KR20190136512A - Composition for preventing or treating menopausal syndrome of women comprising Aristotelia chilensis extract, Angelica sinensis extract and Passiflora incarnata extract as an active ingredient - Google Patents
Composition for preventing or treating menopausal syndrome of women comprising Aristotelia chilensis extract, Angelica sinensis extract and Passiflora incarnata extract as an active ingredient Download PDFInfo
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- KR20190136512A KR20190136512A KR1020180062338A KR20180062338A KR20190136512A KR 20190136512 A KR20190136512 A KR 20190136512A KR 1020180062338 A KR1020180062338 A KR 1020180062338A KR 20180062338 A KR20180062338 A KR 20180062338A KR 20190136512 A KR20190136512 A KR 20190136512A
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- extract
- menopausal symptoms
- preventing
- makiberry
- female menopausal
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Abstract
Description
본 발명은 마키베리(Aristotelia chilensis) 추출물, 당귀(Angelica sinensis) 추출물 및 시계꽃(Passiflora incarnata) 추출물을 유효성분으로 함유하는 갱년기 증상 예방 또는 치료용 약학적 조성물, 및 갱년기 증상 예방 또는 개선용 건강기능식품에 관한 것이다.The present invention is a pharmaceutical composition for preventing or treating menopausal symptoms containing Aristotelia chilensis extract, Angelica sinensis extract and Passiflora incarnata extract as active ingredients, and health function for preventing or improving menopausal symptoms. It is about food.
여성은 폐경 전후 10년, 보통 45세에서 55세 사이에 갱년기 증상이 서서히 시작되며, 이로 인해 신체적 및 정신적 어려움을 겪고 있다. 건강보험심사평가원의 통계에 따르면, 2013년 기준 갱년기 증상으로 내원하는 환자가 약 43만 명에 이르며, 여성의 사회진출이 활발해지면서 스트레스, 흡연, 음주 비율 증가 등의 영향으로 인해 갱년기 증상의 발현 시기가 점차 낮아지고 있어, 여성의 갱년기 증상에 대한 관리가 필요한 실정이다.Menopausal symptoms begin slowly between 10 years before and after menopause, usually between 45 and 55 years, resulting in physical and mental difficulties. According to the statistics of the Health Insurance Review and Assessment Service, about 430,000 patients visited with menopausal symptoms as of 2013, and when menopausal symptoms appeared due to the increase in the rate of stress, smoking, and alcohol consumption as women entered the society. Is gradually lowering, and management of menopausal symptoms in women is needed.
갱년기란 내분비 증후군의 일종으로 난소기능의 전반적이고 점진적인 노화로 인한 여성호르몬, 즉 에스트로겐의 감소로 인해 생리적 기능 및 성기능이 감소 내지 소실되는 과도기를 말한다. 이러한 갱년기의 증상으로는 안면홍조, 빈맥, 발한 또는 두통과 같은 혈관성 변화에 의한 증상이 있고, 근육통, 관절통 및 요통과 같은 근골격계 변화에 의한 증상이 있으며, 빈뇨 또는 요실금과 같은 비뇨생식기 변화에 의한 증상이 있고, 기억력 감퇴, 우울증, 집중력 감퇴 및 현기증과 같은 뇌신경계 변화에 의한 증상이 있으며, 이 외에도 시력감퇴 및 피부와 모발이 변화되는 증상들이 발생되며, 호르몬 변화로 인한 골다공증이나 심혈관계 질환 등 여성의 건강에 치명적인 질환이 발생할 수 있다. Menopausal is a type of endocrine syndrome that refers to a transitional period in which physiological and sexual function is reduced or lost due to a decrease in female hormone, ie, estrogen, due to gradual aging of ovarian function. Symptoms of menopausal symptoms include vascular changes such as hot flashes, tachycardia, sweating or headaches, symptoms of musculoskeletal changes such as myalgia, arthralgia and back pain, and symptoms of urogenital changes such as urinary or urinary incontinence. In addition, there are symptoms caused by changes in the brain's nervous system such as memory loss, depression, concentration decline, and dizziness. In addition, symptoms such as decreased vision and changes in skin and hair occur, and women such as osteoporosis or cardiovascular diseases caused by hormonal changes. The disease can be fatal to your health.
따라서 중년 여성들의 신체적, 정신적 건강 및 삶의 질을 개선하기 위하여 갱년기 증상을 개선할 수 있는 치료제의 개발이 요구되었으며, 이러한 갱년기 증상의 개선을 위해 호르몬 대체요법 및 비스테로이드계 제제 등의 약물들이 개발된 바 있다. 그러나 이들 약물의 경우 대부분이 두통 및 체중증가 등의 부작용이 있는 것으로 알려져 있으며, 특히, 에스트로겐 대체요법의 경우에도 인위적으로 체내에 호르몬을 투여하는 것이기 때문에 이에 대한 거부반응과 함께 자궁출혈, 뇌졸중, 심장발작, 유방암 및 자궁암의 발생 위험이 증가할 수 있는 것으로 알려져 있다.Therefore, in order to improve the physical and mental health and quality of life of middle-aged women, it was required to develop treatments that can improve menopausal symptoms, and drugs such as hormone replacement therapy and nonsteroidal preparations were developed to improve these menopausal symptoms. It has been. However, most of these drugs are known to have side effects such as headache and weight gain. In particular, estrogen replacement therapy artificially administers hormones to the body, and therefore, hemorrhage, stroke, heart It is known that the risk of developing seizures, breast cancer and uterine cancer may be increased.
이와 같은 문제점들 때문에 식품이나 첨가물의 형태로 섭취하는 자연적인 방법으로 에스트로겐 요법을 대체하고자 하는 관심이 높아지고 있으며, 부작용이 없으면서도 갱년기의 증상을 완화하는 효과가 우수한 새로운 갱년기 증상 치료제의 개발이 요구되고 있는 실정이다. Due to these problems, there is a growing interest in replacing estrogen therapy with a natural method of ingesting it in the form of foods or additives, and there is a need for the development of a new menopausal symptom remedy that has no side effects and is excellent in relieving menopausal symptoms. There is a situation.
한편, 에스트로겐(estrogen)은 세포 수의 증가와 분화를 포함하는 다양한 생물학적 작용을 한다. 에스트로겐의 생물학적 작용들은 핵 수용체 슈퍼패밀리(superfamily)에 속하는 두 개의 에스트로겐 수용체 알파(ERα; estrogen receptorα)와 에스트로겐 수용체 베타(ERβ)를 통하여 그 활성을 발휘한다. 에스트로겐 수용체의 작용메커니즘은 에스트로겐과 세포 내 에스트로겐 수용체들과의 결합으로 수용체들의 이합체(dimer)를 형성하고 이들이 표적 유전자(target gene)의 프로모터(promoters)에 위치한 특정한 에스트로겐 반응서열(estrogen response elements, EREs)와 결합함으로써 표적 유전자의 발현을 조절한다. 두 개의 에스트로겐 수용체는 서로 다른 조직분포 패턴, 리간드 결합력을 가지므로 이러한 차이는 다른 조직에서 에스트로겐 수용체의 작용제(agonists)와 길항제(antagonists)의 서로 다른 선택적 역할을 가능하게 한다. 아울러, 에스트로겐 수용체에 작용하는 물질들은 폐경기여성의 호르몬 대체요법과 생식기암의 화학요법제 개발을 위한 표적으로 활용되고 있다. 따라서, 인체에 부작용이 적은 천연물을 대상으로 에스트로겐 수용체를 활성화시키는 천연물을 발굴한다면, 여성 갱년기 증상 치료 및 예방에 유용하게 사용될 수 있으므로, 관련 연구가 꾸준히 진행되고 있는 실정이다.Estrogens, on the other hand, have a variety of biological functions, including increased cell numbers and differentiation. The biological actions of estrogens are activated through two estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) belonging to the nuclear receptor superfamily. The mechanism of action of estrogen receptors is the binding of estrogens to intracellular estrogen receptors to form dimers of the receptors, where they are located in specific estrogen response elements (EREs) located in the promoters of the target gene. ) Regulates the expression of the target gene. Since the two estrogen receptors have different tissue distribution patterns and ligand binding capacities, this difference enables different selective roles of agonists and antagonists of estrogen receptors in different tissues. In addition, substances acting on the estrogen receptor have been used as targets for the development of hormone replacement therapy in menopausal women and chemotherapeutic agents in genital cancer. Therefore, if a natural product that activates the estrogen receptor in a natural product with fewer side effects to the human body is discovered, it can be usefully used for the treatment and prevention of women's menopausal symptoms, the current situation is ongoing.
이에, 인체에 안전한 천연물 유래 여성 갱년기 증상 치료 복합제를 개발하기 위해 노력한 결과, 마키베리 추출물, 당귀 추출물 및 시계꽃 추출물을 혼합한 혼합 추출물이 조직선택적으로 세포 내에서 에스트로겐 활성을 갖고 부작용 없이 에스트로겐 수용체 작용제(estrogen receptor agonist)로 작용함을 확인하여, 상기 혼합 추출물을 갱년기 여성에서 에스트로겐 결핍으로 유래된 갱년기 증상을 예방 및 치료하기 위한 여성호르몬 대체요법제로 이용할 수 있음을 밝힘으로써, 본 발명을 완성하였다.Therefore, as a result of efforts to develop a safe treatment product for women's menopausal symptoms derived from natural products, the mixed extract of makiberry extract, Angelica extract and passion flower extract has a selective estrogen activity in the tissue and without any side effects estrogen receptor agonist By confirming that it acts as an (estrogen receptor agonist), the present invention was completed by revealing that the mixed extract can be used as a female hormone replacement therapy for preventing and treating menopausal symptoms caused by estrogen deficiency in menopausal women.
본 발명의 목적은 마키베리(Aristotelia chilensis) 추출물, 당귀(Angelica sinensis) 추출물 및 시계꽃(Passiflora incarnata) 추출물을 유효성분으로 함유하는, 여성 갱년기 증상 예방 또는 치료용 약학적 조성물을 제공하는 것이다.It is an object of the present invention to provide a pharmaceutical composition for preventing or treating female menopausal symptoms, containing machiberry ( Aristotelia chilensis ) extract, Angelica sinensis extract and Passiflora incarnata extract as an active ingredient.
본 발명의 다른 목적은 마키베리 추출물, 당귀 추출물 및 시계꽃 추출물을 유효성분으로 함유하는, 여성 갱년기 증상 예방 또는 개선용 건강기능식품을 제공하는 것이다.Another object of the present invention is to provide a health functional food for preventing or improving female menopausal symptoms, containing makiberry extract, Angelica extract and passion flower extract as an active ingredient.
상기 목적을 달성하기 위하여, 본 발명은 마키베리(Aristotelia chilensis) 추출물, 당귀(Angelica sinensis) 추출물 및 시계꽃(Passiflora incarnata) 추출물을 유효성분으로 함유하는, 여성 갱년기 증상 예방 또는 치료용 약학적 조성물을 제공한다.In order to achieve the above object, the present invention comprises a Makiberry ( Aristotelia chilensis ) extract, Angelica sinensis extract and Passiflora incarnata extract as an active ingredient, female menopausal symptoms prevention or treatment pharmaceutical composition to provide.
본 발명은 마키베리 추출물, 당귀 추출물 및 시계꽃 추출물을 유효성분으로 함유하는, 여성 갱년기 증상 예방 또는 개선용 건강기능식품을 제공한다.The present invention provides a health functional food for preventing or improving female menopausal symptoms, containing makiberry extract, Angelica extract and passion flower extract as an active ingredient.
본 발명의 마키베리 추출물, 당귀 추출물 및 시계꽃 추출물을 혼합한 혼합 추출물은 조직선택적으로 세포 내에서 에스트로겐 활성을 갖고 부작용 없이 에스트로겐 수용체 작용제(estrogen receptor agonist)로 작용하므로, 갱년기 여성에서 에스트로겐 결핍으로 유래된 갱년기 증상을 예방 및 치료하기 위한 여성호르몬 대체요법에 이용될 수 있다.The mixed extract of Makiberry extract, Angelica extract and Passionflower extract of the present invention are derived from estrogen deficiency in menopausal women because it has tissue-selective estrogen activity and acts as an estrogen receptor agonist without side effects. It can be used for female hormone replacement therapy to prevent and treat menopausal symptoms.
도 1은 에스트로겐 수용체-양성 유방암 세포주 MCF-7에 에스트로겐 수용체(estrogen receptor; ER) 작용제(agonist), ER 작용제 및 ER 길항제(antagonist), 마키베리(Aristotelia chilensis) 추출물, 당귀(Angelica sinensis) 추출물, 시계꽃(Passiflora incarnata) 추출물 또는 본 발명의 실시예에 따라 다양한 혼합비율로 혼합하여 제조한 마키베리, 당귀 및 시계꽃 혼합 추출물을 처리한 후 ER-매개 전사활성을 확인한 도이다:
DMSO: DMSO(Dimethyl sulfoxide) 처리;
E2: ER 작용제 E2(17β-estradiol) 1 nM 처리;
E2+ICI: E2 1 nM 및 ER 길항제 ICI(ICI 182,780) 1 μM 처리;
4-1 내지 4-9: 본 발명의 실시예에 따라 표 1의 혼합조성으로 혼합하여 제조한 실시예 4-1 내지 4-9의 마키베리, 당귀 및 시계꽃 혼합 추출물 200 ㎍/㎖ 처리;
1: 본 발명의 실시예 1의 마키베리 추출물 200 ㎍/㎖ 처리;
2: 본 발명의 실시예 2의 당귀 추출물 200 ㎍/㎖ 처리;
3: 본 발명의 실시예 3의 당귀 추출물 200 ㎍/㎖ 처리.
도 2는 에스트로겐 수용체-양성 유방암 세포주 MCF-7에 마키베리 추출물, 당귀 추출물, 시계꽃 추출물, 또는 본 발명의 실시예에 따라 우수한 효과를 나타내는 혼합비율로 혼합하여 제조한 마키베리, 당귀 및 시계꽃 혼합 추출물을 처리한 후 ER-매개 전사활성을 비교하여 본 발명의 마키베리, 당귀 및 시계꽃 혼합 추출물의 시너지 효과를 확인한 도이다:
DMSO: DMSO 처리;
E2: E2 1 nM 처리;
E2+ICI: E2 1 nM 및 ICI 1 μM 처리;
마당시750 또는 마당시1500: 본 발명의 실시예에 따라 표 2의 혼합조성으로 혼합하여 제조한 마키베리, 당귀 및 시계꽃 혼합 추출물 750 ㎍/㎖ 또는 1500 ㎍/㎖ 처리;
마키베리375 또는 마키베리750: 마키베리 추출물 375 ㎍/㎖ 또는 750 ㎍/㎖ 처리;
당귀187.5 또는 당귀375: 당귀 추출물 187.5 ㎍/㎖ 또는 375 ㎍/㎖ 처리;
시계꽃187.5 또는 시계꽃375: 시계꽃 추출물 187.5 ㎍/㎖ 또는 375 ㎍/㎖ 처리.
도 3은 랫트에 마키베리 추출물, 당귀 추출물, 시계꽃 추출물 또는 본 발명의 마키베리, 당귀 및 시계꽃 혼합 추출물을 투여한 후 자궁 무게를 확인한 도이다:
E2: E2를 5 ㎍/kg/d 용량으로 피하주사;
마키베리100, 마키베리200 또는 마키베리500: 마키베리 추출물을 100, 200 또는 500 mg/kg/d 용량으로 피하주사;
당귀500: 당귀 추출물을 500 mg/kg/d 용량으로 피하주사;
시계꽃500: 시계꽃 추출물을 500 mg/kg/d 용량으로 피하주사;
마당시500: 본 발명의 마키베리, 당귀 및 시계꽃 혼합 추출 500 mg/kg/d 용량으로 피하주사.1 shows an estrogen receptor (ER) agonist, an ER agonist and an ER antagonist, Aristotelia chilensis extract, Angelica sinensis extract, in the estrogen receptor-positive breast cancer cell line MCF-7. ER-mediated transcriptional activity after treatment with Passiflora incarnata extract or makiberry , donkey and passion flower mixed extract prepared by mixing in various mixing ratios according to an embodiment of the present invention:
DMSO: Dimethyl sulfoxide (DMSO) treatment;
E2: ER agonist E2 (17β-estradiol) 1 nM treatment;
E2 + ICI: treatment with
4-1 to 4-9: 200 µg / ml treatment of makiberry, donkey and passion flower mixed extracts of Examples 4-1 to 4-9 prepared by mixing in the mixing composition of Table 1 according to the embodiment of the present invention;
1: 200 g / ml treatment of makiberry extract of Example 1 of the present invention;
2: 200 μg / ml treatment of Angelica extract of Example 2 of the present invention;
3: 200 μg / ml treatment of Angelica extract, Example 3 of the present invention.
2 is a makiberry, donkey and passion flower prepared by mixing the estrogen receptor-positive breast cancer cell line MCF-7 with makiberry extract, Angelica extract, passion flower extract, or a mixed ratio showing an excellent effect according to an embodiment of the present invention Figure 3 shows the synergy effect of the mixed extract of Makiberry, Angelica and Passionflower according to the ER-mediated transcriptional activity after treating the mixed extract:
DMSO: DMSO treatment;
E2:
E2 + ICI: treatment with
Madang 750 or Madang 1500: 750 ㎍ / ㎖ or 1500 ㎍ / ㎖ Makiberry, Angelica and passion flower mixed extract prepared by mixing in the mixing composition of Table 2 according to an embodiment of the present invention;
Makiberry 375 or makiberry 750: treated with makiberry extract 375 μg / ml or 750 μg / ml;
Angelica 187.5 or Angel 375: treated with Angelica extract 187.5 μg / ml or 375 μg / ml;
Passion Flower 187.5 or Passion Flower 375: Treatment of Passion Flower Extract 187.5 μg / ml or 375 μg / ml.
Figure 3 is a rat confirming the weight of the uterus after administering Makiberry extract, Angelica extract, passion flower extract or Makiberry, Angelica and passion flower mixed extract of the present invention:
E2: subcutaneous injection of E2 at a dose of 5 μg / kg / d;
Makiberry 100, Makiberry 200 or Makiberry 500: Makiberry extract is injected subcutaneously at a dose of 100, 200 or 500 mg / kg / d;
Angelica 500: subcutaneous injection of Angelica extract at a dose of 500 mg / kg / d;
Passion Flower 500: Subcutaneous injection of Passion Flower Extract at a dose of 500 mg / kg / d;
Madang 500: Subcutaneous injection of 500 mg / kg / d dose of the extract of Makiberry, Angelica and Passionflower of the present invention.
이하, 본 발명을 보다 상세히 설명한다. Hereinafter, the present invention will be described in more detail.
본 발명은 마키베리(Aristotelia chilensis) 추출물, 당귀(Angelica sinensis) 추출물 및 시계꽃(Passiflora incarnata) 추출물을 유효성분으로 함유하는, 여성 갱년기 증상 예방 또는 치료용 약학적 조성물을 제공한다.The present invention provides a pharmaceutical composition for the prevention or treatment of female menopausal symptoms, containing makiberry ( Aristotelia chilensis ) extract, Angelica sinensis extract and Passiflora incarnata extract as an active ingredient.
본 발명의 유효성분인 마키베리 추출물, 당귀 추출물 및 시계꽃 추출물 각각은 하기의 단계들을 포함하는 방법에 의해 제조되는 것이 바람직하나, 이에 한정되지 않는다: Makiberry extract, Angelica extract and passion flower extract of the active ingredient of the present invention is preferably prepared by a method comprising the following steps, but is not limited thereto:
1) 마키베리, 당귀 및 시계꽃 각각에 추출용매를 가하여 추출하는 단계; 및1) extracting by adding an extraction solvent to each of maki berry, donkey and passion flower; And
2) 단계 1)의 마키베리 추출물, 당귀 추출물 및 시계꽃 추출물 각각을 여과하는 단계.2) filtering the makiberry extract, Angelica extract and passion flower extract of step 1).
본 발명에서, 상기 단계 1)의 마키베리, 당귀 또는 시계꽃은 재배한 것 또는 시판되는 것을 제한 없이 사용할 수 있다. 또한 상기 마키베리, 당귀 또는 시계꽃의 꽃, 가지, 줄기, 잎, 열매, 지상부, 뿌리줄기, 뿌리 또는 이들의 조합을 사용할 수 있으나 이에 한정되지 않는다.In the present invention, the makiberry, donkey or passion flower of step 1) can be used without limitation, those grown or commercially available. In addition, flowers, branches, stems, leaves, berries, ground portions, rhizomes, roots, or combinations thereof may be used, but are not limited thereto.
본 발명에서, 상기 단계 1)의 추출용매는 물, 알코올 또는 이의 혼합물을 사용하는 것이 바람직하다. 상기 알코올로는 C1 내지 C2의 저급 알코올을 이용하는 것이 바람직하고, 저급 알코올로는 에탄올 또는 메탄올을 이용하는 것이 바람직하다. 추출방법으로는 초음파추출, 진탕추출, Soxhelt 추출 또는 환류 추출을 이용하는 것이 바람직하나, 이에 한정되지 않는다. 상기 추출용매를 세척하고 잘 건조된 마키베리, 당귀 또는 시계꽃 분량의 1 내지 15배 첨가하여 추출하는 것이 바람직하며, 2 내지 10배 첨가하여 추출하는 것이 보다 바람직하다. 추출 온도는 20 내지 110℃인 것이 바람직하나, 이에 한정하지 않는다. 또한, 추출시간은 10분 내지 72시간이 바람직하며, 20분 내지 48시간이 더욱 바람직하나, 이에 한정되지 않는다. 아울러 추출 횟수는 1 내지 5회인 것이 바람직하나, 이에 한정되지 않는다. In the present invention, the extraction solvent of step 1) is preferably water, alcohol or a mixture thereof. As in the above-mentioned alcohol it is preferably using a lower alcohol of C 1 to C 2, a lower alcohol is preferably an ethanol or methanol. As the extraction method, it is preferable to use ultrasonic extraction, shaking extraction, Soxhelt extraction or reflux extraction, but is not limited thereto. The extraction solvent is washed and preferably dried by adding 1 to 15 times the amount of dried makiberry, donkey or passion flower, and more preferably by adding 2 to 10 times. The extraction temperature is preferably 20 to 110 ° C., but is not limited thereto. In addition, the extraction time is preferably 10 minutes to 72 hours, more preferably 20 minutes to 48 hours, but is not limited thereto. In addition, the number of extraction is preferably 1 to 5 times, but is not limited thereto.
본 발명에서, 상기 마키베리 추출물, 당귀 추출물 및 시계꽃 추출물은 각각의 추출물을 제조한 후 혼합할 수 있으나, 마키베리, 당귀 및 시계꽃을 혼합한 후 이의 추출물을 수득하는 형태로 제조되는 것도 가능하다.In the present invention, the makiberry extract, Angelica extract and passion flower extract may be mixed after the preparation of each extract, but may also be prepared in the form of obtaining the extract after mixing makiberry, donkey and passion flower. Do.
본 발명에서, 상기 단계 2)를 거친 후 하기의 단계들을 추가적으로 포함할 수 있다:In the present invention, after the step 2) may further include the following steps:
3) 단계 2)의 여과물 각각을 감압 농축하는 단계; 및3) concentrating the filtrate of step 2) under reduced pressure; And
4) 단계 3)의 농축물 각각을 건조하는 단계. 4) drying each of the concentrates of step 3).
본 발명에서, 상기 단계 3)의 감압농축은 진공 감압 농축기 또는 진공회전증발기를 이용하는 것이 바람직하나 이에 한정하지 않는다. 또한, 건조는 감압건조, 진공건조, 비등건조, 분무건조 또는 동결건조하는 것이 바람직하나 이에 한정하지 않는다.In the present invention, the reduced pressure concentration of step 3) is preferably used as a vacuum vacuum concentrator or 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 발명에서, 마키베리, 당귀 및 시계꽃을 혼합한 후 이의 추출물을 수득하고, 이를 감압 농축 및 건조시키는 단계를 거칠 수 있다.In the present invention, after the makiberry, donkey and passion flower are mixed, an extract thereof is obtained, which may be subjected to a step of concentration under reduced pressure and drying.
본 발명에서, 상기 조성물은 마키베리 추출물 : 당귀 추출물 : 시계꽃 추출물을 1 : 0.25 내지 5 : 0.25 내지 4의 중량비로 함유할 수 있고, 보다 구체적으로 1 : 0.3 내지 4.5 : 0.3 내지 3.5의 중량비로 함유할 수 있으며, 보다 더 구체적으로 1 : 0.5 내지 4 : 0.5 내지 3의 중량비로 함유할 수 있다.In the present invention, the composition may contain makiberry extract: Angelica extract: passion flower extract in a weight ratio of 1: 0.25 to 5: 0.25 to 4, more specifically 1: 0.3 to 4.5: 0.3 to 3.5 by weight ratio It may be contained, and more specifically may be contained in a weight ratio of 1: 0.5 to 4: 0.5 to 3.
본 발명에서, 상기 여성 갱년기 증상이란, 난소의 노화로 인하여 에스트로겐의 분비가 감소됨에 따라 폐경을 전후로 걸쳐 여성에게 나타나는 증상 및 질환을 총칭하는 것으로, 안면홍조, 발한, 피부건조, 질건조증, 질위축, 하부 요도 위축, 질염, 방광염, 배뇨통, 급뇨, 집중장애, 단기 기억장애, 불안, 신경과민, 기억력 감퇴, 근육통, 관절통 또는 골다공증일 수 있으나 이에 한정되는 것은 아니다.In the present invention, the female menopausal symptoms is a generic term for symptoms and diseases that appear in women before and after menopause as the secretion of estrogen decreases due to aging of the ovary, hot flashes, sweating, skin drying, vaginal dryness, vaginal atrophy , Lower urethra atrophy, vaginitis, cystitis, urination pain, urination, concentration disorders, short-term memory disorders, anxiety, nervousness, memory loss, myalgia, arthralgia or osteoporosis, but is not limited thereto.
본 발명에서, 상기 조성물은 에스트로겐 활성을 갖고, 에스트로겐 수용체(estrogen receptor; ER) 작용제(agonist) 활성을 나타내어, 여성 갱년기 증상 치료 효과를 갖는다.In the present invention, the composition has estrogen activity, exhibits estrogen receptor (ER) agonist activity, and has a therapeutic effect on female menopausal symptoms.
본 발명의 구체적인 실시예에서, 본 발명자들은 마키베리 추출물, 당귀 추출물 및 시계꽃 추출물을 제조하고, 상기 추출물을 다양한 혼합 비율로 혼합하여 마키베리, 당귀 및 시계꽃 혼합 추출물을 제조하였다. In a specific embodiment of the present invention, the present inventors prepared makiberry extract, Angelica extract and passion flower extract, and the extract was mixed in various mixing ratios to prepare a mixed extract of makiberry, donkey and passion flower.
또한, 본 발명자들은 마키베리, 당귀 및 시계꽃 혼합 추출물을 에스트로겐 수용체-양성 유방암 세포주 MCF-7에 처리하여 ER-매개 전사활성 정도를 측정한 결과, 마키베리, 당귀 및 시계꽃 추출물 각각을 처리한 경우에 비해 상기 혼합 추출물을 처리한 경우 ER-매개 전사활성이 현저히 우수하고, 특히 마키베리 추출물 : 당귀 추출물 : 시계꽃 추출물을 1 : 0.5 내지 4 : 0.5 내지 3의 혼합 비율로 혼합한 경우 그 활성이 보다 우수함을 확인하였다(도 1 참조).In addition, the present inventors treated makiberry, donkey and passion flower mixed extract to the estrogen receptor-positive breast cancer cell line MCF-7 to measure the degree of ER-mediated transcriptional activity, and treated each of makiberry, donkey and passion flower extract. Compared to the case, the ER-mediated transcriptional activity was remarkably excellent when the mixed extract was treated, especially when the Makiberry extract: Angelica extract: Passion flower extract was mixed at a mixing ratio of 1: 0.5 to 4: 0.5 to 3. It was confirmed to be superior to this (see FIG. 1).
또한, 본 발명자들은 상기 혼합 추출물을 처리한 경우 농도 의존적으로 ER-매개 전사활성이 증가하고, 마키베리, 당귀 및 시계 꽃 추출물을 모두 혼합할 경우 추출물 각각의 ER-매개 전사활성의 합보다 그 활성이 증가하여 시너지 효과를 나타냄을 확인하였다(도 2a 및 도 2b 참조).In addition, the present inventors increase the ER-mediated transcriptional activity in a concentration-dependent manner when the mixed extract is treated, and its activity is higher than the sum of the ER-mediated transcriptional activity of each of the extracts when all of the extracts of Maquiberry, Angelica and Passiflorum are mixed. This increase was confirmed to exhibit a synergistic effect (see FIGS. 2A and 2B).
아울러, 본 발명자들은 상기 혼합 추출물을 랫트에 경우 투여하고 자궁무게를 측정한 결과, 투여 유무에 따른 자궁무게 변화가 나타나지 않으므로, ER 작용제의 부작용 중 하나인 자궁증식 증상이 없음을 확인하였다(도 3 참조).In addition, the present inventors confirmed that there is no uterine growth symptom, which is one of the side effects of the ER agonist since the mixed extract was administered to rats and the uterine weight was measured as a result of uterine weight measurement. Reference).
따라서 본 발명의 마키베리, 당귀 및 시계꽃 혼합 추출물이 에스트로겐 활성을 갖고, 부작용 없이 ER 작용제로서의 활성을 나타내므로, 본 발명의 마키베리 추출물, 당귀 추출물 및 시계꽃 추출물을 갱년기 여성에서 에스트로겐 결핍으로 유래된 갱년기 증상을 예방 또는 치료하기 위한 약학적 조성물의 유효성분으로 유용하게 사용할 수 있다.Therefore, the makiberry, donkey and passion flower mixture extract of the present invention has estrogen activity and shows activity as an ER agonist without side effects. Therefore, the makiberry extract, donkey extract and passion flower extract of the present invention are derived from estrogen deficiency in menopausal women. It can be usefully used as an active ingredient of a pharmaceutical composition for preventing or treating menopausal symptoms.
본 발명에 따른 약학적 조성물은 약학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다.The pharmaceutical compositions according to the invention may further comprise suitable carriers, excipients and diluents conventionally used in the preparation of pharmaceutical compositions.
본 발명에 따른 약학적 조성물은 경구 또는 비경구 투여할 수 있으며, 비경구 투여시 피부 외용 또는 복강내주사, 직장내주사, 피하주사, 정맥주사, 근육내 주사 또는 흉부내 주사 주입방식을 선택하는 것이 바람직하며, 이에 한정되는 것은 아니다.The pharmaceutical composition according to the present invention may be administered orally or parenterally, and when parenteral administration is selected for external skin or intraperitoneal injection, rectal injection, subcutaneous injection, intravenous injection, intramuscular injection or intrathoracic injection injection method. It is preferable, but it is not limited to this.
본 발명에 따른 약학적 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. 상기 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 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. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 혼합생약재에 적어도 하나 이상의 부형제 예를 들면, 전분, 탄산칼슘(calcium carbonate), 수크로스(sucrose) 또는 락토오스(lactose), 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 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌 글리콜(propylene glycol), 폴리에틸렌 글리콜(polyethylene glycol), 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로젤라틴 등이 사용될 수 있다. 또한, 필요에 따라 항산화제, 완충액, 정균제 등 다른 통상의 첨가제를 첨가할 수 있다. The pharmaceutical compositions according to the present invention may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories, and sterile injectable solutions, respectively, according to conventional methods. Can be used. Carriers, excipients and diluents that may be included in the composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, Methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations may contain at least one excipient such as starch, calcium carbonate, sucrose in mixed herbal medicines. ) Or lactose, gelatin and the like are mixed. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. 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. In addition, other conventional additives such as antioxidants, buffers, bacteriostatics and the like may be added as necessary.
본 발명에 따른 약학적 조성물의 바람직한 투여량은 체내에서 활성성분의 흡수도, 환자의 연령, 성별 및 증상의 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 1000 mg/kg으로, 바람직하게는 0.001 내지 500 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 pharmaceutical compositions according to the present invention vary depending on the absorption of the active ingredient in the body, the age, sex and degree of symptoms of the patient, but may be appropriately selected by those skilled in the art. For the desired effect, however, in the case of oral dosages, it is generally advisable to administer the composition of the present invention to an adult at 0.0001 to 1000 mg / kg per day, preferably from 0.001 to 500 mg / kg per kg body weight per day good. 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.
본 발명은 마키베리 추출물, 당귀 추출물 및 시계꽃 추출물을 유효성분으로 함유하는, 여성 갱년기 증상 예방 또는 개선용 건강기능식품을 제공한다. The present invention provides a health functional food for preventing or improving female menopausal symptoms, containing makiberry extract, Angelica extract and passion flower extract as an active ingredient.
상기 마키베리 추출물, 당귀 추출물, 시계꽃 추출물, 이들의 혼합 비율, 여성 갱년기 증상에 대해서는 상기 여성 갱년기 증상 예방 또는 치료용 약학적 조성물에 대한 설명과 동일한 바, 구체적인 설명은 상기 내용을 원용하고, 이하에서는 건강기능식품의 특유한 구성에 대해서만 설명하도록 한다.The makiberry extract, Angelica extract, Passion flower extract, the mixing ratio thereof, female menopausal symptoms are the same as the description of the pharmaceutical composition for preventing or treating the female menopausal symptoms, the specific description is used above, Will only describe the specific composition of dietary supplements.
한편, 본 발명의 마키베리, 당귀 및 시계꽃 혼합 추출물이 에스트로겐 활성을 갖고, 부작용 없이 ER 작용제로서의 활성을 나타내므로, 본 발명의 마키베리 추출물, 당귀 추출물 및 시계꽃 추출물을 갱년기 여성에서 에스트로겐 결핍으로 유래된 갱년기 증상을 예방 또는 개선하기 위한 건강기능식품의 유효성분으로 유용하게 사용할 수 있다.On the other hand, the makiberry, Angelica and passion flower extract of the present invention has estrogen activity, and shows the activity as an ER agent without side effects, the makiberry extract, Angelica extract and passion flower extract of the present invention to estrogen deficiency in menopausal women It can be usefully used as an active ingredient of health functional food for preventing or improving the resulting menopausal symptoms.
본 발명의 3종의 추출물은 식품학적으로 허용된 담체와 혼합하여 식품 조성물로서 제공될 수 있다.The three extracts of the present invention may be provided as a food composition by mixing with a food acceptable carrier.
본 발명의 3종의 추출물을 식품 또는 음료 첨가물로 사용할 경우, 상기 3종의 추출물을 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용되고, 통상적인 방법에 따라 적절하게 사용될 수 있다. 상기 3종의 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 3종의 추출물은 안전성 면에서 아무런 문제가 없기 때문에, 장기간 복용이 가능하다. 상기 식품의 종류에는 특별한 제한은 없다. When the three extracts of the present invention are used as food or beverage additives, the three extracts may be added as they are or used together with other food or food ingredients, and may be appropriately used according to conventional methods. The mixed amount of the three 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 three 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 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 3종의 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 ㎖당 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 foods 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 three extracts when formulated into a beverage is not limited to the above, but may contain various flavors or natural carbohydrates as additional ingredients, such as conventional beverages. Examples of the natural carbohydrates described above 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 such natural carbohydrates is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention. As flavoring agents other than those described 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 proportion 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.
<실시예 1> 마키베리(Example 1 Marquiberry ( Aristotelia chilensisAristotelia chilensis ) 추출물의 제조) Preparation of Extract
마키베리(Aristotelia chilensis) 동결건조 분말은 칠레 원산지로서 미국 Terrasoul Superfoods 사의 수입/소분 제품을 구매하여 사용하였다. 상기 마키베리 동결건조 분말 2 g에 10 ㎖의 70% 메탄올을 가한 후 15분 동안 초음파 추출하였다. 초음파 추출한 마키베리 추출물은 3,000 rpm에서 10분간 원심분리한 후, 상층액을 분리하고 0.45 ㎛ PTFE-syringe filter로 여과하여 사용하였다.The Aristotelia chilensis lyophilized powder was originally from Chile and purchased from the United States Terrasoul Superfoods. 10 ml of 70% methanol was added to 2 g of the makiberry lyophilized powder, followed by ultrasonic extraction for 15 minutes. After ultrasonic extraction of makiberry extract was centrifuged at 3,000 rpm for 10 minutes, the supernatant was separated and filtered using a 0.45 ㎛ PTFE-syringe filter.
<실시예 2> 당귀(<Example 2> Angelica ( Angelica sinensisAngelica sinensis ) 추출물의 제조) Preparation of Extract
당귀(Angelica sinensis) 추출물은 미국 크로마덱스 사(Irvine, CA, US)의 제품을 구매하여 사용하였다. 이 제품은 당귀 건조분말을 열수추출법으로 추출한 후 농축 및 건조한 분말이다. 당귀 추출물 2 g에 10 ㎖의 70% 메탄올을 가한 후 15분 동안 초음파 추출하였다. 초음파 추출한 당귀 추출물은 3,000 rpm에서 10분간 원심분리한 후, 상층액을 분리하고 0.45 ㎛ PTFE-syringe filter로 여과하여 사용하였다. Angelica sinensis extract was purchased from the company Chromadex (Irvine, CA, US). This product is concentrated and dried powder after extracting Angelica dry powder by hot water extraction method. 10 ml of 70% methanol was added to 2 g of Angelica extract, and ultrasonic extraction was performed for 15 minutes. The ultrasonically extracted Angelica extract was centrifuged at 3,000 rpm for 10 minutes, and the supernatant was separated and filtered using a 0.45 μm PTFE-syringe filter.
<실시예 3> 시계꽃(Example 3 Clock Flower Passiflora incarnataPassiflora incarnata ) 추출물의 제조) Preparation of Extract
시계꽃(Passiflora incarnata) 추출물은 미국 크로마덱스 사(Irvine, CA, US)의 제품을 구매하여 사용하였다. 이 제품은 지상부의 건조분말을 이 제품은 지상부의 건조분말을 열수추출법으로 추출한 후 농축 및 건조한 분말이다. 시계꽃 추출물 2 g에 10 ㎖의 70% 메탄올을 가한 후 15분 동안 초음파 추출하였다. 초음파 추출한 시계꽃 추출물은 3,000 rpm에서 10분간 원심분리한 후, 상층액을 분리하고 0.45 ㎛ PTFE-syringe filter로 여과하여 사용하였다. Passiflora incarnata extract was used by purchasing a product of US Chromadex (Irvine, CA, US). This product is dry powder on the ground and this product is concentrated and dried powder after extracting the dry powder on the ground by hot water extraction method. 10 g of 70% methanol was added to 2 g of the passion flower extract, followed by ultrasonic extraction for 15 minutes. The ultrasonic extract extracted from the clock flower was centrifuged at 3,000 rpm for 10 minutes, and the supernatant was separated and filtered using a 0.45 μm PTFE-syringe filter.
<실시예 4> 마키베리, 당귀 및 시계꽃 혼합 추출물의 제조Example 4 Preparation of Makiberry, Angelica, and Passion Fruit Extract
상기 <실시예 1>에서 제조한 마키베리 추출물, <실시예 2>에서 제조한 당귀 추출물 및 <실시예 3>에서 제조한 시계꽃 추출물을 하기 [표 1]의 조성으로 혼합하여 마키베리, 당귀 및 시계꽃 혼합 추출물을 제조하였다.Makiberry extract prepared in <Example 1>, Angelica extract prepared in <Example 2> and Passion flower extract prepared in <Example 3> by mixing the composition of the following [Table 1] makiberry, Angelica And passion flower mixed extract was prepared.
<실험예 1> 마키베리, 당귀 및 시계꽃 혼합 추출물의 에스트로겐 수용체(estrogen receptor; ER) 작용제(agonist) 활성 확인Experimental Example 1 Confirmation of Estrogen Receptor (ER) Agonist Activity of Mixed Extracts of Makiberry, Angelica and Passionflower
<1-1> 마키베리, 당귀 및 시계꽃 혼합 추출물의 혼합 비율에 따른 ER 작용제 활성 확인 <1-1> Confirmation of ER agonist activity according to the mixing ratio of Makiberry, Angelica and Passionflower extract
에스트로겐의 생물학적 작용은 에스트로겐이 리간드로서 에스트로겐 수용체(estrogen receptor; ER)와 결합에 의해 매개되고, 상기 ER은 전사 인자로 작용하여 ERE(estrogen response element)에 결합하므로, ERE 리포터, 즉 ER-반응성 루시퍼라제를 이용하여 ER-매개 전사 활성을 확인함으로써 치료제의 효과를 모니터링할 수 있는 것으로 알려져 있다. 따라서 마키베리, 당귀 및 시계꽃 혼합 추출물이 ER 작용제로 작용하여 갱년기 여성에서 에스트로겐 결핍으로 유래된 갱년기 증상을 개선할 수 있는지 알아보기 위하여, ERE-루시퍼라제를 포함하는 플라스미드로 형질감염한 세포에 다양한 혼합 비율로 혼합하여 제조한 마키베리, 당귀 및 시계꽃 혼합 추출물을 처리한 후 ER-매개 전사활성 정도를 측정하였다.The biological action of estrogens is mediated by the binding of the estrogen to the estrogen receptor (ER) as a ligand, which acts as a transcription factor and binds to the estrogen response element (ERE), thus the ERE reporter, ie ER-reactive lucifer It is known that the effects of a therapeutic agent can be monitored by identifying the ER-mediated transcriptional activity with the enzyme. Therefore, in order to determine whether Makiberry, Angelica and Periflorum extracts can act as ER agents to improve menopausal symptoms caused by estrogen deficiency in menopausal women, a variety of cells transfected with plasmids containing ERE-Luciferase After processing the mixed extracts of Makiberry, Angelica and Passionfruit prepared by mixing at a mixing ratio, the degree of ER-mediated transcriptional activity was measured.
구체적으로, American Type Culture Collection (ATCC)에서 구입한 에스트로겐 수용체-양성 유방암 세포주 MCF-7은 RPMI 1680 배지에 비-필수 아미노산(non-essential amino acids), 항생제/항진균제(antibiotics/antimycotics), 피루브산나트륨(sodium pyruvate) 및 10% 소태아혈청(fetal bovine serum)을 첨가한 용액을 기본배지로 하여 세포를 배양하였다. 평균 일주일에 1회 계대배양(subculture)하였다. 세포 접종(Cell seeding)을 하기 48~60 시간(2-3일) 전 혈청을 덱스트론-차콜(dextran-charcoal)로 3회 처리한 stripped serum을 함유하고, 페놀-레드(phenol-red)가 없는 RPMI 1680으로 제조된 배지를 이용하여 세포를 배양하였다. 이 배지는 루시퍼라제 활성평가(luciferase assay)가 끝나는 시점까지 계속 사용하였다. 상기 배지를 사용하는 이유는 페놀-레드 자체의 에스트로겐 특성과 혈청에 다량 포함되어 있는 호르몬 및 성장인자 등에 의한 에스트로겐 수용체 상호작용에 의한 결과를 배제하기 위함이다.Specifically, the estrogen receptor-positive breast cancer cell line MCF-7, purchased from the American Type Culture Collection (ATCC), contains non-essential amino acids, antibiotics / antimycotics, and sodium pyruvate in RPMI 1680 medium. (Sodium pyruvate) and 10% fetal bovine serum (fetal bovine serum) solution was added to the culture medium as a base medium. Subcultures were made once a week on average. 48 to 60 hours (2-3 days) before cell seeding, the serum was treated with stripped serum three times with dextran-charcoal, and phenol-red Cells were cultured using media prepared with no RPMI 1680. This medium was used until the end of the luciferase assay. The reason for using the medium is to exclude the result of the estrogen receptor interaction by the estrogen properties of phenol-red itself and the hormones and growth factors contained in a large amount of serum.
그 다음, 상기 배양한 유방암 세포주 MCF-7을 24-웰 플레이트(well plate)에 형질감염 하루 전에 접종(105 cells/well)한 다음, ERE-luciferase plasmid DNA(0.25 ㎍/well)를 Lipofectamine 2000 transfection reagent(Invitrogen)을 이용하여 상기 유방암 세포주에 형질감염하였다.Next, the cultured breast cancer cell line MCF-7 was inoculated (10 5 cells / well) one day before transfection into a 24-well plate, and then ERE-luciferase plasmid DNA (0.25 μg / well) was added to Lipofectamine 2000. The breast cancer cell line was transfected with a transfection reagent (Invitrogen).
그 후, 대조군으로 E2(17β-estradiol)(ER agonist, 1 nM, Sigma) 및 ICI 182,780(Pure ER antagonist, 1 μM, Tocris)을 에탄올에 용해하여 사용하였다. 비교군으로 <실시예 1>에서 제조한 마키베리 추출물, <실시예 2>에서 제조한 당귀 추출물 및 <실시예 3>에서 제조한 시계꽃 추출물을 사용하였고, 추출물 각각은 200 ㎍/㎖의 농도에서 실험을 진행하였다. 실험군으로 상기 <실시예 4>에서 다양한 혼합 비율로 혼합하여 제조한 마키베리, 당귀 및 시계꽃 혼합 추출물을 사용하였고, 혼합 추출물 각각은 200 ㎍/㎖의 농도에서 실험을 진행하였다. 한편, 마키베리, 당귀 및 시계꽃 혼합 추출물, 및 대조군을 세포에 처리하고, 평균 18~24시간을 더 배양한 후 루시퍼라제 활성평가(luciferase assay)를 수행하였으며, 상기 루시퍼라제 활성평가는 배지를 제거한 후 세포를 차가운 PBS로 2회 세척한 후, 1X passive lysis buffer(Promega)로 세포수용성물질(lysate)을 추출하였고, 50 ㎕의 세포수용성물질에 50 ㎕ luciferase assay reagent (luciferase의 기질이 되는 luciferin과 효소반응에 적당한 완충액을 포함하는 용액, Promega)를 혼합한 후, 발생한 luminescence 세기를 SpectraMax M5e(Molecular Device)를 이용하여 측정하였다.Then, E2 (17β-estradiol) (ER agonist, 1 nM, Sigma) and ICI 182,780 (Pure ER antagonist, 1 μM, Tocris) were used as a control in ethanol. As a comparison group, the makiberry extract prepared in <Example 1>, the Angelica extract prepared in <Example 2> and the passion flower extract prepared in <Example 3> were used, and each of the extracts had a concentration of 200 µg / ml. The experiment was carried out in. As an experimental group, Makiberry, Angelica, and passion flower mixed extracts prepared by mixing at various mixing ratios were used in <Example 4>, and each of the mixed extracts was experimented at a concentration of 200 ㎍ / mL. On the other hand, makiberry, Angelica and passion flower mixed extract, and the control group was treated with cells, and further cultured for an average of 18 to 24 hours, and then performed luciferase assay (luciferase assay), the luciferase activity evaluation medium After removal, the cells were washed twice with cold PBS, and then cell lysates were extracted with 1X passive lysis buffer (Promega). After mixing a solution containing a suitable buffer for the enzyme reaction, Promega), the generated luminescence intensity was measured using SpectraMax M5 e (Molecular Device).
그 결과, 도 1에 나타낸 바와 같이, 마키베리 추출물, 당귀 추출물 또는 시계꽃 추출물을 처리한 세포군의 경우 ER-매개 전사활성이 거의 나타나지 않는 것을 확인하였다. 반면, 무처리 대조군에 비해 마키베리, 당귀 및 시계꽃 혼합 추출물을 처리한 세포군의 경우 ER-매개 전사활성 정도가 증가하므로, 마키베리, 당귀 및 시계꽃 혼합 추출물이 에스트로겐 활성을 갖고 ER 작용제로서의 활성을 나타냄을 확인하였다. 또한, 혼합 추출물 중에서도 실시예 4-1, 4-2, 4-4 및 4-7의 혼합 비율로 제조한 혼합 추출물의 ER-매개 전사활성 정도가 현저히 증가하므로, 마키베리, 당귀 및 시계꽃 추출물의 혼합 비율이 1 : 0.5 내지 4 : 0.5 내지 3일 때 보다 우수한 활성을 나타냄을 확인하였다(도 1).As a result, as shown in Figure 1, it was confirmed that the ER-mediated transcriptional activity in the cell group treated with Machiberry extract, Angelica extract or passion flower extract did not appear. On the other hand, since the level of ER-mediated transcriptional activity was increased in the cell group treated with the mixed extract of Makiberry, Angelica and Passion Fructus compared to the untreated control, the mixture of Makiberry, Angelica and Periflorum had an estrogen activity and acted as an ER agent. It confirmed that it represents. In addition, among the mixed extracts, the level of ER-mediated transcriptional activity of the mixed extracts prepared at the mixing ratios of Examples 4-1, 4-2, 4-4, and 4-7 was significantly increased. When the mixing ratio of 1: 0.5 to 4: 0.5 to 3 was confirmed to show a better activity (Fig. 1).
상기 결과를 통해 본 발명의 마키베리, 당귀 및 시계꽃 혼합 추출물은 ER 작용제로서의 활성을 나타내고, ER 작용제로서 보다 우수한 활성을 나타내는 마키베리, 당귀 및 시계꽃 추출물의 최적 혼합 비율은 1 : 0.5 내지 4 : 0.5 내지 3임을 확인하였다.Through the above results, the Makiberry, Angelica and Passiflora mixed extract of the present invention exhibited activity as an ER agonist, and the optimum mixing ratio of Makiberry, Angelica and Passiflorum extract, which exhibited better activity as an ER agonist, was 1: 0.5 to 4 : It was confirmed that it is 0.5 to 3.
<1-2> 마키베리, 당귀 및 시계꽃 혼합 추출물의 ER 작용제로서 시너지 효과 확인 <1-2> Confirmation of synergy effect as ER agonist of mixed extracts of Makiberry, Angelica and Passionflower
마키베리, 당귀 및 시계꽃 혼합 추출물을 갱년기 여성에서 에스트로겐 결핍으로 유래된 갱년기 증상을 개선할 수 있는지 알아보기 위하여, ERE-루시퍼라제를 포함하는 플라스미드로 형질감염한 세포에 마키베리, 당귀 및 시계꽃 혼합 추출물을 농도별로 처리한 후 ER-매개 전사활성 정도를 측정하였다. To determine whether Makiberry, Angelica, and Passion Fruit Extracts can improve menopausal symptoms caused by estrogen deficiency in menopausal women, Makiberry, Angelica, and Passionflower were found on cells transfected with plasmids containing ERE-luciferase. After treating the mixed extracts by concentration, the degree of ER-mediated transcriptional activity was measured.
구체적으로, ER 작용제로서의 활성이 보다 우수한 마키베리, 당귀 및 시계꽃 혼합 추출물로 마키베리 추출물 : 당귀 추출물 : 시계꽃 추출물이 1 : 0.5 : 0.5의 혼합 비율로 혼합된 혼합 추출물을 하기 [표 2]의 조성으로 농도를 달리하여 제조하고, 이를 이용하여 상기 <실험예 1>에 기재된 방법과 동일한 방법으로 ER 매개 전사활성 정도를 측정하였다. 비교군으로 <실시예 1>에서 제조한 마키베리 추출물, <실시예 2>에서 제조한 당귀 추출물 및 <실시예 3>에서 제조한 시계꽃 추출물을 사용하였고, 추출물 각각의 농도는 하기 [표 2]와 동일하게 하였다. 또한, 비교군 각각의 ER-매개 전사활성 정도의 합 대비 마키베리, 당귀 및 시계꽃 혼합 추출물 처리군의 ER-매개 전사활성 정도의 %증가값(%Increase)를 다음의 수학식을 이용하여 계산하였다: %Increase=[(마키베리, 당귀 및 시계꽃 혼합 추출물 처리군의 ER-매개 전사활성 정도 - 비교군 각각의 ER-매개 전사활성 정도의 합)/비교군 각각의 ER-매개 전사활성 정도의 합]×100.Specifically, Maki berry extract: Angelica extract: Angelica extract: Passion flower extract with a mixture ratio of 1: 0.5: 0.5 with a more excellent activity as an ER agonist, Angelica extract and bergamot [Table 2] It was prepared by varying the concentration in the composition of, using the same method as described in <Experimental Example 1> was measured the degree of ER mediated transcriptional activity. As a comparison group, the makiberry extract prepared in <Example 1>, the Angelica extract prepared in <Example 2> and the passion flower extract prepared in <Example 3> were used, and the concentration of each extract was shown in Table 2 below. ]. In addition, the% increase value of the degree of ER-mediated transcriptional activity of the Makiberry, Angelica, and passion flower mixed extract treatment group compared to the sum of the degree of ER-mediated transcriptional activity of each comparison group was calculated using the following equation. % Increase = [(Degree of ER-Mediated Transcriptional Activity of Makiberry, Angelica, and Passion Flower Extracts Treated Groups-Sum of ER-Mediated Transcriptional Activities of Comparative Groups) Sum] × 100.
농도Mixed extract
density
그 결과, 도 2에 나타낸 바와 같이, 혼합 추출물 750 ㎍/㎖ 처리군 및 1500 ㎍/㎖ 처리군의 %증가값이 각각 17.5%, 78.7%로, 혼합 추출물에 포함된 농도와 동일한 농도로 처리한 마키베리 추출물 처리군, 당귀 추출물 처리군 및 시계꽃 추출물 처리군 각각의 ER-매개 전사활성 정도의 합보다 혼합 추출물 처리군의 ER-매개 전사 활성 정도가 현저히 증가함을 확인하였다(도 2).As a result, as shown in Figure 2, the percentage increase of the mixed extract 750 ㎍ / ㎖ treated group and 1500 ㎍ / ㎖ treated group was 17.5%, 78.7%, respectively, treated with the same concentration as the concentration contained in the mixed extract It was confirmed that the level of ER-mediated transcriptional activity of the mixed extract treatment group was significantly increased compared to the sum of the degree of ER-mediated transcriptional activity of the Makiberry extract treatment group, Angelica extract treatment group, and passion flower extract treatment group (FIG. 2).
상기 결과를 통해 본 발명의 혼합 추출물은 마키베리 추출물, 당귀 추출물 및 시계꽃 추출물을 모두 포함하여 ER 작용제로서 시너지 효과를 나타냄을 확인하였다.Through the above results, it was confirmed that the mixed extract of the present invention exhibited synergistic effects as ER agonist, including both makiberry extract, Angelica extract and passion flower extract.
<실험예 3> 마키베리, 당귀 및 시계꽃 혼합 추출물의 안전성 확인Experimental Example 3 Safety Confirmation of Makiberry, Angelica and Passion Fruit Extract
에스트로겐 활성은 자궁내막세포 증식 등의 메커니즘과 직간접적인 연관성이 있는 것으로 알려져 있으며, 이에 자궁증식 증상이 에스트로겐류 화합물의 부작용 중 하나로 인식되어 있다. 따라서, 마키베리, 당귀 및 시계꽃 혼합 추출물이 인체 적용에 있어 안전한지 알아보기 위하여, 랫트에 마키베리, 당귀 및 시계꽃 혼합 추출물을 투여한 후 자궁 증식 정도를 측정하였다.It is known that estrogen activity is directly or indirectly related to mechanisms such as endometrial cell proliferation. Thus, uterine proliferation is recognized as one of the side effects of estrogen compounds. Therefore, in order to find out whether the Makiberry, Angelica and Passiflora mixed extracts are safe for human application, rats were treated with Makiberry, Angelica and Cauliflower mixed extracts, and then the degree of uterine proliferation was measured.
구체적으로, 3주령 Sprague-Dawley(SD) 랫트(45-55 g, 자성)는 오리엔트 바이오에서 분양받아 실험동물용 사육상자에 일주일간 적응시킨 후 실험에 사용하였다. 동물의 사육은 온도 22±1℃, 습도 55±5%, 밤낮주기(12 시간 낮/ 12 시간 밤), 조도 300 Lux의 조건하에 이루어졌으며, 사료 및 음수는 자유 급여하였다. 모든 동물들은 SMWU-IACUC(Sookmyung Women's University, Institutional Animal Care and Use Committee)의 실험동물 사용지침에 의해 관리되었다. 적응 후 정상으로 판단된 동물에 대하여 체중을 측정하고 무작위적으로 음성대조군(Control), 양성대조군(E2), 실험군 및 비교군으로 분리하였다. Specifically, three-week-old Sprague-Dawley (SD) rats (45-55 g, magnetic) were used in the experiment after being adapted to a breeding box for experimental animals received from Orient Bio. Animals were reared under conditions of
그 다음, 마키베리 추출물 : 당귀 추출물 : 시계꽃 추출물이 1 : 0.5 : 0.5의 혼합 비율로 혼합된 혼합 추출물 시료를 멸균한 PBS에 적정 농도로 용해 및 현탁시켜 제조하고 실험군에 피하주사 하였다. 상기와 동일한 방법으로 마키베리 추출물 시료, 당귀 추출물 시료, 시계꽃 추출물 시료를 각각 제조하고 비교군에 피하주사 하였다. Then, Makiberry extract: Angelica extract: Passion flower extract was prepared by dissolving and suspending the mixed extract sample mixed in a mixing ratio of 1: 0.5: 0.5 at a suitable concentration in sterile PBS and injected into the experimental group subcutaneously. Makiberry extract sample, Angelica extract sample, Passion flower extract samples were prepared in the same manner as above and subcutaneously injected into the comparison group.
제조된 혼합 추출물 시료는 매일 1회 3일 동안 500 mg/kg/d 용량으로 피하주사 하였다. 제조된 마키베리 추출물 시료는 매일 1회 3일 동안 100, 250 또는 500 mg/kg/d 용량으로 피하주사 하였다. 제조된 당귀 추출물 시료는 매일 1회 3일 동안 500 mg/kg/d 용량으로 피하주사 하였다. 제조된 시계꽃 추출물 시료는 매일 1회 3일 동안 500 mg/kg/d 용량으로 피하주사 하였다. 또한, 음성대조군은 동량의 멸균한 PBS를 피하주사 하였고, 양성대조군으로 사용한 E2는 5 ㎍/kg/d의 용량으로 3일 동안 매일 1회 피하주사 하였다.The prepared mixed extract sample was injected subcutaneously at a dose of 500 mg / kg / d for 3 days once daily. Prepared makiberry extract samples were injected subcutaneously at a dose of 100, 250 or 500 mg / kg / d once daily for 3 days. The prepared Angelica extract sample was injected subcutaneously at a dose of 500 mg / kg / d once daily for 3 days. The prepared passion flower extract sample was injected subcutaneously at a dose of 500 mg / kg / d once daily for 3 days. In addition, the negative control group was injected subcutaneously with the same amount of sterile PBS, E2 used as a positive control group was injected once daily for 3 days at a dose of 5 ㎍ / kg / d.
그 후 실험동물을 희생하고 자궁을 적출한 후, 자궁의 무게를 측정하였다.Thereafter, the animals were sacrificed and the uterus was extracted, and the weight of the uterus was measured.
그 결과, 도 3에 나타낸 바와 같이, 양성대조군의 경우 대조군에 비해 자궁 무게가 증가하는 반면, 마키베리, 당귀 및 시계꽃 혼합 추출물을 투여한 군은 음성대조군과 유사한 수준의 자궁 무게를 나타내므로, 본 발명의 혼합 추출물은 ER 작용제로서 자궁 증식의 부작용이 없고 안전함을 확인하였다(도 3).As a result, as shown in Figure 3, the positive control group uterine weight is increased compared to the control group, while the group administered Makiberry, Angelica and passion flower mixture extract shows a uterine weight similar to the negative control group, The mixed extract of the present invention was confirmed to be safe and no side effects of uterine proliferation as an ER agonist (FIG. 3).
따라서 상기 <실험예 1> 내지 <실험예 3>의 결과를 통해 본 발명의 마키베리, 당귀 및 시계꽃 혼합 추출물이 에스트로겐 활성을 갖고 부작용 없이 ER 작용제로 작용함을 확인하였으므로, 본 발명의 마키베리, 당귀 및 시계꽃 혼합 추출물을 갱년기 여성에서 에스트로겐 결핍으로 유래된 갱년기 증상을 예방 및 치료하기 위한 여성호르몬 대체요법에 이용할 수 있다.Therefore, through the results of the <Experimental Example 1> to <Experimental Example 3> it was confirmed that the Makiberry, Angelica and passion flower mixed extract of the present invention has estrogen activity and acts as an ER agent without side effects, the makiberry of the present invention Extracts of Angelica sinensis and Angelica sinensis can be used in female hormone replacement therapy to prevent and treat menopausal symptoms caused by estrogen deficiency in menopausal women.
이하, 본 발명에 따른 각 제제의 제조예를 예시한다. 하기 제조예는 본 발명의 실시에 대한 이해를 돕기 위한 것이지 본 발명에 따른 제형의 제조방법이 하기 제조예로 한정되는 것을 의미하지 않는다.Hereinafter, the manufacture example of each formulation which concerns on this invention is illustrated. The following preparation examples are intended to aid the understanding of the practice of the present invention and do not mean that the preparation method of the formulation according to the present invention is limited to the following preparation examples.
<제조예 1> 약학적 제제의 제조Preparation Example 1 Preparation of Pharmaceutical Formulation
<1-1> 산제의 제조<1-1> Preparation of Powder
본 발명의 혼합 추출물 2 g2 g of the mixed 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 혼합 추출물 100 mg100 mg of the extract of the present invention
미결정셀룰로오스 100 mg 100 mg of microcrystalline cellulose
유당 100 mg
전분글리콘산 나트륨 18 mgSodium starch glycolate 18 mg
스테아린산 마그네슘 2 mg 2 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 혼합 추출물 100 mg100 mg of the extract of the present invention
옥수수전분 100 mg
유 당 100 mg
스테아린산 마그네슘 2 mg 2 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 혼합 추출물 1 g1 g of the mixed 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 혼합 추출물 150 mg 150 mg of the mixed extract of the present invention
대두 추출물 50 mg
포도당 200 mg Glucose 200 mg
전분 600 mg Starch 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> 식품의 제조Production Example 2 Preparation of Food
<2-1> 과자 및 분식의 제조<2-1> Preparation of sweets and snacks
본 발명의 혼합 추출물 0.5~5.0 중량부를 밀가루에 첨가하고, 이 혼합물을 이용하여 빵, 케이크, 쿠키, 크래커 및 면류를 제조하여 건강 증진용 식품을 제조하였다.0.5-5.0 parts by weight of the mixed extract of the present invention was added to the flour, using the mixture to prepare bread, cakes, cookies, crackers and noodles to prepare foods for health promotion.
<2-2> 유제품의 제조<2-2> Production of Dairy Products
본 발명의 혼합 추출물 5~10 중량부를 우유에 첨가하고, 상기 우유를 이용하여 버터 및 아이스크림과 같은 다양한 유제품을 제조하였다.5-10 parts by weight of the mixed extract of the present invention was added to milk, and various milk products such as butter and ice cream were prepared using the milk.
<2-3> 선식의 제조<2-3> Preparation of Wire
현미, 보리, 찹쌀, 율무를 공지의 방법으로 알파화시켜 건조시킨 것을 배전한 후 분쇄기로 입도 60 메쉬의 분말로 제조하였다. 검정콩, 검정깨, 들깨도 공지의 방법으로 쪄서 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. Black beans, black sesame seeds, and perilla were also steamed and dried by a known method, and then ground to a powder having a particle size of 60 mesh.
본 발명의 혼합 추출물을 진공 농축기에서 감압 농축하고, 분무, 열풍건조기로 건조하여 얻은 건조물을 분쇄기로 입도 60 메쉬로 분쇄하여 건조분말을 얻었다. 상기에서 제조한 곡물류, 종실류 및 SBE의 건조분말을 다음의 비율로 배합하여 제조하였다.The mixed extract of the present invention was concentrated under reduced pressure in a vacuum concentrator, dried by spraying and drying with a hot air dryer, and then pulverized with a particle size of 60 mesh using a grinder to obtain a dry powder. The grains, seeds, and dry powders of SBE prepared above were combined and prepared 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 마키베리 추출물 또는 이의 효소 가수분해물 건조분말(3 중량부),Makiberry extract or enzyme hydrolyzate dry powder thereof (3 parts by weight) of the present invention,
영지(0.5 중량부), 및 지황(0.5 중량부)Ganoderma lucidum (0.5 parts by weight), and Sulfur (0.5 parts by weight)
<제조예 3> 음료의 제조Preparation Example 3 Preparation of Beverage
본 발명의 혼합 추출물 1000 mg1000 mg of the extract of the present invention
구연산 1000 mgCitric acid 1000 mg
올리고당 100 g100 g oligosaccharides
매실농축액 2 gPlum concentrate 2 g
타우린 1 g1 g of taurine
정제수를 가하여 전체 900 ㎖Add 900 ml of purified water
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간 동안 85℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2 ℓ 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강식품 제조에 사용한다.After mixing the above components according to the conventional healthy beverage production method, and stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed sterilization and refrigerated Used in the manufacture of the health food of the invention.
상기 조성비는 비교적 기호 음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 수요계층, 수요국가, 사용 용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.Although the composition ratio is a composition suitable for a preferred beverage in a preferred embodiment, the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and intended use.
Claims (16)
A pharmaceutical composition for preventing or treating female menopausal symptoms, comprising makiberry ( Aristotelia chilensis ) extract, Angelica sinensis extract and Passiflora incarnata extract as active ingredients.
The pharmaceutical composition for preventing or treating female menopausal symptoms according to claim 1, wherein the extract is extracted with water, C 1 to C 2 lower alcohols, or a mixed solvent thereof.
According to claim 2, wherein the extract is water, methanol, ethanol and a mixed composition thereof, characterized in that extracted with one or more solvents selected from the group consisting of, female menopausal symptoms preventive or therapeutic pharmaceutical composition.
According to claim 1, The extract is characterized in that the extract of any one or more selected from flowers, branches, stems, leaves, fruits, ground, rhizomes and roots, female menopausal symptoms preventive or therapeutic pharmaceutical composition.
The pharmaceutical composition for preventing or treating female menopausal symptoms according to claim 1, wherein the composition contains Makiberry extract: Angelica extract: Passion flower extract in a weight ratio of 1: 0.25 to 5: 0.25 to 4.
The pharmaceutical composition for preventing or treating female menopausal symptoms according to claim 1, wherein the composition contains Makiberry extract: Angelica extract: Passion flower extract in a weight ratio of 1: 0.3 to 4.5: 0.3 to 3.5.
According to claim 1, wherein the female menopausal symptoms are hot flashes, sweating, dry skin, vaginal dryness, vaginal atrophy, lower urethral atrophy, vaginitis, cystitis, urination pain, urination, concentration disorders, short-term memory disorders, anxiety, nervousness, memory A pharmaceutical composition for preventing or treating female menopausal symptoms, characterized in that any one or more selected from the group consisting of decay, myalgia, arthralgia and osteoporosis.
The pharmaceutical composition for preventing or treating female menopausal symptoms according to claim 1, wherein the composition is an estrogen receptor agonist.
The pharmaceutical composition for preventing or treating female menopausal symptoms according to claim 1, wherein the composition has estrogen activity.
Health functional food for preventing or improving female menopausal symptoms, containing makiberry extract, Angelica extract and passion flower extract as active ingredients.
The health functional food for preventing or improving female menopausal symptoms according to claim 10, wherein the extract is extracted with water, C 1 to C 2 lower alcohols, or a mixed solvent thereof.
The health functional food for preventing or improving female menopausal symptoms according to claim 10, wherein the extract is any one or more extracts selected from flowers, branches, stems, leaves, fruits, ground parts, rhizomes and roots.
The method according to claim 10, wherein the composition comprises makiberry extract: Angelica extract: passion flower extract in a weight ratio of 1: 0.25 to 5: 0.25 to 4, preventing or improving female menopausal symptoms or female menopausal symptoms Dietary supplements.
11. The method of claim 10, wherein the female menopausal symptoms are hot flashes, sweating, dry skin, vaginal dryness, vaginal atrophy, lower urethral atrophy, vaginitis, cystitis, urination pain, urination, concentration disorders, short-term memory disorders, anxiety, nervousness, memory Health functional food for preventing or improving female menopausal symptoms, characterized in that at least one selected from the group consisting of decay, myalgia, arthralgia and osteoporosis.
Food composition for preventing or improving female menopausal symptoms, containing makiberry extract, Angelica extract and passion flower extract as an active ingredient.
The method of claim 15, wherein the female menopausal symptoms are hot flashes, sweating, dry skin, vaginal dryness, vaginal atrophy, lower urethral atrophy, vaginitis, cystitis, urination pain, urination, concentration disorders, short-term memory disorders, anxiety, nervousness, memory It is one or more selected from the group consisting of decay, myalgia, arthralgia and osteoporosis, food composition for preventing or improving female menopausal symptoms.
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