KR102469256B1 - Compositions for preventing or treating depression comprising extracts of Xanthii fructus - Google Patents
Compositions for preventing or treating depression comprising extracts of Xanthii fructus Download PDFInfo
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- KR102469256B1 KR102469256B1 KR1020170136538A KR20170136538A KR102469256B1 KR 102469256 B1 KR102469256 B1 KR 102469256B1 KR 1020170136538 A KR1020170136538 A KR 1020170136538A KR 20170136538 A KR20170136538 A KR 20170136538A KR 102469256 B1 KR102469256 B1 KR 102469256B1
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- extract
- depression
- peony
- angelica
- serotonin
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Abstract
본 발명은 창이자 추출물을 유효성분으로 포함하는 우울증의 예방 또는 치료용 조성물에 관한 것으로, 구체적으로 창이자 추출물 또는 이의 분획물을 유효성분으로 포함하는 우울증의 예방 또는 치료용 약학 조성물, 식품 조성물 및 우울증의 치료 방법을 제공한다.
창이자 추출물, 또는 이에 당귀 추출물, 박하 추출물 및 작약 추출물이 혼합된 혼합물은 마우스의 우울 행동을 개선하고, 혈중 세로토닌, 세로토닌 수용체 및 가바 수용체 발현을 증가시키므로, 이를 포함하는 본 발명의 조성물은 우울증의 예방, 개선 또는 치료에 유용하게 사용될 수 있다.The present invention relates to a composition for the prevention or treatment of depression comprising an extract of Panax japonica as an active ingredient, and more specifically, a pharmaceutical composition for preventing or treating depression, a food composition and a treatment for depression, containing an extract or a fraction thereof as an active ingredient. provides a way
Changja extract, or a mixture of angelica extract, peppermint extract and peony extract, improves depressive behavior in mice and increases the expression of serotonin, serotonin receptors and GABA receptors in the blood, so the composition of the present invention containing it prevents depression , can be usefully used for improvement or treatment.
Description
본 발명은 창이자 추출물을 유효성분으로 포함하는 우울증의 예방 또는 치료용 조성물에 관한 것으로, 구체적으로 창이자 추출물 또는 이의 분획물을 유효성분으로 포함하는 우울증의 예방 또는 치료용 약학 조성물, 식품 조성물 및 우울증의 치료 방법을 제공한다.The present invention relates to a composition for the prevention or treatment of depression comprising an extract of Panax japonica as an active ingredient, and more specifically, a pharmaceutical composition for preventing or treating depression, a food composition and a treatment for depression, containing an extract or a fraction thereof as an active ingredient. provides a way
급격한 사회의 발전과 다변화로 인해 현대인들은 불규칙한 식생활과 부족한 수면 등의 다양한 스트레스 상황에 끊임없이 노출되고 있다. 이와 같은 스트레스의 지속적인 노출로 인해 수면장애, 불안장애, 또는 우울증과 같은 정신질환을 겪는 사람들이 증가하고 있다. 보건복지부에서 시행한 2016년도 정신질환실태 역학조사에 따르면, 정신질환 평생 유병률은 25.4%인 것으로 나타났다.Due to the rapid development and diversification of society, modern people are constantly exposed to various stressful situations such as irregular eating habits and insufficient sleep. Due to such continuous exposure to stress, an increasing number of people suffer from mental disorders such as sleep disorders, anxiety disorders, or depression. According to the 2016 Epidemiologic Survey of Mental Disorders conducted by the Ministry of Health and Welfare, the lifetime prevalence of mental disorders was 25.4%.
특히, 우울증은 의욕 저하와 우울감을 주요 증상으로 하여 다양한 인지 및 정신 신체적 증상을 일으켜 일상 기능의 저하를 가져오며 감정, 생각, 신체 상태, 그리고 행동 등에 변화를 일으키는 심각한 질환이다. 우울증은 일시적인 우울감과는 다르며 개인적인 약함의 표현이거나 의지로 없앨 수 있는 것이 아니다. 즉, 우울증은 신경전달물질의 불균형 등으로 인해 초래되는 뇌 신경계 질환으로서, 단순한 심리적 증상이 아닌 약을 복용하여야 치료할 수 있는 질환으로 여겨진다. In particular, depression is a serious disease that causes various cognitive and psychosomatic symptoms with decreased motivation and depression as the main symptoms, resulting in a decrease in daily function and causing changes in emotions, thoughts, physical conditions, and behaviors. Depression is different from temporary depression and is not an expression of personal weakness or something that can be eliminated by will. That is, depression is a brain nervous system disease caused by an imbalance of neurotransmitters, etc., and is considered a disease that can be treated only by taking medicine, not a simple psychological symptom.
현재까지 사용되고 있는 항우울제는 대부분이 중추신경계의 시냅스 내에 모노아민(monoamine)계 신경전달물질인 아드레날린, 도파민(dopamine), 노르에피네프린(norepinephrine), 세로토닌(serotonin) 등의 농도를 높여주는 메커니즘 이용하였다. 이는 주로 치료제인 삼환계 항우울제(tricyclic antidepressant, TAC), 모노아민 옥시다제 억제제(monoamine oxidase inhibitor, MAOI) 또는 세로토닌 재흡수 차단제(selective serotonin re-uptake inhibitor, SSRI)의 작용에서 추정된 것이다. Most of the antidepressants that have been used to date have used a mechanism that increases the concentration of monoamine neurotransmitters such as adrenaline, dopamine, norepinephrine, and serotonin in synapses of the central nervous system. This is presumed from the action of the predominantly therapeutic tricyclic antidepressants (TACs), monoamine oxidase inhibitors (MAOIs) or selective serotonin re-uptake inhibitors (SSRIs).
현재 이러한 항우울제들이 효과적으로 사용되고 있지만, 약물에 대한 환자의 민감도에 따른 효력 저하나 일부 부작용 등이 나타나는 경우가 있다. 대표적인 사례로 항우울제인 파록세틴(paroxetine)은 소아와 청소년에게 사용시 자살 시도 및 자해 행위가 2-3배 증가하며, 적대감은 6배가 증가한다. 또한 가장 널리 사용되는 항우울제인 플루옥세틴(fluoxetine)은 위장관 출혈 또는 성기능 장애 등을 유발한다. 그렇기 때문에 기존 항우울제 보다 효과적이며 부작용이 적은 새로운 치료제 개발이 필요한 상황이다.Currently, these antidepressants are effectively used, but there are cases in which efficacy decreases or some side effects occur according to the patient's sensitivity to the drug. As a representative example, paroxetine, an antidepressant, increases suicide attempts and self-harm by 2-3 times and increases hostility by 6 times when used in children and adolescents. In addition, fluoxetine, the most widely used antidepressant, causes gastrointestinal bleeding or sexual dysfunction. Therefore, there is a need to develop new treatments that are more effective than existing antidepressants and have fewer side effects.
이에 따라, 목근(Hibiscus syriacus) 추출물을 유효성분으로 함유하는 우울증의 치료용 조성물(한국 공개특허공보 제10-2017-0096586호), 연자육, 황금, 원지, 단삼, 용안육 등의 혼합 생약제 추출물을 유효성분으로 하는 우울증 예방 및 치료 조성물(한국 등록특허공보 제10-1697474호) 등 천연 유래 물질을 이용한 우울증의 치료제가 개발된바 있다. 그러나, 다양한 천연 물질을 이용한 연구가 여전히 필요한 실정이다. Accordingly, a composition for the treatment of depression containing Hibiscus syriacus extract as an active ingredient (Korean Patent Publication No. 10-2017-0096586), mixed herbal medicine extracts such as Yeonjayuk, Hwanggeum, Wonji, Dansam, and Yonganyuk are effective A treatment for depression using a natural substance, such as a composition for preventing and treating depression (Korean Patent Registration No. 10-1697474), has been developed. However, research using various natural materials is still required.
이러한 배경하에, 본 발명자들은 천연 유래 물질을 이용한 우울증 치료제를 개발하고자 예의 노력연구한 결과, 창이자 추출물은 스트레스를 받은 실험동물의 우울행동을 개선시키고, 혈중 세로토닌의 함량, 세로토닌 수용체 및 가바 수용체의 발현량을 증가시키는 우수한 항우울 효과가 있음을 확인하여, 본 발명을 완성하였다.Under this background, the inventors of the present inventors diligently studied to develop a treatment for depression using naturally derived substances. As a result, the intestinal extract improved the depressive behavior of stressed experimental animals, the content of serotonin in the blood, and the expression of serotonin receptors and GABA receptors. It was confirmed that there is an excellent antidepressant effect by increasing the amount, and the present invention was completed.
본 발명의 하나의 목적은 창이자 추출물 또는 이의 분획물을 유효성분으로 포함하는, 우울증의 예방 또는 치료용 약학 조성을 제공하는 것이다.One object of the present invention is to provide a pharmaceutical composition for preventing or treating depression, comprising an extract or a fraction thereof as an active ingredient.
본 발명의 다른 하나의 목적은 상기 조성물을 우울증 의심 개체에 투여하는 단계를 포함하는, 우울증의 치료 방법을 제공하는 것이다.Another object of the present invention is to provide a method for treating depression, comprising administering the composition to a subject suspected of depression.
본 발명의 또 다른 하나의 목적은 창이자 추출물 또는 이의 분획물을 유효성분으로 포함하는, 우울증의 예방 또는 개선용 식품 조성물을 제공하는 것이다.Another object of the present invention is to provide a food composition for preventing or ameliorating depression, comprising an extract or a fraction thereof as an active ingredient.
상기 목적을 달성하기 위하여, 본 발명의 하나의 양태는 창이자 추출물 또는 이의 분획물을 유효성분으로 포함하는, 우울증의 예방 또는 치료용 약학 조성물을 제공한다.In order to achieve the above object, one aspect of the present invention provides a pharmaceutical composition for the prevention or treatment of depression, containing as an active ingredient a spear extract or a fraction thereof.
본 발명의 조성물은 창이자 추출물 또는 이의 분획물을 단독으로 포함할 수 있고, 또는 당귀, 박하 및 작약으로 이루어진 군에서 선택되는 하나 이상의 추출물 또는 분획물을 추가로 포함할 수 있다.The composition of the present invention may include a spear extract or a fraction thereof alone, or may further include one or more extracts or fractions selected from the group consisting of angelica quasi, peppermint and peony.
본 발명에서, 창이자 추출물; 또는 창이자 추출물에 당귀 추출물, 박하 추출물 및 작약 추출물이 추가로 포함된 추출물의 혼합물은 스트레스가 가해진 마우스의 우울 행동을 개선시키고, 혈중 세로토닌의 함량 및 가바 수용체의 발현을 증가시키므로, 우울증의 예방, 개선 또는 치료에 유용하게 사용될 수 있다.In the present invention, the intestines extract; Or, a mixture of extracts further comprising angelica extract, peppermint extract, and peony extract in changja extract improves depressive behavior of stressed mice and increases blood serotonin content and expression of GABA receptors, thereby preventing and improving depression Or it can be usefully used for treatment.
본 발명의 용어, "우울증"은 의욕 저하와 우울감을 주요 증상으로 하여 다양한 인지 및 정신 신체적 증상을 일으켜 일상 기능의 저하를 가져오는 질환을 의미한다. 우울장애는 감정, 생각, 신체 상태, 그리고 행동 등에 변화를 일으키는 심각한 질환이다. 세로토닌, 도파민, 옥시토닌, 가바(GABA), 노르에피네프린 등의 다양한 신경전달물질에 의해 사람의 감정이 조절되는데, 우울증, 공황장애, 강박증 등의 각종 정신과적 신경증을 앓는 환자는 특히 세로토닌의 농도나 활성도가 상대적으로 보통의 일반인들에 비해 낮다는 연구 결과가 발표된 바 있다.As used herein, the term "depression" refers to a disease that causes a decrease in daily function by causing various cognitive and psychosomatic symptoms with low motivation and feeling of depression as the main symptoms. Depressive disorder is a serious illness that causes changes in emotions, thoughts, physical condition, and behavior. Emotions of people are controlled by various neurotransmitters such as serotonin, dopamine, oxytonin, GABA, and norepinephrine. Research results have been published that the activity is relatively lower than that of the general public.
따라서, 세로토닌의 흡수를 억제하여 혈중 세로토닌의 농도를 높이는 메커니즘으로 항우울제의 개발이 이루어지고 있으며, 대표적인 예로 플루옥세틴이 있다. 상기와 같은 플루옥세틴은 세로토닌과 함께 가바의 작용을 증진시켜 글루탐산의 활성을 저해하고 도파민, 노르에피네프린 등 다양한 신경전달물질의 작용을 억제함으로써 우울감, 인지기능 등을 저하하는 기전으로 작용한다.Therefore, antidepressants have been developed as a mechanism to increase the concentration of serotonin in the blood by suppressing the absorption of serotonin, and fluoxetine is a representative example. Fluoxetine as described above acts as a mechanism to reduce depression, cognitive function, etc. by inhibiting the activity of glutamic acid by promoting the action of GABA together with serotonin and inhibiting the action of various neurotransmitters such as dopamine and norepinephrine.
본 발명의 용어, "창이자"는 국화과 도꼬마리의 열매를 의미하며, 생약명은 'Xanthii Fructus'이다. 도꼬마리는 국화과에 속하는 일년생 초본식물로서, 이의 열매인 창이자는 주로 두통, 치통, 사지동통 등에 효과가 있는 것으로 알려져 있다. 그러나, 창이자의 우울증과 관련한 효과는 전혀 알려진바 없으며, 본 발명자에 의해 최초로 규명되었다.The term of the present invention, "Changja" refers to the fruit of Asteraceae cockle, and the crude drug name is 'Xanthii Fructus'. Corkscrew is an annual herbaceous plant belonging to the Asteraceae family, and its fruit, Changja, is known to be effective for headache, toothache, and limb pain. However, the effect related to depression in the intestine has not been known at all, and was first identified by the present inventors.
본 발명의 용어, "당귀"는 산형과 참당귀 뿌리를 건조시킨 것을 의미하며, 생약명은 'Angelica gigas Nakai'이다. 당귀는 가장 흔히 쓰이는 한약재 중의 하나인데, 혈액 순환 불량, 신체 허약, 관절통, 두통, 복통, 어지러움, 변비, 소화 기능 쇠약으로 인해 수척할 때, 타박상, 삔 데, 혈관 질환으로 인해 생긴 내출혈, 혈류 정체, 종창, 동통 등 다양한 용도로 사용될 수 있다. 그러나, 당귀의 우울증과 관련한 효과는 전혀 알려진바 없으며, 본 발명자에 의해 최초로 규명되었다.The term of the present invention, "Angelica gigas" means dried roots of Sanhyeong and Angelica gigas, and the herbal medicine name is 'Angelica gigas Nakai'. Dong Quai is one of the most commonly used oriental medicines. It is used for poor blood circulation, physical weakness, joint pain, headache, abdominal pain, dizziness, constipation, when emaciated due to digestive weakness, bruises, sprains, internal bleeding caused by vascular disease, and blood flow congestion. It can be used for various purposes such as , swelling and pain. However, the effects related to depression in Angelica quai have not been known at all, and were identified for the first time by the present inventors.
본 발명의 용어, "박하"는 통화식물목 꿀풀과의 식물을 의미하며, 학명은 'Mentha arvensis var. piperascens'이다. 박하의 주성분인 멘톨은 도포제, 진통제, 흥분제, 건위제 등으로 약용하고, 치약, 사탕, 잼, 화장품, 담배 등에 향료나 청량제 등 다양한 용도로 사용될 수 있다. 그러나, 박하의 우울증과 관련한 효과는 전혀 알려진바 없으며, 본 발명자에 의해 최초로 규명되었다.The term of the present invention, "mint" means a plant of the currency plant Lamiaceae, scientific name ' Mentha arvensis var. piperascens '. Menthol, the main component of mint, is used medicinally as a liniment, analgesic, stimulant, stomachic, etc., and can be used for various purposes such as flavoring or cooling agent in toothpaste, candy, jam, cosmetics, cigarettes, etc. However, the effect of peppermint on depression has not been known at all, and was identified for the first time by the present inventors.
본 발명의 용어, "작약"은 작약속 다년초인 작약의 뿌리를 의미하며, 학명은 'Paeonia lactiflora'이다. 작약은 진통제, 해열제 또는 이뇨제 등 다양한 용도로 사용될 수 있다. 그러나, 작약의 우울증과 관련한 효과는 전혀 알려진바 없으며, 본 발명자에 의해 최초로 규명되었다.As used herein, the term "peony" refers to the root of peony, a perennial plant of the genus Peony, and its scientific name is ' Paeonia lactiflora '. Peony can be used for a variety of purposes, such as analgesic, antipyretic or diuretic. However, the effect of peony on depression has not been known at all, and was first identified by the present inventors.
본 발명의 용어, "추출물"은 상기 창이자; 또는 창이자, 당귀, 박하, 작약 또는 이들의 혼합물을 추출 처리하여 얻어지는 추출액, 상기 추출액의 희석액이나 농축액, 상기 추출액을 건조하여 얻어지는 건조물, 상기 추출액의 조정제물이나 정제물, 또는 이들의 혼합물 등 추출액 자체 및 추출액을 이용하여 형성 가능한 모든 제형의 추출물을 포함한다. The term of the present invention, "extract" is the window; Alternatively, the extract itself, such as an extract obtained by extraction treatment of spear japonica, angelica quasi, mint, peony, or a mixture thereof, a diluted or concentrated liquid of the extract, a dried product obtained by drying the extract, a refined or purified product of the extract, or a mixture thereof, etc. and extracts of all formulations that can be formed using the extract solution.
또한, 상기 추출물은, 상기 각각의 해당 식물의 천연, 잡종 또는 변종 식물로부터 추출될 수 있고, 식물 조직 배양물로부터도 추출이 가능하다.In addition, the extract may be extracted from natural, hybrid or mutant plants of each corresponding plant, and may also be extracted from plant tissue culture.
구체적으로, 본 발명의 조성물은 창이자 추출물을 단독으로 포함할 수 있고, 또는 창이자 추출물에 당귀 추출물, 박하 추출물 및 작약 추출물을 추가로 포함할 수 있다.Specifically, the composition of the present invention may include the Changija extract alone, or may further include the Angelica gigas extract, peppermint extract, and peony extract in the Changjaja extract.
보다 구체적으로, 상기 조성물은 창이자 추출물, 당귀 추출물, 박하 추출물 및 작약 추출물을 1.5 내지 5.5 : 1.5 내지 5.5 : 0.1 내지 4 : 0.1 내지 3의 부피비로 포함할 수 있고, 보다 더 구체적으로 2.5 내지 4.5 : 2.5 내지 4.5 : 1 내지 3 : 0.1 내지 2의 부피비로 포함할 수 있고, 가장 구체적으로 3.5 : 3.5 : 3 : 2로 포함할 수 있으나, 우울증의 예방, 개선 또는 치료 효과를 나타내는 한, 이에 제한되지 않는다.More specifically, the composition may include Changja extract, Angelica extract, Peppermint extract, and Peony extract in a volume ratio of 1.5 to 5.5: 1.5 to 5.5: 0.1 to 4: 0.1 to 3, more specifically 2.5 to 4.5: It may be included in a volume ratio of 2.5 to 4.5: 1 to 3: 0.1 to 2, and most specifically 3.5: 3.5: 3: 2, but it is not limited thereto, as long as it shows the effect of preventing, improving or treating depression. don't
특히, 상기 창이자 추출물에 당귀 추출물, 박하 추출물 및 작약 추출물이 혼합된 혼합물의 경우 창이자 추출물 단독에 비하여 우울증의 예방, 개선 또는 치료 효과가 더욱 증대될 수 있다.In particular, in the case of a mixture in which the Angelica gigas extract, peppermint extract, and Peony extract are mixed with the Changjaja extract, the effect of preventing, alleviating or treating depression can be further increased compared to the Changjaja extract alone.
본 발명에서, 상기 창이자, 당귀, 박하, 작약 또는 이들의 혼합물을 추출하는 방법은 특별히 제한되지 않으며, 당해 기술 분야에서 통상적으로 사용하는 방법에 따라 추출할 수 있다. 상기 추출 방법의 비제한적인 예로는, 열수 추출, 초음파 추출, 환류 추출, 초임계 추출 등을 들 수 있으며, 이들은 단독으로 수행되거나 2종 이상의 방법을 병용하여 수행될 수 있다. In the present invention, a method for extracting the spear, angelica quasi, mint, peony, or a mixture thereof is not particularly limited, and may be extracted according to a method commonly used in the art. Non-limiting examples of the extraction method include hot water extraction, ultrasonic extraction, reflux extraction, supercritical extraction, and the like, which may be performed alone or in combination of two or more methods.
본 발명에서, 상기 추출물은 초임계 추출에 의해 제조되는 것일 수 있다.In the present invention, the extract may be prepared by supercritical extraction.
본 발명의 용어, "초임계 추출"(supercritical point extraction)은 초임계 유체를 사용하여, 물질 고유의 임계온도 및 임계압력을 초월한 조건으로 추출하는 추출 방법이다. 물질을 빠른 속도 및 높은 효율로 추출할 수 있는 장점이 있다.The term of the present invention, "supercritical point extraction" (supercritical point extraction) is an extraction method using a supercritical fluid, extraction under conditions that exceed the critical temperature and critical pressure inherent in a material. It has the advantage of being able to extract materials at high speed and high efficiency.
초임계 유체로는 이산화탄소, 물, 에탄(ethane), 에틸렌(ethylene), 프로판(propane) 등이 사용될 수 있으며, 더욱 구체적으로 이산화탄소가 사용될 수 있으나, 이에 제한되는 것은 아니다.As the supercritical fluid, carbon dioxide, water, ethane, ethylene, propane, etc. may be used, and more specifically, carbon dioxide may be used, but is not limited thereto.
구체적으로, 상기 초임계 추출은 330 내지 370기압 및 40 내지 60℃에서 수행될 수 있고, 더욱 구체적으로 350기압 및 50℃에서 수행될 수 있으나, 이에 제한지 않는다.Specifically, the supercritical extraction may be performed at 330 to 370 atm and 40 to 60°C, more specifically at 350 atm and 50°C, but is not limited thereto.
본 발명의 용어, "분획물"은 여러 다양한 구성 성분들을 포함하는 혼합물로부터 특정 성분 또는 특정 성분 그룹을 분리하기 위하여 분획을 수행하여 얻어진 결과물을 의미한다.As used herein, the term "fraction" refers to a product obtained by performing fractionation in order to separate a specific component or a specific component group from a mixture containing various components.
본 발명에서, 상기 분획물을 얻는 분획 방법은 특별히 제한되지 않으며, 당해 기술 분야에서 통상적으로 사용하는 방법에 따라 수행될 수 있다. 상기 분획 방법의 비제한적인 예로는, 다양한 용매를 처리하여 수행하는 용매 분획법, 일정한 분자량 컷-오프 값을 갖는 한외 여과막을 통과시켜 수행하는 한외여과 분획법, 다양한 크로마토그래피(크기, 전하, 소수성 또는 친화성에 따른 분리를 위해 제작된 것)를 수행하는 크로마토그래피 분획법, 및 이들의 조합 등이 있다. 구체적으로, 본 발명의 창이자, 당귀, 박하 또는 작약을 추출하여 얻은 추출물에 소정의 용매를 처리하여 상기 추출물로부터 분획물을 얻는 방법을 들 수 있다.In the present invention, the fractionation method for obtaining the fraction is not particularly limited, and may be performed according to a method commonly used in the art. Non-limiting examples of the fractionation method include a solvent fractionation method performed by treating various solvents, an ultrafiltration fractionation method performed by passing an ultrafiltration membrane having a constant molecular weight cut-off value, and various chromatography (size, charge, hydrophobicity). or a chromatographic fractionation method that performs separation based on affinity), and a combination thereof. Specifically, a method of obtaining a fraction from the extract by treating the extract obtained by extracting the spear, angelica mint, or peony of the present invention with a predetermined solvent may be mentioned.
본 발명에서, 상기 분획물을 얻는데 사용되는 분획 용매의 종류는 특별히 제한되지 않으며, 당해 기술 분야에서 공지된 임의의 용매를 사용할 수 있다. 상기 분획 용매의 비제한적인 예로는 물, 탄소수 1 내지 4의 알코올 등의 극성 용매; 헥산(Hexan), 에틸 아세테이트(Ethyl acetate) 등의 비극성 용매; 또는 이들의 혼합용매 등을 들 수 있다. 이들은 단독으로 사용되거나 1종 이상 혼합하여 사용될 수 있지만, 이에 제한되지 않는다.In the present invention, the type of fractionation solvent used to obtain the fraction is not particularly limited, and any solvent known in the art may be used. Non-limiting examples of the fractionation solvent include polar solvents such as water and alcohol having 1 to 4 carbon atoms; non-polar solvents such as hexane and ethyl acetate; or mixed solvents thereof. These may be used alone or in combination of one or more, but are not limited thereto.
본 발명에서, 상기 조성물은 혈중 세로토닌의 함량, 세로토닌 수용체의 발현 또는 가바 수용체의 발현을 증가시키는 것일 수 있다.In the present invention, the composition may increase the content of serotonin in the blood, the expression of serotonin receptors or the expression of GABA receptors.
본 발명의 용어, "세로토닌"은 뇌의 시상하부 중추에 존재하는 신경전달물질을 의미하며, 혈중 세로토닌의 농도 감소는 우울증을 야기할 수 있다.As used herein, "serotonin" refers to a neurotransmitter present in the hypothalamic center of the brain, and a decrease in the concentration of serotonin in the blood can cause depression.
본 발명의 용어, "세로토닌 수용체"는 상기 세로토닌이 작용하는 수용체 단백질을 의미하며, 세로토닌의 활성이 감소하는 경우 우울증이 야기될 수 있는바, 세로토닌 수용체의 발현 또는 활성 감소에 의한 기능 저하는 우울증을 야기할 수 있다.As used herein, the term "serotonin receptor" refers to a receptor protein on which serotonin acts, and when the activity of serotonin decreases, depression can be caused. Therefore, the decrease in expression or activity of the serotonin receptor causes depression. can cause
본 발명의 용어, "가바 수용체"는 신경전달물질인 가바가 작용하는 수용체 단백질을 의미하며, 가바의 활성이 감소하는 경우 우울증이 야기될 수 있는바, 가바 수용체의 발현 또는 활성 감소에 의한 기능 저하는 우울증을 야기할 수 있다.As used herein, the term "GABA receptor" refers to a receptor protein on which the neurotransmitter GABA acts, and when the activity of GABA is reduced, depression may be caused. can cause depression.
본 발명의 용어, "예방"은 상기 창이자 추출물 또는 이의 분획물을 포함하거나; 또는 이에 당귀, 박하 및 작약의 추출물 또는 이의 분획물을 추가로 포함하는 조성물의 투여로 우울증을 억제 또는 지연시키는 모든 행위를 의미한다. The term of the present invention, "prophylaxis" includes the above intestinal lice extract or fractions thereof; Alternatively, it refers to any action that suppresses or delays depression by administering a composition further comprising extracts or fractions of Angelica quai, mint, and peony.
본 발명의 용어, "치료"는 상기 조성물의 투여로 우울증의 증세가 호전되거나 이롭게 변경되는 모든 행위를 의미한다.As used herein, the term "treatment" refers to any activity in which symptoms of depression are improved or beneficially changed by administration of the composition.
본 발명의 구체적인 일 실시예에서는, 창이자 추출물; 또는 창이자, 당귀, 박하 및 작약 추출물의 혼합물을 제조하였고, 상기 추출물 또는 혼합물은 꼬리 매달기 또는 강제 수영에 의해 스트레스를 받은 마우스의 우울 행동을 개선시키고, 나아가 혈중 세로토닌의 함량, 세로토닌 및 가바 수용체의 발현을 증가시킴을 확인하였다(도 1 내지 5).In a specific embodiment of the present invention, changja extract; Or, a mixture of extracts of Angelica, Angelica mint, and peony was prepared, and the extract or mixture improved the depressive behavior of mice stressed by tail hanging or forced swimming, and furthermore, the content of serotonin in the blood, serotonin and GABA receptors. It was confirmed that the expression was increased (Figs. 1 to 5).
이는, 상기 추출물 또는 혼합물을 포함하는 본 발명의 조성물은 우울증의 예방 또는 치료에 유용하게 사용될 수 있음을 시사하는 것이다.This suggests that the composition of the present invention comprising the extract or mixture can be usefully used for preventing or treating depression.
본 발명의 약학적 조성물은, 조성물 총 중량에 대하여 상기 창이자 추출물 또는 이의 분획물; 또는 창이자, 당귀, 박하 및 작약으로 이루어진 군에서 선택되는 하나 이상의 추출물 또는 분획물을 0.001 내지 80, 구체적으로 0.001 내지 70, 더욱 구체적으로 0.001 내지 60 중량%로 포함할 수 있으나, 이에 제한되지 않는다.The pharmaceutical composition of the present invention, based on the total weight of the composition, the extract or fraction thereof; Alternatively, it may include 0.001 to 80, specifically 0.001 to 70, and more specifically 0.001 to 60% by weight of one or more extracts or fractions selected from the group consisting of changija, angelica quasi, mint and peony, but is not limited thereto.
또한, 상기 약학적 조성물은 약학적 조성물의 제조에 통상적으로 사용하는 약학적으로 허용가능한 담체, 부형제 또는 희석제를 추가로 포함할 수 있고, 상기 담체는 비자연적 담체(non-naturally occuring carrier)를 포함할 수 있다. 상기 담체, 부형제 및 희석제의 구체적인 예로는 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 또는 광물유 등이 사용될 수 있으나, 이에 제한되지 않는다.In addition, the pharmaceutical composition may further include a pharmaceutically acceptable carrier, excipient or diluent commonly used in the preparation of pharmaceutical compositions, and the carrier includes a non-naturally occurring carrier. can do. Specific examples of the carrier, excipient, and diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, Microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, or mineral oil may be used, but is not limited thereto.
또한, 상기 약학적 조성물은 각각 통상의 방법에 따라 정제, 환제, 산제, 과립제, 캡슐제, 현탁제, 내용액제, 유제, 시럽제, 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결 건조제 및 좌제으로 이루어진 군으로부터 선택되는 어느 하나의 제형을 가질 수 있으며, 경구 또는 비경구의 여러 가지 제형일 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 사용될 수 있으며, 상기 고형제제는 적어도 하나 이상의 부형제 예를 들면, 전분, 탄산칼슘, 수크로오스(sucrose) 또는 락토오스(lactose), 젤라틴 등이 사용될 수 있다. 또한, 단순한 부형제 이외에 스테아린산 마그네슘, 탈크 등과 같은 윤활제 등이 사용될 수 있다. 경구투여를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 사용될 수 있으며, 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 사용될 수 있다. 비경구투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제 또는 좌제 등이 사용될 수 있다. 비수성용제, 현탁용제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테로 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로젤라틴 등이 사용될 수 있으나, 이에 제한되지 않는다.In addition, the pharmaceutical compositions may be formulated into tablets, pills, powders, granules, capsules, suspensions, internal solutions, emulsions, syrups, sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried agents, and suppositories, respectively, according to conventional methods. It may have any one formulation selected from the group consisting of, and may be various oral or parenteral formulations. When formulated, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration may include tablets, pills, powders, granules, capsules, etc., and the solid preparations may contain at least one excipient such as starch, calcium carbonate, sucrose or lactose, Gelatin and the like may be used. In addition to simple excipients, lubricants such as magnesium stearate and talc may be used. Liquid formulations for oral administration may include suspensions, internal solutions, emulsions, syrups, etc., and various excipients such as wetting agents, sweeteners, aromatics, and preservatives in addition to water and liquid paraffin, which are commonly used simple diluents can be used Sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized formulations or suppositories may be used as preparations for parenteral administration. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents. As a base for the suppository, witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerogelatin, etc. may be used, but is not limited thereto.
다른 하나의 양태는 상기 조성물을 우울증 의심 개체에 투여하는 단계를 포함하는, 우울증의 치료 방법을 제공한다.Another aspect provides a method for treating depression, comprising administering the composition to a subject suspected of depression.
이때, 상기 "우울증" 및 "치료"에 대한 설명은 전술한 바와 같다.At this time, the description of the "depression" and "treatment" is as described above.
본 발명의 용어, "투여"는 적절한 방법으로 개체에게 상기 약학 조성물을 도입하는 것을 의미한다.As used herein, the term "administration" means introducing the pharmaceutical composition to a subject in an appropriate manner.
본 발명의 용어, "개체"는 우울증이 발병하였거나, 발병할 수 있는 인간을 포함한 쥐, 생쥐, 가축 등의 모든 동물을 의미한다. 구체적인 예로, 인간을 포함한 포유동물일 수 있다.As used herein, the term "subject" refers to all animals, such as rats, mice, livestock, and the like, including humans who have or may develop depression. As a specific example, it may be mammals including humans.
본 발명의 약학적 조성물은 약학적으로 유효한 양으로 투여할 수 있다.The pharmaceutical composition of the present invention can be administered in a pharmaceutically effective amount.
상기 용어, "약학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 유효 용량 수준은 개체 종류 및 중증도, 연령, 성별, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출 비율, 치료 기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. 또한, 본 발명의 조성물은 우울증 발생 전, 우울증 발생 즉시 장기간 우울증이 발생한 개체에 투여될 수 있으며, 개체의 우울증 상태에 따라 예방 및 치료를 위해 적절한 시기에 투여될 수 있다.The term "pharmaceutically effective amount" means an amount sufficient to treat a disease with a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level is dependent on the type and severity of the subject, age, sex, drug activity, It may be determined according to factors including sensitivity to the drug, time of administration, route of administration and excretion rate, duration of treatment, drugs used concurrently, and other factors well known in the medical field. In addition, the composition of the present invention can be administered to an individual suffering from depression for a long time before depression, immediately after depression, and can be administered at an appropriate time for prevention and treatment according to the state of depression of the individual.
상기 약학적 조성물은 개별 치료제로 투여하거나 다른 치료제와 병용하여 투여할 수 있고 종래의 치료제와는 순차적 또는 동시에 투여할 수 있다. 또한, 단일 또는 다중 투여할 수 있다. 상기 요소를 모두 고려하여 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 이는 당업자에 의해 용이하게 결정될 수 있다.The pharmaceutical composition may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. In addition, single or multiple administrations may be possible. Considering all of the above factors, it is important to administer an amount that can obtain the maximum effect with the minimum amount without side effects, which can be easily determined by those skilled in the art.
또한, 상기 약학적 조성물은 목적하는 방법에 따라 경구 투여하거나 비경구 투여(예를 들어, 정맥 내, 피하, 복강 내 또는 국소에 적용)할 수 있으며, 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 시간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 구체적인 예로, 상기 약학적 조성물은 일반적으로 0.001 내지 1000 mg/kg, 더욱 구체적으로 0.05 내지 200 mg/kg, 가장 구체적으로 0.1 내지 100 mg/kg의 양을 1일 1회 내지 수회로 나누어 투여할 수 있으나, 바람직한 투여량은 개체의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 당업자에 의해 적절하게 선택될 수 있다.In addition, the pharmaceutical composition may be administered orally or parenterally (for example, intravenously, subcutaneously, intraperitoneally or topically applied) depending on the desired method, and the dosage is dependent on the patient's condition, body weight, and disease. Depending on the degree, drug form, administration route and time, it can be appropriately selected by those skilled in the art. As a specific example, the pharmaceutical composition may be administered in an amount of generally 0.001 to 1000 mg/kg, more specifically 0.05 to 200 mg/kg, and most specifically 0.1 to 100 mg/kg once or several times a day. However, a preferred dosage can be appropriately selected by those skilled in the art according to the condition and weight of the subject, the severity of the disease, the form of the drug, the route and period of administration.
또 다른 하나의 양태는 창이자 추출물 또는 이의 분획물을 유효성분으로 포함하는, 우울증의 예방 또는 개선용 식품 조성물을 제공한다.Another aspect provides a food composition for preventing or ameliorating depression, comprising an extract or a fraction thereof as an active ingredient.
이때, 상기 "창이자", "추출물", "분획물", "우울증" 및 "예방"에 대한 설명은 전술한 바와 같다.At this time, the description of the "changja", "extract", "fraction", "depression" and "prevention" is as described above.
본 발명에서, 상기 식품 조성물은 창이자 추출물 또는 이의 분획물을 단독으로 포함할 수 있고, 또는 당귀, 박하 및 작약으로 이루어진 군에서 선택되는 하나 이상의 추출물 또는 분획물을 추가로 포함할 수 있다.In the present invention, the food composition may include a spear extract or a fraction thereof alone, or may further include one or more extracts or fractions selected from the group consisting of dong quai, peppermint and peony.
구체적으로, 본 발명의 조성물은 창이자 추출물을 단독으로 포함할 수 있고, 또는 창이자 추출물에 당귀 추출물, 박하 추출물 및 작약 추출물을 추가로 포함할 수 있다.Specifically, the composition of the present invention may include the Changija extract alone, or may further include the Angelica gigas extract, peppermint extract, and peony extract in the Changjaja extract.
더욱 구체적으로, 상기 조성물은 창이자 추출물, 당귀 추출물, 박하 추출물 및 작약 추출물을 1.5 내지 5.5 : 1.5 내지 5.5 : 0.1 내지 4 : 0.1 내지 3의 부피비로 포함할 수 있고, 보다 더 구체적으로 2.5 내지 4.5 : 2.5 내지 4.5 : 1 내지 3 : 0.1 내지 2의 부피비로 포함할 수 있고, 가장 구체적으로 3.5 : 3.5 : 3 : 2로 포함할 수 있으나, 우울증의 예방, 개선 또는 치료 효과를 나타내는 한, 이에 제한되지 않는다.More specifically, the composition may include Changja extract, Angelica extract, peppermint extract, and Peony extract in a volume ratio of 1.5 to 5.5: 1.5 to 5.5: 0.1 to 4: 0.1 to 3, and more specifically 2.5 to 4.5: It may be included in a volume ratio of 2.5 to 4.5: 1 to 3: 0.1 to 2, and most specifically 3.5: 3.5: 3: 2, but it is not limited thereto, as long as it shows the effect of preventing, improving or treating depression. don't
이때, 상기 "당귀", "박하" 및 "작약"에 대한 설명은 전술한 바와 같다.At this time, the description of "Angelica", "Mint" and "Peonyak" is as described above.
본 발명의 식품 조성물은 일상적으로 섭취하는 것이 가능하기 때문에 우울증의 우수한 개선 효과를 기대할 수 있으며, 일반 약품과는 달리 천연물을 원료로 하여 약품의 장기 복용 시 발생할 수 있는 부작용 등이 없는 장점이 있으므로, 우울증의 예방 또는 개선 목적으로 매우 유용하게 사용될 수 있다.Since the food composition of the present invention can be consumed on a daily basis, an excellent improvement effect on depression can be expected, and unlike general drugs, it is made of natural products as raw materials and has no side effects that may occur when taking drugs for a long time. It can be used very usefully for the purpose of preventing or improving depression.
본 발명의 용어, "개선"은 상기 식품 조성물의 투여로 치료되는 상태와 관련된 파라미터, 예를 들면 증상의 정도를 감소시키는 모든 행위를 의미한다.As used herein, the term "improvement" refers to any activity that reduces a parameter related to a condition to be treated by administration of the food composition, for example, the severity of a symptom.
본 발명의 용어, "식품"은 육류, 소시지, 빵, 초콜릿, 캔디류, 스낵류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알코올음료, 비타민 복합제, 건강기능식품 및 건강식품 등이 있으며, 통상적인 의미에서의 식품을 모두 포함한다.As used herein, the term "food" refers to meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, chewing gum, dairy products including ice cream, various soups, beverages, tea, drinks, and alcoholic beverages. , vitamin complex, health functional food and health food, etc., and includes all foods in the usual sense.
상기 건강기능(성)식품(health functional food)은 특정보건용 식품(food for special health use, FoSHU)과 동일한 용어로, 영양 공급 외에도 생체조절기능이 효율적으로 나타나도록 가공된 의학, 의료효과가 높은 식품을 의미한다. 여기서 '기능(성)'은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건용도에 유용한 효과를 얻는 것을 의미한다. 상기 건강식품(health food)은 일반식품에 비해 적극적인 건강유지나 증진 효과를 가지는 식품을 의미하고, 건강보조식품(health supplement food)은 건강보조 목적의 식품을 의미한다. 경우에 따라, 건강기능식품, 건강식품, 건강보조식품의 용어는 호용될 수 있다.The health functional food (health functional food) is the same term as food for special health use (FoSHU), and in addition to supplying nutrients, it is processed to efficiently display bioregulatory functions, and has high medical effects. means food. Here, 'function (sex)' means obtaining useful effects for health purposes such as regulating nutrients for the structure and function of the human body or physiological functions. The health food (health food) means a food that has an active health maintenance or promotion effect compared to general food, and health supplement food (health supplement food) means food for the purpose of health supplement. In some cases, the terms health functional food, health food, and health supplement food may be used interchangeably.
구체적으로, 상기 건강기능식품은 본 발명의 창이자 추출물 또는 이의 분획물; 또는 창이자, 당귀, 박하 및 작약의 추출물 또는 이의 분획물을 음료, 차류, 향신료, 껌, 과자류 등의 식품 소재에 첨가하거나, 캡슐화, 분말화, 현탁액 등으로 제조한 식품으로, 이를 섭취할 경우 건강상 특정한 효과를 가져오는 것을 의미하나, 일반 약품과는 달리 식품을 원료로 하여 약품의 장기 복용 시 발생할 수 있는 부작용이 없는 장점이 있다.Specifically, the health functional food is the intestine extract or fraction thereof of the present invention; Or a food prepared by adding extracts or fractions of spearmint, angelica, mint, and peony to food materials such as beverages, teas, spices, chewing gum, confectionery, etc., or encapsulated, powdered, or suspended. It means to bring a specific effect, but unlike general drugs, it has the advantage of not having side effects that can occur when taking a drug for a long time by using food as a raw material.
본 발명의 식품은 당업계에서 통상적으로 사용되는 방법에 의하여 제조 가능하며, 당업계에서 통상적으로 첨가하는 원료 및 성분을 첨가하여 제조할 수 있다. 또한, 상기 식품 조성물은 식품으로 인정되는 제형이면 다양한 형태의 제형으로 제한 없이 제조될 수 있다.The food of the present invention can be prepared by a method commonly used in the art, and can be prepared by adding raw materials and ingredients commonly added in the art. In addition, the food composition can be prepared without limitation in various types of formulations as long as they are recognized as food.
또한, 상기 식품 조성물은 생리학적으로 허용 가능한 담체를 추가로 포함할 수 있는데, 담체의 종류는 특별히 제한되지 않으며 당해 기술 분야에서 통상적으로 사용되는 담체라면 어느 것이든 사용할 수 있다.In addition, the food composition may further include a physiologically acceptable carrier, the type of carrier is not particularly limited, any carrier commonly used in the art may be used.
또한, 상기 식품 조성물은 식품 조성물에 통상 사용되어 냄새, 맛, 시각 등을 향상시킬 수 있는 추가 성분을 포함할 수 있다. 예들 들어, 비타민 A, C, D, E, B1, B2, B6, B12, 니아신(niacin), 비오틴(biotin), 폴레이트(folate), 판토텐산(panthotenic acid) 등을 포함할 수 있다. 또한, 아연(Zn), 철(Fe), 칼슘(Ca), 크롬(Cr), 마그네슘(Mg), 망간(Mn), 구리(Cu), 크륨(Cr) 등의 미네랄; 및 라이신, 트립토판, 시스테인, 발린 등의 아미노산을 포함할 수 있다.In addition, the food composition may include additional ingredients that are commonly used in food compositions and can improve smell, taste, and vision. For example, vitamins A, C, D, E, B1, B2, B6, B12, niacin, biotin, folate, panthotenic acid, and the like may be included. In addition, minerals such as zinc (Zn), iron (Fe), calcium (Ca), chromium (Cr), magnesium (Mg), manganese (Mn), copper (Cu), and chrome (Cr); and amino acids such as lysine, tryptophan, cysteine, and valine.
또한, 상기 식품 조성물은 방부제(소르빈산 칼륨, 벤조산나트륨, 살리실산, 데히드로초산나트륨 등), 살균제(표백분과 고도 표백분, 차아염소산나트륨 등), 산화방지제(부틸히드록시아니졸(BHA), 부틸히드록시톨류엔(BHT) 등), 착색제(타르색소 등), 발색제(아질산 나트륨, 아초산 나트륨 등), 표백제(아황산나트륨), 조미료(MSG 글루타민산나트륨 등), 감미료(둘신, 사이클레메이트, 사카린, 나트륨 등), 향료(바닐린, 락톤류 등), 팽창제(명반, D-주석산수소칼륨 등), 강화제, 유화제, 증점제(호료), 피막제, 검기초제, 거품억제제, 용제, 개량제 등의 식품 첨가물(food additives)을 포함할 수 있다. 상기 첨가물은 식품의 종류에 따라 선별하고 적절한 양으로 사용할 수 있다.In addition, the food composition may include preservatives (potassium sorbate, sodium benzoate, salicylic acid, sodium dehydroacetate, etc.), bactericides (bleaching powder, high bleaching powder, sodium hypochlorite, etc.), antioxidants (butylhydroxyanisole (BHA), butyl hydroxy Loxytoluene (BHT), etc.), coloring agents (tar color, etc.), coloring agents (sodium nitrite, sodium nitrite, etc.), bleaching agents (sodium sulfite, etc.), seasonings (MSG sodium glutamate, etc.), sweeteners (dulcin, cyclemate, saccharin) , sodium, etc.), flavoring (vanillin, lactones, etc.), expanding agent (alum, D-potassium hydrogen stannate, etc.), strengthening agent, emulsifier, thickener (thickener), coating agent, gum base agent, foam inhibitor, solvent, improver, etc. food May contain food additives. The additives may be selected according to the type of food and used in an appropriate amount.
창이자 추출물, 또는 이에 당귀 추출물, 박하 추출물 및 작약 추출물이 혼합된 혼합물은 우울 행동을 개선하고, 혈중 세로토닌, 세로토닌 수용체의 함량 및 가바 수용체 발현을 증가시키므로, 이를 포함하는 본 발명의 조성물은 우울증의 예방, 개선 또는 치료에 유용하게 사용될 수 있다.Changja extract, or a mixture of angelica extract, peppermint extract and peony extract, improves depressive behavior and increases blood serotonin, serotonin receptor content and GABA receptor expression, so the composition of the present invention containing it prevents depression , can be usefully used for improvement or treatment.
도 1은 본 발명의 일 실시예에 따라 제조한, 창이자 추출물; 또는 창이자 추출물, 당귀 추출물, 박하 추출물 및 작약 추출물이 혼합된 혼합물의 우울 행동 개선 효과를 보여주는 그래프이다. 꼬리 매달기 실험(TST)의 결과로서, 꼬리 매달기에 의한 스트레스가 가해진 마우스가 부동 상태를 유지하는 시간(immobility time, 초)을 보여준다. 이때, TST는 화합물 또는 추출물이 투여되지 않은 대조군, Fluoxetine은 플루옥세틴이 투여된 양성대조군을 의미한다.
도 2는 본 발명의 일 실시예에 따라 제조한, 창이자 추출물; 또는 창이자 추출물, 당귀 추출물, 박하 추출물 및 작약 추출물이 혼합된 혼합물의 우울 행동 개선 효과를 보여주는 그래프이다. 강제 수영 실험(FST)의 결과로서, 강제 수영에 의한 스트레스가 가해진 마우스가 부동 상태를 유지하는 시간(immobility time, 초)을 보여준다. 이때, FST는 화합물 또는 추출물이 투여되지 않은 대조군, Fluoxetine은 플루옥세틴이 투여된 양성대조군을 의미한다.
도 3은 본 발명의 일 실시예에 따라 제조한, 창이자 추출물; 또는 창이자 추출물, 당귀 추출물, 박하 추출물 및 작약 추출물이 혼합된 혼합물의 혈중 세로토닌(serotonin) 증가 효과를 보여주는 그래프이다. 이때, Control은 화합물 또는 추출물이 투여되지 않은 대조군, Fluoxetine은 플루옥세틴이 투여된 양성대조군을 의미한다.
도 4는 본 발명의 일 실시예에 따라 제조한, 창이자 추출물; 또는 창이자 추출물, 당귀 추출물, 박하 추출물 및 작약 추출물이 혼합된 혼합물의 세로토닌 수용체(5-HT2C) 단백질 발현 증가 효과를 보여주는 그래프이다. 이때, Control은 화합물 또는 추출물이 투여되지 않은 대조군, Fluoxetine은 플루옥세틴이 투여된 양성대조군을 의미한다.
도 5는 본 발명의 일 실시예에 따라 제조한, 창이자 추출물; 또는 창이자 추출물, 당귀 추출물, 박하 추출물 및 작약 추출물이 혼합된 혼합물의 가바 수용체(A1) 단백질 발현 증가 효과를 보여주는 그래프이다. 이때, Control은 화합물 또는 추출물이 투여되지 않은 대조군, Fluoxetine은 플루옥세틴이 투여된 양성대조군을 의미한다.Figure 1 is prepared according to an embodiment of the present invention, changja extract; Or, it is a graph showing the effect of improving depressive behavior of a mixture of Changja extract, Angelica extract, peppermint extract, and peony extract. As a result of the tail hanging experiment (TST), the time (immobility time, sec) for which the mouse subjected to tail hanging stress is maintained in an immobility state is shown. At this time, TST refers to a control group in which no compound or extract is administered, and Fluoxetine refers to a positive control group in which fluoxetine is administered.
Figure 2 is prepared according to an embodiment of the present invention, changja extract; Or, it is a graph showing the effect of improving depressive behavior of a mixture of Changja extract, Angelica extract, peppermint extract, and peony extract. As a result of the forced swimming experiment (FST), the time (immobility time, seconds) for which mice subjected to stress by forced swimming remain immobilized is shown. At this time, FST means a control group in which no compound or extract is administered, and Fluoxetine means a positive control group in which fluoxetine is administered.
Figure 3 is prepared according to an embodiment of the present invention, changja extract; Alternatively, it is a graph showing the effect of increasing serotonin in the blood of a mixture of a spear extract, angelica extract, peppermint extract, and peony extract. At this time, Control refers to a control group in which no compound or extract is administered, and Fluoxetine refers to a positive control group in which fluoxetine is administered.
Figure 4 is prepared according to an embodiment of the present invention, changja extract; Alternatively, it is a graph showing the effect of increasing the serotonin receptor (5-HT2C) protein expression of a mixture of changja extract, angelica extract, peppermint extract, and peony extract. At this time, Control refers to a control group in which no compound or extract is administered, and Fluoxetine refers to a positive control group in which fluoxetine is administered.
Figure 5 is prepared according to an embodiment of the present invention, changja extract; Alternatively, it is a graph showing the effect of increasing the expression of GABA receptor (A1) protein by a mixture of changja extract, angelica extract, peppermint extract, and peony extract. At this time, Control refers to a control group in which no compound or extract is administered, and Fluoxetine refers to a positive control group in which fluoxetine is administered.
이하 본 발명을 다음의 실시예에 의하여 보다 구체적으로 설명하고자 한다. 그러나 이들은 본 발명을 예시하기 위한 것일 뿐이며, 본 발명의 범위가 이들 실시예에 의하여 제한되는 것은 아니다.Hereinafter, the present invention will be described in more detail by the following examples. However, these are only for exemplifying the present invention, and the scope of the present invention is not limited by these examples.
제조예 1. 창이자 추출물의 제조방법Preparation Example 1. Manufacturing method of intestinal japonica extract
창이자(Xanthii fructus)를 초임계 추출하여 창이자 추출물을 제조하였다.Changjaja ( Xanthii fructus ) Supercritical extraction was performed to prepare a Changjaja extract.
구체적으로, 초임계 추출조에 탈취한 창이자의 원물 300g을 넣고, 추출조를 밀봉하였다. 추출조의 온도를 50℃까지 승온하고, 이산화탄소를 고압용 기체 펌프를 이용하여 투입하여 압력을 350기압까지 올렸다. 특히, 추출조의 출구에 부착된 압력조절 밸브를 이용하여 추출물을 방출시키면서 압력과 온도를 350기압, 50℃로 일정하게 유지하였다. 상기 과정으로부터 수득한 추출액을 올리브오일에 녹여 창이자 추출물(수율: 0.003%)을 제조하였다. Specifically, 300 g of the raw material of deodorized Changija was put in a supercritical extraction tank, and the extraction tank was sealed. The temperature of the extraction tank was raised to 50° C., and the pressure was raised to 350 atm by introducing carbon dioxide using a high-pressure gas pump. In particular, the pressure and temperature were kept constant at 350 atm and 50° C. while releasing the extract using a pressure control valve attached to the outlet of the extraction tank. The extract obtained from the above process was dissolved in olive oil to prepare a changja extract (yield: 0.003%).
제조예 2. 창이자, 당귀, 박하 및 작약 추출물의 혼합물의 제조방법Preparation Example 2. Method for preparing a mixture of extracts of Changjaja, Angelica quai, peppermint and peony
당귀, 박하 또는 작약을 초임계 추출하여 각각의 초임계 추출물을 제조하였다. 구체적으로, 당귀, 박하 또는 작약을 각각 300g 준비하였고, 상기 제조에 1에 따른 방법으로 초임계 추출하였다. Each supercritical extract was prepared by supercritical extraction of Angelica quai, peppermint or peony. Specifically, 300 g of Angelica quail, peppermint or peony were prepared, and supercritical extraction was performed by the method according to Preparation 1 above.
이후, 각각의 초임계 추출물에 대하여, 창이자 추출물 35%(v/v), 당귀 추출물 35%(v/v), 박하 추출물 20%(v/v) 및 작약 추출물 10%(v/v)로 혼합하여 창이자, 당귀, 박하 및 작약 추출물의 혼합물(이하, '혼합물'로 명명)을 제조하였다.Then, for each supercritical extract, 35% (v/v) of Changija extract, 35% (v/v) of Angelica extract, 20% (v/v) of peppermint extract and 10% (v/v) of peony extract. A mixture (hereinafter referred to as a 'mixture') of the extracts of Changija, Angelica mint, and Peony was prepared by mixing.
실시예 1. 창이자 추출물 및 혼합물의 항우울 효과 확인Example 1. Confirmation of antidepressant effect of intestinal japonica extract and mixture
실시예 1-1. 스트레스가 유도된 실험동물의 행동 변화 확인Example 1-1. Confirmation of behavioral changes in experimental animals induced by stress
실시예 1-1-1. 꼬리 매달기 실험(Tail Suspension Test; TST)Example 1-1-1. Tail Suspension Test (TST)
상기 제조예 1 및 2에서 제조한 창이자 추출물과 창이자, 당귀, 박하 및 작약 추출물이 혼합된 혼합물의 항우울 효과를 확인하기 위하여, 스트레스가 유도된 실험동물의 행동 변화를 확인하였다.In order to confirm the antidepressant effect of the mixture containing the extracts prepared in Preparation Examples 1 and 2 and the extracts of Changija, Angelica gigas, peppermint, and peony, the behavioral changes of the stress-induced experimental animals were confirmed.
구체적으로, 7주령 수컷 ICR 마우스(㈜오리엔트 바이오 코리아)를 사용하였고, 한국과학기술연구원의 동물실험실 시설에서 7일간 적응시킨 후 실험을 진행하였다. 실험을 위해 스트레스만 주는 스트레스 대조군(Control); 스트레스를 받은 대조군에 시판 항우울제(플루옥세틴; Fluoxetine, 10 mg/kg)를 투여하는 양성대조군; 및 스트레스를 받은 대조군에 창이자 추출물만을 투여하는 실험군 1(12.5, 25 또는 50 mg/kg); 및 스트레스를 받은 대조군에 창이자, 당귀, 박하 및 작약 추출물이 혼합된 혼합물을 투여하는 실험군 2(12.5, 25 또는 50 mg/kg)로 구분하였다. Specifically, 7-week-old male ICR mice (Orient Bio Korea Co., Ltd.) were used, and the experiment was conducted after acclimatization for 7 days in the animal laboratory facility of the Korea Institute of Science and Technology. A stress control group (Control) that gives only stress for the experiment; A positive control group administered with a commercially available antidepressant (Fluoxetine, 10 mg/kg) to a stressed control group; and Experimental Group 1 (12.5, 25 or 50 mg/kg) administered with only the intestinal tract extract to a stressed control group; and experimental group 2 (12.5, 25, or 50 mg/kg), in which a mixture of extracts of Angelica gigas, Angelica mint, and peony was administered to a stressed control group.
이후, 꼬리 매달기 실험(Tail Suspension Test; TST)을 수행하였다. 스트레스가 유도된 마우스에 양성대조군인 플루옥세틴(10 mg/kg), 창이자 추출물(12.5, 25 또는 50 ㎎/㎏) 또는 혼합물(12.5, 25 또는 50 ㎎/㎏)을 각각 경구투여한 후, 높이 80cm의 모서리에 접착력이 강한 테이프를 마우스 꼬리 끝 1~2cm를 붙여서 마우스를 매달고, 1시간 후 6분 동안 비디오 레코더를 사용하여 녹화하였다. 녹화된 결과에서 처음 2분간을 제외한 나머지 4분 동안을 기준으로 마우스가 움직임 없이 가만히 있는 부동 상태를 유지하는 시간(immobility time, 초)을 측정하였다.Then, a tail suspension test (TST) was performed. After orally administering fluoxetine (10 mg/kg), intestinal extract (12.5, 25, or 50 mg/kg) or a mixture (12.5, 25, or 50 mg/kg) as a positive control to stress-induced mice, respectively, their height was 80 cm. The mouse was suspended by attaching 1 to 2 cm of the end of the mouse tail to the edge of the mouse with strong adhesive tape, and after 1 hour, it was recorded using a video recorder for 6 minutes. From the recorded results, the time (immobility time, seconds) that the mouse maintains a still immobility state without movement was measured for the remaining 4 minutes except for the first 2 minutes.
그 결과, 도 1에서 볼 수 있듯이, 꼬리 매달기 스트레스(TST)를 주는 경우 마우스가 부동 상태를 유지하는 시간이 약 110초 이상으로 현저히 증가하는 것을 확인하였다. 그러나, 양성대조군인 플루옥세틴을 투여하는 경우 부동 상태 유지 시간은 절반 이상 감소하여 약 50초 정도임을 확인하였다.As a result, as can be seen in Figure 1, it was confirmed that when the tail suspension stress (TST) was given, the time for the mouse to maintain the immobility state was significantly increased to about 110 seconds or more. However, in the case of administration of fluoxetine, which is a positive control group, it was confirmed that the time to maintain the immobility state was reduced by more than half to about 50 seconds.
특히, 창이자 추출물을 투여하는 경우 스트레스에 의해 증가한 부동 상태 시간이 용량 의존적으로 감소하고, 창이자, 당귀, 박하 및 작약 추출물이 혼합된 혼합물을 투여하는 경우에도 부동 상태 시간이 용량 의존적으로 감소하는 것을 확인하였다. 또한, 혼합물 50 mg/kg를 투여하는 경우 양성대조군인 플루옥세틴과 유사한 시간 감소 효과를 나타냄을 확인하였다.In particular, it was confirmed that the immobility time increased by stress decreased in a dose-dependent manner when the extract of Changjaja extract was administered, and the immobility time was decreased in a dose-dependent manner even when a mixture of extracts of Changjaja, Angelica, mint, and peony was administered. did In addition, it was confirmed that when 50 mg/kg of the mixture was administered, a time reduction effect similar to that of fluoxetine, a positive control group, was shown.
상기 결과를 통해, 창이자 추출물; 및 창이자, 당귀, 박하 및 작약 추출물이 혼합된 혼합물은 스트레스를 받은 마우스의 우울 행동인 부동 상태를 개선시키는 항우울 효과를 나타내며, 시판되는 우울증 치료제인 플루옥세틴과 유사한 정도의 항우울 효과를 나타냄을 알 수 있었다.Through the above results, changija extract; And a mixture of spearmint, angelica, mint, and peony extracts exhibits an antidepressant effect that improves the immobility state, a depressive behavior of stressed mice, and exhibits an antidepressant effect similar to that of fluoxetine, a commercially available antidepressant drug. could
실시예 1-1-2. 강제수영 실험(Forced Swimming Test, FST)Example 1-1-2. Forced Swimming Test (FST)
나아가, 상기 실시예 1-1-1과 동일한 방법으로 플루옥세틴, 창이자 추출물 또는 혼합물을 마우스에 투여하였고, 강제수영 실험(Forced Swimming Test, FST)을 수행하였다. 높이 50cm 이상의 투명 비이커에 30cm를 물로 채운 뒤, 1시간 후 마우스를 입수시켜 6분 동안 비디오 레코더를 사용하여 녹화하였다. 녹화된 결과에서 처음 2분간을 제외한 나머지 4분 동안을 기준으로 마우스가 움직임 없이 가만히 있는 부동 상태를 유지하는 시간(immobility time, 초)을 측정하였다.Furthermore, in the same manner as in Example 1-1-1, fluoxetine, intestinal tract extract or mixture was administered to mice, and a forced swimming test (FST) was performed. After filling 30 cm of water in a transparent beaker with a height of 50 cm or more, after 1 hour, mice were obtained and recorded using a video recorder for 6 minutes. From the recorded results, the time (immobility time, seconds) that the mouse maintains a still immobility state without movement was measured for the remaining 4 minutes except for the first 2 minutes.
그 결과, 도 2에서 볼 수 있듯이, 강제수영 스트레스(FST)를 주는 경우 마우스가 부동 상태를 유지하는 시간이 약 130초 이상으로 현저히 증가하는 것을 확인하였다. 그러나, 양성대조군인 플루옥세틴을 투여하는 경우 부동 상태 유지 시간은 세 배 이상 감소하여 약 40초 정도임을 확인하였다.As a result, as can be seen in Figure 2, it was confirmed that the time for the mouse to maintain the immobility state significantly increased to about 130 seconds or more when the forced swimming stress (FST) was applied. However, in the case of administration of fluoxetine, which is a positive control group, it was confirmed that the time to maintain the immobility state was reduced by more than three times to about 40 seconds.
특히, 창이자 추출물을 투여하는 경우 스트레스에 의해 증가한 부동 상태 시간이 용량 의존적으로 감소하고, 그 감소 정도는 약 2배 이상임을 확인하였다. 또한, 창이자, 당귀, 박하 및 작약 추출물이 혼합된 혼합물을 투여하는 경우에도 부동 상태 시간이 용량 의존적으로 감소하고, 그 감소 정도는 약 2배 이상임을 확인하였다.In particular, it was confirmed that the immobility time increased by stress decreased in a dose-dependent manner, and the degree of reduction was about 2 times or more when administering the extract of the intestine. In addition, it was confirmed that the immobility time was decreased in a dose-dependent manner even when the mixture of the extracts of Changjae, Angelica, Mint, and Peony was administered, and the degree of reduction was about 2 times or more.
상기 결과를 통해, 창이자 추출물; 및 창이자, 당귀, 박하 및 작약 추출물이 혼합된 혼합물은 스트레스를 받은 마우스의 우울 행동인 부동 상태를 개선시키는 항우울 효과를 나타내며, 이를 투여하지 않는 경우보다 약 2배 이상의 현저한 항우울 효과를 나타냄을 알 수 있었다.Through the above results, changija extract; And a mixture of Changjaja, Angelica quai, mint and peony extracts exhibits an antidepressant effect that improves the immobility state, which is a depressive behavior of stressed mice, and exhibits a significant antidepressant effect about twice as much as when not administered. Could know.
실시예 1-2. 혈중 세로토닌 양 확인Example 1-2. Checking the amount of serotonin in the blood
현재 사용되고 있는 항우울제는 중추 신경계 내 신경전달물질인 세로토닌의 농도를 높여주는 메커니즘을 사용하고 있는바, 상기 제조예 1 및 2에서 제조한 창이자 추출물과 창이자, 당귀, 박하 및 작약 추출물이 혼합된 혼합물의 항우울 효과를 확인하기 위하여, 이를 투여한 실험동물의 혈중 세로토닌 양을 비교하였다.Currently used antidepressants use a mechanism that increases the concentration of serotonin, a neurotransmitter in the central nervous system, and the mixture of Changja extract prepared in Preparation Examples 1 and 2 and Changjaja, Angelica, Mint and Peony extracts In order to confirm the antidepressant effect, the amount of serotonin in the blood of the experimental animals administered with it was compared.
구체적으로, 마우스에 양성대조군인 플루옥세틴(10 mg/kg), 창이자 추출물(12.5, 25 또는 50 ㎎/㎏) 또는 혼합물(12.5, 25 또는 50 ㎎/㎏)을 각각 경구투여한 후 혈액을 채취하였고, ELISA(enzyme-linked immunosorbent assay)를 이용하여 상기 혈액의 혈중 내 세로토닌의 양을 측정하였다.Specifically, mice were orally administered with fluoxetine (10 mg/kg), intestine extract (12.5, 25, or 50 mg/kg) or a mixture (12.5, 25, or 50 mg/kg) as a positive control, respectively, and then blood was collected. , ELISA (enzyme-linked immunosorbent assay) was used to measure the amount of serotonin in the blood.
그 결과, 도 3에서 볼 수 있듯이, 플루옥세틴 또는 추출물 등을 투여하지 않은 일반적인 대조군 마우스는 혈중 세로토닌의 양이 약 5 ng/ml 정도임을 확인하였다. 그러나, 양성대조군인 플루옥세틴을 투여하는 경우 혈중 세로토닌의 양은 급격히 증가하여 약 20 ng/ml 정도임을 확인하였다.As a result, as can be seen in FIG. 3, it was confirmed that the amount of serotonin in blood was about 5 ng/ml in general control mice not administered with fluoxetine or the extract. However, when fluoxetine, which is a positive control group, was administered, the amount of serotonin in the blood increased rapidly and was confirmed to be about 20 ng/ml.
특히, 창이자 추출물을 투여하는 경우 혈중 세로토닌의 양이 용량 의존적으로 증가하고, 창이자, 당귀, 박하 및 작약 추출물이 혼합된 혼합물을 투여하는 경우에도 혈중 세로토닌의 양이 용량 의존적으로 증가하는 것을 확인하였다. 나아가, 상기 창이자 추출물 또는 혼합물의 혈중 세로토닌 증가 효과는 양성대조군인 플루옥세틴과 유사하거나 더 우수함을 확인하였다.In particular, it was confirmed that the amount of serotonin in the blood increased in a dose-dependent manner when the extract was administered, and the amount of serotonin in the blood increased in a dose-dependent manner even when a mixture of the extracts of Changjaja, Angelica mint, and Peony was administered. Furthermore, it was confirmed that the effect of increasing serotonin in the blood of the extract or mixture of the intestine japonica was similar to or superior to that of fluoxetine, a positive control group.
상기 결과를 통해, 창이자 추출물; 및 창이자, 당귀, 박하 및 작약 추출물이 혼합된 혼합물은 마우스의 혈중 세로토닌의 양을 증가시켜 항우울 효과를 나타내며, 시판되는 우울증 치료제인 플루옥세틴과 유사하거나 더 우수한 정도의 항우울 효과를 나타냄을 알 수 있었다.Through the above results, changija extract; And a mixture of spear, angelica, peppermint, and peony extracts increases the amount of serotonin in the blood of mice to exhibit antidepressant effects, and exhibits antidepressant effects similar to or superior to fluoxetine, a commercially available antidepressant drug. there was.
실시예 1-3. 세로토닌 수용체 발현양 확인Example 1-3. Confirmation of serotonin receptor expression level
현재 사용되고 있는 항우울제는 세로토닌의 농도를 높여줄뿐만 아니라 이의 활성을 증진시키는 메커니즘을 사용하고 있는바, 상기 제조예 1 및 2에서 제조한 창이자 추출물과 창이자, 당귀, 박하 및 작약 추출물이 혼합된 혼합물의 항우울 효과를 확인하기 위하여, 이를 투여한 실험동물의 세로토닌 수용체 발현양을 비교하였다.Currently used antidepressants not only increase the concentration of serotonin but also use a mechanism that enhances its activity. The mixture of the Changis extract prepared in Preparation Examples 1 and 2 and the Changis, Angelica, Mint and Peony extracts were mixed. In order to confirm the antidepressant effect, the serotonin receptor expression level of the experimental animals administered with the same was compared.
구체적으로, 마우스에 양성대조군인 플루옥세틴(10 mg/kg), 창이자 추출물(12.5, 25 또는 50 ㎎/㎏) 또는 혼합물(12.5, 25 또는 50 ㎎/㎏)을 각각 경구투여한 후 뇌조직을 채취하였고, 웨스턴블롯을 통해 세로토닌 수용체인 5-HT2C 수용체 단백질의 발현량을 측정하였다.Specifically, after orally administering fluoxetine (10 mg/kg), intestinal extract (12.5, 25 or 50 mg/kg) or a mixture (12.5, 25 or 50 mg/kg) as a positive control to mice, respectively, brain tissue was collected And, the expression level of 5-HT2C receptor protein, which is a serotonin receptor, was measured through Western blotting.
그 결과, 도 4에서 볼 수 있듯이, 플루옥세틴 또는 추출물 등을 투여하지 않은 일반적인 대조군 마우스는 세로토닌 수용체의 발현양이 약 0.8 정도임을 확인하였다. 그러나, 양성대조군인 플루옥세틴을 투여하는 경우에는 세로토닌 수용체의 발현양이 증가하여 약 약 1.0 정도임을 확인하였다.As a result, as can be seen in FIG. 4, it was confirmed that the expression level of the serotonin receptor was about 0.8 in the general control mice not administered with fluoxetine or the extract. However, when fluoxetine, a positive control group, was administered, it was confirmed that the expression level of the serotonin receptor increased to about 1.0.
또한, 창이자 추출물을 50 mg/kg 농도로 투여하는 경우 대조군에 비하여 세로토닌 수용체의 발현양이 증가하는 것을 확인하였고, 창이자, 당귀, 박하 및 작약 추출물이 혼합된 혼합물을 투여하는 경우에도 세로토닌 수용체의 발현이 용량 의존적으로 증가하는 것을 확인하였다. 특히, 상기 혼합물을 50 mg/kg 농도로 투여하는 경우 세로토닌 수용체 발현 증가 효과는 양성대조군인 플루옥세틴과 유사한 정도임을 확인하였다.In addition, it was confirmed that the expression level of serotonin receptors increased compared to the control group when the extract of Changjaja extract was administered at a concentration of 50 mg/kg, and the expression of serotonin receptors was also administered when a mixture of extracts of Changjaja, Angelica, Mint and Peony was administered. It was confirmed that this increased in a dose-dependent manner. In particular, when the mixture was administered at a concentration of 50 mg/kg, it was confirmed that the effect of increasing serotonin receptor expression was similar to that of fluoxetine, a positive control group.
상기 결과를 통해, 창이자 추출물; 및 창이자, 당귀, 박하 및 작약 추출물이 혼합된 혼합물은 세로토닌 수용체의 발현양을 증가시켜 항우울 효과를 나타내며, 시판되는 우울증 치료제인 플루옥세틴보다도 더 우수한 정도의 항우울 효과를 나타냄을 알 수 있었다.Through the above results, changija extract; And it was found that the mixture of extracts of Angelica quai, mint, and peony exhibited an antidepressant effect by increasing the expression level of serotonin receptors, and exhibited a better antidepressant effect than fluoxetine, a commercial antidepressant.
실시예 1-4. 가바(GABA) 수용체 발현양 확인Example 1-4. GABA receptor expression level confirmation
현재 사용되고 있는 항우울제는 중추 신경계 내 신경전달물질인 가바의 작용을 증진시키는 메커니즘을 사용하고 있는바, 상기 제조예 1 및 2에서 제조한 창이자 추출물과 창이자, 당귀, 박하 및 작약 추출물이 혼합된 혼합물의 항우울 효과를 확인하기 위하여, 이를 투여한 실험동물에서 가바 수용체의 발현 증가 효과를 비교하였다.Currently used antidepressants use a mechanism that enhances the action of GABA, a neurotransmitter in the central nervous system, and the mixture of the Changija extract prepared in Preparation Examples 1 and 2 and the Changjaja, Angelica, Mint, and Peony extracts were mixed. In order to confirm the antidepressant effect, the effect of increasing the expression of GABA receptors in experimental animals administered with the same was compared.
구체적으로, 마우스에 양성대조군인 플루옥세틴(10 mg/kg), 창이자 추출물(12.5, 25 또는 50 ㎎/㎏) 또는 혼합물(12.5, 25 또는 50 ㎎/㎏)을 각각 경구투여한 후 뇌조직을 채취하였고, 웨스턴블롯을 통해 가바 수용체 A1의 단백질 발현량을 측정하였다.Specifically, after orally administering fluoxetine (10 mg/kg), intestinal extract (12.5, 25 or 50 mg/kg) or a mixture (12.5, 25 or 50 mg/kg) as a positive control to mice, respectively, brain tissue was collected and the protein expression level of GABA receptor A1 was measured through Western blotting.
그 결과, 도 5에서 볼 수 있듯이, 플루옥세틴 또는 추출물 등을 투여하지 않은 일반적인 대조군 마우스는 가바 수용체의 발현양이 약 0.5 정도임을 확인하였다. 다만, 양성대조군인 플루옥세틴을 투여하는 경우에도 가바 수용체의 발현양이 증가하지 않음을 확인하였다.As a result, as can be seen in FIG. 5 , it was confirmed that the expression level of the GABA receptor was about 0.5 in the general control mice not administered with fluoxetine or the extract. However, it was confirmed that the expression level of the GABA receptor did not increase even when fluoxetine, a positive control group, was administered.
반면, 창이자 추출물을 투여하는 경우 가바 수용체의 발현양이 용량 의존적으로 증가하고, 창이자, 당귀, 박하 및 작약 추출물이 혼합된 혼합물을 투여하는 경우에도 가바 수용체의 발현이 용량 의존적으로 증가하는 것을 확인하였다. 특히, 상기 창이자 추출물 또는 혼합물의 가바 수용체 발현양 증가 효과는 양성대조군인 플루옥세틴보다 현저히 우수함을 확인하였다.On the other hand, it was confirmed that the expression of GABA receptors increased in a dose-dependent manner when the extract was administered, and the expression of GABA receptors increased in a dose-dependent manner even when a mixture of extracts of Changjaja, Angelica, Mint, and Peony was administered. . In particular, it was confirmed that the effect of increasing the expression level of GABA receptors of the extract or the mixture of the spear japonica was significantly better than that of fluoxetine, a positive control group.
상기 결과를 통해, 창이자 추출물; 및 창이자, 당귀, 박하 및 작약 추출물이 혼합된 혼합물은 가바 수용체의 발현양을 증가시켜 항우울 효과를 나타내며, 시판되는 우울증 치료제인 플루옥세틴보다도 더 우수한 정도의 항우울 효과를 나타냄을 알 수 있었다.Through the above results, changija extract; And it was found that the mixture of the extracts of Angelica quai, mint and peony extracts increased the expression of GABA receptors to exhibit antidepressant effects, and exhibited antidepressant effects that were superior to fluoxetine, a commercially available antidepressant drug.
이상의 설명으로부터, 본 발명이 속하는 기술분야의 당업자는 본 발명이 그 기술적 사상이나 필수적 특징을 변경하지 않고서 다른 구체적인 형태로 실시될 수 있다는 것을 이해할 수 있을 것이다. 이와 관련하여, 이상에서 기술한 실시 예들은 모든 면에서 예시적인 것이며 한정적인 것이 아닌 것으로서 이해해야만 한다. 본 발명의 범위는 상기 상세한 설명보다는 후술하는 특허 청구범위의 의미 및 범위 그리고 그 등가 개념으로부터 도출되는 모든 변경 또는 변형된 형태가 본 발명의 범위에 포함되는 것으로 해석되어야 한다.From the above description, those skilled in the art to which the present invention pertains will be able to understand that the present invention may be embodied in other specific forms without changing its technical spirit or essential features. In this regard, the embodiments described above should be understood as illustrative in all respects and not limiting. The scope of the present invention should be construed as including all changes or modifications derived from the meaning and scope of the claims to be described later and equivalent concepts rather than the detailed description above are included in the scope of the present invention.
Claims (10)
A pharmaceutical composition for the prevention or treatment of depression, comprising a supercritical extract or a fraction thereof as an active ingredient.
The pharmaceutical composition according to claim 1, wherein the composition further comprises at least one extract or fraction selected from the group consisting of angelica quasi, mint and peony.
[Claim 3] The pharmaceutical composition according to claim 2, wherein the composition comprises changbae extract, angelica extract, peppermint extract, and peony extract in a volume ratio of 2.5 to 4.5: 2.5 to 4.5: 1 to 3: 0.1 to 2.
The pharmaceutical composition according to claim 1, wherein the supercritical extraction is performed at 330 to 370 atmospheric pressure and 40 to 60 °C.
According to claim 1, wherein the supercritical extraction is carried out at 350 atm and 50 ℃, the pharmaceutical composition.
The pharmaceutical composition according to claim 1, wherein the composition increases the level of serotonin in the blood, the expression of serotonin receptors or the expression of GABA receptors.
A food composition for preventing or ameliorating depression, comprising a supercritical extract or a fraction thereof as an active ingredient.
[Claim 9] The food composition according to claim 8, wherein the composition further comprises at least one extract or fraction selected from the group consisting of dong quai, mint and peony.
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