KR102202224B1 - A composition for the prevention or treatment of depression comprising herb extract YJ06 - Google Patents
A composition for the prevention or treatment of depression comprising herb extract YJ06 Download PDFInfo
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- KR102202224B1 KR102202224B1 KR1020190003123A KR20190003123A KR102202224B1 KR 102202224 B1 KR102202224 B1 KR 102202224B1 KR 1020190003123 A KR1020190003123 A KR 1020190003123A KR 20190003123 A KR20190003123 A KR 20190003123A KR 102202224 B1 KR102202224 B1 KR 102202224B1
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- dansam
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Abstract
본 발명은 우울 증상의 개선, 예방 또는 치료용 조성물에 관한 것으로 목단피, 백복령, 택사 및 단삼로 이루어진 혼합 추출물을 유효성분으로 함유함으로써, 우울 증상을 개선, 예방 또는 치료할 수 있다. 또한, 독성이 없으므로 식품의 형태로 섭취할 수 있다.The present invention relates to a composition for improving, preventing or treating depressive symptoms. By containing a mixed extract consisting of Mokdanpi, Baekbokryeong, Taeksa and Dansam as an active ingredient, depressive symptoms can be improved, prevented or treated. In addition, since it is not toxic, it can be consumed in the form of food.
Description
본 발명은 목단피, 백복령, 택사 및 단삼으로 이루어진 혼합 추출물(YJ06이라 함)을 함유하여 우울 증상을 개선, 예방 또는 치료할 수 있는 조성물에 관한 것이다.The present invention relates to a composition capable of improving, preventing or treating depressive symptoms by containing a mixed extract (referred to as YJ06) consisting of Mokdanpi, Baekbokryeong, Taeksa and Dansam.
현대의 역병(modern epidemics)이라 불리는 우울 증상은 우리나라의 경우 특히 더 심각한 사회 문제로 대두되고 있으며, 이에 따른 사회적, 경제적 비용이 증가하고 국가적 근심사가 되고 있다. 상기 우울 증상의 발병원인은 다양하나 스트레스가 중요한 원인으로 간주된다. Depressive symptoms, called modern epidemics, are emerging as a particularly serious social problem in Korea, resulting in increased social and economic costs, and a national concern. The causes of the depressive symptoms vary, but stress is considered an important cause.
상기 우울 증상은 정서적 장애만 나타내는 것이 아니라, 인지적 및 신체 생리적 증상으로도 나타난다. 구체적으로 우울 증상은 우울, 슬픔 등이 장기간 지속되는 기분장애 등의 정서적 증상을 유발하고; 주의집중력, 기억력, 판단력 등의 인지기능 저하, 죄책적 망상, 자기비하, 피해망상, 비관적 생각 등의 인지적 증상을 유발할 뿐만 아니라; 체중 및 식욕 변화(과다, 과소), 활력 및 생기 저하, 심한 피로감, 수면장애(불면증 또는 과다수면), 소화불량, 두통, 면역력 저하 등의 신체 생리적 증상을 유발한다.The depressive symptoms are not only indicative of emotional disorders, but also in cognitive and physical physiological symptoms. Specifically, depressive symptoms cause emotional symptoms such as mood disorders in which depression, sadness, and the like last a long time; It not only causes cognitive symptoms such as decreased cognitive function such as attention, memory, judgment, guilt delusion, self-deprecation, damage delusion, and pessimistic thoughts; It causes body physiological symptoms such as changes in weight and appetite (excessive, underrepresented), decreased vitality and vitality, severe fatigue, sleep disturbances (insomnia or excessive sleep), indigestion, headache, and decreased immunity.
상기 우울 증상은 크게 유전적 요인과 스트레스 등의 환경적 요인에 의해 발생될 수 있다. 이러한 원인에 수반되는 세부기전으로는 도파민, 세로토닌 등의 신경전달물질의 감소, 신경영양인자 발현의 감소 및 이와 관련된 새로운 신경세포 생성의 저하, 후생유전학적 기전의 영향으로 장기적으로 신경계 핵심 유전자들의 발현이 억제되거나 증가, 신경세포의 에너지 대사의 변화, 산화성 스트레스의 축적으로 인한 신경세포의 손상 등이 제시되고 있다. The depressive symptoms can be largely caused by genetic factors and environmental factors such as stress. The detailed mechanisms accompanying these causes include the reduction of neurotransmitters such as dopamine and serotonin, the decrease in the expression of neurotrophic factors, and the decrease in the generation of new neurons related to this, and the expression of key genes in the nervous system in the long term due to the influence of epigenetic mechanisms. Inhibition or increase, changes in energy metabolism of nerve cells, damage to nerve cells due to accumulation of oxidative stress, etc. have been suggested.
이와 같이, 우울 증상의 원인이 다양하다는 것은 우울 증상의 예방이나 치료 방법도 그에 맞게 개발될 필요가 있음을 의미한다. As described above, the fact that the causes of depressive symptoms are diverse means that a method of preventing or treating depressive symptoms needs to be developed accordingly.
현재 임상에서 사용되는 우울 증상 치료제는 대체로 우울 증상 동물 모델을 통해 개발되고 검정되고 있다. 우울 증상 치료제는 모두 뇌 신경세포 간의 신경전달물질인 도파민, 세로토닌, 노에피네프린 등의 모노아민의 분해, 재흡수 등을 억제하여 시냅스에서 약물 작용을 강화하는 약물 작용을 갖는 것으로 이해되고 있다. 다만, 상기 약물은 환자에 따라 약효의 차이가 커서 이러한 문제를 보완하거나 대체하는 새로운 항우울제의 개발을 필요로 하고 있다. Currently, treatments for depressive symptoms used in clinical practice are generally developed and tested through animal models of depressive symptoms. All treatments for depressive symptoms are understood to have a drug action that enhances drug action at synapses by inhibiting the decomposition and reabsorption of monoamines such as dopamine, serotonin, and noepinephrine, which are neurotransmitters between brain neurons. However, since the drug has a large difference in efficacy depending on the patient, it is necessary to develop a new antidepressant that supplements or replaces this problem.
국민건강보험공단이 최근 발표한 우울 증상 진료 통계를 보면 2007년에 비해 2011년의 우울증 환자가 12.4% 증가했고, 2009~2010년 자살원인 유형별 현황을 살펴보면 정신적, 정신과적 문제로 인한 자살이 자살원인 1위이며, 해당 원인으로 자살을 한 사람이 2009년에 4,132명(28.1%), 2010년엔 4,357명(29.5%)으로 증가하고 있는 추세를 보인다. 우울증뿐만 아니라 주의력 결핍/과잉행동 장애인 ADHD(Attention Deficit/Hyperactivity Disorder) 환자도 2007년 4만 8천명에서 2012년 5만 7천명으로 5년간 9천명이 증가하였고, 연 평균 4.4%의 증가율을 보이고 있다. According to the statistics on the treatment of depressive symptoms recently released by the National Health Insurance Service, the number of depressed patients increased by 12.4% in 2011 compared to 2007. In 2009-2010, suicide caused by mental and psychiatric problems is the cause of suicide. It ranks first, and the number of people who committed suicide as a cause of this is increasing to 4,132 (28.1%) in 2009 and 4,357 (29.5%) in 2010. In addition to depression, attention deficit/hyperactivity disorder (ADHD) patients also increased from 48,000 in 2007 to 57,000 in 2012, an increase of 9,000 for five years, and an average annual increase of 4.4%. .
따라서, 우울 증상을 신속하게 개선, 예방 또는 치료할 수 있으며, 안정하고 부작용이 없는 천연 한약재로부터의 추출물이 요구되고 있다.Therefore, it is possible to quickly improve, prevent or treat depressive symptoms, and there is a need for extracts from natural herbal medicines that are stable and have no side effects.
본 발명의 목적은 목단피, 백복령, 택사 및 단삼으로 이루어진 혼합 추출물(YJ06)을 유효성분으로 함유하는 우울 증상을 개선, 예방 또는 치료용 약학 조성물을 제공하는데 있다.An object of the present invention is to provide a pharmaceutical composition for improving, preventing or treating depressive symptoms containing a mixed extract (YJ06) consisting of Mokdanpi, Baekbokryeong, Taeksa and Dansam as an active ingredient.
또한, 본 발명의 다른 목적은 목단피, 백복령, 택사 및 단삼으로 이루어진 혼합 추출물(YJ06)을 유효성분으로 함유하는 통증의 예방 또는 개선용 식품 조성물을 제공하는데 있다.In addition, another object of the present invention is to provide a food composition for preventing or improving pain containing a mixed extract (YJ06) consisting of Mokdanpi, Baekbokryeong, Taeksa and Dansam as an active ingredient.
상기한 목적을 달성하기 위한 본 발명의 우울 증상을 예방 또는 치료할 수 있는 약학 조성물은 목단피, 백복령, 택사 및 단삼으로 이루어진 혼합 추출물을 유효성분으로 함유하는 것일 수 있다.A pharmaceutical composition capable of preventing or treating depressive symptoms of the present invention for achieving the above object may contain a mixed extract consisting of Mokdanpi, Baekbokryeong, Taeksa and Dansam as an active ingredient.
상기 목단피, 백복령, 택사 및 단삼은 1 : 0.5-2 : 0.5-2 : 0.5-2의 중량비, 바람직하게는 1 : 1 : 1 : 1의 중량비로 혼합되는 것일 수 있다.The Mokdanpi, Baekbokryeong, Taeksa, and Dansam may be mixed in a weight ratio of 1: 0.5-2: 0.5-2: 0.5-2, preferably 1: 1: 1: 1.
상기 혼합 추출물은 물, 탄소수 1 내지 4의 저급알코올, 에틸렌글리콜, 에틸에테르 또는 이들의 혼합용매로 추출된 것일 수 있다.The mixed extract may be extracted with water, a lower alcohol having 1 to 4 carbon atoms, ethylene glycol, ethyl ether, or a mixed solvent thereof.
또한, 상기한 다른 목적을 달성하기 위한 본 발명의 우울 증상을 예방 또는 개선할 수 있는 식품 조성물은 목단피, 백복령, 택사 및 단삼으로 이루어진 혼합 추출물을 유효성분으로 함유할 수 있다.In addition, the food composition capable of preventing or improving the depressive symptoms of the present invention for achieving the other objects described above may contain a mixed extract consisting of mokdanpi, baekbokryeong, taeksa and dansam as an active ingredient.
본 발명의 목단피, 백복령, 택사 및 단삼으로 이루어진 혼합 추출물을 유효성분으로 함유하는 우울 증상의 개선, 예방 또는 치료할 수 있는 조성물은 독성이 없으며, 우울 증상에 대한 개선, 예방 또는 치료 효과가 매우 뛰어나 경쟁력 있는 식품 조성물 및 의약 조성물의 제조에 효과적이다. The composition capable of improving, preventing or treating depressive symptoms containing a mixed extract consisting of Mokdanpi, Baekbokryong, Taeksa and Dansam as an active ingredient of the present invention is not toxic, and has excellent improvement, prevention or treatment effects on depressive symptoms, and is competitive. It is effective in the manufacture of food compositions and pharmaceutical compositions.
도 1은 우울 증상을 측정하기 위하여 강제 수영 실험을 실시할 때 분석을 위한 동물의 움직임을 나타낸 사진이다.1 is a photograph showing the movement of an animal for analysis when a forced swimming experiment is performed to measure depressive symptoms.
본 발명은 목단피, 백복령, 택사 및 단삼으로 이루어진 혼합 추출물(YJ06)을 함유하여 우울 증상을 개선, 예방 또는 치료할 수 있는 조성물에 관한 것이다.The present invention relates to a composition capable of improving, preventing or treating depressive symptoms by containing a mixed extract (YJ06) consisting of Mokdanpi, Baekbokryeong, Taeksa and Dansam.
이하, 본 발명을 상세하게 설명한다. Hereinafter, the present invention will be described in detail.
본 발명의 우울 증상을 개선, 예방 또는 치료할 수 있는 조성물은 목단피, 백복령, 택사 및 단삼으로 이루어진 혼합 추출물을 유효성분으로 함유한다.The composition capable of improving, preventing or treating depressive symptoms of the present invention contains a mixed extract consisting of Mokdanpi, Baekbokryeong, Taeksa and Dansam as an active ingredient.
상기 목단피(Paeonia suffruticosa)는 특이한 냄새가 있으며 맛은 조금 쓰고 매우며 성질은 약간 차가운 것으로서, 진통, 진정, 해열, 항경련, 항염증, 항혈전, 항알레르기, 위액분비억제, 자궁점막충혈, 항균작용 등이 보고되었다. Paeonia suffruticosa has a peculiar smell, a bit bitter taste, and a little cold in nature, and pain relief , soothing, antipyretic, anticonvulsant, anti-inflammatory, antithrombotic, antiallergic, gastric secretion inhibition, uterine mucosa congestion, antibacterial Actions and the like have been reported.
또한, 상기 백복령(Poria cocos)은 이뇨작용과 혈당량을 낮추는 작용, 진정작용 등을 하는 것으로 밝혀졌으며, 면역 부활작용을 하는 것으로도 알려져 있다.In addition, the Baekbokryung ( Poria cocos ) has been found to have a diuretic effect, lowering blood sugar levels, and sedation, and is also known to have an immune reactivation effect.
또한, 상기 택사(Alisma orientale)는 택사과에 속하는 다년생 초본식물로서, 소변불리(小便不利), 수종창만(水腫脹滿), 신장염, 방광염, 요도염, 임신부종, 각기, 설사, 번갈(煩渴), 당뇨, 고혈압, 지방, 간 등의 증상에 사용한다. In addition, Alisma orientale is a perennial herbaceous plant belonging to the family Taeksa family.渴), diabetes, high blood pressure, fat, liver and other symptoms.
또한, 상기 단삼(Salvia miltiorrhiza)은 꿀풀과에 속하는 다년생 초본식물로서, 항균작용, 월경통ㅇ생리불순 및 산후의 하복부 통증, 만성간염, 간기능 장애, 간경변증의 초기 증상에도 효능이 있다.In addition, Salvia miltiorrhiza is a perennial herbaceous plant belonging to the Lamiaceae family, and is effective in antibacterial action, menstrual pain, menstrual impurities and postpartum lower abdominal pain, chronic hepatitis, liver dysfunction, and early symptoms of cirrhosis.
상기 목단피, 백복령, 택사 및 단삼은 1 : 0.5-2 : 0.5-2 : 0.5-2의 중량비, 바람직하게는 1 : 1 : 1 : 1의 중량비로 혼합된다. The Mokdanpi, Baekbokryeong, Taeksa and Dansam are mixed in a weight ratio of 1: 0.5-2: 0.5-2: 0.5-2, preferably 1: 1: 1: 1.
목단피를 기준으로 백복령, 택사 및 단삼의 함량이 상기 하한치 미만인 경우에는 우울 증상을 개선, 예방 또는 치료하는 효과가 각 한약재를 단독으로 사용하는 경우보다도 낮을 수 있으며, 상기 상한치 초과인 경우에는 우울 증상을 개선, 예방 또는 치료하는 효과가 저하될 수 있다.If the content of Baekbokryeong, Taeksa, and Dansam is less than the lower limit of Mokdanpi, the effect of improving, preventing or treating depressive symptoms may be lower than that of using each herbal medicine alone. The effect of improving, preventing or treating may be diminished.
상기 목단피, 백복령, 택사 및 단삼을 단독으로 사용하는 경우에는 목단피, 백복령, 택사 및 단삼을 함께 사용하는 경우에 비하여 1.5 내지 20배로 낮은 효능을 보인다.When the Mokdanpi, Baekbokryeong, Taeksa, and Dansam are used alone, the efficacy is 1.5 to 20 times lower than that of Mokdanpi, Baekbokryeong, Taeksa and Dansam.
상기 목단피, 백복령, 택사 및 단삼의 혼합물은 추출용매와 1 : 5 내지 25, 바람직하게는 1 : 8 내지 15의 중량비로 혼합하여 90 내지 110 ℃에서 추출한 후 50 내지 60 ℃에서 감압농축을 수행하여 추출물을 제조한다. 상기 목단피, 백복령, 택사 및 단삼의 혼합물과 추출용매의 중량비가 상기 범위를 벗어나는 경우에는 추출물에 목단피, 백복령, 택사 및 단삼의 혼합물의 유효성분이 적은 양으로 추출될 수 있다.The mixture of Mokdanpi, Baekbokryeong, Taeksa and Dansam is mixed with an extraction solvent in a weight ratio of 1: 5 to 25, preferably 1: 8 to 15, extracted at 90 to 110°C, and concentrated under reduced pressure at 50 to 60°C. Prepare the extract. When the weight ratio of the mixture of Mokdanpi, Baekbokryeong, Taeksa and Dansam and the extraction solvent is out of the above range, the active ingredient of the mixture of Mokdanpi, Baekbokryeong, Taeksa and Dansam in the extract may be extracted in a small amount.
상기 각 추출물을 추출하는 추출용매는 물, 탄소수 1 내지 4의 저급알코올, 에틸렌글리콜, 에틸에테르 또는 이들의 혼합용매이다. 상기 추출용매로는 특별히 한정하는 것은 아니지만 물로 추출된 추출물이 우울 증상의 개선, 예방 또는 치료에 바람직하게 작용한다.The extraction solvent for extracting each extract is water, a lower alcohol having 1 to 4 carbon atoms, ethylene glycol, ethyl ether, or a mixed solvent thereof. The extraction solvent is not particularly limited, but the extract extracted with water works preferably for improvement, prevention or treatment of depressive symptoms.
본 명세서에서 목단피, 백복령, 택사 및 단삼의 혼합물을 언급하면서 사용되는 용어 '추출물'은 추출용매를 처리하여 얻은 조추출물뿐만 아니라 목단피, 백복령, 택사 및 단삼의 혼합 추출물의 가공물도 포함한다. 예를 들어, 목단피, 백복령, 택사 및 단삼의 혼합 추출물은 감압 증류 및 동결 건조 또는 분무 건조 등과 같은 추가적인 과정에 의해 분말 상태로 제조될 수 있다.In the present specification, the term'extract' used while referring to a mixture of Mokdanpi, Baekbokryeong, Taeksa and Dansam includes not only crude extract obtained by treatment with an extraction solvent, but also a processed product of a mixed extract of Mokdanpi, Baekbokryeong, Taeksa and Dansam. For example, the mixed extract of Mokdanpi, Baekbokryeong, Taeksa, and Dansam may be prepared in a powder state by additional processes such as distillation under reduced pressure and freeze drying or spray drying.
또한, 본 발명의 목단피, 백복령, 택사 및 단삼의 혼합 추출물은 광의로는 목단피, 백복령, 택사 및 단삼의 혼합물을 동물에게 투여할 수 있도록 제형화된 목단피, 백복령, 택사 및 단삼의 혼합 가공물, 예컨대, 목단피, 백복령, 택사 및 단삼의 혼합 분말도 포함하는 의미를 갖는다. 비록 본 발명에서 목단피, 백복령, 택사 및 단삼의 혼합물로 실험을 진행하긴 하였으나, 목단피, 백복령, 택사 및 단삼의 혼합 가공물과 같은 형태로도 목적하는 효과를 달성할 수 있음은 당업자라면 예상가능할 것이다.In addition, the mixed extract of Mokdanpi, Baekbokryeong, Taeksa and Dansam of the present invention is a mixed processed product of Mokdanpi, Baekbokryeong, Taeksa and Dansam, formulated to administer a mixture of Mokdanpi, Baekbokryeong, Taeksa and Dansam in a broad sense, such as , Mokdanpi, Baekbokryeong, Taeksa and Dansam mixed powders are also meant to be included. Although the experiment was conducted with a mixture of Mokdanpi, Baekbokryeong, Taeksa, and Dansam in the present invention, it will be expected by those skilled in the art that the desired effect can be achieved even in the form of a mixed processed product of Mokdanpi, Baekbokryeong, Taeksa and Dansam.
한편, 본 명세서에서 용어 '유효성분으로 함유하는'이란 목단피, 백복령, 택사 및 단삼의 혼합 추출물의 효능 또는 활성을 달성하는 데 충분한 양을 포함하는 것을 의미한다. 일예로, 상기 목단피, 백복령, 택사 및 단삼의 혼합 추출물은 10 내지 1500 ㎍/㎖, 바람직하게는 100 내지 1000 ㎍/㎖의 농도로 사용된다. 목단피, 백복령, 택사 및 단삼의 혼합 추출물은 천연물로서 과량 투여하여도 인체에 부작용이 없으므로 본 발명의 조성물 내에 포함되는 목단피, 백복령, 택사 및 단삼의 혼합 추출물의 양적 상한은 당업자가 적절한 범위 내에서 선택하여 실시할 수 있다.Meanwhile, in the present specification, the term "contained as an active ingredient" means including an amount sufficient to achieve the efficacy or activity of the mixed extract of Mokdanpi, Baekbokryeong, Taeksa and Dansam. For example, the mixed extract of Mokdanpi, Baekbokryeong, Taeksa and Dansam is used at a concentration of 10 to 1500 µg/ml, preferably 100 to 1000 µg/ml. Since the mixed extract of Mokdanpi, Baekbokryeong, Taeksa and Dansam is a natural product and does not have side effects on the human body even if it is administered in excessive amounts, the upper limit of the quantity of the mixed extract of Mokdanpi, Baekbokryeong, Taeksa and Dansam contained in the composition of the present invention is selected within an appropriate range It can be done.
본 발명의 약제학적 조성물은 상기 유효 성분 이외에 약제학적으로 적합하고 생리학적으로 허용되는 보조제를 사용하여 제조될 수 있으며, 상기 보조제로는 부형제, 붕해제, 감미제, 결합제, 피복제, 팽창제, 윤활제, 활택제 또는 향미제 등을 사용할 수 있다.The pharmaceutical composition of the present invention may be prepared using a pharmaceutically suitable and physiologically acceptable adjuvant in addition to the active ingredient, and the adjuvant includes excipients, disintegrants, sweeteners, binders, coating agents, expanding agents, lubricants, It is possible to use a lubricant or flavoring agent.
상기 약제학적 조성물은 투여를 위해서 상기 기재한 유효 성분 이외에 추가로 약제학적으로 허용 가능한 담체를 1종 이상 포함하여 약제학적 조성물로 바람직하게 제제화할 수 있다.For administration, the pharmaceutical composition may contain one or more pharmaceutically acceptable carriers in addition to the above-described active ingredients, and may be preferably formulated into a pharmaceutical composition.
상기 약제학적 조성물의 제제 형태는 과립제, 산제, 정제, 피복정, 캡슐제, 좌제, 액제, 시럽, 즙, 현탁제, 유제, 점적제 또는 주사 가능한 액제 등이 될 수 있다. 예를 들어, 정제 또는 캡슐제의 형태로의 제제화를 위해, 유효 성분은 에탄올, 글리세롤, 물 등과 같은 경구, 무독성의 약제학적으로 허용 가능한 불활성 담체와 결합될 수 있다. 또한, 원하거나 필요한 경우, 적합한 결합제, 윤활제, 붕해제 및 발색제 또한 혼합물로 포함될 수 있다. 적합한 결합제는 이에 제한되는 것은 아니나, 녹말, 젤라틴, 글루코스 또는 베타-락토오스와 같은 천연 당, 옥수수 감미제, 아카시아, 트래커캔스 또는 소듐올레이트와 같은 천연 및 합성 검, 소듐 스테아레이트, 마그네슘 스테아레이트, 소듐 벤조에이트, 소듐 아세테이트, 소듐 클로라이드 등을 포함한다. 붕해제는 이에 제한되는 것은 아니나, 녹말, 메틸 셀룰로스, 아가, 벤토니트, 잔탄 검 등을 포함한다.The formulation form of the pharmaceutical composition may be granules, powders, tablets, coated tablets, capsules, suppositories, solutions, syrups, juices, suspensions, emulsions, drops, or injectable solutions. For example, for formulation in the form of tablets or capsules, the active ingredient may be combined with an oral, non-toxic pharmaceutically acceptable inert carrier such as ethanol, glycerol, water and the like. In addition, if desired or necessary, suitable binders, lubricants, disintegrants and coloring agents may also be included in the mixture. Suitable binders are, but are not limited to, natural sugars such as starch, gelatin, glucose or beta-lactose, corn sweeteners, natural and synthetic gums such as acacia, lacquercanth or sodium oleate, sodium stearate, magnesium stearate, sodium Benzoate, sodium acetate, sodium chloride, and the like. Disintegrants include, but are not limited to, starch, methyl cellulose, agar, bentonite, xanthan gum, and the like.
액상 용액으로 제제화되는 조성물에 있어서 허용 가능한 약제학적 담체로는, 멸균 및 생체에 적합한 것으로서, 식염수, 멸균수, 링거액, 완충 식염수, 알부민 주사용액, 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, 환약, 캡슐, 과립 또는 정제로 제제화할 수 있다.As acceptable pharmaceutical carriers for compositions formulated as liquid solutions, sterilization and biocompatible, saline, sterile water, Ringer's solution, buffered saline, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol, and One or more of these components may be mixed and used, and other conventional additives such as antioxidants, buffers, and bacteriostatic agents may be added as necessary. In addition, diluents, dispersants, surfactants, binders, and lubricants may be additionally added to prepare injectable formulations such as aqueous solutions, suspensions, emulsions, etc., pills, capsules, granules, or tablets.
더 나아가 해당분야의 적절한 방법으로 Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA에 개시되어 있는 방법을 이용하여 각 질환에 따라 또는 성분에 따라 바람직하게 제제화할 수 있다.Furthermore, it can be preferably formulated according to each disease or ingredient using a method disclosed in Remington's Pharmaceutical Science, Mack Publishing Company, Easton PA as an appropriate method in the field.
본 발명의 약제학적 조성물은 경구 또는 비경구로 투여할 수 있고, 비경구 투여인 경우에는 정맥내 주입, 피하 주입, 근육 주입, 복강 주입, 경피 투여 등으로 투여할 수 있으며, 바람직하게는 경구 투여이다.The pharmaceutical composition of the present invention may be administered orally or parenterally, and in the case of parenteral administration, it may be administered by intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, etc., preferably oral administration. .
본 발명의 약제학적 조성물의 적합한 투여량은 제제화 방법, 투여 방식, 환자의 연령, 체중, 성, 병적 상태, 음식, 투여 시간, 투여 경로, 배설 속도 및 반응 감응성과 같은 요인들에 의해 다양하며, 보통으로 숙련된 의사는 소망하는 치료 또는 예방에 효과적인 투여량을 용이하게 결정 및 처방할 수 있다. 본 발명의 바람직한 구현예에 따르면, 본 발명의 약제학적 조성물의 1일 투여량은 0.001-10 g/㎏이다.A suitable dosage of the pharmaceutical composition of the present invention varies depending on factors such as formulation method, mode of administration, age, weight, sex, pathological condition, food, administration time, route of administration, excretion rate and response sensitivity of the patient, Usually, the skilled practitioner can readily determine and prescribe the dosage effective for the desired treatment or prophylaxis. According to a preferred embodiment of the present invention, the daily dosage of the pharmaceutical composition of the present invention is 0.001-10 g/kg.
본 발명의 약제학적 조성물은 약제학적으로 허용되는 담체 및/또는 부형제를 이용하여 제제화함으로써 단위 용량 형태로 제조되거나 또는 다용량 용기 내에 내입시켜 제조될 수 있다. 이때 제형은 오일 또는 수성 매질중의 용액, 현탁액 또는 유화액 형태이거나 엑스제, 분말제, 과립제, 정제 또는 캅셀제 형태일 수도 있으며, 분산제 또는 안정화제를 추가적으로 포함할 수 있다.The pharmaceutical composition of the present invention may be prepared in a unit dosage form by formulation using a pharmaceutically acceptable carrier and/or excipient, or may be prepared by placing it in a multi-dose container. At this time, the formulation may be in the form of a solution, suspension, or emulsion in an oil or aqueous medium, or may be in the form of an extract, powder, granule, tablet or capsule, and may additionally include a dispersant or a stabilizer.
또한, 본 발명은 목단피, 백복령, 택사 및 단삼의 혼합 추출물을 유효성분으로 함유하는 우울 증상의 개선, 예방 또는 치료용 식품 조성물을 제공한다.In addition, the present invention provides a food composition for improving, preventing or treating depressive symptoms containing a mixed extract of Mokdanpi, Baekbokryeong, Taeksa and Dansam as an active ingredient.
본 발명에 따른 식품 조성물은 상기 약제학적 조성물과 동일한 방식으로 제제화되어 기능성 식품으로 이용하거나, 각종 식품에 첨가할 수 있다. 본 발명의 조성물을 첨가할 수 있는 식품으로는 예를 들어, 음료류, 알코올 음료류, 과자류, 다이어트바, 유제품, 육류, 초코렛, 피자, 라면, 기타 면류, 껌류, 아이스크림류, 비타민 복합제, 건강보조식품류 등이 있다.The food composition according to the present invention may be formulated in the same manner as the pharmaceutical composition and used as a functional food or added to various foods. Foods to which the composition of the present invention can be added include, for example, beverages, alcoholic beverages, confectionery, diet bars, dairy products, meat, chocolate, pizza, ramen, other noodles, gum, ice cream, vitamin complexes, health supplements. Etc.
본 발명의 식품 조성물은 유효성분으로서 목단피, 백복령, 택사 및 단삼의 혼합 추출물뿐만 아니라, 식품 제조 시에 통상적으로 첨가되는 성분을 포함할 수 있으며, 예를 들어, 단백질, 탄수화물, 지방, 영양소, 조미제 및 향미제를 포함한다. 상술한 탄수화물의 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스, 올리고당 등; 및 폴리사카라이드, 예를 들어 덱스트린, 사이클로덱스트린 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 향미제로서 천연 향미제 [타우마틴, 스테비아 추출물 (예를 들어 레바우디오시드 A, 글리시르히진 등]) 및 합성 향미제(사카린, 아스파르탐 등)를 사용할 수 있다. 예컨대, 본 발명의 식품 조성물이 드링크제와 음료류로 제조되는 경우에는 본 발명의 목단피, 백복령, 택사 및 단삼의 혼합 추출물 이외에 구연산, 액상과당, 설탕, 포도당, 초산, 사과산, 과즙, 및 각종 식물 추출액 등을 추가로 포함시킬 수 있다.The food composition of the present invention may include mixed extracts of Mokdanpi, Baekbokryeong, Taeksa and Dansam as an active ingredient, as well as ingredients commonly added during food production, for example, protein, carbohydrate, fat, nutrients, seasoning And flavoring agents. Examples of the aforementioned carbohydrates include monosaccharides such as glucose, fructose, and the like; Disaccharides such as maltose, sucrose, oligosaccharides, and the like; And polysaccharides, for example, common sugars such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents, natural flavoring agents [taumatin, stevia extract (eg, rebaudioside A, glycyrrhizin, etc.]) and synthetic flavoring agents (saccharin, aspartame, etc.) can be used. For example, when the food composition of the present invention is made of drinks and beverages, citric acid, liquid fructose, sugar, glucose, acetic acid, malic acid, fruit juice, and various plant extracts, etc., in addition to the mixed extract of Mokdanpi, Baekbokryeong, Taeksa and Dansam of the present invention. May be additionally included.
본 발명은 상기 목단피, 백복령, 택사 및 단삼의 혼합 추출물을 유효성분으로 포함하는 우울 증상의 개선, 예방 또는 치료용 식품 조성물을 포함하는 건강기능식품을 제공한다. 건강기능식품이란, 목단피, 백복령, 택사 및 단삼의 혼합 추출물을 음료, 차류, 향신료, 껌, 과자류 등의 식품소재에 첨가하거나, 캡슐화, 분말화, 현탁액 등으로 제조한 식품으로, 이를 섭취할 경우 건강상 특정한 효과를 가져오는 것을 의미하나, 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용시 발생할 수 있는 부작용 등이 없는 장점이 있다. 이와 같이 하여 얻어지는 본 발명의 건강기능식품은, 일상적으로 섭취하는 것이 가능하기 때문에 매우 유용하다. 이와 같은 건강기능식품에 있어서의 목단피, 백복령, 택사 및 단삼의 혼합 추출물의 첨가량은, 대상인 건강기능식품의 종류에 따라 달라 일률적으로 규정할 수 없지만, 식품 본래의 맛을 손상시키지 않는 범위에서 첨가하면 되며, 대상 식품에 대하여 통상 0.01 내지 50 중량%, 바람직하기로는 0.1 내지 20 중량%의 범위이다. 또한, 환제, 과립제, 정제 또는 캡슐제 형태의 건강기능식품의 경우에는 통상 0.1 내지 100 중량% 바람직하기로는 0.5 내지 80 중량%의 범위에서 첨가하면 된다. 한 구체예에서, 본 발명의 건강기능식품은 환제, 정제, 캡슐제 또는 음료의 형태일 수 있다.The present invention provides a health functional food comprising a food composition for improving, preventing or treating depressive symptoms comprising a mixed extract of Mokdanpi, Baekbokryeong, Taeksa and Dansam as an active ingredient. Health functional foods are foods prepared by adding mixed extracts of Mokdanpi, Baekbokryong, Taeksa, and Dansam to food ingredients such as beverages, teas, spices, gums, confectionery, etc., or prepared as encapsulated, powdered, suspension, etc. It means bringing a specific effect on health, but unlike general drugs, it has the advantage of not having side effects that may occur when taking the drug for a long time by using food as a raw material. The health functional food of the present invention obtained in this way is very useful because it can be consumed on a daily basis. The amount of mixed extract of Mokdanpi, Baekbokryeong, Taeksa, and Dansam in such health functional foods cannot be uniformly regulated depending on the type of health functional food to be targeted, but if added within the range that does not damage the original taste of the food And, it is usually in the range of 0.01 to 50% by weight, preferably 0.1 to 20% by weight, based on the target food. In addition, in the case of health functional foods in the form of pills, granules, tablets or capsules, it is usually added in the range of 0.1 to 100% by weight, preferably 0.5 to 80% by weight. In one embodiment, the health functional food of the present invention may be in the form of a pill, tablet, capsule or beverage.
또한, 본 발명은 우울 증상의 개선, 예방 또는 치료용 의약 또는 식품의 제조를 위한 목단피, 백복령, 택사 및 단삼의 혼합 추출물의 용도를 제공한다. 상기한 바와 같이 목단피, 백복령, 택사 및 단삼의 혼합 추출물은 우울 증상의 개선, 예방 또는 치료를 위한 용도로 이용될 수 있다.In addition, the present invention provides a use of a mixed extract of Mokdanpi, Baekbokryeong, Taeksa and Dansam for the manufacture of medicines or foods for improving, preventing or treating depressive symptoms. As described above, the mixed extract of Mokdanpi, Baekbokryeong, Taeksa and Dansam may be used for improving, preventing or treating depressive symptoms.
또한, 본 발명은 포유동물에게 유효량의 목단피, 백복령, 택사 및 단삼의 혼합 추출물을 투여하는 것을 포함하는 우울 증상의 개선, 예방 또는 치료 방법을 제공한다.In addition, the present invention provides a method for improving, preventing or treating depressive symptoms, comprising administering an effective amount of a mixed extract of Mokdanpi, Baekbokryeong, Taeksa and Dansam to a mammal.
여기에서 사용된 용어 "포유동물"은 치료, 관찰 또는 실험의 대상인 포유동물을 말하며, 바람직하게는 인간을 말한다.The term "mammal" as used herein refers to a mammal that is the subject of treatment, observation or experimentation, and preferably refers to a human.
여기에서 사용된 용어 "유효량"은 연구자, 수의사, 의사 또는 기타 임상의에 의해 생각되는 조직계, 동물 또는 인간에서 생물학적 또는 의학적 반응을 유도하는 유효 성분 또는 약학적 조성물의 양을 의미하는 것으로, 이는 해당 질환 또는 장애의 증상의 완화를 유도하는 양을 포함한다. 본 발명의 유효 성분에 대한 유효량 및 투여횟수는 원하는 효과에 따라 변화될 수 있다. 그러므로, 투여될 최적의 투여량은 당업자에 의해 쉽게 결정될 수 있으며, 질환의 종류, 질환의 중증도, 조성물에 함유된 유효성분 및 다른 성분의 함량, 제형의 종류, 및 환자의 연령, 체중, 일반 건강 상태, 성별 및 식이, 투여 시간, 투여 경로 및 조성물의 분비율, 치료기간, 동시 사용되는 약물을 비롯한 다양한 인자에 따라 조절될 수 있다. 본 발명의 예방, 치료 또는 개선 방법에 있어서, 성인의 경우, 목단피, 백복령, 택사 및 단삼의 혼합 추출물을 1일 1회 내지 수회 투여시, 0.001 g/kg 내지 10 g/kg의 용량으로 투여하는 것이 바람직하다.The term "effective amount" as used herein refers to the amount of an active ingredient or pharmaceutical composition that induces a biological or medical response in a tissue system, animal or human, which is considered by a researcher, veterinarian, doctor or other clinician, Includes an amount that induces relief of symptoms of the disease or disorder. The effective amount and the number of administrations for the active ingredient of the present invention may vary depending on the desired effect. Therefore, the optimal dosage to be administered can be easily determined by those skilled in the art, and the type of disease, the severity of the disease, the amount of active ingredients and other ingredients contained in the composition, the type of formulation, and the age, weight, and general health of the patient. It can be adjusted according to various factors including condition, sex and diet, time of administration, route of administration and secretion rate of the composition, duration of treatment, and drugs used simultaneously. In the prevention, treatment or improvement method of the present invention, in the case of an adult, when a mixed extract of Mokdanpi, Baekbokryeong, Taeksa and Dansam is administered once to several times a day, it is administered at a dose of 0.001 g/kg to 10 g/kg. It is desirable.
본 발명의 치료방법에서 목단피, 백복령, 택사 및 단삼의 혼합 추출물을 유효 성분으로 포함하는 조성물은 경구, 직장, 정맥내, 동맥내, 복강내, 근육내, 흉골내, 경피, 국소, 안구내 또는 피내 경로를 통해 통상적인 방식으로 투여할 수 있다.In the treatment method of the present invention, a composition comprising a mixed extract of Mokdanpi, Baekbokryeong, Taeksa and Dansam as an active ingredient is oral, rectal, intravenous, intraarterial, intraperitoneal, intramuscular, intrasternal, transdermal, topical, intraocular or It can be administered in a conventional manner via the intradermal route.
이하, 본 발명의 이해를 돕기 위하여 바람직한 실시예를 제시하나, 하기 실시예는 본 발명을 예시하는 것일 뿐 본 발명의 범주 및 기술사상 범위 내에서 다양한 변경 및 수정이 가능함은 당업자에게 있어서 명백한 것이며, 이러한 변형 및 수정이 첨부된 특허청구범위에 속하는 것도 당연한 것이다.Hereinafter, a preferred embodiment is presented to aid the understanding of the present invention, but the following examples are only illustrative of the present invention, and it is obvious to those skilled in the art that various changes and modifications are possible within the scope and spirit of the present invention, It is natural that such modifications and modifications fall within the appended claims.
실시예 1. 목단피:백복령:택사:단삼= 1:1:1:1의 중량비Example 1.Mokdanpi: Baekbokryeong:Taeksa: Dansam = 1:1:1:1 by weight
한국신약 주식회사(Han Kook Shin Yak Pharmaceutical Co., Ltd., Nonsan, Korea)에서 구입한 목단피, 백복령, 택사 및 단삼을 1 : 1 : 1 : 1의 중량비로 혼합한 후 상기 혼합물과 물을 1 : 10의 중량비로 혼합하여 100 ℃에서 3시간 동안 열수 추출하여 목단피, 백복령, 택사 및 단삼의 혼합 추출물을 수득하였다.After mixing Mokdanpi, Baekbokryeong, Taeksa, and Dansam purchased from Han Kook Shin Yak Pharmaceutical Co., Ltd., Nonsan, Korea in a weight ratio of 1:1, the mixture and water are 1: The mixture was mixed at a weight ratio of 10 and extracted with hot water at 100° C. for 3 hours to obtain a mixed extract of Mokdanpi, Baekbokryeong, Taeksa and Dansam.
실시예 2. 목단피:백복령:택사:단삼= 1:1.5:1:1.5의 중량비Example 2. Mokdanpi: Baekbokryeong:Taeksa: Dansam = 1:1.5:1:1.5 weight ratio
상기 실시예 1과 동일하게 실시하되, 목단피, 백복령, 택사 및 단삼을 1 : 1.5 : 1 : 1.5의 중량비로 혼합하여 혼합 추출물을 수득하였다.In the same manner as in Example 1, Mokdanpi, Baekbokryeong, Taeksa and Dansam were mixed in a weight ratio of 1:1.5:1:1.5 to obtain a mixed extract.
<시험예><Test Example>
실시예 및 비교예에서 제조된 추출액을 여과한 후 여액을 60 ℃ 이하에서 감압농축하여 이용하였다.Prepared in Examples and Comparative Examples After filtering the extract, the filtrate was concentrated under reduced pressure at 60° C. or lower and used.
250~300 g의 Wistar 랫트(25~25 g의 ICR 마우스)(SAMTAKO, Korea, 숫컷)를 실험에 사용하였다. 아크릴 케이지(45 X 60 X 25 cm)에서 사육되었으며, 충분한 사료와 물이 공급되며 적절한 인공조도로 12시간의 낮, 밤을 조절하였다(am 8:00부터 낮). 그리고 일정한 온도(20~24℃) 및 습도(45~65%)를 유지시켜 주었다. 바뀐 환경에 적응하도록 일주일간 살펴보며 수면주기를 유지하고, 이상행동을 확인하였다. 250-300 g of Wistar rats (25-25 g of ICR mice) (SAMTAKO, Korea, male) were used in the experiment. It was bred in an acrylic cage (45 X 60 X 25 cm), provided with sufficient feed and water, and controlled the day and night for 12 hours with appropriate artificial illumination (from 8:00 am to daytime). And it maintained a constant temperature (20 ~ 24 ℃) and humidity (45 ~ 65%). They looked for a week to adapt to the changed environment, maintained the sleep cycle, and confirmed abnormal behavior.
동물을 사용한 모든 실험은 MFDS's(Ministry of Food and Drug Safety) National Institute of Toxicological Research for the care and use of laboratory animals(KHUASP(SE)-14-051)를 준수하고, 대전대 동물실험윤리위원회에서 실험 방법을 승인하였다.All experiments using animals comply with MFDS's (Ministry of Food and Drug Safety) National Institute of Toxicological Research for the care and use of laboratory animals (KHUASP(SE)-14-051), and the experimental method was conducted by Daejeon University Animal Experimental Ethics Committee. Approved.
실험동물은 체중변화가 일정하고 건강한 동물만을 선별하여 임의 배치법에 의해 생리식염수를 투여한 정상군, 레세르핀(reserpine)을 투여한 대조군, 레세르핀(reserpine)을 투여한 군에 실시예 1 및 2의 추출물을 투여한 시료 투여군으로 나누었으며 정상군, 대조군 1은 5마리씩 사용하고, 대조군 2 및 나머지 군들은 5마리씩 사용하였다.Experimental animals were selected only healthy animals with a constant body weight change, the normal group administered with physiological saline by a random batch method, the control group administered with reserpine, and the group administered with reserpine. Example 1 And the sample administration group to which the extract of 2 was administered, and 5 mice were used for the normal group and the control group 1, and 5 mice were used for the control group 2 and the remaining groups.
이때 레세르핀(reserpine)은 7일 동안 하루에 한번 일정한 시간에 1 mg/kg씩 주사로 투여하였으며, 실시예 1 및 2의 추출물은 하기 농도(100, 200, 300 mg/kg)로 식염수에 녹여 100 ul 경구 투여하였다.At this time, reserpine was administered by injection of 1 mg/kg at a certain time once a day for 7 days, and the extracts of Examples 1 and 2 were in saline at the following concentrations (100, 200, 300 mg/kg). It was dissolved and administered orally 100 ul.
-8개 군의 마우스--8 groups of mice-
정상군: 생리식염수 7일 투여_1 mg/kg/dayNormal group: physiological saline solution administered for 7 days_1 mg/kg/day
대조군 1: 레세르핀 7일 투여_1 mg/kg/dayControl 1: Reserpine 7 day administration_1 mg/kg/day
대조군 2: 레세르핀 7일 투여_1 mg/kg/day + 플루옥세틴(fluoxetine)_50 mg/kg(복강 투여)Control 2: Reserpine 7-day administration_1 mg/kg/day + fluoxetine_50 mg/kg (intraperitoneal administration)
실시예 1(100): 레세르핀 7일 투여_1 mg/kg/day + 실시예 1의 추출물 100 mg/kgExample 1 (100): 7-day administration of reserpine_1 mg/kg/day + 100 mg/kg of extract of Example 1
실시예 1(200): 레세르핀 7일 투여_1 mg/kg/day + 실시예 1의 추출물 200 mg/kgExample 1 (200): 7-day administration of reserpine_1 mg/kg/day + 200 mg/kg of extract of Example 1
실시예 1(300): 레세르핀 7일 투여_1 mg/kg/day + 실시예 1의 추출물 300 mg/kgExample 1 (300): 7-day administration of reserpine_1 mg/kg/day + 300 mg/kg of extract of Example 1
실시예 2(100): 레세르핀 7일 투여_1 mg/kg/day + 실시예 2의 추출물 100 mg/kgExample 2 (100): 7-day administration of reserpine_1 mg/kg/day + 100 mg/kg of extract of Example 2
실시예 2(200): 레세르핀 7일 투여_1 mg/kg/day + 실시예 2의 추출물 200 mg/kgExample 2 (200): 7-day administration of reserpin_1 mg/kg/day + 200 mg/kg of extract of Example 2
실시예 2(300): 레세르핀 7일 투여_1 mg/kg/day + 실시예 2의 추출물 300 mg/kgExample 2 (300): 7-day administration of reserpine_1 mg/kg/day + 300 mg/kg of extract of Example 2
시험예 1. 체중측정Test Example 1. Weight measurement
우울증의 증상 중 하나인 식욕 감소를 확인하기 위하여 체중 변화를 측정하였다. 체중 측정은 실험 기간 동안 매일 동일한 시간에 1회 측정하였다.Weight change was measured to confirm loss of appetite, one of the symptoms of depression. Body weight was measured once every day at the same time during the experiment.
[표 1][Table 1]
위 표 1에 나타낸 바와 같이, 본 발명의 실시예 1에 따라 제조된 추출물은 우울증의 중상 중 하나인 체중 감소가 나타나지 않은 것을 확인하였다. 즉, 고농도로 실시예 1의 추출물을 투여시에도 체중 감소가 나타나지 않으므로 고농도에 의한 부작용이 없는 것을 의미한다.As shown in Table 1 above, it was confirmed that the extract prepared according to Example 1 of the present invention did not show weight loss, which is one of the serious injuries of depression. That is, even when the extract of Example 1 is administered at a high concentration, weight loss does not appear, which means that there is no side effect due to the high concentration.
반면, 실시예 2에 따라 제조된 추출물은 체중 감소가 나타나는 것을 확인하였으며, 약한 설사, 털빠짐 등의 증상을 보이는 것을 확인하였다. On the other hand, it was confirmed that the extract prepared according to Example 2 exhibited weight loss and showed symptoms such as weak diarrhea and hair loss.
시험예 2.Test Example 2. 항우울증 검증_강제 수영 실험(Forced swimming test)Antidepressant verification_Forced swimming test
강제 수영 실험을 통해 긴급 상황에서의 회피 능력에 대한 항우울 실험을 행동 약리학적 관점에서 수행하였다. Through the forced swimming experiment, an antidepressant experiment on evasion ability in emergency situations was performed from a behavioral pharmacological perspective.
마우스의 FST 측정법을 위해 높이 50 cm 이상의 투명 비이커에 30 cm만큼 물로 채우고 1시간 후 마우스를 입수시켜 6분 동안 비디오 레코더를 사용하여 녹화하였다. 녹화된 결과는 처음 1분간을 제외한 나머지 5분 동안을 기준으로 마우스가 움직임 없이 가만히 있는 시간(immobility time, sec, 마우스가 어떠한 미동도 없이 수면에 부유되는 상태)을 측정하였다. 동물의 움직임을 각각 수영(swimming), 등반(climbing), 부동자세(immobility/floating)로 나누어 분석하였다(도 1). For the FST measurement method of mice, a transparent beaker having a height of 50 cm or more was filled with water by 30 cm, and after 1 hour, the mice were acquired and recorded using a video recorder for 6 minutes. The recorded result was measured for the remaining 5 minutes except for the first 1 minute, the time the mouse remains still without movement (immobility time, sec, the state in which the mouse is suspended on the surface without any movement). Animal movements were analyzed by dividing into swimming (swimming), climbing (climbing), and immobility/floating positions, respectively (FIG. 1).
모든 실험결과는 S.E.M. 값으로 표기하며, Prism 5.0(GraphPad software, Inc., USA)를 이용하여 bonferroni post-hoc 방법에 의한 one-way ANOVA 통계처리를 한다. 통계적인 유의적인 p<0.05 범위 내에서 허용하여 처리하였다.All experimental results were obtained from S.E.M. It is expressed as a value, and one-way ANOVA statistical processing is performed by the bonferroni post-hoc method using Prism 5.0 (GraphPad software, Inc., USA). Treatment was allowed within the range of statistically significant p<0.05.
[표 2][Table 2]
위 표 2에 나타낸 바와 같이, 본 발명의 실시예 1에 따라 제조된 추출물은 레세르핀을 투여한 그룹에 비하여 움직임 없이 가만히 있는 시간(immobility time)이 현저히 감소한 것을 확인하였다. As shown in Table 2 above, it was confirmed that the extract prepared according to Example 1 of the present invention significantly reduced the immobility time compared to the group to which reserpine was administered.
반면, 실시예 2에 따라 제조된 추출물은 움직임 없이 가만히 있는 시간(immobility time)이 거의 감소하지 않았으나, 200 mg/kg를 투여한 군에서만 유의한 감소를 보였다.On the other hand, the extract prepared according to Example 2 showed little decrease in immobility time, but only in the group administered 200 mg/kg.
즉, 실시예 1에 따라 제조된 추출물이 실시예 2의 추출물에 비하여 움직임 없이 가만히 있는 시간(immobility time)이 감소된 것을 확인하였다.That is, it was confirmed that the immobility time of the extract prepared according to Example 1 was reduced compared to the extract of Example 2.
이는, 실시예 1 및 2의 추출물이 항우울에 효능이 있다는 것이며, 더욱이 실시예 1의 모든 추출물이 실시예 2의 200 mg/kg 추출물에 비하여 항우울에 효능이 있다는 것을 의미한다. This means that the extracts of Examples 1 and 2 are effective against antidepressant, and furthermore, all extracts of Example 1 are effective against antidepressant compared to the 200 mg/kg extract of Example 2.
시험예 3. 항우울증 검증_오픈필드테스트(Open-field test)Test Example 3. Antidepressant Verification_Open-field Test
마우스의 움직임을 관찰하는 단순한 테스트로서, 임의 크기의 뚜껑이 없는 직육면체 상자 안에 마우스를 넣고 움직임을 관찰하는 실험이다. 일정 공간 내에서의 이동 거리 또는 횡단 횟수의 증감을 비교, 분석하여 공포 또는 불안감과 관련된 우울함의 척도로 사용한다.As a simple test to observe the movement of the mouse, it is an experiment to observe the movement of the mouse by placing it in a rectangular box without a lid of any size. It is used as a measure of depression related to fear or anxiety by comparing and analyzing the increase or decrease of the movement distance or the number of crossings within a certain space.
[표 3][Table 3]
[표 4][Table 4]
위 표 3 및 4에 나타낸 바와 같이, 본 발명의 실시예 1에 따라 제조된 추출물은 레세르핀을 투여한 그룹에 비해 이동 거리가 많이 증가한 것을 확인하였으며, 실시예 2는 모든 추출물에서 유의한 이동거리 증가 효과가 나타나지 않았다.As shown in Tables 3 and 4 above, it was confirmed that the extract prepared according to Example 1 of the present invention increased the travel distance significantly compared to the group to which reserpine was administered, and Example 2 showed significant movement in all extracts. There was no effect of increasing the distance.
실시예 1에 따라 제조된 추출물이 실시예 2의 추출물에 비하여 이동 거리가 많이 증가한 것을 별도로 확인하였다.It was separately confirmed that the travel distance of the extract prepared according to Example 1 increased a lot compared to the extract of Example 2.
이는, 실시예 1 및 2의 추출물이 항우울에 효능이 있다는 것이며, 더욱이 실시예 1의 추출물이 실시예 2의 추출물에 비하여 항우울에 효능이 있다는 것을 의미한다. This means that the extracts of Examples 1 and 2 are effective for antidepressant, and furthermore, the extract of Example 1 is effective for antidepressant compared to the extract of Example 2.
시험예 4. 진통효과 측정Test Example 4. Analgesic effect measurement
경구투여 30분 후 물리적 이질통(mechanical allodynia) 실험을 실시하였으며, 상기 물리적 이질통은 건강한 상태에서는 통증을 일으키지 않고 단순한 촉각반응만을 일으킬 정도의 약한 자극을 가했을 때 통증을 느끼는 반응을 의미한다(도 1). 동물을 기계적 이질통의 측정을 위해 와이어 플로어(wire floor)가 있는 케이지에 두었다. 회피 역치(withdrawal threshold)는 전자 폰 프레이 필라멘트(von Frey filament)(Somedic AB, Malmo, Sweden)에 의해 동측성 및/또는 대측성 뒷발에서 측정하였다. 5가지 자극의 중앙값이 데이터 포인트를 제공하였다. 상응하는 95% 신뢰도 한계를 갖는 절반-최대 유효량(ED50)은 최대 작용시의 반-대수 회귀 분석에 의해 측정하였다.A physical allodynia experiment was performed 30 minutes after oral administration, and the physical allodynia refers to a reaction to feel pain when a weak stimulus is applied that only causes a simple tactile reaction without causing pain in a healthy state (Fig. 1). . Animals were placed in cages with wire floors for the measurement of mechanical allodynia. The withdrawal threshold was measured in ipsilateral and/or contralateral hind paws by electronic von Frey filament (Somedic AB, Malmo, Sweden). The median of the 5 stimuli provided the data points. The half-maximal effective amount (ED50) with the corresponding 95% confidence limit was determined by semi-logarithmic regression analysis at maximum action.
수득된 곡선 아래 면적(MA area under the curve)으로 진통의 정도를 나타내었다. The degree of analgesia was indicated by the area under the curve obtained (MA area under the curve).
[표 5][Table 5]
위 표 5에 나타낸 바와 같이, 실시예 2에 따라 제조된 추출물은 모든 농도에서 유의한 신경병증성 통증에 대한 진통효과가 있는 것을 확인하였다.As shown in Table 5 above, it was confirmed that the extract prepared according to Example 2 had an analgesic effect on significant neuropathic pain at all concentrations.
반면, 실시예 1의 추출물은 300 mg/kg 투여 시에만 신경병증성 통증에 대한 진통효과를 보이는 것을 확인하였다. On the other hand, it was confirmed that the extract of Example 1 exhibited an analgesic effect on neuropathic pain only when 300 mg/kg was administered.
결과적으로, 실시예 1의 추출물은 투여에 따른 부작용 없이 우울증 및 통증에 고른 효능을 보이는 반면, 실시예 2의 추출물은 약간의 부작용을 보이고 우울증보다는 통증에서 더 높은 효능을 보이는 것으로 판단된다.As a result, it is judged that the extract of Example 1 shows an even effect on depression and pain without side effects from administration, while the extract of Example 2 shows a slight side effect and shows higher efficacy in pain than depression.
상기 통증은 레세르핀(reserpine)의 투여로 인해 유발되는 통증으로서, 구체적으로는 섬유근 통증일 수 있다.The pain is a pain caused by administration of reserpine, and may be specifically fibromyal pain.
하기에 본 발명의 분말을 함유하는 조성물의 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Hereinafter, examples of the formulation of the composition containing the powder of the present invention will be described, but the present invention is not intended to limit this, but is intended to be described in detail.
제제예 1. 산제의 제조Formulation Example 1. Preparation of powder
실시예 1에서 얻은 추출물 분말 500 mg500 mg of extract powder obtained in Example 1
유당 100 mg100 mg lactose
탈크 10 mg10 mg of talc
상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 제조한다.The above ingredients are mixed and filled in an airtight cloth to prepare a powder.
제제예 2. 정제의 제조Formulation Example 2. Preparation of tablet
실시예 1에서 얻은 추출물 분말 300 mg300 mg of extract powder obtained in Example 1
옥수수전분 100 mg100 mg corn starch
유당 100 mg100 mg lactose
스테아린산 마그네슘 2 mg2 mg of magnesium stearate
상기의 성분들을 혼합한 후 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조한다.After mixing the above ingredients, tablets are prepared by tableting according to a conventional tablet preparation method.
제제예 3. 캅셀제의 제조Formulation Example 3. Preparation of Capsule
실시예 1에서 얻은 추출물 분말 200 mg200 mg of extract powder obtained in Example 1
결정성 셀룰로오스 3 mg3 mg of crystalline cellulose
락토오스 14.8 mg14.8 mg lactose
마그네슘 스테아레이트 0.2 mgMagnesium stearate 0.2 mg
통상의 캡슐제 제조방법에 따라 상기의 성분을 혼합하고 젤라틴 캡슐에 충전하여 캡슐제를 제조한다.According to a conventional capsule preparation method, the above ingredients are mixed and filled into gelatin capsules to prepare a capsule.
제제예 4. 주사제의 제조Formulation Example 4. Preparation of injection
실시예 1에서 얻은 추출물 분말 600 mg600 mg of extract powder obtained in Example 1
만니톨 180 mgMannitol 180 mg
주사용 멸균 증류수 2974 mg2974 mg of sterile distilled water for injection
Na2HPO4,12H2O 26 mgNa 2 HPO 4, 12H 2 O 26 mg
통상의 주사제의 제조방법에 따라 1 앰플 당 상기의 성분 함량으로 제조한다.It is prepared with the above ingredients per ampoule according to a conventional injection preparation method.
제제예 5. 액제의 제조Formulation Example 5. Preparation of liquid formulation
실시예 1에서 얻은 추출물 분말 4 g4 g of extract powder obtained in Example 1
이성화당 10 g10 g of isomerized sugar
만니톨 5 g5 g of mannitol
정제수 적량Purified water appropriate amount
통상의 액제의 제조방법에 따라 정제수에 각각의 성분을 가하여 용해시키고 레몬향을 적량 가한 다음 상기의 성분을 혼합한 다음 정제수를 가하여 전체를 정제수를 가하여 전체 100g으로 조절한 후 갈색병에 충진하여 멸균시켜 액제를 제조한다.According to the usual preparation method of liquid preparation, add each ingredient to purified water to dissolve it, add lemon zest, mix the above ingredients, add purified water and add purified water to adjust the total to 100g, then fill in a brown bottle for sterilization. To prepare a solution.
제제예 6. 과립제의 제조Formulation Example 6. Preparation of granules
실시예 1에서 얻은 추출물 분말 1,000 mg1,000 mg of extract powder obtained in Example 1
비타민 혼합물 적량Vitamin mixture right amount
비타민 A 아세테이트 70 ㎍Vitamin A acetate 70 ㎍
비타민 E 1.0 mg1.0 mg of vitamin E
비타민 B1 0.13 mgVitamin B1 0.13 mg
비타민 B2 0.15 mgVitamin B2 0.15 mg
비타민 B6 0.5 mg0.5 mg of vitamin B6
비타민 B12 0.2 ㎍Vitamin B12 0.2 ㎍
비타민 C 10 mgVitamin C 10 mg
비오틴 10 ㎍Biotin 10 ㎍
니코틴산아미드 1.7 mg1.7 mg of nicotinic acid amide
엽산 50 ㎍Folic acid 50 ㎍
판토텐산 칼슘 0.5 mg0.5 mg of calcium pantothenate
무기질 혼합물 적량Suitable amount of inorganic mixture
황산제1철 1.75 mg1.75 mg ferrous sulfate
산화아연 0.82 mgZinc oxide 0.82 mg
탄산마그네슘 25.3 mgMagnesium carbonate 25.3 mg
제1인산칼륨 15 mgPotassium monophosphate 15 mg
제2인산칼슘 55 mgDicalcium phosphate 55 mg
구연산칼륨 90 mg90 mg of potassium citrate
탄산칼슘 100 mg100 mg of calcium carbonate
염화마그네슘 24.8 mgMagnesium chloride 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 과립제에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 과립제 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강기능식품 조성물 제조에 사용할 수 있다.The composition ratio of the vitamin and mineral mixture is relatively suitable for granules, but it is possible to arbitrarily modify the mixing ratio. After mixing the above ingredients according to a conventional granule preparation method, granules And can be used to prepare a health functional food composition according to a conventional method.
제제예 7. 기능성 음료의 제조Formulation Example 7. Preparation of functional beverage
실시예 1에서 얻은 추출물 분말 1,000 mg 1,000 mg of extract powder obtained in Example 1
구연산 1,000 mg1,000 mg citric acid
올리고당 100 g100 g oligosaccharides
매실농축액 2 g2 g of plum concentrate
타우린 1 g1 g taurine
정제수를 가하여 전체 900 mLTotal 900 mL with purified water
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1 시간 동안 85 ℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2 L 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 기능성 음료 조성물 제조에 사용한다. After mixing the above ingredients according to the normal health drink manufacturing method, stirring and heating the mixture at 85°C for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed and sterilized, and stored in a refrigerator. It is used to prepare the functional beverage composition of the invention.
상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 수요계층, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.The composition ratio is composed of ingredients suitable for a relatively preferred beverage in a preferred embodiment, but the mixing ratio may be arbitrarily modified according to regional and ethnic preferences, such as the demand class, the country of demand, and the purpose of use.
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CN1317027C (en) | 2005-02-21 | 2007-05-23 | 李有田 | Chinese medicine for treating depression |
KR101769972B1 (en) | 2016-09-02 | 2017-08-21 | 대전대학교 산학협력단 | A composition for improving, preventing and treating pulmonary disease comprising herb extract |
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US7318939B2 (en) | 2006-05-08 | 2008-01-15 | Vita Green Health Products Co., Ltd. | Herbal formulation for treatment of depression and other related disorders and method of preparing the same |
KR101282759B1 (en) | 2011-06-24 | 2013-07-05 | 서범구 | Fermented herbal medicine foods using effective micro-organisms and manufacturing method thereof |
KR101302658B1 (en) * | 2011-08-01 | 2013-09-03 | 주식회사 함소아제약 | Oriental medicine composition for chidren's night crying disease and manufacturing method thereof |
KR20140062958A (en) | 2012-11-15 | 2014-05-27 | 대구한의대학교산학협력단 | A aromatic oil composition and cometic composition comprising the essential oil fraction from asarum heterotropoides fr. mandshuricum for preventing and treating depression |
KR101697474B1 (en) * | 2014-04-14 | 2017-01-18 | 천지인초 주식회사 | The herbal mixture extract as an active ingredient for prevention and treatment of depression composition and its manufacture method |
KR20190003092A (en) * | 2017-06-30 | 2019-01-09 | 한국 한의학 연구원 | Composition for preventing, improving or treating stress and depression comprising medicinal herb complex extract as effective component |
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CN1317027C (en) | 2005-02-21 | 2007-05-23 | 李有田 | Chinese medicine for treating depression |
KR101769972B1 (en) | 2016-09-02 | 2017-08-21 | 대전대학교 산학협력단 | A composition for improving, preventing and treating pulmonary disease comprising herb extract |
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공개특허공보 제10-2019-0003092호(2019.01.09.)* |
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