KR100646594B1 - Composition comprising the extract of C. cassia PRESL having anti-anxiety activity - Google Patents
Composition comprising the extract of C. cassia PRESL having anti-anxiety activity Download PDFInfo
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- KR100646594B1 KR100646594B1 KR1020040079325A KR20040079325A KR100646594B1 KR 100646594 B1 KR100646594 B1 KR 100646594B1 KR 1020040079325 A KR1020040079325 A KR 1020040079325A KR 20040079325 A KR20040079325 A KR 20040079325A KR 100646594 B1 KR100646594 B1 KR 100646594B1
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- South Korea
- Prior art keywords
- anxiety
- broiler
- extract
- water
- crude extract
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- A23V2200/00—Function of food ingredients
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- A23V2200/322—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the nervous system or on mental function
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- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
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- A—HUMAN NECESSITIES
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- A61K2236/30—Extraction of the material
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- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
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Abstract
본 발명은 항불안 활성을 갖는 육계 추출물 및 이를 함유하는 조성물에 관한 것으로, 본 발명의 육계 추출물은 다양한 뇌신경계의 이상으로 인한 불안증을 예방 및 치료하는 효과를 갖는 의약품 및 건강기능식품으로 이용될 수 있다.The present invention relates to a broiler extract having anti-anxiety activity and a composition containing the same, the broiler extract of the present invention can be used as a medicine and health functional food having the effect of preventing and treating anxiety caused by various abnormalities of the cranial nervous system. have.
항불안, 불안증, 육계, 약학 조성물, 건강기능식품Anti-anxiety, anxiety, broiler, pharmaceutical composition, dietary supplement
Description
도 1은 마우스의 십자 미로 측정에서 육계 조추출물의 항불안 효과를 나타낸 도로서, 육계 조추출물의 농도별 투여에 따른 열린 길에서 머문 시간(도 1a) 및 열린 길로 들어간 횟수(도 1b)를 나타낸 도이며,1 is a diagram showing the anti-anxiety effect of broiler crude extract in the cross maze measurement of the mouse, showing the time stayed on the open road (Fig. 1a) and the number of times entered the open road (Fig. Degrees,
도 2는 마우스의 십자 미로 측정에서 육계 조추출물의 반복 투여시의 경우에 육계 조추출물의 농도별 투여에 따른 열린 길에서 머문 시간(도 2a), 열린 길로 들어간 횟수(도 2b)를 나타낸 도이며,2 is a view showing the time stayed on the open road (Fig. 2a), the number of times entered the open road (Fig. 2b) according to the concentration of the broiler crude extract in the case of repeated administration of broiler crude extract in the cross maze measurement of the mouse; ,
도 3은 마우스의 십자 미로 측정에서 육계 분획물의 농도별 투여에 따른 열린 길에서 머문 시간(도 3a), 열린 길로 들어간 횟수(도 3b)를 나타낸 도이며,Figure 3 is a diagram showing the time stayed on the open road (Fig. 3a), the number of times entered the open road (Fig. 3b) according to the concentration of broiler fraction in the cross maze measurement of the mouse,
도 4는 마우스에 5HT1a 수용체의 길항제 투여시 육계 조추출물의 항불안 효과를 나타낸 도로서, 열린 길에서 머문 시간(도 4a), 열린 길로 들어간 횟수(도 4b)를 나타낸 도이다.4 is a diagram showing the anti-anxiety effect of broiler crude extract when the antagonist of the 5HT1a receptor is administered to the mouse, showing the time stayed on the open road (Fig. 4a), the number of times the open road (Fig. 4b).
본 발명은 항불안 활성을 갖는 육계 추출물 및 이를 함유하는 조성물로서, 다양한 뇌신경계의 이상으로 인한 불안증을 예방 및 치료하는 약학조성물 및 건강 기능 식품에 관한 것이다.The present invention relates to a pharmaceutical composition and a dietary supplement for preventing and treating anxiety caused by abnormalities of various cranial nervous systems as a broiler extract having anti-anxiety activity and a composition containing the same.
최근 경제성장률이 하락하면서 우울 또는 불안을 느끼는 사람들이 늘어나고 이혼과 자녀문제 등 급격히 변하는 가족 관계와 관련하여 우울증 또는 불안증 환자가 급증하고 있는 추세이다. 불안(anxiety)이란, 광범위하게 매우 불쾌한, 그리고 막연히 불안한 느낌으로, 관련된 신체 증상(가슴 두근거림, 진땀 등)과 행동 증상 (과민성, 서성댐 등)을 동반하는 것이다(Robert F. Scmidt., Human Physiology, pp366; 민성길, 최신 정신 의학, pp238-40; Argyropoulos S.V., et al., Pharmacol. Ther. 88, pp213-27, 2000). 우울증 또는 불안증으로 병원에서 전문적인 정신과 상담치료를 받는 환자도 늘어나고 있으며, 2002년에는 항불안제의 매출도 약 200% 정도 늘어났다고 한다. 이처럼 우울증 또는 불안증은 현대인의 정신질환 중 대부분을 차지한다고 해도 과언이 아니며, 많은 사람들이 이로 인해 고통을 받고 있다.As the economic growth rate has recently declined, more and more people are feeling depressed or anxious, and the number of patients with depression or anxiety is increasing in relation to rapidly changing family relationships such as divorce and child problems. Anxiety is a feeling of widespread, very unpleasant and vague anxiety, accompanied by associated physical symptoms (pumping, sweating, etc.) and behavioral symptoms (irritability, pacing, etc.) (Robert F. Scmidt., Human) Physiology , pp 366; Min Sung Gil, Modern Psychiatry , pp238-40; Argyropoulos SV, et al., Pharmacol. Ther. 88 , pp213-27, 2000). Increasingly, patients are receiving specialized psychiatric counseling at hospitals for depression or anxiety, and anti-anxiety sales increased by 200 percent in 2002. It is no exaggeration to say that depression or anxiety can account for most of the mental illnesses of modern people, and many people suffer from it.
불안이 있을 때 뇌 전체는 각성(arousal) 상태에 들어가며, 따라서 말초의 행동, 자율신경계, 감각, 지각 등에 지장이 나타난다. 주로 관계된 기관은 대뇌 변연계(특히 해마와 대상회), 대뇌 피질(전두엽, 측두엽), 시상하부, 상행망상체, 뇌하수체 등이고 말초에서는 갑상선과 부신 피질이다. 최근 뇌 영상 연구에 의하면 불안은 오른쪽 반구의 장애와 관련되며 기타 전두엽, 측두엽, 후두엽 장애와 관련되어 있다고 알려져 있다(Robert F. Scmidt., Human Physiology, pp366; 민성길, 최신 정신 의학, pp238-40).When there is anxiety, the entire brain enters an arousal state, thus disrupting peripheral behavior, autonomic nervous system, sensations, and perception. The main organs involved are the cerebral limbic system (especially the hippocampus and the subject society), the cerebral cortex (frontal lobe, temporal lobe), hypothalamus, ascending reticular body and pituitary gland. Recent brain imaging studies have shown that anxiety is associated with disorders in the right hemisphere and other frontal, temporal, and occipital lobe disorders (Robert F. Scmidt., Human Physiology , pp366; Min Sung-gil, Modern Psychiatry , pp238-40). .
불안에 대한 치료 약물의 연구는 오래된 약물의 재평가 및 적응증의 확대뿐만 아니라 새로운 약물의 개발, 특히 세로토닌 재흡수 억제제 등의 개발에 관심이 모아지고 있다. 그러나 임상적으로 유효한 항불안 약물들은 항불안의 효과뿐만 아니라 진정, 금단 현상의 유발 등의 부작용 때문에 사용에 신중을 기해야 하는 단점이 있다고 할 수 있다. Research on therapeutic drugs for anxiety has attracted interest in the development of new drugs, especially serotonin reuptake inhibitors, as well as the reevaluation of old drugs and the expansion of indications. However, clinically effective anti-anxiety drugs have the disadvantage of requiring careful use due to side effects such as sedation and withdrawal, as well as anti-anxiety effects.
이상적인 항불안약은 낮 시간에 지나친 졸음을 초래하지 않고 육체적 정신적 의존성을 일으키지 않으며 환자를 침착하게 만드는 것이다. The ideal anti-anxiety medication will not cause excessive drowsiness during the daytime, cause physical and mental dependence, and calm the patient.
현재 상용되는 대표적 항불안제는 벤조디아제핀(benzodiazepine), 디아제팜(diazepam), 옥사제팜(oxazepam), 프라제팜(prazepam), 로라제팜(lorazepam), 알프라졸람(alprazolam), 헬라제팜(helazepam), 클로나제팜(clonazepam) 등이 있으며, 이들 약물들은 주로 진정 및 수면유도의 목적으로도 사용된다(윤도준, 정신과 약물의 부작용, 대한의사협회지, 38(10), pp1196-1202, 1995). 벤조디아제핀은 가장 흔히 사용하는 항불안제로, 이 약물의 작용기전이 중추신경계에서 대표적 억제성 신경전달물질인 GABA 수용체의 친화력을 증가시켜 인접한 Cl- 통로를 더 자주 열어 Cl- 이온의 투과성을 상승시킨다고 밝혀져 있다. 이 벤조디아제핀은 효과가 즉각 나타나지만 습관성과 중독성이 단점으로 전문의의 치료에 따라 약을 사용하지 않으면 증상이 재발하거나 금단증상이 나타나며, 다른 부작용으로 졸음, 운동실조, 기립성 저혈압, 호흡억제, 두통, 만성수면장애, 간질환 등이 나타난다고 보고되고 있다(Mary J. Mycek, et al., Pharmacology 2nd edition, Lipincott Williams & Wilkins, pp89-93, 2000). Representative anti-anxiety agents currently available are benzodiazepine, diazepam, oxazepam, prazepam, lorazepam, alprazolam, helazepam, clonazepam (clonazepam), these drugs are also used primarily for the purpose of sedation and sleep (Yoon Do-jun, side effects of psychiatric drugs, Journal of the Korean Medical Association , 38 (10) , pp1196-1202, 1995). Benzodiazepines are the most commonly used anti-anxiety agents, and their mechanism of action has been shown to increase the affinity of GABA receptors, which are representative inhibitory neurotransmitters in the central nervous system, thus opening adjacent Cl − channels more often to increase Cl − ion permeability. . This benzodiazepine is effective immediately, but it is a habit and addictive disadvantage. If the medicine is not used according to the medical treatment, symptoms recur or withdrawal symptoms. Other side effects include drowsiness, ataxia, orthostatic hypotension, respiratory depression, headache, chronic Sleep disorders and liver disease have been reported (Mary J. Mycek, et al., Pharmacology 2nd edition , Lipincott Williams & Wilkins, pp89-93, 2000).
한방에서는 우울 또는 불안 및 신경과민 등을 혈허(血虛) 및 기허(氣虛) 혹은 간(肝), 심(心), 비(脾)에 열(熱)에 의한 것으로 인식하고 있으며, 이러한 원인에 의해 우울, 불안, 불면, 다몽, 공포, 경련, 광란, 번조 등이 나타난다고 알려져 있다. 또한 장조(臟躁), 기역(氣逆), 분돈기(奔豚氣), 경계(驚悸) 등의 증상이 나타나는 경우를 주로 공황장애로 분류한다. 강력한 스트레스에 대하여 현저한 정신장해가 일어난 경우에 기란 (氣亂)이라고도 하여 현대 의학의 우울증 또는 불안증 범주에 포함시키고 있다. Oriental medicine recognizes depression, anxiety, and nervousness as being caused by fever in the blood and blood, or liver, heart, and rain. It is known that depression, anxiety, insomnia, dreams, fears, cramps, frenzy, falsification. In addition, symptoms such as major (臟 躁), air force (氣 逆), dividers (경계), alert (驚悸) is mainly classified as a panic disorder. Significant mental disorders in response to strong stress, also called giran, are included in the category of depression or anxiety in modern medicine.
이러한 정신 신경계 질환을 주로 안신약물(安神藥物)이라는 약물군으로 치료하는데, 이러한 약물은 우울 또는 불안을 감소시키며, 진정최면 작용 및 항경련 작용이 있다. 이 치료법에 대해서 한방의약학에서는 놀라거나 공포감, 우울감, 불안감 등이 나타나는 경우에 심신 안정법을 사용하여 진정시킴으로써 치료할 수 있다고 보고 있다. 안신약물에 속하는 약물들은 각각 약물들 고유의 특성이 있기는 하지만 공통적으로 신경 안정의 효능을 갖는다고 알려져 있다(송본극산(松本克産), 신경증의 동의학적 고찰, 동양의학, pp65-8, 1986). These mental nervous system diseases are mainly treated with a drug group called anxin drug (安神 藥物), which reduces depression or anxiety, and has a sedative hypnotic and anticonvulsive effect. About this treatment, herbal medicine says that it can be cured by using mental and physical stabilization in case of surprise, fear, depression or anxiety. Drugs belonging to Ahnsin are known to have the effect of nerve stabilization, although they have their own characteristics (Songbon polar acid, synergistic consideration of neurosis, Oriental Medicine , pp65-8, 1986) ).
안신 작용을 갖는 약물에 대한 신경 약리학적 연구가 많이 보고되어 있는데, 특히 산조인(Zyziphus jujuba Mill., 酸棗仁)은 저용량에서는 항불안 효과를 나타 내며 고용량에서는 진정 작용을 가진다고 알려져 있으며(Wu S.X., et al., China Journal of Chinese Materia Medica., 18, pp685-704), 안신 약물군 외에도 천마 (Gastrodia elata Blume., 天麻)는 마우스를 이용한 연구에서 자발운동량의 감소 및 펜토바비탈(phentobarbital)에 의해 유도된 수면의 연장 작용 등 진정작용을 가진다고 알려져 있다(Huang J.H., Yi Xue Ke Xue Yuan Xue Bao., 11, pp147-50, 1989). Numerous neuropharmacological studies have been reported on drugs with antagonism . In particular, Sanjoin ( Zyziphus jujuba Mill., 酸棗仁 ) is known to have anti-anxiety effects at low doses and to be sedative at high doses (Wu SX, et. al., China Journal of Chinese Materia Medica ., 18 , pp685-704), In addition to the Anxin drug group, Gastrodia elata Blume. (天麻) was induced by reduction of spontaneous momentum and phentobarbital in mouse studies. It is known to have sedative effects such as prolonged sleep (Huang JH, Yi Xue Ke Xue Yuan Xue Bao. , 11 , pp147-50, 1989).
본 발명에서 사용한 육계는 육계나무(Cinnamomum loueirii NEES) 또는 계피나무(C. cassia PRESL)의 간피(幹皮) 또는 지피(枝皮)이다. 계피나무의 껍질에는 정유(cassa oil) 1 내지 2 %가 함유되어 있고 그 중요성분은 계피(桂皮) 알데히드(aldehyde)로 75 내지 90%, 또 소량의 계피 알코올 초산(醋酸) 에스테르(ester), 페닐프로파놀(phenylpropanol) 초산 에스테르 등이다. 또한 점액, 탄닌(tannin)등이 함유되어 있다. 육계는 중추신경계에 작용하고, 하압작용, 주혈흡충병(住血吸蟲病)의 예방작용 또한 계피유에는 강한 항균작용이 있다(정보섭, 신민교저, 향약대사전, 영림사, pp453-455, 1998).The broiler used in the present invention is the bark or ground skin of Cinnamomum loueirii NEES or C. cassia PRESL. The bark of cinnamon contains 1 to 2% of essential oil (cassa oil), the main component of which is 75 to 90% of cinnamon aldehyde, a small amount of cinnamon alcohol acetic acid ester, Phenylpropanol acetate ester and the like. It also contains mucus, tannins, etc. Broilers are acting on the central nervous system, and haap action, preventive action of juhyeol fluke disease (住血吸蟲病) cinnamon oil also has a strong antibacterial activity (jeongboseop, sinmingyo low, hyangyak Dictionary, Younglim four, pp453-455, 1998).
본 발명에서는 육계 추출물이 마우스에서 항불안 효과를 나타나며, 또한 육계의 항불안 효과가 5HT1a 수용체의 활성을 통하여 나타난다는 것을 확인함으로써, 본 발명을 완성하였다.In the present invention, the broiler extract showed anti-anxiety effect in the mouse, and further confirmed that the anti-anxiety effect of broiler appears through the activity of the 5HT1a receptor, the present invention was completed.
본 발명은 항불안 효능을 갖는 육계 추출물 및 이를 유효성분으로 함유하는 다양한 뇌신경계의 이상으로 인한 불안증의 예방 및 치료를 위한 약학조성을 제공하는 것이다.
The present invention is to provide a pharmaceutical composition for the prevention and treatment of anxiety caused by the abnormality of various cranial nervous system containing the broiler extract and anti-anxiety effect as an active ingredient.
상기 목적에 따라, 본 발명은 항불안 활성을 갖는 육계 조추출물을 포함하고 약학적으로 허용 가능한 담체, 희석제 또는 부형제를 포함하는 뇌신경계 관련 불안증의 예방 및 치료용 약학 조성물을 제공한다.In accordance with the above object, the present invention provides a pharmaceutical composition for the prevention and treatment of cerebral nervous system-related anxiety, comprising a broiler crude extract having anti-anxiety activity and a pharmaceutically acceptable carrier, diluent or excipient.
상기 조추출물은 물, 탄소수 1 내지 4의 저급알코올 및 이들의 혼합용매로부터 선택된 극성용매, 바람직하게는 물에 가용한 추출물을 포함한다.The crude extract includes water, a lower alcohol having 1 to 4 carbon atoms, and a polar solvent selected from a mixed solvent thereof, preferably an extract soluble in water.
또한, 본 발명은 항불안 활성을 갖는 육계의 극성용매 가용추출물을 포함하고 약학적으로 허용 가능한 담체, 희석제 또는 부형제를 포함하는 뇌신경계 관련 불안증의 예방 및 치료용 약학 조성물을 제공한다.The present invention also provides a pharmaceutical composition for the prevention and treatment of cerebral nervous system-related anxiety, comprising a soluble extract of a polar solvent having an anti-anxiety activity and comprising a pharmaceutically acceptable carrier, diluent or excipient.
상기 극성용매 가용추출물은, 상기 조추출물로부터 비극성용매 가용부를 제외한 추출물로서, 물, 탄소수 1 내지 4의 저급 알코올 및 이들의 혼합용매로부터 선택된 극성용매, 바람직하게는 물 또는 저급알코올, 좀더 바람직하게는 물에 가용한 추출물을 포함한다.The polar solvent soluble extract is an extract excluding the non-polar solvent soluble part from the crude extract, and a polar solvent selected from water, a lower alcohol having 1 to 4 carbon atoms and a mixed solvent thereof, preferably water or lower alcohol, more preferably Contains extracts soluble in water.
이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
본 발명의 육계 추출물은 음건하여 세절한 육계를 그 중량의 약 1 내지 10 배, 바람직하게는 약 2 내지 5배 부피의 물, 탄소수 1 내지 4의 저급 알코올 또는 이들의 약 1:0.1 내지 1:10, 바람직하게는 1:0.2 내지 1:3의 혼합비를 갖는 혼합용매로 20 내지 100℃, 바람직하게는 30 내지 70℃의 추출 온도에서 약 1 시간 내지 2일, 바람직하게는 2 시간 내지 1일 동안 열수 추출, 환류냉각 추출, 초음파 추출 등의 추출방법, 바람직하게는 초음파 추출의 추출방법으로 1회 내지 5회, 바람직하게는 2회 내지 3회 반복하여 추출물을 수득한 후, 감압여과하고 여과한 추출물을 혼합하여 회전진공농축기로 20 내지 100℃, 바람직하게는 50 내지 70℃에서 감압 농축하여 용매를 제거하여 물, 탄소수 1 내지 4의 저급 알코올 또는 이들의 혼합용매에 따른 가용추출물인 조추출물을 얻을 수 있다.The broiler extract of the present invention is dried and dried broiler broiler about 1 to 10 times, preferably about 2 to 5 times the volume of water, lower alcohol having 1 to 4 carbon atoms or about 1: 0.1 to 1: 10, preferably a mixed solvent having a mixing ratio of 1: 0.2 to 1: 3 at an extraction temperature of 20 to 100 ° C, preferably 30 to 70 ° C, for about 1 hour to 2 days, preferably 2 hours to 1 day Extraction methods such as hot water extraction, reflux cooling extraction, and ultrasonic extraction, preferably by extraction method of ultrasonic extraction, are repeated once to five times, preferably two to three times, followed by filtration under reduced pressure and filtration. One extract was mixed and concentrated under reduced pressure at 20 to 100 ° C., preferably at 50 to 70 ° C., using a rotary vacuum concentrator to remove the solvent, thereby obtaining crude extract which is a soluble extract according to water, a lower alcohol having 1 to 4 carbon atoms or a mixed solvent thereof. To get have.
또한, 극성용매 가용추출물은 비극성 용매 가용성분 추출과정을 거친 수가용성 분획부에 약 1 내지 10배, 바람직하게는 약 1 내지 5배 부피의 부탄올을 가하여 1 내지 5회, 바람직하게는 2 내지 4회 분획하여 부탄올 가용성 분획부와 수가용성 분획부를 수득할 수 있으며, 용매 분획부를 회전 진공 농축기로 감압농축시켜 용매를 제거하여 각각의 추출물을 얻을 수 있다. In addition, the polar solvent soluble extract is 1 to 5 times, preferably 2 to 4 times by adding about 1 to 10 times, preferably about 1 to 5 times the volume of butanol to the water-soluble fraction that has undergone the extraction process of the non-polar solvent soluble component. Butanol soluble fraction and water-soluble fraction may be obtained by fractionation, and the solvent fraction may be concentrated under reduced pressure with a rotary vacuum concentrator to remove the solvent to obtain respective extracts.
또한, 극성용매 가용 추출물은 상기 추출분리 공정 이외에도, 인체에 유해한 유기용매로부터의 노출을 방지하기 위하여, 직접 상기의 조추출물에 디아니온 크로마토그래피(Dianion Chromatography)법을 수행할 수 있다. In addition, the polar solvent soluble extract, in addition to the extraction separation process, may be directly subjected to Diion Chromatography (Dianion Chromatography) to the crude extract in order to prevent exposure to harmful organic solvents.
상기 방법에서, 정지상으로 사용한 충진제는 SP207, HP20SS 또는 HP 20을 사용할 수 있으나, HP 20 충진제를 사용함이 바람직하며, In the above method, the filler used as the stationary phase may use SP207, HP20SS or HP 20, but it is preferable to use HP 20 filler,
이동상 용매로는 먼저, 극성이 가장 큰 물을 이동시킨 후, 순차적으로 극성 이 낮은 용매로 치환시키는 단계를 수행하는데, 예를 들어 물, 물:메탄올 혼합용매, 메탄올 또는 추가적으로 좀더 비극성 용매인 아세톤 등의 전개용매를 사용가능하며, 바람직하게는 메탄올을 전개용매로 하여 유출된 분획물을 수득 가능하다.As the mobile phase solvent, first, water having the highest polarity is transferred, and then a step of substituting with a solvent having a lower polarity is performed, for example, water, water: methanol mixed solvent, methanol, or acetone, which is an additional nonpolar solvent. It is possible to use a developing solvent of, and it is possible to obtain a fraction distilled off, preferably using methanol as a developing solvent.
상기의 방법을 통하여 유출된 분획물은 통상 사용하는 추출분리공정에 의한 극성용매 가용 추출물과 동일한 내지 유사한 성분상을 갖는 분획물들을 얻을 수 있으며, 이러한 분리공정을 통하여 얻는 분획물들은 인체에 유해한 유기용매로부터의 노출방지 효과, 분리공정의 단순화 등의 장점을 갖는다.Fractions spilled through the above method can be obtained fractions having the same or similar component phase as the polar solvent soluble extract by a conventional extraction separation process, fractions obtained through such separation process from organic solvents harmful to humans It has advantages such as exposure prevention effect and simplification of separation process.
따라서, 본 발명은 상기와 같은 디아니온 크로마토그래피법을 수행하여 얻어지는 분획물들을 함유한 약학 조성물을 제공한다.Accordingly, the present invention provides a pharmaceutical composition containing the fractions obtained by performing the dianion chromatography method as described above.
또한 본 발명은 항불안 활성을 갖는 육계의 조추출물로부터 상기한 바와 같은 추출분리 공정을 통한 극성용매 가용 추출물을 포함하고 약학적으로 허용 가능한 담체, 희석제 또는 부형제를 포함하는 뇌신경계 관련 불안증의 예방 및 치료용 약학 조성물을 제공한다.In another aspect, the present invention provides the prevention of cerebral nervous system-related anxiety comprising a soluble extract of a polar solvent and a pharmaceutically acceptable carrier, diluent or excipient from the crude extract of broiler having anti-anxiety activity through the extraction separation process as described above; Provided is a therapeutic pharmaceutical composition.
본 발명의 조성물은 상기 제조방법에 따라 얻어진 육계 조추출물 또는 극성용매 가용추출물을 포함한다.The composition of the present invention comprises a broiler crude extract or a polar solvent soluble extract obtained according to the production method.
본 발명의 조성물은, 조성물 총 중량에 대하여 상기 추출물을 0.1 내지 50 % 중량으로 포함한다.The composition of the present invention comprises 0.1 to 50% by weight of the extract relative to the total weight of the composition.
본 발명의 육계 추출물을 포함하는 조성물은 통상의 방법에 따른 적절한 담체, 부형제 또는 희석제를 더 포함할 수 있다. The composition comprising the broiler extract of the present invention may further comprise a suitable carrier, excipient or diluent according to conventional methods.
본 발명의 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱 스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. Carriers, excipients and diluents that may be included in the compositions of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
본 발명에 따른 추출물을 포함하는 조성물은, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 또는 멸균 주사용액의 형태로 제형화하여 사용될 수 있다. Compositions comprising extracts according to the invention are each formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories or sterile injectable solutions according to conventional methods. Can be used.
상세하게는, 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제될 수 있다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 추출물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(calcium carbonate), 수크로스(sucrose), 락토오스(lactose), 젤라틴 등을 섞어 조제될 수 있다. 또한, 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용될 수 있다. 경구를 위한 액상 제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는 데, 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제 및 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로젤라틴 등이 사용될 수 있다.Specifically, when formulated, it may be prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, and the like. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and the solid preparations may include at least one excipient such as starch, calcium carbonate, sucrose in the extract. ), Lactose, gelatin and the like can be mixed. In addition to simple excipients, lubricants such as magnesium stearate, talc can also be used. Liquid preparations for oral use include suspensions, solvents, emulsions, and syrups, and include various excipients such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. Can be. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations and suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
본 발명의 추출물은 환자의 나이, 성별, 체중에 따라 달라질 수 있으나, 일반적으로 0.01 내지 500mg/㎏의 양, 바람직하게는 0.1 내지 100mg/㎏의 양을 일일 1회 내지 수회로 나누어 투여할 수 있다. 또한 그 추출물의 투여량은 투여경로, 질병의 정도, 성별, 체중, 나이 등에 따라서 증감될 수 있다. 따라서, 상기 투여량은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.The extract of the present invention may vary depending on the age, sex, and weight of the patient, but may generally be administered in an amount of 0.01 to 500 mg / kg, preferably 0.1 to 100 mg / kg, divided once or several times daily. . In addition, the dosage of the extract can be increased or decreased depending on the route of administration, the degree of disease, sex, weight, age and the like. Therefore, the above dosage does not limit the scope of the present invention in any aspect.
본 발명의 약학 조성물은 랫트, 마우스, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁내 경막 또는 뇌혈관내(intracerebroventricular) 주사에 의해 투여될 수 있다.The pharmaceutical composition of the present invention can be administered to mammals such as rats, mice, livestock, humans, etc. by various routes. All modes of administration can be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.
본 발명의 육계 추출물은 독성 및 부작용은 거의 없으므로 예방 목적으로 장기간 복용시에도 안심하고 사용할 수 있는 약제이다. Broiler extract of the present invention is a drug that can be used with confidence even for long-term use for the purpose of prevention because there is little toxicity and side effects.
본 발명은 상기 육계 추출물 및 식품학적으로 허용 가능한 식품보조 첨가제를 포함하는 뇌신경계 관련 불안증의 예방을 위한 건강 기능 식품을 제공한다.The present invention provides a dietary supplement for the prevention of cerebral nervous system-related anxiety comprising the broiler extract and food supplements.
본 발명의 육계 추출물을 포함하는 조성물은 뇌신경계 관련 불안증의 예방을 위한 약제, 식품 및 음료 등에 다양하게 이용될 수 있다. 본 발명의 추출물을 첨가할 수 있는 식품으로는, 각종 식품류, 예를 들어, 음료, 껌, 차, 비타민 복합제, 건강보조 식품류 등이 있으며, 환제, 분말, 과립, 침제, 정제, 캡슐 또는 음료인 형태로 사용할 수 있다.The composition containing the broiler extract of the present invention can be used in various ways, such as drugs, foods and beverages for the prevention of cerebral nervous system-related anxiety. Foods to which the extract of the present invention may be added include various foods, for example, beverages, gums, teas, vitamin complexes, dietary supplements, and the like, which are pills, powders, granules, tablets, tablets, capsules or beverages. Available in form.
이때, 식품 또는 음료 중의 상기 추출물의 양은, 일반적으로 본 발명의 건강식품 조성물의 경우 전체 식품 중량의 0.01 내지 15 중량%로 가할 수 있으며, 건강 음료 조성물의 경우 100㎖를 기준으로 0.02 내지 10g, 바람직하게는 0.3 내지 1g의 비율로 가할 수 있다. At this time, the amount of the extract in the food or beverage, in general, may be added to 0.01 to 15% by weight of the total food weight in the case of the health food composition of the present invention, 0.02 to 10g, based on 100ml for the health drink composition, preferably It may be added at a ratio of 0.3 to 1g.
본원에서 정의되는 식품보조첨가제는 당업계에 통상적인 식품첨가제, 예를 들어 향미제, 풍미제, 착색제, 충진제, 안정화제 등을 포함하며 하기에 예시한다.Food supplement additives as defined herein include food additives customary in the art, such as flavorings, flavoring agents, colorants, fillers, stabilizers, and the like, and are exemplified below.
본 발명의 건강 음료 조성물은 지시된 비율로 필수 성분으로서 상기 추출물을 함유하는 외에는 액체성분에는 특별한 제한점은 없으며 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물의 예로는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린; 등과 같은 통상적인 당 및 자일리톨, 소르비톨, 에리트리톨 등의 당알콜이다. 상술한 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 조성물 100 ㎖당 일반적으로 약 1 내지 20g, 바람직하게는 약 5 내지 12g이다.The health beverage composition of the present invention has no particular limitation on the liquid component except for containing the extract as an essential ingredient in the indicated ratio, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; Polysaccharides such as dextrin, cyclodextrin; Conventional sugars such as and the like and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those described above, natural flavoring agents (tauumatin, stevia extract (e.g., Rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. have. The proportion of such natural carbohydrates is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.
상기 외에 본 발명의 조성물은 여러가지 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, 알콜, 탄산 음료에 사용되는 탄산화제 등을 함유할 수 있다. 그밖에 본 발명의 조성물들은 천연 과일 쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이러한 첨가제의 비율은 그렇게 중요하진 않지만 본 발명의 조성물 100 중량부 당 0 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof, alginic acid and salts thereof. , Organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. The compositions of the present invention may also contain pulp for the production of natural fruit juices and fruit juice beverages and vegetable beverages. These components can be used independently or in combination. The proportion of such additives is not so critical but is generally selected from the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.
이하, 본 발명을 하기의 실시예 및 실험예에 의해 상세히 설명한다.Below, The invention is illustrated in detail by the following examples and experimental examples.
단, 하기 실시예 및 실험예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실시예 및 실험예에 의해 한정되는 것은 아니다.However, the following Examples and Experimental Examples are merely illustrative of the present invention, and the content of the present invention is not limited by the following Examples and Experimental Examples.
실시예 1. 육계 조추출물의 제조Example 1 Preparation of Broiler Crude Extracts
계피나무의 껍질부위인 육계는 경동시장에서 구입하여 사용하였다. 건조된 육계 300g을 정선하여 세절한 후, 50% EtOH 3ℓ를 가하여 3시간 동안 2회 초음파 추출한 후, 이를 합하여 여과지(Whatman사, 미국)로 여과한 다음 이를 감압농축기 (EYELA사, N-1000, 일본)로 감압농축한 후, 동결건조하여 육계의 조추출물 17.4g을 수득하였다.Broiler, the bark of cinnamon, was purchased from Gyeongdong Market. 300 g of dried broilers are cut and sliced, followed by ultrasonication twice for 3 hours with 3 L of 50% EtOH. After extraction, the resultant was combined and filtered with a filter paper (Whatman, USA), and then concentrated under reduced pressure with a reduced pressure concentrator (EYELA, N-1000, Japan), and then lyophilized to obtain 17.4 g of crude extract of broilers. Obtained.
실시예 2. 디아니온 크로마토그래피(Dianion Chromatography)법을 이용한 비극성 용매 가용유출물 및 극성용매 가용유출물의 제조 Example 2 Preparation of Nonpolar Solvent Soluble and Polar Solvent Soluble Using Diion Chromatography
육계 조추출물의 분획물을 얻기 위해 디아니온(Dianion) 크로마토그래피 (Biotage, Flash 75, USA)법을 이용하여 실시예 1을 수회 반복하여 얻어진 육계 조추출물 1000g에 HP20 (Biotage, USA) 충진제로 충진시키고 이동상으로 극성이 가장 큰 물로부터 시작하여 물:메탄올(1:1)혼합용매, 극성이 낮은 메탄올을 순차적으로 유출시켜 각각의 유출물을 감압농축한 후, 동결건조하여 물 가용유출물 102g, 물:메탄올(1:1)혼합용매 가용유출물 9.6g 및 메탄올 가용유출물 5.3g을 수득하였다.To obtain a fraction of broiler crude extract, 1000 g of broiler crude extract obtained by repeating Example 1 several times using Diionion chromatography (Biotage,
참조예 1. 실험동물Reference Example 1. Experimental Animal
4주령의 ICR계 수컷 마우스(18 - 20 g)를 (주) MJ Ltd. (서울, Korea)에서 공급받아 성균관대학교 약학대학의 동물사육실에서 1주일 이상 사육하여 적응시켜 사용하였으며, 물과 사료는 자유롭게 섭취하도록 하였고, 온도 (23 ± 2 ℃), 습도 (55 ± 10 %) 및 명암주기(12 시간)는 자동으로 조절되도록 하였다. 각 실험에 1군당 8 내지 16마리의 마우스를 사용하였다.Four-week old ICR male mouse (18-20 g) was used by MJ Ltd. It was supplied from (Seoul, Korea) and used for breeding at the animal breeding room of Sungkyunkwan University College of Pharmacy for more than 1 week. The water and feed were consumed freely, and the temperature (23 ± 2 ℃) and humidity (55 ± 10%) were used. And the contrast period (12 hours) were adjusted automatically. 8-16 mice per group were used for each experiment.
실험예 1. 십자 미로 측정법에 의한 육계 조추출물의 항불안 효과Experimental Example 1. Anti-Anxiety Effect of Broiler Crude Extracts by the Cross Maze Method
마우스의 십자 미로 측정법은 53 ㎝ 높이의 십자 형태의 미로로써, 길이 30 cm, 너비 5 cm 의 사방이 개방되어 있고 마주보고 있는 두 길과 같은 길이와 너비로 중앙부위를 제외한 전 부분이 막혀있는 두 길이 25 cm2 의 중앙부위를 중심으로 교차되어 있는 미로에 마우스의 시선이 열린 길의 바깥을 향하도록 하여 놓은 후, 마우스가 자발적으로 열린 길 또는 막힌 길을 택하여 머무르도록 하여 각 길에 머 무른 시간을 일정시간(5분) 동안의 불안증상을 측정하였다. 마우스에 실시예 1에서 수득한 육계 조추출물 500, 750, 1000 ㎎/㎏ 또는 용매를 각각 경구 투여하여 1 시간 후 카메라를 이용하여 실시간 측정하였다. The cross-maze of the mouse is a 53-cm-high cross-shaped labyrinth that is open at 30 cm in length and 5 cm in width, and has two sides with the same length and width as the two paths facing each other except the central part. Place the gaze of the mouse in the labyrinth that intersects the central part of
상기 실험 수행의 결과 십자 미로 측정법에서 용매를 투약한 군과 비교하여 육계 조추출물 750 ㎎/㎏을 투약한 군에서 93 % 의 유의한 증가를 보임으로써 항불안 효과를 확인할 수 있었다(*P<0.05)(참조 도 1a). As a result of the experiment, the anti-anxiety effect was confirmed by showing a significant increase of 93 % in the group administered with broiler
또한, 마우스의 열린 길로 들어간 횟수를 확인하기 위하여 상기와 동일한 실험 방법을 수행하여 관찰한 결과, 도 1b에서 나타난 바와 같이 육계 조추출물 750 ㎎/㎏을 투약한 군에서 10.2번의 열린 길로 들어간 횟수를 보임으로써 육계 조추출물의 항불안 효과를 확인하였다.In addition, as a result of performing the same experimental method as described above to confirm the number of times entered into the open path of the mouse, as shown in Figure 1b shows the number of times entered into the open path of 10.2 times in the group administered 750 mg / kg of broiler crude extract The anti-anxiety effect of broiler crude extract was confirmed.
실험예 2. 십자 미로 측정법에 의한 육계 조추출물의 반복 투여시 항불안 효과Experimental Example 2. Anti-anxiety effect of repeated administration of broiler crude extract by cross maze method
육계 조추출물의 반복 투여시에 마우스의 항불안 효과를 시험하기 위하여 상기 실시예 1과 동일한 실험 방법을 수행하였다. 다만, 여기서는 마우스에 육계 조추출물을 50, 100 ,200 ㎎/㎏을 1일 1회에 걸쳐, 5일 동안 경구 투여한 후에 상기 실험을 수행하였다.In order to test the anti-anxiety effect of mice upon repeated administration of broiler crude extract, the same experimental method as in Example 1 was performed. Here, the experiment was performed after oral administration of 50, 100, 200 mg / kg broiler crude extract to the mice once a day for 5 days.
상기 실험 수행의 결과, 도 2a에서 나타난 바와 같이 용매를 투약한 군과 비교하여 육계 100 mg을 투여한 군에서 173%의 유의한 증가를 보임으로써 항불안 효과를 확인할 수 있었다.As a result of the experiment, the anti-anxiety effect was confirmed by showing a significant increase of 173 % in the group administered 100 mg of broiler as compared to the group administered with the solvent as shown in Figure 2a.
또한, 마우스의 열린 길로 들어간 횟수를 확인하기 위하여 상기와 동일한 실 험 방법을 수행하여 관찰한 결과, 도 2b에서 나타난 바와 같이 용매를 투약한 군과 비교하여 육계 50, 100 mg을 투약한 군에서 각각 8.5번의 열린 길로 들어간 횟수를 보임으로써 육계 조추출물의 항불안 효과를 확인할 수 있었다. In addition, as a result of performing the same test method as described above to confirm the number of times entered the open path of the mouse, as shown in Figure 2b compared with the group administered with the solvent as compared to the group administered with
실험예 3. 십자 미로 측정법에 의한 육계 분획물의 항불안 효과Experimental Example 3. Anti-Anxiety Effect of Broiler Fractions by Cross Maze Method
상기 실시예 2에서 수득한 디아니온 크로마토그래피법을 이용하여 유출한 물, 물:메탄올(1:1)혼합용매, 메탄올 가용추출물을 200 ㎎/㎏로 경구 투여하여 상기 실험예 1과 동일한 방법으로 관찰한 결과, 대조군에 비하여 육계 물 가용 추출물 투여군에서 126%의 가장 유의한 증가를 보여 육계 분획물의 항불안 효과를 확인할 수 있었다(도 3a참조).The distillation chromatography obtained in Example 2 was used to orally administer the distilled water, water: methanol (1: 1) mixed solvent, and methanol soluble extract at 200 mg / kg in the same manner as in Experimental Example 1. As a result, the anti-anxiety effect of broiler fraction was confirmed by showing the most significant increase of 126 % in the broiler soluble extract administration group compared to the control group (see FIG. 3a).
또한, 마우스의 열린 길로 들어간 횟수를 확인하기 위하여 상기와 동일한 실험방법을 수해한 결과, 도 3b에서 보는 바와 같이 육계 물 가용 추출물을 투여한 군에서 12.8번의 열린 들어간 횟수를 보임으로써 육계 분획물의 항불안 효과를 확인할 수 있었다.In addition, as a result of performing the same test method as described above to confirm the number of times entered into the open path of the mouse, the anti-anxiety of the broiler fraction by showing the number of open times of 12.8 times in the group administered the broiler water soluble extract as shown in Figure 3b The effect could be confirmed.
실험예 4. 십자 미로 측정법에서 5HT1a 수용체 길항제 투여시 육계 추출물의 항불안 효과Experimental Example 4. Anti-anxiety effect of broiler extract on administration of 5HT1a receptor antagonist in cross maze assay
마우스의 십자 미로 측정법을 이용하여 5HT1a 수용체에 선택적인 길항제인 WAY-100635 말레이트염(maleate salt)을 각각 0.3, 1 ㎎/㎏ 씩 피하주사를 이용하여 투여하고 30분 후에 상기 실시예 1에서 수득한 육계 조추출물 750 ㎎/㎏을 경구 투여하였다. 육계 조추출물 투여 1시간 후 십자 미로 실험을 수행하여 측정하였다. 이때 WAY-100635 말레이트염의 투여 대신 생리식염수를 투여하여 이를 대조군으로 하였다.By using a mouse maze method, WAY-100635 maleate salt, a selective antagonist for 5HT1a receptor, was administered by subcutaneous injection of 0.3 and 1 mg / kg, respectively, and obtained in Example 1 30 minutes later. One
상기 실험 수행의 결과, 도 4a에서 보는 바와 같이 WAY-100635 말레이트염 0.3, 1 ㎎/㎏ 을 투약한 후 육계 조추출물을 투여한 군에서는 열린 길에서 각각 39.6초, 34.1초동안 머물렀으며, 대조군의 경우에는 71.4초동안 열린 길에서 머물러 WAY-100635 말레이트염 투여군에서 저조한 항불안 효과를 나타내었는바, 이는 5HT1a 수용체에 선택적인 길항제인 WAY-100635 말레이트염이 육계의 항불안 작용을 억제하였으며, 이는 육계의 항불안 작용이 5HT1a 수용체의 활성을 통하여 나타낸다고 볼 수 있다.As a result of the experiment, as shown in Figure 4a, the group administered the broiler crude extract after the administration of 0.3, 1 mg / kg WAY-100635 maleate salt stayed on the open road for 39.6 seconds, 34.1 seconds, respectively, In the case of the control group, they stayed on the open road for 71.4 seconds and exhibited a low anti-anxiety effect in the WAY-100635 maleate salt-administered group. This suggests that the anti-anxiety action of broilers is shown through the activity of 5HT1a receptor.
또한 마우스의 열린 길로 들어간 회수를 측정하기 위하여 상기와 동일한 실험 방법을 수행한 결과, 도 4b에서 보는 바와 같이 10번의 열린 길로 들어간 횟수를 보인 대조군과 비교하여, WAY-100635 말레이트염 0.3, 1 ㎎/㎏ 을 투약한 후 육계 조추출물을 투여한 군에서 각각 8.7번, 6.9번의 항불안 횟수를 보임으로써 육계의 조추출물의 항불안 작용을 5HT1a 수용체에 선택적인 길항제인 WAY-100635 말레이트염이 억제함을 확인할 수 있었다.In addition, as a result of performing the same experimental method as described above to measure the number of enter into the open path of the mouse, WAY-100635 maleate salt 0.3, 1 mg as compared to the control group showed the number of enter into the
실험예 5. 급성 독성 연구Experimental Example 5. Acute Toxicity Study
25 ± 5 g의 ICR계 마우스(대한실험동물)와 235 ± 10 g의 특정병원부재(SPF) 스프라그-도올리(Sprague Dawley, Biogenomics사) 랫트를 각각 3마리씩 4군 으로 나누어 본 발명의 실시예 1 내지 2의 육계 추출물들을 각각 1000 mg/㎏, 100 mg/㎏, 10 mg/㎏의 용량으로 복강투여한 후 24시간 동안 독성여부를 관찰하였다.The present invention was divided into three groups of 25 ± 5 g of ICR mice (Korean experimental animals) and 235 ± 10 g of SPF Sprague Dawley (Biogenomics) rats. The broiler extracts of Examples 1 and 2 were intraperitoneally administered at doses of 1000 mg / kg, 100 mg / kg and 10 mg / kg, respectively, and then observed for toxicity for 24 hours.
실험 결과, 4군 모두에서 사망한 예를 전혀 관찰할 수 없었고, 체중 증가, 사료 섭취량 등에서 외견상 대조군과 별다른 증상을 찾아볼 수 없었다. 따라서 본 발명의 추출물이 안전한 약물임을 확인할 수 있었다.As a result, no deaths were observed in all four groups, and no significant symptoms were found in weight gain and feed intake. Therefore, it was confirmed that the extract of the present invention is a safe drug.
본 발명의 육계 추출물을 포함하는 약학조성물의 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.It describes an example of the formulation of a pharmaceutical composition comprising a broiler extract of the present invention, the present invention is not intended to limit it, but is intended to explain in detail only.
제제예 1. 산제의 제조Formulation Example 1 Preparation of Powder
실시예 1의 육계 조추출물의 건조분말 300 mg300 mg of dry powder of broiler crude extract of Example 1
유당 100 mg
탈크 10 mg
상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 제조한다.The above ingredients are mixed and filled in an airtight cloth to prepare a powder.
제제예 2. 정제의 제조Formulation Example 2 Preparation of Tablet
실시예 2의 육계 물 가용 추출물의 건조분말 50 mgDry powder of broiler water soluble extract of Example 2 50 mg
옥수수전분 100 mg
유당 100 mg
스테아린산 마그네슘 2 mg2 mg magnesium stearate
상기의 성분들을 혼합한 후 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조한다.After mixing the above components, tablets are prepared by tableting according to a conventional method for preparing tablets.
제제예 3. 캅셀제의 제조Formulation Example 3 Preparation of Capsule
실시예 1의 육계 조추출물의 건조분말 50 mgDry powder of broiler crude extract of Example 1 50 mg
옥수수전분 100 mg
유당 100 mg
스테아린산 마그네슘 2 mg2 mg magnesium stearate
통상의 캡슐제 제조방법에 따라 상기의 성분을 혼합하고 젤라틴 캡슐에 충전하여 캡슐제를 제조한다.According to a conventional capsule preparation method, the above ingredients are mixed and filled into gelatin capsules to prepare capsules.
제제예 4. 주사제의 제조Formulation Example 4 Preparation of Injection
실시예 2의 육계 물 가용 추출물의 건조분말 50 mgDry powder of broiler water soluble extract of Example 2 50 mg
주사용 멸균 증류수 적량Appropriate sterile distilled water for injection
pH 조절제 적량pH adjuster
통상의 주사제의 제조방법에 따라 1 앰플당(2㎖) 상기의 성분 함량으로 제조한다.According to the conventional method for preparing an injection, the amount of the above ingredient is prepared per ampoule (2 ml).
제제예 5. 액제의 제조Formulation Example 5 Preparation of Liquid
실시예 1의 육계 조추출물의 건조분말 100 mg100 mg of dry powder of broiler crude extract of Example 1
이성화당 10 g10 g of isomerized sugar
만니톨 5 g5 g of mannitol
정제수 적량Purified water
통상의 액제의 제조방법에 따라 정제수에 각각의 성분을 가하여 용해시키고 레몬향을 적량 가한 다음 상기의 성분을 혼합한 다음 정제수를 가하여 전체를 정제수를 가하여 전체 100 ㎖로 조절한 후 갈색병에 충진하여 멸균시켜 액제를 제조한다.According to the conventional method of preparing a liquid solution, each component is added to the purified water to dissolve it, the lemon flavor is added appropriately, the above components are mixed, purified water is added, the whole is adjusted to 100 ml by the addition of purified water, and then filled in a brown bottle. The solution is prepared by sterilization.
제제예 6. 건강 식품의 제조Formulation Example 6 Preparation of Healthy Food
실시예 2의 육계 물 가용 추출물의 건조분말 1000 ㎎1000 mg of dry powder of soluble extract of broiler water of Example 2
비타민 혼합물 적량Vitamin Mixture
비타민 A 아세테이트 70 ㎍70 μg of Vitamin A Acetate
비타민 E 1.0 ㎎Vitamin E 1.0 mg
비타민 B1 0.13 ㎎Vitamin B 1 0.13 mg
비타민 B2 0.15 ㎎Vitamin B 2 0.15 mg
비타민 B6 0.5 ㎎Vitamin B 6 0.5 mg
비타민 B12 0.2 ㎍0.2 μg of vitamin B 12
비타민 C 10 ㎎
비오틴 10 ㎍10 μg biotin
니코틴산아미드 1.7 ㎎Nicotinic Acid 1.7 mg
엽산 50 ㎍
판토텐산 칼슘 0.5 ㎎Calcium Pantothenate 0.5mg
무기질 혼합물 적량Mineral mixture
황산제1철 1.75 ㎎Ferrous Sulfate 1.75 mg
산화아연 0.82 ㎎Zinc Oxide 0.82 mg
탄산마그네슘 25.3 ㎎Magnesium carbonate 25.3 mg
제1인산칼륨 15 ㎎Potassium monophosphate 15 mg
제2인산칼슘 55 ㎎Dibasic calcium phosphate 55 mg
구연산칼륨 90 ㎎Potassium Citrate 90 mg
탄산칼슘 100 ㎎
염화마그네슘 24.8 ㎎Magnesium chloride 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강식품 조성물 제조에 사용할 수 있다.Although the composition ratio of the above-mentioned vitamin and mineral mixtures is mixed with a component suitable for a health food in a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method. The granules may be prepared and used for preparing a health food composition according to a conventional method.
제제예 7. 건강 음료의 제조Formulation Example 7 Preparation of Healthy Drink
실시예 1의 육계 조추출물의 건조분말 1000 ㎎1000 mg of dry powder of broiler crude extract of Example 1
구연산 1000 ㎎
올리고당 100 g100 g oligosaccharides
매실농축액 2 gPlum concentrate 2 g
타우린 1 g1 g of taurine
정제수를 가하여 전체 900 ㎖Add 900 ml of purified water
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간동안 85℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2ℓ용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강음료 조성물 제조에 사용한다. After mixing the above components according to a conventional healthy beverage manufacturing method, and then stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed and sterilized and then refrigerated and stored in the present invention For the preparation of healthy beverage compositions.
상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만 수요계층이나, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.Although the composition ratio is mixed with a component suitable for a favorite beverage in a preferred embodiment, the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.
상술한 바와 같이, 본 발명의 육계 추출물 및 이를 유효성분으로 함유하는 조성물은 항불안 효과를 나타내므로, 다양한 뇌신경계의 이상으로 인한 불안증의 예방 및 치료를 위한 약학조성물 및 건강기능식품으로써 이용될 수 있다.As described above, since the broiler extract of the present invention and the composition containing it as an active ingredient exhibit an anti-anxiety effect, it can be used as a pharmaceutical composition and health functional food for the prevention and treatment of anxiety caused by various cranial nervous system abnormalities. have.
Claims (7)
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