KR101862836B1 - Pharmaceutical composition comprising heracleum moellendorffii hance extract for preventing or treating depression - Google Patents
Pharmaceutical composition comprising heracleum moellendorffii hance extract for preventing or treating depression Download PDFInfo
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- KR101862836B1 KR101862836B1 KR1020170017719A KR20170017719A KR101862836B1 KR 101862836 B1 KR101862836 B1 KR 101862836B1 KR 1020170017719 A KR1020170017719 A KR 1020170017719A KR 20170017719 A KR20170017719 A KR 20170017719A KR 101862836 B1 KR101862836 B1 KR 101862836B1
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Abstract
Description
본 발명은 어수리(Heracleum moellendorffii Hance) 추출물을 포함하는, 스트레스성 질환의 예방 또는 치료용 약학적 조성물, 스트레스성 질환의 개선을 위한 식품 조성물에 관한 것이다. The invention eosuri (Heracleum moellendorffii The present invention relates to a pharmaceutical composition for the prevention or treatment of a stress-related disease, and a food composition for improving a stress-related disease.
현대 산업 사회는 구조적으로나 기능적으로 빠르고 복잡하게 변화하고 있다. 뿐만 아니라 개인이 소화하기 어려울 정도의 엄청난 양의 정보가 매일 쏟아지고 있다. 새로운 기술, 새로운 환경에 계속 적응해 나가야 하는 현대인들의 대부분은 많은 신체적· 심리적 부담감을 느끼게 된다. 이런 부담감을 일명 스트레스(stress)라 한다.Modern industrial society is changing rapidly and complexly structurally and functionally. In addition, there is an enormous amount of information coming out daily, which is difficult for an individual to digest. Most of the modern people who have to adapt to new technology and new environment feel a lot of physical and psychological burden. This stress is called stress.
신체가 허용할 수 있는 수준의 스트레스는 우리 몸의 적절한 자극제로 작용을 하게 되지만, 허용 범위를 벗어난 강하고도 지속적으로 가해지는 심리적 육체적 스트레스는 당질코르티코이드를 장시간 동안 과량 분비하게 유도한다. 이렇게 장기간 과량 분비되는 당질코르티코이드는 몸의 면역력을 떨어뜨리게 되므로, 외부 감염에 의한 저항성을 떨어뜨리게 되고, 우리 몸에 다양한 질병을 유발하게 된다. 면역력 감퇴뿐만 아니라 특히 뇌세포 손상 및 재생을 억제하여 불면증, 무기력증, 기억력 감퇴, 우울증 유발은 물론 자살 충동까지 일으킨다.The body's acceptable levels of stress will act as an appropriate stimulant for our body, but strong and persistent psychological and physical stresses outside the acceptable range induce hyperglycemia of glucocorticoids for prolonged periods of time. This long-term over-secretion of glucocorticoids lowers the body's immune system, reducing resistance to external infections and causing a variety of diseases in our bodies. In addition to diminishing immunity, it also inhibits brain cell damage and regeneration, resulting in insomnia, lethargy, memory loss, depression, as well as suicide.
우울증을 치료하기 위한 치료제로서 1960년대 개발된 삼환계 약물을 필두로 하여 현재는 세로토닌 재흡수 억제제로 알려진 프로작, 졸로푸트, 세로자트, 이팩사, 레메론 등 다양한 종류의 항우울증 치료제가 개발되어 왔다. 또한 이와 같은 항 우울증 치료제와 더불어 스트레스 반응의 1차 물질인 CRH가 결합하는 CRH 수용체 억제제 개발 연구 또한 많이 이루어지고 있다. 그러나 아직까지도 스트레스에 의한 우울증, 신경질환을 완치시킬 수 있는 치료제 개발은 미미한 상태이다. 또한, 기존의 항우울제에 잘 반응하지 않거나, 재발률이 높으며, 심한 부작용에 의해 약물복용이 불가능한 환자들도 많은 실정이다. A variety of antidepressant drugs such as Prozac, Zoloft, Serzat, Ipasa, and Remeron, which are now known as serotonin reuptake inhibitors, have been developed, including tricyclic drugs developed in the 1960s as therapeutic agents for the treatment of depression. In addition, CRH receptor antagonists that bind CRH, the first substance of the stress response, have been developed in addition to these antidepressant drugs. However, development of therapeutic agents that can cure depression and neurological diseases caused by stress is still insufficient. In addition, many patients are not responding well to conventional antidepressants, have a high recurrence rate, and are unable to take medications due to severe side effects.
삼환계 항우울제(tricyclic antidepressants: TCA)인 이미프라민(imipramine), 데시프라민(desipramine)등은 저혈압, 심장기능장애 등의 부작용이 심하게 나타나며, 가장 널리 쓰이는 플루아크서틴(fluoxetine)이나 서트랄린(sertraline) 등의 선택적 세로토닌 재흡수 억제제는 구역, 위장관 출혈 또는 성기능 장애 등을 유발한다. Tricyclic antidepressants (TCAs) such as imipramine and desipramine have been associated with severe side effects such as hypotension and cardiac dysfunction, and the most commonly used fluoxetine or sertraline sertraline, etc.) cause zone, gastrointestinal bleeding or sexual dysfunction.
또한, 항우울제는 대체로 장기 복용으로 이어지는데, 화학 요법제는 장기 복용에 의한 부작용 및 독성을 나타내는 경우가 매우 빈번하여 인체에 무해하면서도 질병을 효과적으로 치료할 수 있는 새로운 치료제를 천연물로부터 탐색하려는 연구에 관심이 집중되고 있다. In addition, antidepressants usually lead to long-term use. Chemotherapeutic agents are very frequently used for long-term side effects and toxicity, so they are interested in research to search for new therapeutic agents that can treat diseases effectively and harmlessly to humans. .
그러나, 천연 소재로서 부작용이 없고 안전성이 인정되면서 우울증에 대한 개선 또는 치료효과가 우수한 치료제의 제시는 아직도 미흡한 실정이며, 이에 따라 천연 추출물을 이용한 치료제에 대한 지속적인 요구를 충족시키기 위한 새로운 기술의 개발이 요구되고 있다.However, since there is no side effect as a natural material and safety is recognized, the present invention is still not satisfactory in terms of improving or treating depression, and accordingly, development of a new technology for meeting the continuous demand for therapeutic agents using natural extracts Is required.
본 발명의 목적은 어수리(Heracleum moellendorffii Hance) 추출물을 포함하는 스트레스성 질환의 예방 또는 치료용 약학적 조성물을 제공하는 것이다. An object of the present invention is eosuri (Heracleum moellendorffii The present invention also provides a pharmaceutical composition for preventing or treating a stress disorder,
본 발명의 다른 목적은 어수리 추출물을 포함하는 스트레스성 질환의 개선을 위한 식품 조성물을 제공하는 것이다.It is another object of the present invention to provide a food composition for the improvement of a stress disorder comprising an aquatic extract.
상기와 같은 목적을 달성하기 위한 본 발명의 일 측면은 어수리(Heracleum moellendorffii Hance) 추출물을 포함하는, 스트레스성 질환의 예방 또는 치료용 약학적 조성물을 제공한다. According to an aspect of the present invention, there is provided a pharmaceutical composition for preventing or treating a stress disorder, which comprises an extract of Heracleum moellendorffii Hance .
본 발명에서, “어수리(Heracleum moellendorffii Hance)”는 산형과(Umbelliferae)의 식물로 우리나라의 산야에서 비교적 흔하게 자라는 다년초이다. 한방에서는 어수리의 뿌리를 백지(白芷)라 하여 봄에 파종한 것은 10월에 가을에 파종한 것은 이듬해 7~9월에 경엽이 누렇게 말랐을 때 뿌리를 캐내어 줄기와 잔뿌리를 제거하고 햇볕에 말려 보관하여 근육통, 관절염, 요통 치료에 사용하고 있으며, 또한 피부 가려움증, 종기, 두통, 오한, 발열 등의 치료에도 활용하고 있다. 민간에서는 어수리의 어린 잎을 식용으로 하고 있으며, 열매와 뿌리를 치루, 감기, 미용, 배농 등의 목적으로 사용하고 있다.In the present invention, " Heracleum moellendorffii Hance ) is a plant of Umbelliferae, a perennial plant that grows relatively commonly in mountainous areas of Korea. It is said that the root of an aquatic plant is sown in spring and it is planted in spring in October when the leaves are yellowish in July ~ September of the following year. When the leaves are yellowish, they take root and remove stem and root, Muscle aches, arthritis, back pain, and it is also used for treatment of itchy skin, swelling, headache, chills and fever. In the private sector, the young leaves of the aquarius are used for edible purposes, and the fruits and roots are used for the purpose of feces, cold, beauty, and drainage.
본 발명의 “추출물”은 어수리의 추출액 뿐 아니라 상기 추출액의 희석액이나 농축액, 상기 추출액을 건조하여 얻어지는 건조물, 상기 추출액의 조제물이나 정제물, 또는 이들의 혼합물 등, 추출액 자체 및 추출액을 이용하여 형성 가능한 모든 제형의 추출물을 포함한다. 또한, 추출액에 분획 용매, 예를 들어 헥산, 클로로포름, 에틸아세테이트, 부탄올 및 물 순서로 가한 후에 층분리한 헥산 분획물, 클로로포름 분획물, 에틸아세테이트 분획물, 부탄올 분획물 및 물 분획물도 포함될 수 있으며, 분획 용매는 이에 제한되는 것은 아니다.The " extract " of the present invention is formed by using not only an extract of an aquarium but also a diluent or concentrate of the extract, a dried product obtained by drying the extract, a preparation or a purified product of the extract, Includes extracts of all possible formulations. The extract may also contain fractionated hexane fractions, chloroform fractions, ethyl acetate fractions, butanol fractions and water fractions after addition of the fractions in the order of fraction solvent, such as hexane, chloroform, ethyl acetate, butanol and water, But is not limited thereto.
본 발명의 상기 추출물은, 상기 각각의 해당 식물의 천연, 잡종 또는 변종 식물로부터 추출될 수 있고, 식물 조직 배양물로부터도 추출이 가능하다.The extract of the present invention can be extracted from natural, hybrid, or mutant plants of the respective plants, and can also be extracted from plant tissue cultures.
본 발명의 추출물을 추출하는 방법은 특별히 제한되지 아니하며, 당해 기술 분야에서 통상적으로 사용하는 방법에 따라 추출할 수 있다. 상기 추출 방법의 비제한적인 예로는, 열수 추출법, 초음파 추출법, 여과법, 환류 추출법 등을 들 수 있으며, 이들은 단독으로 수행되거나 2 종 이상의 방법을 병용하여 수행될 수 있다. The method for extracting the extract of the present invention is not particularly limited and may be carried out according to a method commonly used in the art. Non-limiting examples of the extraction method include hydrothermal extraction, ultrasonic extraction, filtration, and reflux extraction. These may be performed alone or in combination with two or more methods.
본 발명에서 사용되는 추출용매의 종류는 특별히 제한되지 아니하며, 당해 기술 분야에서 공지된 임의의 용매를 사용할 수 있다. 상기 추출 용매의 비제한적인 예로는 물, C1 내지 C4의 무수 또는 저급 알코올, 상기 물과 저급 알코올의 혼합 용매, 아세톤, 1,3-부틸렌글리콜, 에틸아세테이트, 클로로포름으로 이루어진 군에서 선택되는 1 종 이상으로, 단독으로 2종 이상 혼합하여 사용할 수 있다. The kind of the extraction solvent used in the present invention is not particularly limited, and any solvent known in the art can be used. Non-limiting examples of the extraction solvent include water, anhydrous or lower alcohol of C 1 to C 4 , a mixed solvent of water and lower alcohol, acetone, 1,3-butylene glycol, ethyl acetate, chloroform Or a mixture of two or more of them.
본 발명에서 추출 용매로 더욱 구체적으로는 물(또는 증류수), 물과 저급 알코올의 혼합 용매를 사용할 수 있다. 상기 용매를 사용하여 어수리를 1회 이상 추출하여 용매 추출물을 제조할 수 있으며, 상기 용매 추출물을 감압 증류한 후 동결건조 또는 분무 건조하여 얻은 건조 추출물을 제조할 수 있다.More specifically, water (or distilled water), a mixed solvent of water and a lower alcohol may be used as an extraction solvent in the present invention. A solvent extract can be prepared by extracting the aquarium at least once using the above solvent, and the dry extract obtained by vacuum distillation or spray drying the solvent extract can be prepared.
본 발명의 구체적인 일 실시예에서는 물(또는 증류수)을 사용하여 어수리 추출물을 제조하거나(실시예 1), 물과 에틸 알코올의 혼합 용매를 이용하여 어수리 추출물을 제조하였다(실시예 2). In one specific embodiment of the present invention, an aqua extract is prepared using water (or distilled water) (Example 1) or a mixed solvent of water and ethyl alcohol (Example 2).
본 발명의 추출물은 부유하는 고체 입자를 제거하기 위해 여과, 예를 들어 나일론 등을 이용해 입자를 걸러내거나 냉동여과법 등을 이용해 여과한 후, 그대로 사용하거나 이를 동결건조, 열풍건조, 분무건조 등을 이용해 건조시켜 사용할 수 있다.In order to remove suspended solid particles, the extract of the present invention may be filtered using a filter, for example, nylon or the like, filtered using a freeze filtration method or the like, and then used as it is or may be directly used by freeze drying, hot air drying, spray drying And dried.
본 발명에서, “스트레스성 질환”은 스트레스에 기인한 정신 질환, 예를 들어, 무기력증, 우울, 불안 장애, 권태 뿐 아니라 신체적 증상, 예를 들어 피로감, 소화 불량, 호흡 곤란 등을 모두 포함할 수 있다. 구체적으로는 우울증 또는 불안 장애일 수 있다.In the present invention, the term " stress disorder " may include not only psychological diseases caused by stress such as lethargy, depression, anxiety disorder, boredom but also physical symptoms such as fatigue, indigestion, dyspnea have. Specifically, it may be depression or anxiety disorder.
본 발명 일 실시예에서는 일반 운동 활성 검사를 통해 불안 증세 완화 효과가 우수함을 확인하였다(도 2). 또한, 꼬리 매달기 검사를 통해 어수리 추출물을 투여한 마우스의 경우 움직인시간이 현저히 증가된 것을 확인함으로써 어수리 추출물이 항우울 효과를 나타냄을 확인하였다(도 3). In one embodiment of the present invention, it was confirmed that an effect of alleviating anxiety was excellent through a general locomotor activity test (Fig. 2). In addition, it was confirmed that the mouse administered with the aquatic extract through the tail suspension test significantly increased the moving time, thereby confirming that the aquatic extract had an antidepressant effect (Fig. 3).
본 발명의 약학적 조성물은 사용형태에 따라 과립제, 산제, 시럽제, 액제, 현탁제, 전제, 침제, 정제, 좌제, 주사제, 주정제, 캅셀제, 환제, 연질 또는 경질 젤라틴 캅셀 등일 수 있다. 더 나아가 본 발명의 치료용 조성물은 당해 기술 분야의 공지된 적절한 방법을 사용하여 또는 레밍턴의 문헌(Remington's Pharmaceutical Science(최근판), Mack Publishing Company, Easton PA)에 개시되어 있는 방법을 이용하여 제형화 될 수 있다.The pharmaceutical composition of the present invention may be a granule, a powder, a syrup, a liquid, a suspension, an agent, an infusion, a tablet, a suppository, an injection, a main tablet, a capsule, a pill, a soft or hard gelatin capsule and the like. Further, the therapeutic compositions of the present invention may be formulated using methods known in the art or as disclosed in Remington ' s Pharmaceutical Sciences (recent edition), Mack Publishing Company, Easton PA) .
나아가, 어수리 추출물을 포함하는 약학적 조성물의 제조에 있어서, 통상적으로 사용되는 적절한 담체, 부형제 및 희석제를 더욱 포함할 수 있으며, 어수리 추출물은 약학적 조성물 총 중량에 대하여 0.01 내지 90중량%, 보다 구체적으로 0.1 내지 50중량% 포함될 수 있다.Further, the pharmaceutical composition may further comprise an appropriate carrier, excipient and diluent which are conventionally used in the preparation of a pharmaceutical composition containing an aquatic extract, wherein the aquatic extract is present in an amount of 0.01 to 90% by weight, 0.1 to 50% by weight.
상기 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸 히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제될 수 있다. Examples of the carrier, excipient and diluent which may be included include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose , Microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, it can be prepared using diluents or excipients such as fillers, extenders, binders, humectants, disintegrants, surfactants and the like which are usually used.
경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 추출액에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(calcium carbonate), 수크로스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제될 수 있다. 또한 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용될 수 있다. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose ) Or lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used.
경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당될 수 있으며, 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. Examples of liquid formulations for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, .
비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함될 수 있다. 비수성용제, 현탁제로는 프로필렌글리콜, 폴리에틸렌글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다.Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like.
좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.As a base for suppositories, witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like can be used.
본 발명 조성물의 투여량은 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 적절히 선택 또는 변형될 수 있다. 바람직하게는 본 발명의 치료용 조성물은 어수리 추출물의 양을 기준으로 1일 0.0001 내지 1000mg/kg으로, 보다 효과적이기 위해서는 0.01 내지 100mg/kg으로 투여될 수 있다. 투여횟수는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다. 상기 투여량과 투여횟수는 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.The dosage of the composition of the present invention may be appropriately selected or modified depending on the condition and body weight, degree of disease, drug form, administration route and period. Preferably, the therapeutic composition of the present invention may be administered at a dose of 0.0001 to 1000 mg / kg per day based on the amount of the aquatic extract, and preferably 0.01 to 100 mg / kg per day to be more effective. The number of administrations may be administered once a day or divided into several administrations. The dose and the number of administrations do not limit the scope of the present invention in any aspect.
본 발명의 다른 일 측면은 어수리 추출물을 포함하는, 스트레스성 질환의 개선을 위한 식품 조성물을 제공한다. 구체적으로, 상기 어수리 추출물은 항스트레스 및 항우울 효과를 나타태며, 이는 상기 설명된 바와 같다.Another aspect of the present invention provides a food composition for improving a stress disorder, comprising an aquatic extract. Specifically, the aquatic extract has antistress and antidepressant effects, as described above.
상기 식품 조성물은 영양소를 한 가지 또는 그 이상 함유하고 있는 천연물 또는 가공품을 의미하며, 어느 정도의 가공 공정을 거쳐 직접 먹을 수 있는 상태가 된 것으로 건강기능식품, 음료, 식품 첨가제 및 음료 첨가제를 모두 포함한다. 상기 식품에는 통상적으로 사용되는 적절한 담체, 부형제 및 희석제를 더욱 포함할 수 있다.The food composition means a natural product or a processed product containing one or more nutrients and can be directly eaten through a certain degree of processing. It includes all kinds of health functional foods, beverages, food additives and beverage additives do. The food may further comprise suitable carriers, excipients and diluents conventionally used.
본 발명에서 식품 조성물은 특히 구체적으로, 건강기능식품일 수 있다. '건강기능식품' 이란, 물리적, 생화학적, 생물공학적 수법 등을 이용하여 해당 식품의 기능을 특정 목적에 작용, 발현하도록 부가가치를 부여한 식품군이나 식품 조성이 갖는 생체방어리듬조절, 질병방지와 회복 등에 관한 체조절기능을 생체에 대하여 충분히 발현하도록 설계하여 가공한 식품을 말한다. In the present invention, the food composition may specifically be a health functional food. 'Health functional food' means the control of the body's defense rhythm, the prevention of disease and the restoration of the food group or the food composition that has added added value to function and express the function of the food by using physical, biochemical and biotechnological techniques. Refers to foods that are processed and designed so that their body control function is sufficiently expressed in living bodies.
또한, 본 발명의 식품 조성물 중 상기 '음료'는 갈증을 해소하거나 맛을 즐기기 위하여 마시는 것의 총칭을 의미하며 건강기능음료를 포함한다. 상기 건강기능음료는 물리적, 생화학적, 생물공학적 수법 등을 이용하여 해당 식품의 기능을 특정 목적에 작용, 발현하도록 부가가치를 부여한 식품군이나 식품 조성이 갖는 생체방어리듬조절, 질병방지와 회복 등에 관한 체조절기능을 생체에 대하여 충분히 발현하도록 설계하여 가공한 음료를 말한다.In addition, the 'beverage' in the food composition of the present invention means a generic term for drinking thirst or for enjoying a taste, and includes a health functional beverage. The above-mentioned health functional beverage includes a food group imparted with added value to function or express the function of the food by using physical, biochemical, biotechnological techniques, etc., or a food group which controls the bio- defense rhythm of the food composition, Refers to a beverage that is processed by designing the control function to be sufficiently expressed in living bodies.
상기 음료는 지시된 비율로 필수 성분으로서 상기 어수리 추출물을 유효성분으로 포함하는 것 외에 다른 성분에는 특별한 제한이 없으며, 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 포함할 수 있다.The beverage is not particularly limited as long as it contains the aquatic extract as an active ingredient as an essential ingredient at the indicated ratio, and may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages .
상기의 천연 탄수화물의 예는 모노사카라이드, 예를 들어 포도당, 과당 등 디사카라이드, 예를 들어 말토스, 수크로스 등 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 소르비톨, 에리트리톨 등의 당알코올이다. 상기한 것 이외의 향미제로서 천연 향미제(타우마틴, 스테비아 추출물(예를 들어 레바우디오시드 A, 글리시르히진 등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 식품 조성물 100㎖ 당 일반적으로 약 1 내지 20g, 보다 구체적으로는 5 내지 12g일 수 있다. 그 밖에 본 발명의 조성물은 천연 과일 주스, 과일 쥬스 음료, 야채 음료의 제조를 위한 과육을 추가로 함유할 수 있다.Examples of such natural carbohydrates include monosaccharides such as disaccharides such as glucose and fructose such as maltose, sucrose and the like and polysaccharides such as dextrins, cyclodextrins and the like, and Xylitol, sorbitol, and erythritol. Natural flavors (tau martin, stevia extract (e.g., rebaudioside A, glycyrrhizin, etc.) and synthetic flavors (saccharin, aspartame, etc.) can be advantageously used as flavors other than those described above The ratio of the natural carbohydrate may be generally about 1 to 20 g, more specifically 5 to 12 g, per 100 ml of the food composition of the present invention. In addition, the composition of the present invention may be natural fruit juice, fruit juice drink, Of the pulp of the present invention.
상기 외에 본 발명의 식품 또는 음료는 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 이러한 성분을 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 어수리 추출물 100 중량부 당 0 내지 20 중량부 범위에서 선택될 수 있으나 이에 제한되는 것은 아니며, 필요에 따라 적절히 변형하여 사용할 수 있다.In addition to the above, the food or beverage of the present invention may contain flavoring agents such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and aging agents (cheese, chocolate etc.), pectic acid and its salts, And salts thereof, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like. These components can be used independently or in combination. The proportion of such an additive may be selected from the range of 0 to 20 parts by weight per 100 parts by weight of the aquatic extract, but is not limited thereto and may be suitably modified and used as necessary.
본 발명의 어수리 추출물은 우수한 항스트레스 및 항우울 효과를 나타내면서도 운동 기능에는 영향을 미치지 않아 안전성이 우수함에 따라 스트레스성 질환에 대한 치료제 및 개선을 위한 식품으로 활용될 수 있다. The aquatic extract of the present invention exhibits excellent anti-stress and anti-depressant effects, but does not affect the exercise function, and thus has excellent safety, and thus can be used as a therapeutic agent for stress-related diseases and as a food for improvement.
본 발명의 효과는 상기한 효과로 한정되는 것은 아니며, 본 발명의 상세한 설명 또는 청구범위에 기재된 발명의 구성으로부터 추론 가능한 모든 효과를 포함하는 것으로 이해되어야 한다.It should be understood that the effects of the present invention are not limited to the effects described above, but include all effects that can be deduced from the description of the invention or the composition of the invention set forth in the claims.
도 1은 보행 활동량을 평가한 일반 운동 활성 검사 결과를 나타낸 것이다.
도 2는 항스트레스 및 항우울 효과를 평가한 일반 운동 활성 검사 결과를 나타낸 것이다.
도 3은 항우울 효과를 평가한 강제수영 검사 결과를 나타낸 것이다.FIG. 1 shows the results of the general motility test that evaluated the amount of gait activity.
FIG. 2 shows the result of the general motility test that evaluated anti-stress and anti-depressant effects.
Figure 3 shows the result of a forced swimming test evaluating the antidepressant effect.
이하, 본 발명을 실시예에 의해 상세히 설명한다. 단, 하기 실시예는 본 발명을 예시하는 것일 뿐, 본 발명이 하기 실시예에 의해 한정되는 것은 아니다.Hereinafter, the present invention will be described in detail by way of examples. However, the following examples are illustrative of the present invention, and the present invention is not limited by the following examples.
실시예 1. 어수리 추출물의 제조Example 1 Preparation of an Aquatic Extract
1-1. 물 용매를 이용한 열수 추출법1-1. Hot water extraction method using water solvent
건조 후 분쇄한 어수리 100g을 1 리터의 증류수에 가하여 잘 교반한 다음 90 내지 95℃를 유지하는 추출온도에서 3시간 동안 환류 추출하였다. 이 후 여액을 분리하고 55~65℃에서 추출물을 감압 농축한 후, 동결 건조시켜 분말 엑기스 21.2g을 얻었다.After drying, 100 g of the ground fishes were added to 1 liter of distilled water, stirred well, and then subjected to reflux extraction at an extraction temperature of 90 to 95 캜 for 3 hours. After that, the filtrate was separated, and the extract was concentrated under reduced pressure at 55 to 65 ° C and then lyophilized to obtain 21.2 g of powdery extract.
1-2. 물-알코올 혼합용매를 이용한 열수 추출법1-2. Hot water extraction method using water-alcohol mixed solvent
건조 후 분쇄한 어수리 100g을 1 리터의 25% 에틸 알코올을 가해 잘 교반한 다음, 열을 가해 80 내지 90℃를 유지하는 추출온도에서 3시간 동안 환류 추출하였다. 이 후 여액을 분리하고 55~65℃에서 추출물을 감압 농축한 후, 동결 건조시켜 분말 엑기스 19.5g을 얻었다.After drying, 100 g of the ground fishes were mixed with 1 liter of 25% ethyl alcohol and stirred well. The mixture was heat-refluxed at an extraction temperature of 80 to 90 ° C for 3 hours. After that, the filtrate was separated, and the extract was concentrated under reduced pressure at 55 to 65 ° C and then lyophilized to obtain 19.5 g of powdery extract.
실험예 1. 실험 동물의 준비Experimental Example 1. Preparation of experimental animals
7 주령의 C57BL/6 수컷 마우스를 (주)오리엔트바이오(경기도 성남시 중원구 상대원동 143-1번지)에서 공급받아 경희의료원 동물 사육실에서 1 주일 이상 사육하여 적응시켜 사용하였으며, 물과 사료는 자유롭게 섭취하도록 하였고, 온도(23 ± 2 ℃), 습도(55 ± 10 %) 및 명암주기는 12시간 간격으로 자동조절 되도록 하였다. 각 실험마다 1 군당 10 내지 12 마리의 마우스를 사용하였다.Seven-week-old C57BL / 6 male mice were supplied from Orient Bio Co., Ltd. (143-1, Jungwon-dong, Jungwon-gu, Seongnam-si, Gyeonggi-do) and used for adaptation for more than one week in Kyunghee Medical Center animal feeding room. Water and feed were freely consumed , Temperature (23 ± 2 ° C), humidity (55 ± 10%) and light intensity were automatically adjusted at intervals of 12 hours. For each experiment, 10 to 12 mice per group were used.
실험예 2. L-AAA 유도 우울증 동물모델 제작Experimental Example 2. Production of an animal model of L-AAA induced depression
별아교세포에 특이적 독성 물질인 L-AAA를 마우스 뇌의 변연전 피질(prelimbic cortex)에 주입하면 지역 특이적으로 별아교세포를 없앰으로써 우울증이 유발된다는 보고에 따라 우울증 마우스 모델을 제작하였다(Banasr M, Duman RS. Glial loss in the prefrontal cortex is sufficient to induce depressive-like behaviors. Biol Psychiatry 2008 Nov 15; 64 (10): 863 -870).A depressive mouse model was constructed by injecting L-AAA, a specific toxic substance in astrocytic cells, into the preliminary cortex of the mouse brain to report depression by eliminating locally specific astrocytes (Banasr M , Duman RS, Glial loss in the prefrontal cortex is sufficient to induce depressive-like behaviors. Biol Psychiatry 2008 Nov 15; 64 (10): 863-870).
L-AAA를 주입하기 전에 가이드 캐뉼라(guide cannula)를 삽입 고정한 후, L-AAA를 대뇌 반구 양쪽에 총 2회를 투입하여 하여 우울증 모델을 제작하였다.A guide cannula was inserted and fixed before injection of L-AAA, and L-AAA was injected twice on both sides of the cerebral hemisphere to prepare a depression model.
이하 실험예 3 및 실험예 4에서 수행한 실험들은 모의 대조군(Sham control), 음성 대조군(Negative control), 실험군A 및 실험군B 각각에 마우스 10마리씩 배정하고 진행하였다. The experiments performed in Experimental Example 3 and Experimental Example 4 were carried out by placing 10 mice in the sham control, the negative control, the experimental group A and the experimental group B, respectively.
모의 대조군(Sham control)은 Sharm surgery후 물만 주입하고, 음성 대조군(Negative control), 실험군A 및 실험군B는 L-AAA로 우울증을 유도하였다. 그 후 음성 대조군은 물을 경구 투여하였고, 실험군 A는 어수리 추출물(도면 내 KH019) 200mg/kg, 실험군 B에는 어수리 추출물 500mg/kg을 경구 투여하였다.Sham control was injected only with water after Sharm surgery, negative control, and experimental group A and experimental group B induced depression with L-AAA. Then, water was orally administered to the negative control group, and 200 mg / kg of the avian extract (KH019 in the figure) was administered to the experimental group A and 500 mg / kg of the avian extract was administered to the experimental group B.
실험예 3. 일반 운동 활성 검사(Open field test)Experimental Example 3: Open field test
마우스의 기본적인 운동성 및 움직임을 평가하기 위하여 모의 대조군(Sham control), 음성 대조군(Negative control), 실험군A 및 실험군B 각각에 마우스 10마리씩 배정하고 일반 운동 활성 검사를 수행하였다. In order to evaluate the basic motility and movement of mice, 10 mice were assigned to each of Sham control, Negative control, Experimental group A and Experimental group B and a general motility test was performed.
모의 대조군(Sham control), 음성 대조군(Negative control), 실험군A 및 실험군B 에 해당하는 마우스 각각을 50 × 50 × 50 ㎝의 흰색 아크릴 박스에 넣고 영상추적시스템(video tracking system, smart v.2.5.21)을 이용하여 10분 동안 행동을 측정하였으며, Open field를 9등분하여 가운데 영역을 central zone으로 설정하였다. 이후 각 군의 자발 운동량을 이용한 보행 활동량을 측정하고, 그 결과를 도 1에 나타내었다.Each mouse corresponding to Sham control, Negative control, Experimental group A and Experimental group B was placed in a 50 × 50 × 50 cm white acrylic box and the video tracking system (smart v.2.5. 21) for 10 min. The open field was divided by 9 and the central zone was set as the central zone. Then, the amount of gait activity using the spontaneous momentum of each group was measured, and the results are shown in FIG.
도 1에 나타난 바와 같이, 모의 대조군, 음성 대조군, 실험군 A 및 실험군 B 모두에서 유의미한 차이가 나타나지 않음을 알 수 있었다. 이는 약물 투여로 인한 보행 활동량에는 변화가 없음을 나타내는 것으로, 약물 투여로 인해 운동 기능에 문제가 생기지 않음을 확인하였으며, 특히 어수리 추출물이 보행 활동량에는 영향을 미치지 않음을 알 수 있었다. 또한, 이를 통해 이어지는 실험 결과에 대한 신빙성을 확보하였다.As shown in FIG. 1, no significant difference was observed in the simulated control, negative control, experimental group A, and experimental group B, respectively. This indicates that there was no change in the amount of gait activity due to the drug administration. It was confirmed that the gait extract did not affect the amount of gait activity. In addition, the reliability of the subsequent experimental results is secured.
또한, Open field를 9등분하여 가운데 영역을 central zone으로 설정하고, 상기 central zone에 머무른 시간 및 진입한 횟수를 지표로 하여 불안행위를 측정함으로써 항스트레스 및 항우울 효과를 확인하였다. central zone에 마우스의 진입 횟수가 높을수록 불안 증세가 완화되는 것으로, 진입횟수가 낮을수록 불안증세가 있는 것으로 평가하였으며, 그 결과를 도 2에 나타내었다.In addition, the open field was divided into nine equal parts, the middle zone was set as the central zone, and the anticipatory and antidepressant effects were confirmed by measuring the anxiety behavior using the time spent in the central zone and the number of times of entry. The anxiety symptom was alleviated with a higher number of mouse entry into the central zone. The lower the entry number, the more anxiety was evaluated. The results are shown in FIG.
도 2에 나타난 바와 같이, 실험군 B의 경우 가운데 영역에의 진입이 현저히 높이 나타났으며, 이로부터 불안 증세 완화 효과가 우수함을 알 수 있었다. 이로부터 항스트레스 및 항우울 효과가 우수함을 확인할 수 있었다.As shown in FIG. 2, in the case of the experimental group B, the entry into the middle region was remarkably high and it was found that the effect of relieving anxiety was excellent. From these results, it was confirmed that anti-stress and anti-depressant effects were excellent.
실험예 4. 꼬리 매달기 검사(Tail suspension Test, TST)Experimental Example 4 Tail Suspension Test (TST)
어수리 추출물의 항우울 효과를 확인하기 위하여 마우스를 대상으로 꼬리 매달기 검사를 수행하였다.In order to confirm the antidepressant effect of the aquatic extracts, a tail suspension test was performed on the mouse.
구체적으로, 높이 45 cm의 모서리에 접착력이 강한 테이프를 마우스의 꼬리 끝 1 내지 2 cm에 붙여서 마우스를 매달아 마우스의 움직이는 시간 측정을 통해 항우울 활성을 평가하였다. 디지털카메라를 사용하여 6분 동안 마우스의 움직임을 촬영하였으며, 6분 동안 마우스가 움직인 시간을 측정하고, 그 결과를 도 3에 나타내었다.Specifically, an anti-depressant activity was evaluated by measuring the moving time of the mouse by attaching a tape having a high adhesive strength to the edge of 45 cm in height at 1 to 2 cm of the tail end of the mouse and suspending the mouse. The movement of the mouse was photographed for 6 minutes using a digital camera, the time for which the mouse was moved for 6 minutes, and the result is shown in FIG.
도 3에 나타난 바와 같이, 실험군 B의 경우 음성 대조군에 비해 움직인 시간이 현저히 증가하였는 바, 이로부터 어수리 추출물의 항우울 효과가 우수함을 알 수 있었다. As shown in FIG. 3, in the experimental group B, the moving time was significantly increased as compared with the negative control group, and it was found that the antidepressant effect of the aqua extract was excellent.
상기 실험들을 통해 본 발명의 어수리 추출물은 항스트레스 및 항우울 효과를 나타냄으로써 스트레스성 질환, 특히 우울증 및 불안 장애에 대해 치료 및 개선효과를 나타낼 수 있음을 확인하였다. Through the above experiments, it was confirmed that the aquatic extract of the present invention exhibits antistress and antidepressant effects, and thus it can exhibit a therapeutic and improving effect on stress diseases, especially depression and anxiety disorders.
이는 본 발명의 조성물이 알코올성 뇌신경계 질환에 대한 치료제 및 개선을 위한 식품으로 활용될 수 있으며, 나아가 알코올에 의해 감소된 인지력을 개선시킬 수 있는 바, 숙취 해소용 조성물로도 활용될 수 있음을 나타내는 것이다.This indicates that the composition of the present invention can be used as a therapeutic agent for alcoholic brain nervous system diseases and as a food for improvement and further can be used as a composition for relieving hangover since it can improve cognitive power reduced by alcohol will be.
전술한 본 발명의 설명은 예시를 위한 것이며, 본 발명이 속하는 기술분야의 통상의 지식을 가진 자는 본 발명의 기술적 사상이나 필수적인 특징을 변경하지 않고서 다른 구체적인 형태로 쉽게 변형이 가능하다는 것을 이해할 수 있을 것이다. 그러므로 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적이 아닌 것으로 이해해야만 한다. 예를 들어, 단일형으로 설명되어 있는 각 구성 요소는 분산되어 실시될 수도 있으며, 마찬가지로 분산된 것으로 설명되어 있는 구성 요소들도 결합된 형태로 실시될 수 있다.It will be understood by those skilled in the art that the foregoing description of the present invention is for illustrative purposes only and that those of ordinary skill in the art can readily understand that various changes and modifications may be made without departing from the spirit or essential characteristics of the present invention. will be. It is therefore to be understood that the above-described embodiments are illustrative in all aspects and not restrictive. For example, each component described as a single entity may be distributed and implemented, and components described as being distributed may also be implemented in a combined form.
본 발명의 범위는 후술하는 청구범위에 의하여 나타내어지며, 청구범위의 의미 및 범위 그리고 그 균등 개념으로부터 도출되는 모든 변경 또는 변형된 형태가 본 발명의 범위에 포함되는 것으로 해석되어야 한다.The scope of the present invention is defined by the appended claims, and all changes or modifications derived from the meaning and scope of the claims and their equivalents should be construed as being included within the scope of the present invention.
Claims (6)
상기 식품 조성물은 건강기능식품인 것인, 식품 조성물.5. The method of claim 4,
Wherein the food composition is a health functional food.
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KR20200122778A (en) | 2019-04-19 | 2020-10-28 | 재단법인 경북바이오산업연구원 | Pharmaceutical composition comprising the extract of heracleum moellendorffi as an effective component for prevention or treatment of thrombosis and health functional food comprising the same |
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