. In the same manner as described above, the presence or absence of cytotoxicity of saw palmetto and honggyeongcheon alone extract against normal prostate cells was confirmed.
그 결과, [도 5]에 나타난 바와 같이 홍경천 추출물을 처리하였을 때는 정소세포의 세포 생존율과 LDH 활성에 영향을 미치지 않았으므로 쏘팔메토 단독처리와는 달리 세포독성이 없음을 확인하였다. As a result, it was confirmed that there was no cytotoxicity, unlike saw palmetto alone, when treatment with the extract of honggyeongcheon as shown in FIG. 5 did not affect the cell viability and LDH activity of testis cells.
그러나, 쏘팔메토 추출물은 정소세포에서 나타난 결과와 마찬가지로 농도 의존적으로 세포생존율이 감소하여 50 ug/mL과 100 ug/mL 농도에서는 각각 74%, 61%의 세포생존율을 나타내었다. 세포손상 증가에 따라 LDH 활성 또한 대조군에 비해 50 ug/mL과 100 ug/mL 농도에서 각각 유의적으로 1.37에서 1.5배 증가하였다.However, the Saw Palmetto extract decreased the cell viability in a concentration-dependent manner, as in the results shown in testis cells, showing 74% and 61% cell viability at concentrations of 50 ug/mL and 100 ug/mL, respectively. As cell damage increased, LDH activity also increased significantly from 1.37 to 1.5 times at 50 ug/mL and 100 ug/mL concentrations, respectively, compared to the control group.
상기 결과로부터 쏘팔메토 추출물은 전립선비대증 개선 효과가 있는 농도에서 정상세포에 대한 세포독성이 매우 크다는 것을 알 수 있다. From the above results, it can be seen that the saw palmetto extract has very high cytotoxicity to normal cells at a concentration that has an effect of improving prostatic hyperplasia.
4. 홍경천 및 쏘팔메토 복합 추출물의 상승적 세포독성 억제 효과 확인4. Confirmation of the synergistic cytotoxic inhibitory effect of the complex extract of honggyeongcheon and saw palmetto
<4-1> 정소세포에 대한 상승적 세포사멸 억제 효과 확인<4-1> Confirmation of synergistic apoptosis inhibition effect on testis cells
쏘팔메토 추출물의 단독 처리가 정소세포에서 농도 의존적인 세포독성이 유도됨을 확인함에 따라 홍경천과 쏘팔메토 복합 추출물이 세포독성을 억제할 수 있는지 확인하였다. 그리고 정소세포는 정자형성을 촉진하는 테스토스테론의 주요 근원지 이므로, 홍경천 추출물과 쏘팔메토 복합 추출물이 세포 내 테스토스테론 농도에 미치는 영향을 확인하였다. As it was confirmed that single treatment of saw palmetto extract induces concentration-dependent cytotoxicity in testis cells, it was confirmed that the combined extract of honggyeongcheon and saw palmetto could inhibit cytotoxicity. And, since testis cells are the main source of testosterone that promotes sperm formation, the effect of the extract of honggyeongcheon and saw palmetto complex on the concentration of testosterone in cells was confirmed.
그 결과 [도 6A]에서 나타난 바와 같이, 쏘팔메토 추출물을 단독으로 처리했을 때보다 복합 추출물을 동일한 양으로 처리했을 때 세포생존율이 유의적으로 증가하였고, 세포생존율 증가에 의해 LDH 활성은 유의적으로 감소하였다. As a result, as shown in [Fig. 6A], cell viability was significantly increased when the complex extract was treated with the same amount than when the saw palmetto extract was treated alone, and LDH activity was significantly increased by the increase in cell viability. Decreased to.
또한 세포 내 테스토스테론 농도는 쏘팔메토 추출물 50 ug/mL과 100 ug/mL에서 농도 의존적으로 감소하여 각각 2.4, 1.2 pg/mL로 나타난 반면, 홍경천 추출물과 복합 처리하였을 때에는 점차적으로 증가하여 100 ug/mL 농도에서는 대조군에 비해서도 높게 나타났다(도 6B). 즉, 쏘팔메토 추출물 단독 처리군에 비해 복합 추출물을 처리하였을 때에 세포독성에 의한 세포사멸을 억제시킴으로써 테스토스테론 함량을 증가시키는 것으로 생각된다. In addition, the concentration of intracellular testosterone decreased in a concentration-dependent manner at 50 ug/mL and 100 ug/mL of saw palmetto extract, resulting in 2.4 and 1.2 pg/mL, respectively, whereas when combined with Rhododendron extract, it gradually increased and increased to 100 ug/mL. The mL concentration was also higher than that of the control group (Fig. 6B). In other words, it is thought that the testosterone content increased by suppressing apoptosis due to cytotoxicity when the complex extract was treated compared to the saw palmetto extract alone treatment group.
<4-2> 전립선 정상세포에 대한 상승적 세포사멸 억제 효과 확인<4-2> Confirmation of synergistic apoptosis inhibitory effect on normal prostate cells
쏘팔메토 추출물의 단독 처리에 의해 전립선 정상세포에서 농도 의존적인 세포독성이 유도됨을 확인함에 따라 홍경천과 쏘팔메토 복합 추출물이 세포독성을 억제할 수 있는지 확인하였다.As it was confirmed that concentration-dependent cytotoxicity was induced in normal prostate cells by treatment with saw palmetto extract alone, it was confirmed that the combined extract of honggyeongcheon and saw palmetto could inhibit cytotoxicity.
그 결과 [도 7]에 나타난 바와 같이, 정소세포에서 나타난 저해효과와 동일하게 전립선 정상세포에서도 복합 추출물 내 홍경천 추출물의 농도가 증가할수록 전립선 정상세포의 생존율이 증가하고, LDH 활성은 감소하는 것으로 나타났다.As a result, as shown in [Fig. 7], it was found that the survival rate of normal prostate cells increased and the LDH activity decreased as the concentration of the honggyeongcheon extract in the complex extract increased in the normal prostate cells, similar to the inhibitory effect shown in testis cells. .
[참고문헌][references]
[1] Wilt TJ, Ishani A, Stark G. 1998. Saw palmetto extracts for treatment of benign prostatic hyperplasia. JAMA 280: 1604-1609.[1] Wilt TJ, Ishani A, Stark G. 1998. Saw palmetto extracts for treatment of benign prostatic hyperplasia. JAMA 280: 1604-1609.
[2] Tacklind J, MacDonald R, Rutks I. 2009. Serenoa repens for benign prostatic hyperplasia. Cochrane Database Syst Rev 2: 1423. [2] Tacklind J, MacDonald R, Rutks I. 2009. Serenoa repens for benign prostatic hyperplasia. Cochrane Database Syst Rev 2: 1423.
[3] Avins AL, Bent S. 2006. Saw palmetto and lower urinary tract symptoms: what is the latest evidence? Curr Urol Reports 7: 260-265.[3] Avins AL, Bent S. 2006. Saw palmetto and lower urinary tract symptoms: what is the latest evidence? Curr Urol Reports 7: 260-265.
[4] Bent S, Kane C, Shinohara K. 2006. Saw palmetto for benign prostatic hyperplasia. N Engl J Med 354: 557-566. [4] Bent S, Kane C, Shinohara K. 2006. Saw palmetto for benign prostatic hyperplasia. N Engl J Med 354: 557-566.
[5] Avins AL, Bent S, Staccone S. 2008. A detailed safety assessment of a saw palmetto extract. Complement Ther Med 2008:147-154. [5] Avins AL, Bent S, Staccone S. 2008. A detailed safety assessment of a saw palmetto extract. Complement Ther Med 2008:147-154.
[6] Barry MJ, Meleth S, Lee JY, et al. 2011. Effect of increasing doses of saw palmetto extract on lower urinary tract symptoms: a randomized trial. JAMA 306: 1344-1351. [6] Barry MJ, Meleth S, Lee JY, et al. 2011. Effect of increasing doses of saw palmetto extract on lower urinary tract symptoms: a randomized trial. JAMA 306: 1344-1351.
[7] Avins AL, Lee JY, Meyers CM, Barry MJ. 2013. Safety and toxicity of Saw palmetto in the complementary and alternative medicine for urological symptoms (CAMUS) trial. J Urol 189: 1415-1420.[7] Avins AL, Lee JY, Meyers CM, Barry MJ. 2013. Safety and toxicity of Saw palmetto in the complementary and alternative medicine for urological symptoms (CAMUS) trial. J Urol 189: 1415-1420.
[8] 식품안전정보원. 2017. 재평가 실시를 위한 기능성원료 등의 자료조사 연구. [8] Food Safety Information Service. 2017. Research on data research on functional raw materials for re-evaluation.
[9] Ming DS, Hillhouse BJ, Guns ES, Eberding A, Xie S, Vimalanathan S, Towers GH. 2005. Bioactive compounds from Rhodiola rosea (Crassulaceae). Phytother Res 19: 740-743. [9] Ming DS, Hillhouse BJ, Guns ES, Eberding A, Xie S, Vimalanathan S, Towers GH. 2005. Bioactive compounds from Rhodiola rosea (Crassulaceae). Phytother Res 19: 740-743.
[10] Panossian A, Wikman G, Sarris J. 2010. Rosen root (Rhodiola rosea): traditional use, chemical composition, pharmacology and clinical efficacy. Phytomedicine 17: 481-493.[10] Panossian A, Wikman G, Sarris J. 2010. Rosen root (Rhodiola rosea): traditional use, chemical composition, pharmacology and clinical efficacy. Phytomedicine 17: 481-493.
Claims (8)
Rhodiola sachalinensis ( Rhodiola sachalinensis ) A pharmaceutical composition for the prevention or treatment of prostatic hyperplasia containing an extract as an active ingredient.
Rhodiola sachalinensis ( Rhodiola sachalinensis ) A pharmaceutical composition for the prevention or treatment of prostatic hyperplasia containing an extract and saw palmetto extract as active ingredients.
상기 홍경천 추출물은 홍경천 분말을 에탄올 용액에 침지한 후 초음파 추출하여 제조한 것을 특징으로 하는 약학적 조성물.
The method according to claim 1 or 2,
The honggyeongcheon extract is a pharmaceutical composition, characterized in that prepared by ultrasonic extraction after immersing the honggyeongcheon powder in an ethanol solution.
상기 홍경천 추출물 및 쏘팔메토 추출물이 조합되어 전립선비대증 세포 사멸 효과가 상승되는 것을 특징으로 하는 약학적 조성물.
The method of claim 2,
The pharmaceutical composition, characterized in that the combination of the honggyeongcheon extract and saw palmetto extract increases the prostatic hyperplasia cell killing effect.
상기 홍경천 추출물 및 쏘팔메토 추출물이 조합되어 정소세포 및 전립선 정상세포에 대한 독성이 감소되는 것을 특징으로 하는 약학적 조성물.
The method of claim 2,
Pharmaceutical composition, characterized in that the combination of the honggyeongcheon extract and saw palmetto extract reduce toxicity to testicular cells and normal prostate cells.
상기 쏘팔메토 추출물은 쏘팔메토 열매 추출물인 것을 특징으로 하는 약학적 조성물.
The method of claim 2,
The saw palmetto extract is a pharmaceutical composition, characterized in that the saw palmetto fruit extract.
상기 홍경천 추출물 및 쏘팔메토 추출물은 1:2 내지 2:1의 중량비로 포함되는 것인, 약학적 조성물.
The method of claim 2,
The honggyeongcheon extract and saw palmetto extract will be contained in a weight ratio of 1:2 to 2:1, pharmaceutical composition.
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