KR20200025093A - Composition for preventing or treating prostatic diseases comprising Stauntonia hexaphylla extract and Cornus officinalis as active ingredients - Google Patents
Composition for preventing or treating prostatic diseases comprising Stauntonia hexaphylla extract and Cornus officinalis as active ingredients Download PDFInfo
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- KR20200025093A KR20200025093A KR1020180101933A KR20180101933A KR20200025093A KR 20200025093 A KR20200025093 A KR 20200025093A KR 1020180101933 A KR1020180101933 A KR 1020180101933A KR 20180101933 A KR20180101933 A KR 20180101933A KR 20200025093 A KR20200025093 A KR 20200025093A
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- extract
- cornus
- honey
- prostate
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Abstract
Description
본 발명은 멀꿀(Stauntonia hexaphylla) 추출물 및 산수유(Cornus officinalis Sieb. et Zucc) 추출물을 유효성분으로 함유하는 전립선 질환의 예방 또는 치료용 조성물에 관한 것이다.
The invention meolkkul (Stauntonia Hexaphylla ) and Cornus officinalis Sieb. et Zucc) relates to a composition for the prevention or treatment of prostate disease containing as an active ingredient.
전립선은 샘조직과 섬유근조직으로 구성된 부속 생식샘으로 정액을 생성, 분비하는 역할을 한다. 전립선에서 만들어진 전립선액은 정소에서 만들어져서 이동해 온 정자에게 영양을 공급하며, 사정된 정액이 굳지 않도록 액체 상태를 유지시킴으로써 정자가 활발하게 운동할 수 있도록 돕는다. 대표적인 전립선 관련 질환으로는 전립선 비대증, 전립선 암 및 전립선염을 들 수 있다.
The prostate is an accessory gonad consisting of gland tissue and fibromyalgia, which produces and secretes semen. Prostate fluid produced in the prostate gland provides nutrition to the sperm that is made in the testis and moves, and helps the sperm to exercise actively by maintaining the liquid state so that the ejaculated semen does not harden. Representative prostate disorders include enlarged prostate, prostate cancer and prostatitis.
전립선 비대증(Benign prostatic hyperplasia, BPH)은 성인 남성에게 흔하게 나타나는 질병의 하나로 50세 이상의 남성의 50%, 80세 이상의 남성의 80% 이상이 이환되는 것으로 보고되고 있어 남성 요로 장애 중 가장 높은 빈도를 차지한다. 한국의 전립선 비대증 환자의 수는 2006년 45만9천명 정도에서 2011년 84만2천명으로 83.5%의 증가율을 나타내며 최근 그 발병이 급속히 증가하고 있다.Benign prostatic hyperplasia (BPH) is one of the most common diseases in adult men, with 50% of men over 50 years old and 80% of men over 80 years old reported the highest frequency of urinary tract disorders. do. The number of patients with prostatic hyperplasia in Korea increased from 45,999 in 2006 to 842,000 in 2011, an increase of 83.5%, and the incidence has recently increased rapidly.
일반적으로 성인의 전립선의 크기는 20g 정도이나, 전립선이 비정상적인 크기로 비대해져 40~400g의 크기로 커지게 되면, 가까이 있는 요로를 압박하여 하루 8회 이상 소변을 보는 빈뇨, 야간 빈뇨, 강하고 갑작스런 요의를 느끼면서 소변이 마려우면 참을 수 없는 절박뇨 등의 방광 저장 증상과 소변을 볼 때 뜸을 들여야 소변이 나오는 지연뇨나 소변의 흐름이 끊기는 단절뇨, 비뇨 시 힘을 주어야 하는 현상 등 방광의 배출 장애 증상이 나타나게 된다. 전립성 비대증을 가진 환자들은 요로폐색이나 기타 합병증이 없으면 외과적 치료를 할 필요는 없으나 80세까지 약 50% 정도는 치료가 필요한 실정이다. 또한 전립성 비대증의 환자 중 일부가 전립선 암과 관련되어 있으며, 그 자체가 치명적인 질환은 아니지만 삶의 질을 저하시킨다는 점에서 초고령화 사회로 진입하고 있는 현 사회의 중요한 의료문제로 대두되고 있다.In general, the size of an adult's prostate is about 20g, but when the prostate enlarges to an abnormal size and grows to 40-400g, urinary pressure, urinary frequency, and urinary urine that squeeze the urinary tract at least 8 times a day Symptoms of bladder storage, such as impure urinary urinary tract and urine when urinating, delayed urine when the urine is released, severed urine that interrupts the flow of urine, or the need to give strength during urination Will appear. Patients with prostatic hypertrophy do not need surgical treatment without urinary obstruction or other complications, but about 50% of patients need to be treated by age 80. In addition, some of the patients with prostatic hyperplasia are associated with prostate cancer, which is not a fatal disease in itself, but it is emerging as an important medical problem in the current society entering the aging society because it lowers the quality of life.
전립선 비대증의 치료방법은 초기에는 거의 수술을 수행하였으나, 80년대 후반부터는 약물 투여방법으로 급속도로 변화하고 있다. 그러나 종래 전립성 비대증의 치료에 사용되는 약물들은 많은 부작용을 나타내고 있고 그 효능에 한계가 있어, 부작용이나 약물 내성을 유발하지 않고, 치료효과가 우수한 새로운 치료제의 개발이 필요하다.
Surgical treatment for enlarged prostate was almost performed at the beginning, but since the late 80's, it has been rapidly changed to drug administration. However, the drugs used in the treatment of conventional prostatic hypertrophy have many side effects and are limited in their efficacy, and thus, it is necessary to develop new therapeutic agents having excellent therapeutic effects without causing side effects or drug resistance.
전립선암은 서양의 경우 남성암 중 가장 흔한 암으로 높은 발생 빈도를 보이며, 우리나라인 경우에도 그 빈도가 급격히 증가하고 있다. 전립선암의 치료는 병의 진행단계에 따라 차이가 있는데, 국소암의 경우 근본적인 치료를 목적으로 치료를 하지만 전이암의 경우에는 전신치료를 시행하게 된다. 국소성 전립선암의 치료를 위해서는 대기요법, 근치적 전립선 적출술, 방사선 요법을 환자의 연령, 건강상태, 성기능 상태, 종양의 병기와 분화도, 환자의 선호도 등을 고려하여 선택할 수 있다. 전이성 전립선암은 호르몬 치료나, 항암요법을 시행할 수 있다.
Prostate cancer is the most common cancer among male cancers in the West, and the incidence of prostate cancer is increasing rapidly in Korea. The treatment of prostate cancer differs according to the stage of the disease. Local cancer is treated for the purpose of radical treatment, but metastatic cancer is treated systemically. For the treatment of localized prostate cancer, atmospheric therapy, radical prostatectomy, and radiation therapy may be selected in consideration of the age, health status, sexual function, tumor stage and differentiation, and patient preference. Metastatic prostate cancer can be treated with hormones or with chemotherapy.
전립선염은 전립선에 염증이 생기는 질병으로, 성인 남성의 약 50%가 평생동안 한번은 증상을 경험한다고 할 정도로 흔한 질환이다. 요로계 감염 시 세균이 요도를 통해 직접 감염이 되는 경우가 가장 흔하며, 이 외에도 전립선액의 배설장애, 전립선 내로의 요 역류, 치질이나 대장염과 같은 염증의 전염 등으로도 야기될 수 있다.
Prostatitis is an inflammation of the prostate gland and is so common that about 50% of adult men experience symptoms once in their lifetime. Urinary tract infections are most often caused by direct infection of bacteria through the urethra, and can also be caused by disorders of excretion of prostate fluid, urinary tract flow into the prostate, and transmission of inflammation such as hemorrhoids or colitis.
상기 전립선암, 전립선 비대증, 전립선염과 같은 전립선 질환은 남성호르몬인 안드로겐과 연관이 있기 때문에 안드로겐 수용체의 발현을 억제하는 항안드로겐 약물에 의해 질환의 치료와 예방 효과 또는 증상의 완화 효과를 얻을 수 있다. 또한, 전립선 특이항원의 발현을 억제하는 전립선 특이항원 억제제 역시 전립선 특이항원의 영향을 받는 상기 전립선 질환의 예방 및 치료/증상 개선에 효과가 있다. 아울러, 남성호르몬을 억제하는 5-알파 환원효소(5-alpha reductase) 억제제가 남성호르몬에 의해 유발되는 남성 질환, 예컨대 전립선비대증, 털빠짐 등의 치료에 사용되고 있다. 보다 구체적으로 남성호르몬인 테스토스테론(testosterone)을 디하이드로테스토스테론(Dihydrotestosterone, DHT)으로 전환시키는 5-알파 환원효소는 미세소체(microsome)의 NADPH 의존성 3-oxo-5α-steroid-dehydrogenase로서 테스토스테론과 같은 이중 결합 스테로이드를 환원시킨다. 5-알파 환원효소는 1형과 2형, 그리고 3형의 아형을 가지며 1형은 주로 피부와 간조직 등의 여러 장기에 존재하고, 2형은 간과 전립선을 포함한 요로생식기에 주로 존재한다. 테스토스테론은 전립선 조직 내에서 5-알파 환원효소에 의해 90% 이상 디하이드로테스토스테론으로 변환되며 디하이드로테스토스테론이 테스토스테론의 대략 10배 이상의 활성도로 전립선 성장을 촉진한다. 따라서, 5-알파 환원효소를 효율적으로 억제하게 되면 생리적 활성이 강한 디하이드로테스토스테론의 합성을 감소시켜 결국, 전립선 비대증을 개선 내지 치료할 수 있다. 또한, 전립선 비대증과 마찬가지로 5-알파 환원효소에 의해 디하이드로테스토스테론이 과량 합성되게 되면 디하이드로테스토스테론이 모낭 주변의 안드로겐 수용체에 결합하여 점점 모낭을 축소 및 황폐화하여 털빠짐 현상이 나타내게 된다. 따라서 5-알파 환원효소를 효율적으로 억제하여 털빠짐을 개선 내지 치료할 수 있다.
Since prostate diseases such as prostate cancer, enlarged prostate, and prostatitis are associated with androgen, a male hormone, anti-androgen drugs that inhibit the expression of androgen receptors can provide a therapeutic and prophylactic effect or relief of symptoms. . In addition, prostate specific antigen inhibitors that inhibit the expression of prostate specific antigens are also effective in the prevention and treatment / symptom improvement of the prostate disease affected by prostate specific antigens. In addition, 5-alpha reductase inhibitors that inhibit male hormones have been used for the treatment of male diseases caused by male hormones such as prostatic hypertrophy and hair loss. More specifically, 5-alpha reductase, which converts testosterone, a male hormone, to dihydrotestosterone (DHT), is a microsome's NADPH-dependent 3-oxo-5α-steroid-dehydrogenase, a testosterone-like Reduce the binding steroid. 5-alpha reductase has type 1,
한편, 멀꿀은 우리나라의 전남, 경남, 충남 등 남쪽지방의 계곡이나 숲 속에서 볼 수 있으며, 으름덩굴과의 상록 덩굴식물로 학명은 Stauntonia Hexaphylla이다. 줄기와, 잎, 뿌리는 약재로 사용하며, 항염증, 해열, 진통 효과가 뛰어난 것으로 알려져 있다. 또한 심장이 약하거나 불완전할 때 기능을 정상으로 돌이키는 데 사용하는 강심제나, 체내의 불필요한 수분의 배출을 촉진하는 이뇨제로도 사용된다. 이외에도 피하지방 축적의 억제, 관절질환, 자궁근종이나 안면신경통 등에도 효과가 있다고 알려져 있다.
On the other hand, honey can be found in valleys and forests in the southern regions of South Korea such as Jeonnam, Gyeongnam, and Chungnam, and is an evergreen vine plant with creeping vines. The scientific name is Stauntonia Hexaphylla. Stems, leaves, and roots are used as medicinal herbs and are known for their anti-inflammatory, antipyretic, analgesic effects. It can also be used as a cardiac medicine used to return function to normal when the heart is weak or incomplete, or as a diuretic to promote the release of unnecessary water from the body. In addition, it is known to be effective in inhibiting subcutaneous fat accumulation, joint diseases, myoma and facial neuralgia.
산수유 (Corni Fructus)의 기원은 Cornus officinalis Siebold et Zuccarini (층층나무과, Cornaceae)의 잘 익은 열매로서 씨를 제거한 것이다. 불규칙한 조각 또는 주머니 모양이고, 길이 10 ∼ 15 mm, 너비 약 1 cm이다. 바깥 면은 어두운 적자색 ∼ 어두운 보라색을 띠며 윤이 나고 거친 주름이 있다. 과육에는 씨를 빼낸 자국이 있고 위쪽에는 꽃받침 자국이 있으며 아래쪽에는 열매꼭지 자국이 있다. 질은 부드럽고, 약간의 냄새가 있으며 맛은 시고 약간 달다. 산수유는 이뇨, 혈압강하작용, 자양작용, 항알러지 작용, 항히스타민 작용, 항아세틸콜린 작용, 항바륨 작용을 나타내며, 항미생물(항진균) 작용 등에 효과가 있는 것으로 알려져 있다.
Cornus Fructus is Cornus officinalis Siebold et Zuccarini (Cornaceae) is the ripe fruit of the seed removed. It is an irregular piece or bag shape, 10-15 mm long, and about 1 cm wide. The outer surface is dark reddish purple to dark purple with shiny and rough wrinkles. The pulp has seed marks, the upper part of the calyx and the lower part of the fruit stalk. The vagina is soft, has a slight smell, tastes sour and slightly sweet. Cornus milk is known to have diuretic, hypotensive, nourishing, anti-allergic, antihistamine, antiacetylcholine, antibarium and antimicrobial effects.
이에, 본 발명자들은 안전성이 확보되어 부작용이 없는 천연물 유래 전립선 질환 치료제를 개발하기 위해 노력한 결과, 멀꿀 및 산수유 복합 추출물은 세포독성이 없고, 안드로겐 수용체, 전립선 특이항원 및 전립선 특이효소의 발현 저해 효과가 우수함을 확인하여, 전립선 질환 예방 또는 치료용 조성물의 유효성분으로 이용할 수 있음을 밝힘으로써, 본 발명을 완성하였다.
Therefore, the present inventors tried to develop a natural product-derived prostate disease treatment agent with no side effects as a result of ensuring safety, the honey and corn coriander extract has no cytotoxicity, and inhibits the expression of androgen receptor, prostate specific antigen and prostate specific enzyme. By confirming the superiority, the present invention was completed by revealing that it can be used as an active ingredient of a composition for preventing or treating prostate disease.
본 발명의 목적은 멀꿀(Stauntonia hexaphylla) 추출물 및 산수유(Cornus officinalis Sieb. et Zucc) 추출물을 유효성분으로 함유하는, 전립선 질환의 예방 또는 치료용 조성물을 제공하기 위한 것이다.
An object of the present invention is meolkkul (Stauntonia Hexaphylla ) and Cornus officinalis Sieb. et Zucc extract to provide a composition for the prevention or treatment of prostate disease, containing as an active ingredient.
상기 목적을 달성하기 위하여, 본 발명은 멀꿀(Stauntonia hexaphylla) 추출물 및 산수유(Cornus officinalis Sieb. et Zucc) 추출물을 유효성분으로 함유하는, 전립선 질환의 예방 또는 치료용 약학 조성물을 제공한다.In order to achieve the above object, the present invention meolkkul (Stauntonia hexaphylla extract and Cornus officinalis Sieb. et Zucc) provides a pharmaceutical composition for the prevention or treatment of prostate disease, containing the extract as an active ingredient.
또한, 본 발명은 멀꿀 추출물 및 산수유 추출물을 유효성분으로 함유하는, 전립선 질환의 예방 또는 개선용 건강식품을 제공한다.The present invention also provides a health food for the prevention or improvement of prostate disease, containing the honey extract and cornus extract as an active ingredient.
아울러, 본 발명은 멀꿀 추출물 및 산수유 추출물을 유효성분으로 함유하는, 전립선 질환의 예방 또는 개선용 식품 조성물을 제공한다.
In addition, the present invention provides a food composition for the prevention or improvement of prostate disease, containing the honey extract and cornus extract as an active ingredient.
본 발명의 멀꿀 및 산수유 복합 추출물은 세포독성이 없고, 안드로겐 수용체, 전립선 특이항원 및 전립선 특이효소의 발현 저해 효과가 우수하므로, 전립선 질환 예방 또는 치료용 조성물의 유효성분으로 이용할 수 있다.
The honey and corn coriander extract of the present invention has no cytotoxicity, and has an excellent inhibitory effect on the expression of androgen receptors, prostate specific antigens and prostate specific enzymes, and thus can be used as an active ingredient for preventing or treating prostate disease.
도 1은 LNCaP 세포에 본 발명의 실시예에서 제조한 멀꿀(Stauntonia hexaphylla) 추출물, 산수유(Cornus officinalis Sieb. et Zucc) 추출물, 또는 멀꿀 및 산수유 복합 추출물을 각각 0, 10, 25, 50 ㎍/㎖로 처리한 후 세포 독성을 확인한 도이다.
도 2는 LNCaP 세포에 테스토스테론 1 μM과 함께 본 발명의 실시예에서 제조한 멀꿀 추출물 25, 50 ㎍/㎖ , 산수유 추출물 50 ㎍/㎖, 또는 멀꿀 및 산수유 복합 추출물 25 ㎍/㎖을 처리한 후 AR, PSA 및 5α-reductase 2 단백질 발현 변화를 확인한 도이다. 1 is an extract of the honey ( Stauntonia hexaphylla ) prepared in the embodiment of the present invention in LNCaP cells, cornus ( Cornus) officinalis Sieb. et Zucc) extract, or a combination of honey and
Figure 2 is treated with 1 μM testosterone 1 μM LNCaP cells in the
이하, 본 발명을 보다 상세히 설명한다.
Hereinafter, the present invention will be described in more detail.
본 발명은 멀꿀(Stauntonia hexaphylla) 추출물 및 산수유(Cornus officinalis Sieb. et Zucc) 추출물을 유효성분으로 함유하는, 전립선 질환의 예방 또는 치료용 약학 조성물을 제공한다.The invention meolkkul (Stauntonia It provides a pharmaceutical composition for the prevention or treatment of prostate disease, containing hexaphylla ) extract and Cornus officinalis Sieb. et Zucc extract as an active ingredient.
본 발명의 유효성분인 멀꿀 추출물 및 산수유 추출물 각각은 하기의 단계들을 포함하는 방법에 의해 제조되는 것이 바람직하나, 이에 한정되지 않는다: Each of the honey extract and cornus extract, which are the active ingredients of the present invention, is preferably prepared by a method comprising the following steps, but is not limited thereto:
1) 멀꿀 및 산수유 각각에 추출용매를 가하여 추출하는 단계;1) extracting by adding an extraction solvent to each of honey and cornus;
2) 단계 1)의 추출물을 여과하는 단계;2) filtering the extract of step 1);
3) 단계 2)의 여과물을 감압 농축하는 단계; 및3) concentrating the filtrate of step 2) under reduced pressure; And
4) 단계 3)의 농축물을 건조하는 단계.4) drying the concentrate of step 3).
본 발명의 제조방법에 있어서, 단계 1)의 멀꿀 또는 산수유는 재배한 것 또는 시판되는 것을 제한 없이 사용할 수 있다. 또한, 상기 멀꿀은 멀꿀의 꽃, 가지, 줄기, 잎, 열매, 지상부, 뿌리줄기, 뿌리 또는 이들의 조합을 사용할 수 있고, 보다 구체적으로 멀꿀 잎을 사용할 수 있다.In the production method of the present invention, the honey or cornus of step 1) can be used without limitation, those grown or commercially available. In addition, the honey may be used for flowers, branches, stems, leaves, fruits, ground, root stems, roots, or a combination thereof, and more specifically, honey leaves of honey.
본 발명의 제조방법에 있어서, 상기 단계 1)의 추출용매는 물, 알코올 또는 이의 혼합물을 사용하는 것이 바람직하다. 상기 알코올로는 C1 내지 C2의 저급 알코올 이용하는 것이 바람직하며, 저급 알코올로는 에탄올 또는 메탄올을 이용하는 것이 바람직하다. 추출방법으로는 진탕추출, Soxhelt 추출 또는 환류 추출을 이용하는 것이 바람직하나, 이에 한정되지 않는다. 상기 추출용매를 건조된 멀꿀 또는 산수유 분량의 1 내지 20배 첨가하여 추출하는 것이 바람직하고, 3 내지 17배 첨가하여 추출하는 것이 보다 바림직하며, 5 내지 15배 첨가하여 추출하는 것이 보다 더 바람직하다. 추출 온도는 10 내지 100인 것이 바람직하나, 이에 한정되지 않는다. 또한, 추출시간은 1 내지 72시간이 바람직하나, 이에 한정되지 않는다. 아울러 추출 횟수는 1 내지 5회인 것이 바람직하며, 3 내지 4회 반복 추출하는 것이 보다 바람직하고, 3회인 것이 보다 더 바람직하나, 이에 한정되지 않는다. In the production method of the present invention, the extraction solvent of step 1) is preferably water, alcohol or a mixture thereof. As the alcohol, C 1 to C 2 lower alcohols are preferably used, and as lower alcohols, ethanol or methanol is preferably used. As the extraction method, it is preferable to use shaking extraction, Soxhelt extraction or reflux extraction, but is not limited thereto. The extraction solvent is preferably extracted by adding 1 to 20 times the amount of dried honey or cornus oil, more preferably by adding 3 to 17 times, and more preferably by adding 5 to 15 times. . The extraction temperature is preferably 10 to 100, but is not limited thereto. In addition, the extraction time is preferably 1 to 72 hours, but is not limited thereto. In addition, the number of extraction is preferably 1 to 5 times, more preferably 3 to 4 repetitions, even more preferably 3 times, but is not limited thereto.
본 발명의 제조방법에 있어서, 단계 3)의 감압농축은 진공 감압 농축기 또는 진공회전증발기를 이용하는 것이 바람직하나 이에 한정되지 않는다. 또한, 건조는 감압건조, 진공건조, 비등건조, 분무건조 또는 동결건조하는 것이 바람직하나 이에 한정되지 않는다. In the production method of the present invention, the reduced pressure concentration of step 3) is preferably a vacuum reduced pressure concentrator or a vacuum rotary evaporator, but is not limited thereto. In addition, the drying is preferably reduced pressure drying, vacuum drying, boiling drying, spray drying or freeze drying, but is not limited thereto.
본 발명의 제조방법에 있어서, 상기 멀꿀 추출물 및 산수유 추출물은 각각의 추출물을 제조한 후 혼합할 수 있으나, 멀꿀 및 산수유를 혼합한 후 이의 추출물을 수득하는 형태로 제조되는 것도 가능하다.In the production method of the present invention, the honey extract and cornus extract may be mixed after the preparation of each extract, it is also possible to be prepared in the form of obtaining the extract after mixing the honey and cornus.
상기 조성물은 멀꿀 추출물 : 산수유 추출물을 5 : 5 내지 9.5 : 0.5의 중량비로 함유할 수 있고, 구체적으로 6 : 4 내지 9.5 : 0.5의 중량비로 함유할 수 있으며, 보다 구체적으로 7 : 3 내지 9.5 : 0.5의 중량비로 함유할 수 있고, 보다 더 구체적으로 8 : 2 내지 9.5 : 0.5의 중량비로 함유할 수 있으며, 보다 더 구체적으로 8.5 : 2.5 내지 9.5 : 0.5의 중량비로 함유할 수 있다. The composition may contain a honey extract: cornus extract in a weight ratio of 5: 5 to 9.5: 0.5, specifically may be contained in a weight ratio of 6: 4 to 9.5: 0.5, more specifically 7: 3: to 9.5: It may be contained in a weight ratio of 0.5, more specifically may be contained in a weight ratio of 8: 2 to 9.5: 0.5, and more specifically may be contained in a weight ratio of 8.5: 2.5 to 9.5: 0.5.
상기 전립선 질환은 예를 들어 전립선암, 전립선 비대증 또는 전립선염일 수 있다.
The prostate disease can be, for example, prostate cancer, enlarged prostate or prostatitis.
본 발명의 구체적인 실시예에서, 본 발명자들은 멀꿀 잎 70% 주정 추출물 및 산수유 70% 주정 추출물을 제조하고, 상기 추출물을 다양한 혼합 비율로 혼합하여 멀꿀 및 산수유 복합 추출물을 제조하였다.In a specific embodiment of the present invention, the present inventors prepared honey extract 70% ethanol extract and wild corn 70% ethanol extract, and mixed the extract in various mixing ratios to prepare a complex extract of honey and cornus.
또한, 본 발명자들은 전립선암 세포에서 상기 멀꿀 및 산수유 복합 추출물의 세포 독성을 확인한 결과, 상기 복합 추출물이 다양한 농도에서 세포 독성이 없음을 확인하였다(도 1 참조).In addition, the present inventors confirmed the cytotoxicity of the honey and cornus extract in the prostate cancer cells, it was confirmed that the complex extract is not cytotoxic at various concentrations (see Figure 1).
또한, 본 발명자들은 테스토스테론과 함께 상기 멀꿀 및 산수유 복합 추출물을 처리한 전립선암 세포에서 안드로겐 수용체(AR), 전립선 특이항원(PSA) 및 전립선 특이효소(5α-reductase 2)의 단백질 발현을 확인한 결과, 상기 복합 추출물이 AR, PSA 및 5α-reductase 2의 단백질 발현 억제 효과가 우수함을 확인하였다(도 2 참조).In addition, the present inventors confirmed the protein expression of androgen receptor (AR), prostate specific antigen (PSA) and prostate specific enzyme (5α-reductase 2) in prostate cancer cells treated with the honey and cornus complex extract with testosterone, The complex extract was confirmed to have excellent protein, inhibitory effect of AR, PSA and 5α-reductase 2 (see Fig. 2).
따라서, 본 발명자들은 본 발명의 멀꿀 및 산수유 복합 추출물이 세포독성이 없고, 안드로겐 수용체, 전립선 특이항원 및 전립선 특이효소의 발현 저해 효과가 우수함을 확인하였으므로, 본 발명의 멀꿀 및 산수유 복합 추출물을 전립선 질환 예방 또는 치료용 약학 조성물, 또는 테스토스테론에 의해 유발되는 남성 질환, 예컨대 털빠짐 예방 또는 치료용 약학 조성물의 유효성분으로 유용하게 이용할 수 있다.
Therefore, the present inventors have confirmed that the honey and cornus complex extract of the present invention has no cytotoxicity, and the effect of inhibiting the expression of androgen receptor, prostate specific antigen and prostate specific enzyme, the honey and cornus complex extract of the present invention is prostate disease It can be usefully used as a prophylactic or therapeutic pharmaceutical composition, or as an active ingredient of a male composition caused by testosterone, such as a pharmaceutical composition for preventing or treating hair loss.
본 발명의 조성물은 경구 또는 비경구 투여(예를 들어, 도포 또는 정맥 내, 피하, 복강 내 주사)할 수 있다. 비투여를 위한 제제로는 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 멸균된 수용액, 액제, 비수성용제, 현탁제, 에멀젼, 시럽, 좌제, 에어로졸 등의 외용제 및 멸균 주사제제의 형태로 제형화하여 사용될 수 있으며, 바람직하게는 크림, 젤, 패취, 분무제, 연고제, 경고제, 로션제, 리니멘트제, 파스타제 또는 카타플 라스마제의 피부 외용 약학적 조성물을 제조하여 사용할 수 있으나, 이에 한정하는 것은 아니다. 국소 투여의 조성물은 임상적 처방에 따라 무수형 또는 수성형일 수 있다. 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. 경구 투여를 위한 고형제제에는 산제, 과립제, 정제, 캡슐제, 연질캅셀제, 환 등이 포함된다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제, 에어로졸 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다.The compositions of the present invention may be oral or parenteral (eg, applied or intravenously, subcutaneously, intraperitoneally). Formulations for non-administration may be in the form of powders, granules, tablets, capsules, sterile aqueous solutions, solutions, non-aqueous solutions, suspensions, emulsions, syrups, suppositories, aerosols, etc. It may be used in the formulation, and preferably used to prepare an external skin pharmaceutical composition of creams, gels, patches, sprays, ointments, warnings, lotions, linings, pasta or cataplasma. It is not limited to this. Compositions of topical administration may be anhydrous or aqueous, depending on the clinical prescription. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters such as ethyl oleate and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used. Solid form preparations for oral administration include powders, granules, tablets, capsules, soft capsules, pills and the like. Oral liquid preparations include suspensions, solvents, emulsions, syrups, and aerosols.In addition to commonly used simple diluents such as water and liquid paraffin, various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. Can be.
상기 조성물은 투여를 위해서 본 발명의 유효성분 이외에 추가로 약제학적으로 허용 가능한 담체를 1종 이상 포함하여 제조할 수 있다. 약제학적으로 허용 가능한 담체는 식염수, 멸균수, 링거액, 완충 식염수, 덱스트로즈 용액, 말토 덱스트린 용액, 글리세롤, 에탄올 및 이들 성분 중 1 성분 이상을 혼합하여 사용할 수 있으며, 필요에 따라 항산화제, 완충액, 정균제 등 다른 통상의 첨가제를 첨가할 수 있다. 또한 희석제, 분산제, 계면활성제, 결합제 및 윤활제를 부가적으로 첨가하여 수용액, 현탁액, 유탁액 등과 같은 주사용 제형 등으로 제제화할 수 있다.The composition may be prepared by including one or more pharmaceutically acceptable carriers in addition to the active ingredient of the present invention for administration. Pharmaceutically acceptable carriers may be used in combination with saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol and one or more of these components, if necessary, as antioxidants, buffers And other conventional additives such as bacteriostatic agents can be added. In addition, diluents, dispersants, surfactants, binders and lubricants may be additionally added to formulate injectable formulations such as aqueous solutions, suspensions, emulsions and the like.
본 발명에 따른 약제학적으로 허용가능한 첨가제는 상기 조성물에 대해 0.1 내지 90 중량부로 포함되는 것이 바람직하다.Pharmaceutically acceptable additives according to the invention are preferably included in an amount of 0.1 to 90 parts by weight based on the composition.
본 발명의 조성물의 바람직한 투여량은 체내에서 활성성분의 흡수도, 환자의 연령, 성별 및 비만의 정도에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 그러나 바람직한 효과를 위해서, 경구 투여제의 경우 일반적으로 성인에게 1일에 체중 1 kg당 본 발명의 조성물을 1일 0.0001 내지 500 mg/kg으로, 바람직하게는 0.001 내지 300 mg/kg으로, 보다 바람직하게는 0.01 내지 200 mg/kg으로 투여하는 것이 좋다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다. 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.
Preferred dosages of the compositions of the present invention vary depending on the degree of absorption of the active ingredient in the body, the age, sex and obesity of the patient, but may be appropriately selected by those skilled in the art. For the desired effect, however, oral dosages generally give the adult composition of the present invention per kg of body weight per day to 0.0001 to 500 mg / kg, preferably 0.001 to 300 mg / kg per day, more preferably. Preferably from 0.01 to 200 mg / kg. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect.
또한, 본 발명은 멀꿀 추출물 및 산수유 추출물을 유효성분으로 함유하는, 전립선 질환의 예방 또는 개선용 건강식품을 제공한다.The present invention also provides a health food for the prevention or improvement of prostate disease, containing the honey extract and cornus extract as an active ingredient.
아울러, 본 발명은 멀꿀 추출물 및 산수유 추출물을 유효성분으로 함유하는, 전립선 질환의 예방 또는 개선용 식품 조성물을 제공한다.In addition, the present invention provides a food composition for the prevention or improvement of prostate disease, containing the honey extract and cornus extract as an active ingredient.
상기 멀꿀 추출물 및 산수유 추출물, 이들의 혼합 비율, 전립선 질환은 상기 전립선 질환의 예방 또는 치료용 약학 조성물에 대한 설명과 동일한 바, 구체적인 설명은 상기 내용을 원용하고, 이하에서는 건강식품 또는 식품 조성물에 특유한 구성에 대해서만 설명하도록 한다.The honey extract and cornus extract, the mixing ratio thereof, prostate disease is the same as the description of the pharmaceutical composition for the prevention or treatment of the prostate disease, the specific description is used for the above, and the following specific to health food or food composition Only the configuration will be described.
한편, 본 발명의 멀꿀 및 산수유 복합 추출물은 세포독성이 없고, 안드로겐 수용체, 전립선 특이항원 및 전립선 특이효소의 발현 저해 효과가 우수함을 확인하였으므로, 본 발명의 복합 추출물을 전립선 질환의 예방 또는 개선용 건강식품 또는 식품 조성물의 유효성분으로 유용하게 이용할 수 있다. 또한, 본 발명의 복합 추출물을 테스토스테론에 의해 유발되는 남성 질환, 예컨대 털빠짐 예방 또는 개선용 건강식품 또는 식품 조성물의 유효성분으로 유용하게 이용할 수 있다.
On the other hand, the honey and corn coriander extract of the present invention has no cytotoxicity, and it was confirmed that the effect of inhibiting the expression of androgen receptors, prostate specific antigens and prostate specific enzymes, the complex extract of the present invention health for the prevention or improvement of prostate disease It can be usefully used as an active ingredient of a food or food composition. In addition, the complex extract of the present invention can be usefully used as an active ingredient of a health food or food composition for preventing or improving hair loss caused by testosterone, such as male disease.
본 발명의 2종의 추출물은 식품학적으로 허용된 담체와 혼합하여 건강식품 또는 식품 조성물로서 제공될 수 있다.The two extracts of the present invention may be provided as a health food or food composition in admixture with a food acceptable carrier.
본 발명의 건강식품은 정제, 캡슐제, 환제 또는 액제 등의 형태를 포함한다.The health food of the present invention includes the form of tablets, capsules, pills or liquids.
본 발명의 2종의 추출물을 식품 또는 음료 첨가물로 사용할 경우, 상기 2종의 추출물을 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용되고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 상기 2종의 추출물의 혼합양은 그의 사용목적(예방, 건강 또는 치료적 처치)에 따라 적합하게 결정될 수 있다. 건강 및 위생을 목적으로 하거나 또는 건강조절을 목적으로 하는 장기간의 섭취의 경우, 상기 2종의 추출물은 안전성 면에서 아무런 문제가 없기 때문에, 장기간 복용이 가능하다. 상기 식품의 종류에는 특별한 제한은 없다. When the two extracts of the present invention are used as food or beverage additives, the two extracts may be added as they are or used together with other food or food ingredients, and may be suitably used according to conventional methods. The mixed amount of the two extracts may be suitably determined according to the purpose of use (prevention, health or therapeutic treatment). In the case of long-term intake for health and hygiene or health control, the two extracts can be taken for a long time because there is no problem in terms of safety. There is no particular limitation on the kind of the food.
상기 물질을 첨가할 수 있는 식품의 예로는 육류, 소세지, 빵, 초콜릿류, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알코올 음료 및 비타민 복합제 등이 있다. 음료수로 제형화할 경우에 상기 2종의 추출물 이외에 첨가되는 액체 성분으로는 이제 한정되지는 않으나, 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예는 모노사카라이드(예, 포도당, 과당 등), 디사카라이드(예, 말토오스, 수크로오스 등) 및 폴리사카라이드(예, 덱스트린, 시클로덱스트린 등과 같은 통상적인 당), 및 자일리톨, 소르비톨, 에리스리톨 등의 당 알코올이다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 mL당 일반적으로 약 1 내지 20 g, 바람직하게는 약 5 내지 12 g이다. 상술한 것 이외의 향미제로서 천연 향미제[타우마린, 스테비아 추출물(예, 레바우디오시드 A, 글리시르히진 등)] 및 합성 향미제(예, 사카린, 아스파르탐 등)를 사용할 수 있다.Examples of the food to which the substance may be added include meat, sausages, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, beverages, teas, and drinks. Alcoholic beverages and vitamin complexes. The liquid component added in addition to the two extracts when formulated into a beverage is not limited to the above, but may contain various flavors or natural carbohydrates, etc. as additional ingredients, as in conventional beverages. Examples of the aforementioned natural carbohydrates include monosaccharides (e.g. glucose, fructose, etc.), disaccharides (e.g. maltose, sucrose, etc.) and polysaccharides (e.g. conventional sugars such as dextrins, cyclodextrins, etc.), and xylitol Sugar alcohols such as sorbitol and erythritol. The proportion of said natural carbohydrates is generally about 1-20 g, preferably about 5-12 g per 100 mL of the composition of the present invention. As flavoring agents other than those mentioned above, natural flavoring agents (taumarin, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (e.g., saccharin, aspartame, etc.) can be used. .
또한, 본 발명의 식품 조성물은 여러 가지 영양제, 비타민, 무기질(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 증진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 또한 본 발명의 식품 조성물은 과일 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 단독으로 또는 조합으로 사용될 수 있으며, 이러한 첨가제의 비율은 조성물 전체 중량당 0.001 내지 50 중량부의 범위에서 선택되는 것이 일반적이다.
In addition, the food composition of the present invention is a variety of nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and enhancers (such as cheese, chocolate), pectic acid and salts thereof, organic acids, protection Sex colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated drinks and the like. The food composition of the present invention may also contain pulp for the production of fruit and vegetable drinks. These components may be used alone or in combination, and the ratio of such additives is generally selected in the range of 0.001 to 50 parts by weight per total weight of the composition.
이하, 본 발명을 실시예, 실험예 및 제조예에 의해 상세히 설명한다.Hereinafter, the present invention will be described in detail by Examples, Experimental Examples and Preparation Examples.
단, 하기 실시예, 실험예 및 제조예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실시예, 실험예 및 제조예에 한정되는 것은 아니다.
However, the following Examples, Experimental Examples and Preparation Examples are merely illustrative of the present invention, and the content of the present invention is not limited to the following Examples, Experimental Examples, and Preparation Examples.
<< 실시예Example 1> 1> 멀꿀Honey 추출물의 제조 Preparation of Extract
건조한 멀꿀(Stauntonia hexaphylla) 잎 20 g에 70% 주정 300 mL를 넣고 소니케이션(sonication)에 의해 12시간 동안 저온추출하였다. 이후 얻어진 추출물을 여과지로 여과하였으며, 여과 잔사를 70% 주정 300 mL로 12시간 동안 저온추출하고 여과하는 과정을 추가로 2회 반복하였다. 추출이 완료되면 여액을 합하여 감압농축 및 동결건조하는 제조공정을 통하여 멀꿀 추출물을 수득하였다.
Meolkkul dried (Stauntonia hexaphylla ) leaves 20 mL of 70% alcohol in 20 g of the leaves and extracted by cold for 12 hours by sonication (sonication). Thereafter, the obtained extract was filtered through a filter paper, and the filtered residue was further extracted twice with cold extraction with 300 mL of 70% alcohol for 12 hours and filtered. When the extraction was completed, the honey extract was obtained through the manufacturing process of combining the filtrates and concentrated under reduced pressure and lyophilization.
<< 실시예Example 2> 산수유 추출물의 제조 2> Preparation of Cornus Extract
건조한 산수유(Cornus officinalis Sieb. et Zucc) 20 g에 70% 주정 300 mL를 넣고 소니케이션(sonication)에 의해 12 시간 동안 저온추출하였다. 이후 얻어진 추출물을 여과지로 여과하였으며, 여과 잔사를 70% 주정 300 mL로 12 시간 동안 저온추출하고 여과하는 과정을 추가로 2회 반복하였다. 추출이 완료되면 여액을 합하여 감압농축 및 동결건조하는 제조공정을 통하여 산수유 추출물을 수득하였다.
Dry Cornus ( Cornus) officinalis Sieb. et Zucc) 300 g of 70% alcohol in 20 g was extracted by cold for 12 hours by sonication. Thereafter, the obtained extract was filtered through a filter paper, and the filtered residue was further extracted twice with cold extraction with 300 mL of 70% alcohol for 12 hours and filtered. When the extraction was completed, the filtrate was combined to obtain a cornus extract through a manufacturing process of concentration under reduced pressure and lyophilization.
<< 실시예Example 3> 3> 멀꿀Honey 및 산수유 복합 추출물의 제조 And Preparation of Cornus Extract
상기 <실시예 1>에서 수득한 멀꿀 추출물 및 상기 <실시예 2>에서 수득한 산수유 추출물을 하기 [표 1]의 혼합 비율로 혼합하여 멀꿀 및 산수유 복합 추출물을 제조하였다.The honey honey extract obtained in <Example 1> and the cornus extract obtained in the <Example 2> was mixed in the mixing ratio of the following [Table 1] to prepare a honey extract of the honey and cornus.
Example
<< 실험예Experimental Example 1> 1> 멀꿀Honey 및 산수유 복합 추출물의 세포 독성 확인 Cytotoxicity of Korean and Cornus Extracts
멀꿀 및 산수유 복합 추출물의 세포 독성을 알아보기 위하여, 전립선암 세포에 멀꿀 및 산수유 복합 추출물을 처리한 후 세포 생존율을 확인하였다.In order to determine the cytotoxicity of the extract of the honey and cornus extract, the survival rate of the prostate cancer cells after treatment with the honey and cornus extract was checked.
구체적으로, 남성 호르몬 의존성 사람 전립선암 세포주인 LNCaP 세포(ATCC, USA)를 10% FBS(fetal bovine serum)가 포함된 RPMI-1640 배지(Gibco)에서 37℃, 5% CO2 조건에서 배양하였다. 상기 배양 세포를 96 웰 플레이트에 1×104 cells/well의 농도로 분주하고, 18시간 동안 상기 조건과 동일한 조건에서 배양하였다. 그 다음, 배양 세포에 상기 <실시예 1>에서 제조한 멀꿀 추출물, 상기 <실시예 2>에서 제조한 산수유 추출물, 또는 상기 <실시예 3>에서 제조한 멀꿀 및 산수유 복합 추출물을 각각 0, 10, 25 또는 50 ㎍/㎖의 농도로 처리한 후 72시간 추가로 배양한 후, cell viability assay kit(EX-cytox; DaeiLab Service, 한국) 용액을 제조사의 절차에 따라 첨가하고 ELISA reader를 이용하여 450 nm에서 흡광도를 측정하여 그래프화 하였다.Specifically, LNCaP cells (ATCC, USA), a testosterone dependent human prostate cancer cell line, were cultured at 37 ° C. and 5% CO 2 in RPMI-1640 medium (Gibco) containing 10% FBS (fetal bovine serum). The cultured cells were dispensed in 96 well plates at a concentration of 1 × 10 4 cells / well and incubated for 18 hours under the same conditions. Subsequently, the honeycomb extract prepared in <Example 1>, the cornus extract prepared in <Example 2>, or the honey and cornus extract extract prepared in <Example 3> was added to the cultured cells, respectively, 0 and 10. After treatment at 25 or 50 ㎍ / ㎖ concentration, and further incubated for 72 hours, cell viability assay kit (EX-cytox; DaeiLab Service, Korea) solution was added according to the manufacturer's procedure and 450 using an ELISA reader The absorbance at nm was measured and graphed.
그 결과, 도 1에 나타낸 바와 같이, 멀꿀 및 산수유 복합 추출물은 세포 독성이 없음을 확인하였다.
As a result, as shown in Figure 1, it was confirmed that the honey and corn coriander extract is not cytotoxic.
<<
실험예Experimental Example
1> 1>
멀꿀Honey
및 산수유 복합 추출물의 PSA, AR 및 5α- And PSA, AR and 5α- of
멀꿀 및 산수유 복합 추출물이 전립선 질환 치료에 효과가 있는지 알아보기 위하여, 전립선암 세포에 테스토스테론(Testosterone)과 멀꿀 및 산수유 복합 추출물을 처리한 후 안드로겐 수용체(AR) 및 전립선 특이항원(PSA), 전립선 특이효소(5α-reductase 2)의 단백질 발현을 확인하였다.To determine whether the extracts of honey and cornus extracts are effective in the treatment of prostate disease, after treatment of testosterone, honey and cornus extracts on prostate cancer cells, androgen receptor (AR) and prostate specific antigen (PSA), prostate specificity Protein expression of the enzyme (5α-reductase 2) was confirmed.
구체적으로, LNCaP 세포(ATCC, USA)를 6 웰 플레이트에 5×104 cells/well의 농도로 분주하고, 18시간 동안 37℃에서 배양하였다. 그 다음, 배양 세포에 테스토스테론 1 μM을 처리하고, 동시에 상기 <실시예 1>에서 제조한 멀꿀 추출물 25 또는 50 ㎍/㎖, 상기 <실시예 2>에서 제조한 산수유 추출물 50 ㎍/㎖, 또는 상기 <실시예 3>에서 제조한 멀꿀 및 산수유 복합 추출물 50 ㎍/㎖의 농도로 처리한 후 72시간 추가로 배양한 후 수거하였다. 양성 대조군(BPH)으로는 추출물은 처리하지 않고 테스토스테론 1μM만을 처리하였으며, 대조군(Fina)로는 추출물 대신 전립선 비대증 치료제인 Finasteride 10μM을 테스토스테론 1μM과 함께 처리하였다. 또한, 대조군(쏘팔)로는 추출물 대신 전립선 비대증 치료제인 쏘팔메토(Saw Palmetto) 100 ㎍/㎖을 테스토스테론 1μM과 함께 처리하였다. 무처리군을 음성 대조군(Control)으로 하였다.Specifically, LNCaP cells (ATCC, USA) were dispensed in 6 well plates at a concentration of 5 × 10 4 cells / well and incubated at 37 ° C. for 18 hours. Subsequently, the cultured cells were treated with 1 μM of testosterone, and at the same time, 25 or 50 μg / ml of the honey extract prepared in <Example 1>, 50 μg / ml of the cornus extract prepared in <Example 2>, or After treating at a concentration of 50 ㎍ / ㎖ honey and cornus extract extract prepared in <Example 3> and further culture for 72 hours and harvested. As a positive control (BPH), only 1 μM of testosterone was treated without the extract, and as a control (Fina), 10 μM of finasteride, a prostate hypertrophy treatment, was treated with 1 μM of testosterone instead of the extract. In addition, as a control (sawpal), 100 μg / ml saw palmetto, a prostate hypertrophy treatment, was treated with 1 μM of testosterone instead of the extract. The untreated group was a negative control (Control).
배양 후 수거한 세포에 RIPA buffer(50 mM Tris-HCl, pH 8.0, with 150 mM sodium chloride, 1% NP-40, 0.5% sodium deoxycholate, and 0.1% sodium dodecyl sulfate, with a protease inhibitor cocktail)를 처리하고 12,000rpm의 속도로 20분간 원심분리하여 단백질을 분리하였다. 분리된 단백질은 BCA(Bicinchoninic acid) 방법으로 정량하였다.After incubation, the cells were treated with RIPA buffer (50 mM Tris-HCl, pH 8.0, with 150 mM sodium chloride, 1% NP-40, 0.5% sodium deoxycholate, and 0.1% sodium dodecyl sulfate, with a protease inhibitor cocktail). Protein was separated by centrifugation for 20 minutes at a speed of 12,000rpm. The isolated protein was quantified by BCA (Bicinchoninic acid) method.
정량한 단백질 중 10 ㎍을 SDS-PEGE 겔에 처리하여 전기영동을 실시한 후 PVDF 멤브레인에 단백질을 옮겨 놓았다. 그 후 PVDF 멤브레인을 5% 스킴밀크(skim milk)에 1시간 정도 반응시켜 표면의 비특이적 결합 단백질들을 제거하고, 1차 항체인 항-AR 항체, 항-PSA 항체, 항-5α-reductase 2 항체, 그리고 항-β-actin 항체를 이용하여 4℃에서 하루 동안 반응시켰다. 그 후 2차 항체를 1시간 동안 상온에서 처리하고 ECL kit(Amersham, UK)를 이용하여 AR, PSA 및 5α-reductase 2의 단백질 발현을 확인하여 그래프화 하였다.10 μg of the quantified protein was treated with SDS-PEGE gel, followed by electrophoresis, and the protein was transferred to the PVDF membrane. Thereafter, the PVDF membrane was reacted with 5% skim milk for about 1 hour to remove nonspecific binding proteins on the surface, and the primary antibodies, anti-AR antibody, anti-PSA antibody, anti-5α-
그 결과, 도 2에 나타낸 바와 같이, 멀꿀 추출물 또는 산수유 추출물을 25 또는 50 ㎍/㎖로 단독 처리한 세포군에 비하여 멀꿀 및 산수유 복합 추출물 25 ㎍/㎖을 처리한 세포군에서 AR 및 PSA 단백질 발현 억제 효과가 현저히 우수함을 확인하였다. 또한, 멀꿀 및 산수유 추출물을 9 : 1의 혼합 비율로 혼합한 멀꿀 및 산수유 복합 추출물을 처리한 세포군에서 AR 및 PSA 단백질 발현 억제 효과가 보다 우수함을 확인하였다. 아울러, 멀꿀 및 산수유 복합 추출물을 처리한 세포군에서 5a-reductase 2 단백질 발현 억제 효과가 우수함을 확인하였다. As a result, as shown in Figure 2, the effect of inhibiting AR and PSA protein expression in the cell group treated with 25 ㎍ / ㎖ honey and corn coriander extract compared to the cell group treated with 25 or 50 ㎍ / ㎖ honey extract or cornus extract alone It was confirmed that the remarkably excellent. In addition, it was confirmed that AR and PSA protein expression inhibitory effect was more excellent in the cell group treated with the honey and cornus extract extract in a mixture ratio of 9: 1. In addition, it was confirmed that the effect of inhibiting the expression of 5a-
하기에 본 발명의 조성물을 위한 제조예를 예시한다.
The preparation examples for the compositions of the present invention are illustrated below.
<제조예 1> 약학적 제제의 제조Preparation Example 1 Preparation of Pharmaceutical Formulation
<1-1> 산제의 제조<1-1> Preparation of Powder
본 발명의 복합 추출물 10 mg10 mg complex extract of the present invention
유당 1 g1 g lactose
상기의 성분을 혼합하고 기밀포에 충진하여 산제를 제조하였다.
The above ingredients were mixed and filled in airtight cloth to prepare a powder.
<1-2> 정제의 제조<1-2> Preparation of Tablet
본 발명의 복합 추출물 0.1 mg0.1 mg complex extract of the present invention
옥수수전분 100 mg
유 당 100 mg
스테아린산 마그네슘 2 mg2 mg magnesium stearate
상기의 성분을 혼합한 후, 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조하였다.
After mixing the above components, tablets were prepared by tableting according to a conventional method for producing tablets.
<1-3> 캡슐제의 제조<1-3> Preparation of Capsule
본 발명의 복합 추출물 0.1 mg0.1 mg complex extract of the present invention
옥수수전분 100 mg
유 당 100 mg
스테아린산 마그네슘 2 mg2 mg magnesium stearate
상기의 성분을 혼합한 후, 통상의 캡슐제의 제조방법에 따라서 젤라틴 캡슐에 충전하여 캡슐제를 제조하였다.
After mixing the above components, the capsule was prepared by filling in gelatin capsules according to the conventional method for producing a capsule.
<1-4> 환의 제조<1-4> Preparation of the ring
본 발명의 복합 추출물 1 mg1 mg complex extract of the present invention
유당 1.5 gLactose 1.5 g
글리세린 1 g1 g of glycerin
자일리톨 0.5 gXylitol 0.5 g
상기의 성분을 혼합한 후, 통상의 방법에 따라 1 환 당 4 g이 되도록 제조하였다.
After mixing the above components, it was prepared to be 4 g per ring in a conventional manner.
<1-5> 과립의 제조<1-5> Preparation of Granules
본 발명의 복합 추출물 0.15 mg0.15 mg complex extract of the present invention
대두 추출물 50 mg
포도당 200 mgGlucose 200 mg
전분 600 mgStarch 600 mg
상기의 성분을 혼합한 후, 30% 에탄올 100 mg을 첨가하여 60℃에서 건조하여 과립을 형성한 후 포에 충진하였다.
After mixing the above ingredients, 100 mg of 30% ethanol was added and dried at 60 ° C. to form granules and then filled into fabrics.
<제조예 2> 건강식품의 제조Preparation Example 2 Preparation of Health Food
본 발명의 복합 추출물을 유효성분으로 함유하는 식품들을 다음과 같이 제조하였다.
Foods containing the complex extract of the present invention as an active ingredient were prepared as follows.
<2-1> 밀가루 식품의 제조<2-1> Preparation of Flour Food
본 발명의 복합 추출물의 0.5 내지 5.0 중량부를 밀가루에 첨가하고, 이 혼합물을 이용하여 빵, 케이크, 쿠키, 크래커 및 면류를 제조하였다.
0.5 to 5.0 parts by weight of the composite extract of the present invention was added to the flour and bread, cake, cookies, crackers and noodles were prepared using this mixture.
<2-2> <2-2> 스프soup 및 육즙(gravies)의 제조 And preparation of gravy
본 발명의 복합 추출물의 0.1 내지 5.0 중량부를 스프 및 육즙에 첨가하여 건강 증진용 육가공 제품, 면류의 수프 및 육즙을 제조하였다.
0.1 to 5.0 parts by weight of the complex extract of the present invention was added to soups and broth to prepare meat products for health promotion, soup of noodles and broth.
<2-3> 그라운드 <2-3> ground 비프(ground beef)의Ground beef 제조 Produce
본 발명의 복합 추출물의 10 중량부를 그라운드 비프에 첨가하여 건강 증진용 그라운드 비프를 제조하였다.
10 parts by weight of the complex extract of the present invention was added to ground beef to prepare a ground beef for health promotion.
<2-4> 유제품(dairy products)의 제조<2-4> Production of Dairy Products
본 발명의 복합 추출물의 5 내지 10 중량부를 우유에 첨가하고, 상기 우유를 이용하여 버터 및 아이스크림과 같은 다양한 유제품을 제조하였다.
5 to 10 parts by weight of the complex extract of the present invention was added to milk, and the milk was used to prepare various dairy products such as butter and ice cream.
<2-5> <2-5> 선식의Linear 제조 Produce
현미, 보리, 찹쌀, 율무를 공지의 방법으로 알파화시켜 건조시킨 것을 배전한 후 분쇄기로 입도 60 메쉬의 분말로 제조하였다.Brown rice, barley, glutinous rice, and yulmu were alphad by a known method, and then dried and roasted to prepare a powder having a particle size of 60 mesh.
검정콩, 검정깨, 들깨도 공지의 방법으로 쪄서 건조시킨 것을 배전한 후 분쇄기로 입도 60 메쉬의 분말로 제조하였다.Black beans, black sesame seeds, and perilla were also steamed and dried in a known manner, and then roasted to prepare a powder having a particle size of 60 mesh.
본 발명의 복합 추출물을 진공 농축기에서 감압농축하고, 분무, 열풍건조기로 건조하여 얻은 건조물을 분쇄기로 입도 60 메쉬로 분쇄하여 건조분말을 얻었다.The complex extract of the present invention was concentrated under reduced pressure in a vacuum concentrator, and the dried product obtained by drying with a sprayer and a hot air dryer was pulverized with a particle size of 60 mesh to obtain a dry powder.
상기에서 제조한 곡물류, 종실류 및 본 발명의 복합 추출물을 다음의 비율로 배합하여 제조하였다.The grains, seeds and the composite extract of the present invention prepared above were formulated in the following ratio.
곡물류(현미 30 중량부, 율무 15 중량부, 보리 20 중량부),Cereals (30 parts by weight brown rice, 15 parts by weight brittle, 20 parts by weight of barley),
종실류(들깨 7 중량부, 검정콩 8 중량부, 검정깨 7 중량부),Seeds (7 parts by weight perilla, 8 parts by weight black beans, 7 parts by weight black sesame seeds),
본 발명의 복합 추출물(3 중량부),Complex extract of the present invention (3 parts by weight),
영지(0.5 중량부),Ganoderma lucidum (0.5 parts by weight),
지황(0.5 중량부)
Foxglove (0.5 weight part)
<< 제조예Production Example 3> 3> 건강음료의Health drink 제조 Produce
<3-1> <3-1> 건강음료의Health drink 제조 Produce
액상과당(0.5%), 올리고당(2%), 설탕(2%), 식염(0.5%), 물(75%)과 같은 부재료와 본 발명의 복합 추출물 0.5 g을 균질하게 배합하여 순간 살균을 한 후 이를 유리병, 패트병 등 소포장 용기에 포장하여 제조하였다.
Instant sterilization by homogeneously mixing 0.5 g of the complex extract of the present invention with subsidiary materials such as liquid fructose (0.5%), oligosaccharide (2%), sugar (2%), salt (0.5%) and water (75%). Then it was prepared by packaging in a small packaging container such as glass bottles, plastic bottles.
<3-2> 야채 주스의 제조<3-2> Preparation of Vegetable Juice
본 발명의 복합 추출물 0.5 g을 토마토 또는 당근 주스 1,000 mL에 가하여 야채 주스를 제조하였다.
0.5 g of the complex extract of the present invention was added to 1,000 mL of tomato or carrot juice to prepare vegetable juice.
<3-3> 과일 주스의 제조<3-3> Preparation of Fruit Juice
본 발명의 복합 추출물 0.1 g을 사과 또는 포도 주스 1,000 mL에 가하여 과일 주스를 제조하였다.
0.1 g of the complex extract of the present invention was added to 1,000 mL of apple or grape juice to prepare a fruit juice.
Claims (9)
Honey ( Stauntonia) hexaphylla extract and Cornus officinalis Sieb. et Zucc) A pharmaceutical composition for preventing or treating prostate disease, comprising the extract as an active ingredient.
The method of claim 1, wherein the extract is characterized in that extracted with water, C 1 to C 2 lower alcohol or a mixed solvent thereof, a pharmaceutical composition for preventing or treating prostate disease.
The method of claim 2, wherein the extract is water, methanol, ethanol and a pharmaceutical composition for the prevention or treatment of prostate disease, characterized in that extracted with one or more solvents selected from the group consisting of these.
The method of claim 1, wherein the extract is characterized in that the extract of any one or more selected from flowers, branches, stems, leaves, fruits, ground, rhizome and root, pharmaceutical composition for preventing or treating prostate disease.
The pharmaceutical composition for preventing or treating prostate disease according to claim 1, wherein the composition contains honey extract: cornus extract in a weight ratio of 5: 5 to 9.5: 0.5.
The pharmaceutical composition for preventing or treating prostate disease according to claim 1, wherein the composition contains honey extract: cornus extract in a weight ratio of 6: 4 to 9.5: 0.5.
According to claim 1, wherein the prostate disease is characterized in that selected from the group consisting of prostate cancer, prostatic hyperplasia and prostatitis, prophylactic or therapeutic pharmaceutical composition for the disease.
Health food for the prevention or improvement of prostate disease, containing the honey extract and cornus extract as an active ingredient.
Food composition for the prevention or improvement of prostate disease, comprising a honey extract and cornus extract as an active ingredient.
Priority Applications (3)
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KR1020180101933A KR102167290B1 (en) | 2018-08-29 | 2018-08-29 | Composition for preventing or treating prostatic diseases comprising Stauntonia hexaphylla extract and Cornus officinalis as active ingredients |
CN201980055052.XA CN112638394A (en) | 2018-08-29 | 2019-07-31 | Composition for preventing or treating prostate disease comprising Japanese stauntonvine extract and dogwood extract as active ingredients |
PCT/KR2019/009518 WO2020045838A1 (en) | 2018-08-29 | 2019-07-31 | Composition for prevention or treatment of prostate disease, containing extract from stauntonia hexaphylla and cornus officinalis as active ingredients |
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KR101652073B1 (en) * | 2015-10-12 | 2016-08-29 | 충남대학교산학협력단 | Composition for Prevention or Treatment of Prostatic Diseases Comprising Stauntonia Hexaphylla Extract |
KR20160143500A (en) | 2015-06-04 | 2016-12-14 | 충남대학교산학협력단 | Composition for Prevention or Treatment of Prostatic Diseases Comprising Albizziae Cortex Extract |
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CN102302717B (en) * | 2011-09-30 | 2012-08-29 | 姜新田 | Traditional Chinese medicine composition and medical pad for treating prostatic disease, and preparation method of medical pad |
KR101523586B1 (en) * | 2013-07-11 | 2015-05-29 | 상지대학교산학협력단 | Pharmaceutical composition for preventing or treating prostatic hyperplasia and preparation method thereof |
CN104173681B (en) * | 2014-09-15 | 2017-05-17 | 程惠华 | Traditional Chinese herbal medicine composition for treating castration-resistant prostate cancer |
KR101675930B1 (en) * | 2015-04-02 | 2016-11-14 | 유의순 | Anticancer composition comprising herbal extracts |
KR20170117339A (en) * | 2016-04-12 | 2017-10-23 | 주식회사 케미메디 | Medical composition for preventing or treating chronic bacterial prostatitis |
KR101895548B1 (en) * | 2017-01-16 | 2018-09-06 | 대구한의대학교산학협력단 | Pharmaceutical composition comprising Korean medicinal herbs for preventing hair loss, melanizing of hair, enhancing hair growth, treating benign prostate hyperplasia and manufacturing method thereof |
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KR20160143500A (en) | 2015-06-04 | 2016-12-14 | 충남대학교산학협력단 | Composition for Prevention or Treatment of Prostatic Diseases Comprising Albizziae Cortex Extract |
KR101652073B1 (en) * | 2015-10-12 | 2016-08-29 | 충남대학교산학협력단 | Composition for Prevention or Treatment of Prostatic Diseases Comprising Stauntonia Hexaphylla Extract |
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Title |
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경희대학교 석사학위논문 "산수유가 테스토스테론으로 유도된 래트의 전립선비대증에 미치는 효과" (2015.08.)* * |
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