KR100526629B1 - Composition comprising the extract of Loncera japonica having monoamine oxidase-inhibiting activity - Google Patents
Composition comprising the extract of Loncera japonica having monoamine oxidase-inhibiting activity Download PDFInfo
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- KR100526629B1 KR100526629B1 KR10-2003-0017646A KR20030017646A KR100526629B1 KR 100526629 B1 KR100526629 B1 KR 100526629B1 KR 20030017646 A KR20030017646 A KR 20030017646A KR 100526629 B1 KR100526629 B1 KR 100526629B1
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- Prior art keywords
- mao
- activity
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- extract
- gold
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- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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Abstract
본 발명은 모노아민산화효소(MAO) 저해 활성을 갖는 금은화(Lonicera japonica)의 추출물을 유효성분으로 함유하는 MAO 관련 각종질환의 예방 및 치료용 조성물 및 스트레스 해소 및 피로회복용 조성물에 관한 것으로, 본 발명의 금은화 추출물은 시험관내 실험에서 MAO 효소활성을 강력히 저해하였고, 금은화 추출물의 경구투여가, 동물의 운동 후 MAO-A 활성을 증가시키고, MAO-B 효소 활성을 저하시켜 정상수준으로 회복시키며, 또한 LDH의 활성을 저하시키고 락테이트의 함량을 저하시키므로써, 본 발명의 금은화 추출물은 MAO 효소와 관련된 우울증, 파킨슨씨병, 알츠하이머와 같은 각종 질환을 위한 의약품, 운동 후 신체의 스트레스 해소, 피로회복 및 운동능력향상을 위한 스포츠 기능성 식음료 및 건강기능식품으로 이용될 수 있다.The present invention relates to a composition for the prevention and treatment of various diseases related to MAO, including the extract of Lonicera japonica having monoamine oxidase (MAO) inhibitory activity as an active ingredient, and a composition for stress relief and fatigue recovery. Geumgum extract was strongly inhibited MAO enzymatic activity in vitro, oral administration of Geumgum extract increased the MAO-A activity after exercise in animals, lowered MAO-B enzyme activity and restored to normal levels. By lowering the activity of LDH and lowering the lactate content, the sterling silver extract of the present invention can be used for medicines for various diseases such as depression, Parkinson's disease, Alzheimer's disease associated with MAO enzymes, stress relief, fatigue recovery and exercise after exercise It can be used as a sports functional food and drink and health functional food for improving ability.
Description
본 발명은 모노아민산화효소 저해활성을 갖는 금은화 추출물을 함유하는 모노아민산화효소저해제 및 스트레스 해소 및 피로회복용 조성물에 관한 것이다.The present invention relates to a monoamine oxidase inhibitor and a composition for stress relief and fatigue containing a gold and silver extract having a monoamine oxidase inhibitory activity.
모노아민산화효소 (Monoamine oxidase, amine:oxygen oxidoreductase (deaminating) EC 1.4.3.4., MAO)는 중추신경계나 말초조직 등 동물조직 중의 미토콘드리아(mitochondria)에 널리 존재하면서 신경 전달물질이나 호르몬성 아민(amines) 화합물의 대사를 관장하는 효소로서 다음과 같은 반응으로 아민 화합물의 산화적 탈아미노기반응(deamination)을 촉매하여 신경전달물질과 식사와 장내 박테리아에 의해 유래되는 호르몬성 아민(hormonal amines)을 분해한다(Cooper, J.R., et al. The biochemical Basis of Neuropharmacology, Oxford university press, New York, 1996).Monoamine oxidase (amine: oxygen oxidoreductase (deaminating) EC 1.4.3.4., MAO) is widely present in mitochondria in animal tissues, such as the central nervous system and peripheral tissues, and is a neurotransmitter or hormone amine (amines). It is an enzyme that regulates metabolism of compounds, and catalyzes the oxidative deaminoation of amine compounds by decomposing neurotransmitters and hormone amines derived from food and intestinal bacteria by the following reactions. (Cooper, JR, et al. The biochemical Basis of Neuropharmacology, Oxford university press, New York, 1996).
: :
MAO는 내인성 기질로서 카테콜아민과 인돌알킬아민(indolealkylamines) 또는 그 유도체를 주로 이용하며 기질 특이성에 따라 세로토닌, 노르에피네프린 (norepinephrine), 에피네프린(epinephrine)을 산화적으로 탈아미노기화 시키는 A-형과, 벤질아민(benzylamine), 펜에틸아민(phenethylamine)의 산화를 촉매 하는 B-형의 두 가지 형태으로 나눌 수 있다(Felner, A.E. and Waldmeier, P.C., Biochem. Pharmac., 28, pp995-1002, 1979).MAO mainly uses catecholamines and indolealkylamines or derivatives thereof as endogenous substrates, and benzyl, A-type, which oxidatively deaminoizes serotonin, norepinephrine, and epinephrine according to substrate specificity. It can be divided into two types, B-type catalyzing the oxidation of benzylamine and phenethylamine (Felner, AE and Waldmeier, PC, Biochem. Pharmac . , 28 , pp995-1002, 1979).
상기 MAO 효소 저해제는 전통적으로 우울증(Youdim MB, Finberg JP, and Tipton, KF. Handbook of Experimental Pharmacology. 90/1, pp119-192, 1988; Sambamoorthi U, et al., Med Care. 41(1), pp180-94, 2003)과 고혈압(Laux G, Philipp M, Kohnen R. Lancet. 11;347(9011):1330, 1996), 편두통(Silberstein SD, Curr Med Res Opin. 17 Suppl 1:s87-93, 2001)을 치료하고 파킨슨병의 진행을 지연하는 약물로 이용되어 왔으며(Danisi F., Geriatrics. 57(3), pp46-50, 2002; Ahlskog JE. Neurology. 60(3), pp381-9, 2003) 그 외에도 여러 원인에 의한 공황증세(Sheehan DV., J Clin. Psychiatry., 63 Suppl 14, pp17-21, 2002), 어린아이의 주의력 결핍과 충동적 과잉 행동을 치료하는 약물로 응용되고 있다(Spencer TJ, et al., J Clin Psychiatry. 63 Suppl 12, pp16-22, 2002). 최근에는 수면 과잉증의 자극제(Annane D, et al., Cochrane Database Syst Rev., (4):CD003218, 2002)로 무언증의 치료제(Berger I, et al., Isr Med Assoc J. 4(12), pp1135-7, 2002)로서, 금연을 돕는 약물로서도(Fowler JS, et al., Neurotoxicology. 24(1), pp75-82, 2003; Berlin I, et al., Addiction. 97(10), pp1347-54., 2002; Vessicchio JC, et al., J. Clin. Psychiatry., 3(7), pp594-5, 2002) 응용되고 있다. 또한 새로운 MAO 저해제의 기능이 연구되고 있어서 알츠하이머씨병(Alzheimer's disease)을 치료하는 강력한 후보물질로서 MAO 저해제들의 새로운 기능이 보고 되었으며(Sterling J, et al., J Med Chem. 21;45(24), pp5260-79, 2002) 십이지장궤양 환자의 헬리코박터 피로리(Helicobacter pylori)균 근절을 위한 약물요법과 (Silva FM, et al., Rev Hosp Clin Fac Med Sao Paulo. 57(5), pp205-8, 2002; Queiroz DM, et al., J. Clin. Gastroenterol., 35(4), pp315-20, 2002; Treiber G, et al., Helicobacter., 7(4), pp225-31, 2002) HIV 감염 환자의 우울증 치료(Brown BR. HIV Clin., 14(3)1, pp5-8, 2002), 알코올 중독 환자를 치료하는 약물의 효과 조절(Wing MK. Chemico-Biological Interactions, 130-132 pp919-930, 2001), 사회적 분노 질환(social anxiety disorder)의 극복을 위한 약물치료에도 응용되고 있다(Stein DJ, et al., Int. Clin. Psychopharmacol., 17(4), pp161-70, 2002). 아직 연구 단계에 있지만 MAO 저해제의 신경모터 자극 효과(Psychomotor stimulant effects, Bergman J, Yasar S, Winger G., Psychopharmacology (Berl). 159(1), pp21-30, 2001), 기억증진활성(memory enhancing activity)(Nowakowska E, et al., J. Physiol. Pharmacol., 52, pp863-73, 2001)이 확인되기도 했다.The MAO enzyme inhibitors have traditionally been described as depression (Youdim MB, Finberg JP, and Tipton, KF. Handbook of Experimental Pharmacology. 90/1 , pp119-192, 1988; Sambamoorthi U, et al., Med Care . 41 (1) , pp180-94, 2003) and hypertension (Laux G, Philipp M, Kohnen R. Lancet. 11 ; 347 (9011): 1330, 1996), migraine (Silberstein SD, Curr Med Res Opin . 17 Suppl 1: s87-93, 2001) has been used as a drug to treat and delay the progression of Parkinson's disease (Danisi F., Geriatrics . 57 (3) , pp46-50, 2002; Ahlskog JE. Neurology . 60 (3) , pp381-9, 2003 In addition, it has been applied as a drug to treat attention deficit and impulsive hyperactivity in children (Sheehan DV., J Clin. Psychiatry. , 63 Suppl 14, pp17-21, 2002). Spencer TJ, et al., J Clin Psychiatry . 63 Suppl 12, pp 16-22, 2002). Recently, stimulants of hypersomnia (Annane D, et al., Cochrane Database Syst Rev. , (4): CD003218, 2002) have been used to treat speechlessness (Berger I, et al., Isr Med Assoc J. 4 (12) , pp1135-7, 2002), as a drug to help quit smoking (Fowler JS, et al., Neurotoxicology . 24 (1) , pp75-82, 2003; Berlin I, et al., Addiction. 97 (10) , pp1347- 54., 2002; Vessicchio JC, et al., J. Clin.Psychiatry., 3 (7) , pp594-5, 2002). In addition, the function of new MAO inhibitors is being studied, and new functions of MAO inhibitors have been reported as potent candidates for treating Alzheimer's disease (Sterling J, et al., J Med Chem. 21 ; 45 (24), Pharmacotherapy for the eradication of Helicobacter pylori bacteria in duodenal ulcer patients (Silva FM, et al., Rev Hosp Clin Fac Med Sao Paulo. 57 (5) , pp205-8, 2002 Queiroz DM, et al., J. Clin.Gastroenterol ., 35 (4) , pp315-20, 2002; Treiber G, et al., Helicobacter ., 7 (4) , pp225-31, 2002) Treatment of depression in children (Brown BR. HIV Clin. , 14 (3) 1, pp5-8, 2002), modulating the effects of drugs to treat alcoholic patients (Wing MK. Chemico-Biological Interactions , 130-132 pp919-930, 2001), and has also been applied to drug therapy for overcoming social anxiety disorders (Stein DJ, et al., Int. Clin. Psychopharmacol ., 17 (4) , pp161-70, 2002). Psychomotor stimulant effects, Bergman J, Yasar S, Winger G., Psychopharmacology (Berl) .159 (1) , pp21-30, 2001), memory enhancing activity of MAO inhibitors activity (Nowakowska E, et al., J. Physiol. Pharmacol. , 52 , pp863-73, 2001).
락테이트 탈수소효소(Lactate dehydrogenase, EC.1.1.1.27)(LDH)는 백색근섬유에서 일어나는 당분해과정의 첫 단계인 Lactate+NAD+=pyruvate+NADH의 화학반응을 촉매 하는 산화환원효소의 한 종류로서 이 반응의 역반응은 심장이나 적색 근섬유에서 일어나는 유산분해과정과 간장에서의 포도당 전환과정의 첫 단계이며 대부분 세포의 세포질에 존재하는 이 효소의 혈중 농도를 확인하여 각종 진단에 이용하고 있다. 혈뇨, 농뇨, 단백뇨, 백혈구증가증이 있는 경우, LDH 레벨이 증가되어 있으며(de Pablo Cardenas A, et al., Arch Esp Urol. 55(10), pp273-6, 2002), 신혈관성 고혈압과 신부전증, 발육부전(Parmar RC, et al., Am. J. Med. Genet., 15;117A(3), pp275-7, 2003), 정신박약, 열과 급성신부전증, 담즙울체성간염, 폐기능 부전을 동반하는 다발성골수증(Vella FS, et al., Am. J. Hematol., 72(1), pp38-42, 2003), 급성 폐부전, 암 환자의 검색, 진단, 예후, 관찰의 마커로서 이용되기도 하고(Riley RD, et al., Eur. J. Cancer., 39(1), pp19-30, 2003) 신경독성을 측정하여 허혈성심장발작을 진단하거나(Dezsi L, et al., Acta Pharm. Hung. 72(2), pp84-91, 2002), 어린아이의 급성 골수성백혈병(Zaki S, et al., J. Pak. Med. Assoc., 52(6), pp247-9, 2002), 고열, 빈혈, 혈소판장애, 골수의 혈구탐식증 (Katsumata Y, et al., Ryumachi., 42(5), pp820-6, 2002), 전립선암(Fernandez Gomez JM, et al., Arch Esp. Urol., 55(8), pp915-22, 2002), 급성 심근경색 (Yamasawa I, Baral R. Nippon Rinsho. 52 Suppl(Pt 2), pp631-5, 1994)에서도 LDH 레벨이 증가되는 것을 진단에 이용하고 있다.Lactate dehydrogenase (EC.1.1.1.27) (LDH) is a type of redox enzyme that catalyzes the chemical reaction of Lactate + NAD + = pyruvate + NADH, the first step in the glycolysis process in white muscle fibers. The reverse reaction of this reaction is the first step in the lactolysis process in the heart or red muscle fibers and the glucose conversion in the liver. The blood concentrations of the enzymes in the cytoplasm of most cells are used for various diagnosis. LDH levels are increased in hematuria, pneumoniae, proteinuria, leukocytosis (de Pablo Cardenas A, et al., Arch Esp Urol. 55 (10 ), pp 273-6, 2002), Renal Vascular Hypertension, Renal Insufficiency, Dysplasia (Parmar RC, et al., Am. J. Med. Genet., 15 ; 117A (3), pp275-7, 2003), Mental Retardation, Fever and Acute Renal Failure, Cholestatic Hepatitis , Multiple myeloma with pulmonary insufficiency (Vella FS, et al., Am. J. Hematol., 72 (1) , pp38-42, 2003), acute lung failure, screening, diagnosis, prognosis of cancer patients, It is also used as a marker of observation (Riley RD, et al., Eur. J. Cancer. , 39 (1) , pp19-30, 2003) to diagnose ischemic heart attack by measuring neurotoxicity (Dezsi L, et al. , Acta Pharm.Hung . 72 (2) , pp84-91, 2002), Acute Myeloid Leukemia in Children (Zaki S, et al., J. Pak. Med. Assoc., 52 (6) , pp247-9 , 2002), high fever, anemia, platelet disorders, hematopoiesis in the bone marrow (Katsumata Y, et al., Ryumachi ., 42 (5) , pp820-6, 2002), prostate cancer (Fernandez Gomez JM, et al., Arch Esp. Urol ., 55 (8) , pp915-22, 2002), and acute myocardial infarction (Yamasawa I, Baral R. Nippon Rinsho. 52 Suppl (Pt 2), pp631-5, 1994). The increase is used for diagnosis.
한편, 근육운동 능력을 향상시키기 위한 운동생리의 연구 분야에서는 최근 세로토닌 수용체(serotonin receptors)의 기능에 대한 체력 훈련영향에 대한 연구에서 쥐의 중추신경계에서 세로토닌과 세로토닌 수용체의 농도가 운동을 전후한 스트레스에 대한 반응으로 급속히 증가하며 운동의 강도와 기간에 따라 세로토닌의 농도와 세로토닌 모듈린 조직(serotonin modulin tissue)의 농도증가 양상이 다르게 나타난다는 사실을 동물실험을 통하여 확인하고 이 기전에 따라 다양한 운동처방이 가능하다고 주장하고 있다. 이러한 주장은 근육운동 시에 조직 내 세로토닌의 농도가 증가한다는 이미 알려진 사실에 대한 카테콜아민(catecholamine) 대사 기전의 구체적 증거이며 이러한 사실에 입각하여 근육운동의 개선과 향상을 위한 새로운 기전이 연구를 위한 바탕을 제공하고 있다. On the other hand, in the field of exercise physiology for improving muscle exercise ability, the recent study on the effect of fitness training on the function of serotonin receptors, the concentration of serotonin and serotonin receptors in the central nervous system of rats before and after exercise It is rapidly increased in response to the test results, and it is confirmed through animal experiments that the concentrations of serotonin and serotonin modulin tissue are different according to the intensity and duration of exercise. It is claimed that this is possible. These claims are concrete evidence of catecholamine metabolism mechanisms for the already known fact that the concentration of serotonin in tissues increases during muscle exercise, and based on these findings, new mechanisms for improving and improving muscle movement. To provide.
한의학의 약리학을 설명하는 이론 중 하나인 기미론 중 기론을 검정하는 지표를 마련하고자 실시한 한성 약물과 열성 약물을 경구투여한 후 동물의 체내에서 일어나는 이 약물들에 의한 모노아민산화효소(monoamine oxidase, MAO)의 활성변화를 관찰함으로서 MAO의 체내활성 변화를 측정하는 방법이 약재의 한열을 구분하는 지표가 될 수 있을 지의 시험과 한성약과 열성약이 시험관 내에서 효소활성에 미치는 효과를 실험하여 한열로 구분된 한약재들이 시험관 내에서 효소활성에 미치는 영향을 비교 관찰한 실험 결과 한성 약물들이 동물의 체내에서와 시험관 내에서 MAO 활성을 저해하는 사실을 확인하여 보고한 바 있다(황금희 외, 생약학회지, 30(2), pp145-150, 1999). 이 사실을 근거로 한성 약물들이 운동 중 체내 세로토닌의 농도 변화에 영향을 미쳐서 운동 능력을 향상하고 운동으로 인한 스트레스를 개선하는 기능을 할 수 있을 것으로 기대하고 한방과 민간에서 중추신경계에 작용하는 것을 목적으로 사용되어온 식물을 대상으로 기론에 의해 한성과 평성, 양성(凉性)으로 분류된 식물을 대상으로 약 300여 종의 식물을 수집하여 MAO 저해활성을 검색한 결과 약 40여종의 식물이 MAO-A 및 MAO-B에 대해 강력한 저해활성을 나타냈음을 확인하였다(Hwang, K.H. and Lim, S.H., Food Science and Biotechnology 투고 중). 이에 본 발명자는 이들 식물 중 식품공전에 수재되어 식품재료로 이용이 가능한 식물 중 인동초의 꽃 부분인 금은화가 강한 MAO 저해활성을 나타내는 것을 확인하여, 금은화를 선정하여 항우울제로 널리 사용되는 MAO 효소 저해제 및 세로토닌 이론을 적용한 스포츠 식품의 재료로 이용할 수 있을 것으로 기대하고 활성성분에 대한 연구를 진행하였다.One of the theories explaining the pharmacology of oriental medicine is the monoamine oxidase (monoamine oxidase) caused by these drugs in the body after oral administration of Hansung drugs and recessive drugs, which were conducted to prepare the indicators to test the theory. By observing the change in activity of MAO), we can test whether the method of measuring the change in body activity of MAO can be an indicator to distinguish the heat of medicine, and the effects of Hansung and heat medicine on enzyme activity in vitro. As a result of comparative observation of the effects of different herbal medicines on enzyme activity in vitro, we confirmed and reported that Korean medicines inhibit MAO activity in animals and in vitro (Hwang, Geum-Hee et al., Journal of Pharmacognosy, 30) (2) , pp 145-150, 1999). Based on this fact, it is expected that Hansung drugs may function to change the concentration of serotonin in the body during exercise to improve exercise ability and improve stress due to exercise, and to act on the central nervous system in oriental medicine and civilian. About 300 plants were collected from plants classified as Han, Pyeong, and Benign by Giron and searched for MAO inhibitory activity. It was confirmed that it showed a strong inhibitory activity against A and MAO-B (during Hwang, KH and Lim, SH, Food Science and Biotechnology). Accordingly, the present inventors confirmed that the gold and silver flower, which is a flower part of Indongcho, among the plants that are harvested in the food industry and can be used as a food material, exhibits a strong MAO inhibitory activity, and selects the gold and silver flower, which are widely used as antidepressants, and MAO enzyme inhibitors. In anticipation that it could be used as a material of sports foods applying serotonin theory, research on active ingredients was conducted.
금은화(Lonicerae flos)는 인동과(Caprifoliaceae)식물인 덩굴성 관목 인동덩굴(Loncera japonica)의 꽃봉오리로 한방이나 민간에서는 이뇨, 건위, 관절염, 화농성 피부염, 기관지염에 사용하고 있다(중약사전, 동경. p.2027. 1985). 금은화의 성분 연구로는 탄닌(tannin), 이노시톨(inositol), 스테롤(sterol), 클로로제닉산(chlorogenic acid), 이소클로로제닉산(isochlorogenic acid), 아피게닌 (apigenin), 퀘르세틴(quercetin) 등이 알려져 있다(Son KH, et al., Arch. Pharm. Res., 15(4), pp365-370. 1992 ;Son KH, et al., Korean J. Pharmacog. , 25(1), pp24-27. 1994). 금은화의 활성에 대한 보고로는 항염증효과 (Kwak WJ, et al., Chem Pharm Bull., 51(3), pp333-335. 2003 ; Lee JH, et al., Int. J. Mol. Med., 7(1), pp79-83, 2001), HIV-1 RT에 대한 선택적 억제효과(Chang CW, et al., Antiviral Res., 27(4), pp367-74, 1995), 포스포리파아제 A2의 불활성화효과 (Chang HW, et al., Biochem. Biophys. Res. Commun., 30;205(1), pp843-9, 1994), 주부습진(Honeysuckle contact dermatitis) 치료(Webster RM. Cutis, 51(6), pp424, 1993), 소아 기관지폐렴의 치료효과(Li YQ, et al., Zhongguo Zhong Xi Yi Jie He Za Zhi, 12(12), pp719-21, 737, 708, 1992), 혈소판 활성 및 내피세포손상억제효과(Chang WC, Hsu FL. Prostaglandins Leukot Essent Fatty Acids, 45(4), pp307-12, 1992), 바이러스성 심근염 치료효과 (Yan HJ. Zhong Xi Yi Jie He Za Zhi, 11(8), pp468-70, 452, 1991), 변형된 세포 매개 면역효과 (Luo ZH. Zhonghua Wai Ke Za Zhi, 28(9), pp562-5, pp574-5, 1990) 등이 알려져 있다. Lonicerae flos is a bud of the vine shrub, Loncera japonica , which is a plant of the Caprifoliaceae family. p. 2027. 1985). Studies on the composition of gold and silver coins include tannin, inositol, sterol, chlorogenic acid, isochlorogenic acid, apigenin, and quercetin. (Son KH, et al., Arch. Pharm. Res. , 15 (4) , pp365-370. 1992; Son KH, et al., Korean J. Pharmacog. , 25 (1) , pp24-27. 1994). Reports on the activity of gold and silver include anti-inflammatory effects (Kwak WJ, et al., Chem Pharm Bull., 51 (3), pp 333-335. 2003; Lee JH, et al., Int. J. Mol. Med. , 7 (1) , pp79-83, 2001), selective inhibitory effect on HIV-1 RT (Chang CW, et al., Antiviral Res ., 27 (4) , pp367-74, 1995), phospholipase A2 Inactivation effect (Chang HW, et al., Biochem. Biophys. Res. Commun. , 30 ; 205 (1), pp843-9, 1994), treatment of Honeysuckle contact dermatitis (Webster RM. Cutis , 51) (6) , pp424, 1993), Therapeutic Effect of Bronchial Pneumonia in Children (Li YQ, et al., Zhongguo Zhong Xi Yi Jie He Za Zhi, 12 (12) , pp719-21, 737, 708, 1992), Platelet Activity And endothelial cell damage suppression effect (Chang WC, Hsu FL. Prostaglandins Leukot Essent Fatty Acids , 45 (4) , pp307-12, 1992), treatment of viral myocarditis (Yan HJ. Zhong Xi Yi Jie He Za Zh i, 11 (8) , pp468-70, 452, 1991), and modified cell mediated immune effects (Luo ZH. Zhonghua Wai Ke Za Zhi , 28 (9) , pp562-5, pp574-5, 1990).
한국 특허등록 제281003호에서는 모노아민산화효소저해활성을 보이는 황련(Coptis japonica)의 추출물로부터 분리된 프로토베르베린 알칼로이드 화합물을 함유하는 항우울제에 대해 개시하고 있고, 한국 특허등록 제 29163호에서는 금은화 및 다른 생약성분을 함유하는 암전이억제조성물을 개시하고 있으며, 제 295395호에서는 나복자, 천련자, 금은화, 작약 및 천궁의 추출물을 포함하여 이루어지는 인플루엔자 바이러스 A형의 예방 및/또는 치료 효과가 탁월한 감기 예방 및 치료용 항바이러스성 약제 및 기능성 식품에 관하여 개시하고 있으며, 한국특허등록 제 354608호에서는 알레르기 질환 예방 및 치료용 의약조성물 및 그 제조방법을 개시하고 있다. 이외에도 한국특허출원 제 2000-4196호는 금은화 및 이외의 다른 한약재를 이용한 좌제형 전립선 질환 및 치질치료용 조성물을 개시하고 있으며, 한국특허출원 제 2002-68267호에서는 이의인, 상백피, 어성초, 길경, 생지황, 금은화를 주성분으로 함유하는 알레르기비염 및 아토피성 피부염 치료의 약학조성물을 개시하고 있다.Korean Patent Registration No. 281003 discloses an antidepressant containing a protoberberine alkaloid compound isolated from the extract of Coptis japonica , which exhibits monoamine oxidase inhibitory activity. A cancer metastasis inhibiting composition containing the ingredient is disclosed, and in 295395, a cold prevention and treatment having an excellent effect of preventing and / or treating influenza virus type A, which includes extracts of moths, lotus roots, gold coins, peony, and horoscopes. An antiviral drug for use and a functional food are disclosed, and Korean Patent Registration No. 354608 discloses a pharmaceutical composition for preventing and treating allergic diseases and a manufacturing method thereof. In addition, Korean Patent Application No. 2000-4196 discloses a composition for treating suppository type prostate disease and hemorrhoids using gold silver flower and other herbal medicines, and in Korean Patent Application No. 2002-68267, objection, Sangbaekpi, Eoseongcho, Gilgyeong, Disclosed is a pharmaceutical composition for treating allergic rhinitis and atopic dermatitis, which contains raw sulfur, gold and silver.
그러나 상기 문헌 어디에도 금은화가 모노아민산화효소를 저해하는 활성을 갖는다고 교시나 개시된 바가 없다.However, none of the literature teaches or discloses that gold and silver have activity that inhibits monoamine oxidase.
이에 본 발명자들은 동물을 이용한 시험관 실험에서 금은화 메탄올 추출물이 추출물 수준에서 MAO 저해활성을 갖는 것을 확인하였으며, 생체내 실험(in vivo)을 통해 체내 MAO 활성에 영향을 미치고 운동으로 변화된 체내 효소활성을 정상 수준으로 회복시키는 것을 확인하였고, 운동을 전후한 스트레스의 반응으로 일어나는 MAO 활성 변화를 조절하여 운동 능력을 향상하고 훈련효과를 높일 수 있음을 확인하여 본 발명을 완성하였다.Therefore, the present inventors confirmed that in vitro experiments with animals, the Methanol extract of gold and silver has a MAO inhibitory activity at the extract level, and in vivo ( in vivo ) affects the MAO activity in the body and normalized the enzyme activity in the body changed by exercise It was confirmed that the recovery to the level, by adjusting the MAO activity changes occurring in response to the stress before and after exercise to confirm that the exercise ability and the training effect can be improved to complete the present invention.
따라서, 본 발명의 목적은 모노아민산화효소(MAO) 저해활성을 나타내는 금은화 추출물을 유효성분으로 함유하는 모노아민산화효소 저해제 및 모노아민산화효소 관련 각종 질환의 예방 및 치료용 조성물을 제공하는 것이다. Accordingly, it is an object of the present invention to provide a composition for the prevention and treatment of various diseases related to monoamine oxidase inhibitors and monoamine oxidase, which contains a gold and silver extract showing monoamine oxidase (MAO) inhibitory activity as an active ingredient.
또한, 본 발명의 목적은 피로회복, 스트레스 해소 및 운동능력향상을 위한 조성물, 스포츠 식음료 및 건강기능식품을 제공하는 것이다. In addition, an object of the present invention is to provide a composition, sports food and beverages and health functional foods for fatigue recovery, stress relief and athletic performance.
상기 목적을 달성하기 위하여, 본 발명은 금은화(Lonicera japonica) 조추출물 또는 비극성용매가용추출물을 함유하는 모노아민산화효소(MAO) 저해제를 제공한다.In order to achieve the above object, the present invention provides a monoamine oxidase (MAO) inhibitor containing a Lonicera japonica crude extract or a non-polar solvent soluble extract.
또한, 본 발명은 모노아민산화효소 저해활성이 있는 금은화 조추출물 또는 비극성용매가용추출물을 함유하는 MAO 효소 관련 각종 질환의 예방 및 치료용 약학조성물을 제공한다.The present invention also provides a pharmaceutical composition for the prevention and treatment of various diseases related to MAO enzymes containing a crude silver extract or a non-polar solvent soluble extract having a monoamine oxidase inhibitory activity.
상기 MAO 효소 관련 각종 질환은 우울증, HIV 감염환자의 우울증, 고혈압, 편두통, 파킨슨씨병, 알쯔하이머씨병, 수면과잉증, 무언증 및 사회적 분노질환 등을 포함한다.The MAO enzyme-related diseases include depression, depression of HIV-infected patients, hypertension, migraine, Parkinson's disease, Alzheimer's disease, hypersomnia, mute and social anger.
또한, 본 발명은 모노아민산화효소 저해활성이 있는 금은화 조추출물을 함유하는 피로회복, 스트레스 해소 및 운동능력향상을 위한 조성물을 제공한다.In addition, the present invention provides a composition for fatigue recovery, stress relief and athletic performance containing a gold-silver crude extract having a monoamine oxidase inhibitory activity.
상기 조추출물은 물, 메탄올, 에탄올 등과 같은 극성용매 및 이들의 혼합용매에 가용한 추출물을 포함한다.The crude extract includes extracts available for polar solvents such as water, methanol, ethanol and the like, and mixed solvents thereof.
상기 비극성 용매 가용 추출물은 에틸아세테이트, 클로로포름, 헥산, 디클로로메탄과 같은 비극성 용매, 바람직하게는 클로로포름에 가용한 추출물을 포함한다.The nonpolar solvent soluble extract includes extracts soluble in nonpolar solvents, preferably chloroform, such as ethyl acetate, chloroform, hexane, dichloromethane.
또한 본 발명은 금은화 조추출물 또는 비극성용매가용추출물을 포함하는 항피로, 항스트레스 및 운동능력향상용 기능성 음료를 제공한다.The present invention also provides an anti-fatigue, anti-stress and exercise performance functional drinks containing crude gold extract or non-polar solvent-soluble extract.
본 발명의 금은화로부터 조추출물 및 비극성용매 가용추출물을 분리하는 방법은 하기와 같다.The method of separating the crude extract and the non-polar solvent soluble extract from the gold and silver of the present invention is as follows.
이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
본 발명의 금은화 추출물은, 건조된 금은화 무게(㎏)의 약 5배 내지 20배, 바람직하게는 약 10배 내지 15배의 물, 저급 알콜 또는 약 1:0.1 내지 1:10, 바람직하게는 1:0.2 내지 1:5의 혼합비(㎏/ℓ)를 갖는 이들의 혼합용매로 20 내지 100℃, 바람직하게는 50 내지 100℃ 추출온도에서 약 1시간 내지 2일, 바람직하게는 약 2시간 내지 1일 정도에서 열수추출, 냉침추출, 초음파 추출, 환류냉각 추출 등의 추출방법에 의하여 1회 내지 5회, 바람직하게는 2회 내지 4회 반복하여 추출한 후, 추출물은 감압농축 또는 동결건조, 열풍건조하여 물, 저급 알콜 또는 이들의 혼합용매에 따른 가용 추출물인 조추출물을 수득할 수 있다. The sterling extract of the present invention comprises about 5 to 20 times, preferably about 10 to 15 times, water, lower alcohol or about 1: 0.1 to 1:10, preferably 1, the weight of dried sterling silver (kg). These mixed solvents having a mixing ratio (kg / L) of: 0.2 to 1: 5 are about 1 to 2 days at an extraction temperature of 20 to 100 ° C, preferably 50 to 100 ° C, preferably about 2 hours to 1 After extracting repeatedly from 1 to 5 times, preferably 2 to 4 times by the extraction method such as hot water extraction, cold sediment extraction, ultrasonic extraction, reflux cooling extraction at about one day, the extract is concentrated under reduced pressure or freeze drying, hot air drying Thus, crude extracts, which are soluble extracts according to water, lower alcohols or mixed solvents thereof, can be obtained.
본 발명은 상기 추출공정에서 얻어지는 금은화의 조추출물을 함유하는 우울증, HIV 감염환자의 우울증, 고혈압, 편두통, 파킨슨씨병, 알쯔하이머씨병, 수면과잉증, 무언증 및 사회적 분노질환과 같은 모노아민산화효소 관련 각종 질환의 예방 및 치료용 약학조성물을 제공한다.The present invention provides various diseases related to monoamine oxidase such as depression containing crude extract of gold and silver coins obtained in the extraction process, depression of HIV infected patients, hypertension, migraine, Parkinson's disease, Alzheimer's disease, hypersomnia, mute speech and social anger disease. It provides a pharmaceutical composition for the prevention and treatment of.
본 발명은 상기 추출공정에서 수득된 조추출물을 포함하는 모노아민산화효소 저해제를 제공한다.The present invention provides a monoamine oxidase inhibitor comprising a crude extract obtained in the extraction process.
또한 본 발명은 상기 추출공정에서 얻어지는 조추출물을 포함하는 피로회복, 스트레스 해소 및 운동능력향상용 조성물을 제공한다.In another aspect, the present invention provides a composition for fatigue recovery, stress relief and athletic performance comprising the crude extract obtained in the extraction process.
금은화의 조추출물은 시험관내 실험에서 모노아민 산화효소(MAO)를 저해하고, 금은화 조추출물을 경구투여한 랫트를 이용한 생체 내 실험에서 운동 후, MAO-A 활성을 증가시키고, MAO-B 효소 활성을 저하시켜 정상수준으로 회복시키며, 혈중 LDH(lactate dehydrogenase) 효소 활성을 저하시키고 혈중 락테이트(lactate)의 함량을 저하시킴으로써 운동시 신체의 스트레스 해소, 피로회복 및 운동능력의 향상에 효과를 나타낸다.Crude silver extract inhibited monoamine oxidase (MAO) in vitro, increased the MAO-A activity after exercise in vivo in rats treated with orally administered the crude silver extract, and MAO-B enzyme activity It lowers to normal levels, lowers blood lactate dehydrogenase (LDH) enzyme activity, and lowers lactate content in blood, which is effective in relieving stress, improving fatigue, and improving athletic performance during exercise.
또한 본 발명의 비극성 용매 가용 추출물은 상기 조추출물을 물에 현탁 한 후, 이를 현탁액이 약 1 내지 100배, 바람직하게는 약 1 내지 5배 부피의 극성 또는 비극성 용매를 가하여 1회 내지 10회, 바람직하게는 2회 내지 5회 분획하여 수득할 수 있다. 또한 추가로 통상의 분획 공정을 수행할 수도 있다(Harborne J.B. Phytochemical methods: A guide to modern techniques of plant analysis. 3rd Ed. pp 6-7, 1998).In addition, the non-polar solvent soluble extract of the present invention, after suspending the crude extract in water, the suspension is added 1 to 10 times by adding about 1 to 100 times, preferably about 1 to 5 times the volume of a polar or nonpolar solvent, Preferably it can be obtained by fractionation 2 to 5 times. It is also possible to further carry out conventional fractionation processes (Harborne JB Phytochemical methods: A guide to modern techniques of plant analysis. 3rd Ed. Pp 6-7, 1998).
본 발명은 상기 추출공정에서 얻어지는 금은화의 비극성용매가용추출물을 함유하는 우울증, HIV 감염환자의 우울증, 고혈압, 편두통, 파킨슨씨병, 알쯔하이머씨병, 수면과잉증, 무언증 및 사회적 분노질환과 같은 모노아민산화효소 관련 각종 질환의 예방 및 치료용 약학조성물을 제공한다.The present invention relates to monoamine oxidase-related enzymes such as depression, hypertension, migraine, Parkinson's disease, Alzheimer's disease, hypersomnia, mute and social anger disease, which contain non-polar solvent-soluble extracts of gold and silver coins obtained in the extraction process. It provides a pharmaceutical composition for the prevention and treatment of various diseases.
본 발명은 상기 추출공정에서 수득된 비극성용매 가용추출물을 포함하는 모노아민산화효소 저해제를 제공한다.The present invention provides a monoamine oxidase inhibitor comprising a non-polar solvent soluble extract obtained in the extraction process.
또한, 본 발명은 상기 추출공정에서 얻어지는 금은화의 비극성용매 가용추출물들을 포함하는 운동능력향상 및 피로회복용 조성물을 제공한다.In addition, the present invention provides a composition for improving athletic performance and fatigue recovery, including non-polar solvent soluble extracts of gold and silver coins obtained in the extraction process.
또한 본 발명의 유효성분이 정제된 정제 분획물은 상기 비극성 용매 가용추출물을 분획하고 농축한 후, 실리카겔 컬럼크로마토그래피 및 박층컬럼크로마토그래피(TLC)를 이용하여 분리할 수 있다.In addition, the purified fraction of the active ingredient of the present invention can be separated by fractionating and concentrating the non-polar solvent soluble extract, using silica gel column chromatography and thin layer column chromatography (TLC).
본 발명의 모노아민산화효소 관련 질환의 예방 및 치료용 조성물 및 신체의 스트레스 해소, 피로회복 및 운동능력향상을 위한 조성물은, 조성물 총 중량에 대하여 상기 금은화 추출물 또는 분획물을 0.5 ~ 50 중량%로 포함한다.The composition for preventing and treating monoamine oxidase-related diseases of the present invention and the composition for relieving stress, recovering from fatigue, and improving athletic performance, comprises 0.5 to 50% by weight of the sterling silver extract or fraction based on the total weight of the composition. do.
본 발명의 금은화 추출물을 포함하는 조성물은 약학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다.The composition comprising the sterling gold extract of the present invention may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.
본 발명의 추출물을 포함하는 조성물은 통상의 방법에 따른 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다.The composition comprising the extract of the present invention may further comprise a suitable carrier, excipient and diluent according to conventional methods.
본 발명의 추출물을 포함하는 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는, 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다.Carriers, excipients and diluents that may be included in the composition comprising the extract 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 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다.Compositions comprising extracts according to the invention are formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterile injectable solutions, respectively, according to conventional methods. Can be used.
본 발명의 추출물의 사용량은 환자의 나이, 성별, 체중에 따라 달라질 수 있으나, 0.1 내지 1000 mg/㎏의 양을 일일 1회 내지 수회 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 amount of the extract of the present invention may vary depending on the age, sex, and weight of the patient, but may be administered once to several times in an amount of 0.1 to 1000 mg / kg. 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 금은화의 추출물을 포함하는 조성물은 신체의 스트레스 해소, 피로회복 및 운동능력향상을 위한 약제, 식품 및 음료 등에 다양하게 이용될 수 있다. 본 금은화 추출물을 첨가할 수 있는 식품으로는, 예를 들어, 각종 식품류, 스포츠용 식음료, 음료, 껌, 차, 비타민 복합제, 건강기능 식품류 등이 있다. The composition containing the extract of the gold and silver coins of the present invention can be used in various ways, such as drugs, foods and beverages for stress relief, fatigue recovery and athletic performance of the body. Examples of the foods to which the extract of gold and silver coins can be added include various foods, sports foods and beverages, beverages, gums, teas, vitamin complexes, and health functional foods.
본 발명의 금은화 추출물 자체는 독성 및 부작용은 거의 없으므로 예방 목적으로 장기간 복용 시에도 안심하고 사용할 수 있는 약제이다. The sterling silver extract of the present invention has almost no toxicity and side effects, and thus is a drug that can be used safely even when taken for long periods of time.
본 발명의 상기 추출물은 운동능력향상 및 피로회복을 목적으로 식품 또는 음료에 첨가될 수 있다. 이 때, 식품 또는 음료 중의 상기 추출물의 양은 일반적으로 본 발명의 건강식품 조성물은 전체 식품 중량의 0.01 내지 30 중량%로 가할 수 있으며, 건강 음료 조성물은 100 ㎖를 기준으로 0.02 내지 30 g, 바람직하게는 0.3 내지 1 g의 비율로 가할 수 있다. The extract of the present invention can be added to food or beverages for the purpose of improving athletic performance and fatigue recovery. At this time, the amount of the extract in the food or beverage is generally added to the health food composition of the present invention to 0.01 to 30% by weight of the total food weight, the health beverage composition is 0.02 to 30 g based on 100 ml, preferably Can be added in a ratio of 0.3 to 1 g.
또한 본 발명은 금은화 조추출물 또는 비극성용매가용추출물을 포함하는 항피로, 항스트레스 및 운동능력향상용 기능성 음료를 제공한다.The present invention also provides an anti-fatigue, anti-stress and exercise performance functional drinks containing crude gold extract or non-polar solvent-soluble extract.
본 발명의 기능성 음료는 안정성이 입증된 금은화 추출물을 포함하여 음료를 제조함으로써, 안전하고 복용이 용이하면서도 피로회복, 스트레스 해소 및 운동능력향상 등의 효과를 갖는 기능성 음료를 제공할 수 있다.The functional beverage of the present invention may provide a functional beverage having the effects of safe and easy to take, but also fatigue recovery, relieves stress and improves exercise ability by preparing a beverage including the proven gold and silver extract.
본 발명의 기능성 음료는, 바람직하게는 금은화 조추출물 또는 금은화 비극성용매가용추출물 0.1 내지 10중량%, 감미제와 산미제등의 통상의 음료 첨가물 10 내지 25 중량 %, 나머지 중량 %의 물을 포함하는 것을 특징으로 한다. 본 발명의 기능성 음료에서 통상적인 음료 첨가물로서는, 액상과당, 설탕, 말토덱스트린, 포도당, 구연산, 니코틴산 아미드, 판토텐산, 안식향산나트륨, 풍미제, 향미제 등이 포함될 수 있다.The functional beverage of the present invention preferably contains 0.1 to 10% by weight of crude gold extract or gold non-solvent solvent soluble extract, 10 to 25% by weight of ordinary beverage additives such as sweetener and acidulant, and the remaining weight% of water. It features. Typical beverage additives in the functional beverage of the present invention may include liquid fructose, sugar, maltodextrin, glucose, citric acid, nicotinic acid amide, pantothenic acid, sodium benzoate, flavoring agents, flavoring agents and the like.
또한, 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 예는 모노사카라이드, 예를 들어, 포도당, 과당 등; 디사카라이드, 예를 들어 말토스, 슈크로스 등; 및 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, 글리시르히진등) 및 합성 향미제(사카린, 아스파르탐 등)를 유리하게 사용할 수 있다. 상기 천연 탄수화물의 비율은 본 발명의 조성물 100 ㎖당 일반적으로 약 1 내지 20 g, 바람직하게는 약 5 내지 12 g이다.In addition, the health beverage composition of the present invention, except for containing the extract as an essential ingredient in the indicated ratio, there is no particular limitation on the liquid component and may contain various flavors or natural carbohydrates, etc. as additional ingredients, like 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; And conventional sugars such as polysaccharides such as dextrin, cyclodextrin, and sugar alcohols such as xylitol, sorbitol, and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of said natural carbohydrates is generally about 1-20 g, preferably about 5-12 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.
본 발명은 다음의 실시 예에 의거하여 더욱 상세히 설명되나, 본 발명이 이에 의해 제한되지는 않는다.The present invention is described in more detail based on the following examples, but the present invention is not limited thereto.
실시예 1. 금은화의 조추출물 제조예 1 Example 1 Crude Extract Preparation Example 1
건조한 금은화(경동시장, 대덕한의원, 서울) 100g을 가정용 분쇄기(mixer)를 이용하여 분말로 만들고 여기에 약 800㎖의 80% 에탄올 용액을 가하여 환류냉각하면서 100℃에서 6시간씩 3회 반복하여 가열 추출하였다. 탈지면으로 여과하고 여액을 40℃ 수욕 상에서 감압 농축하여 에탄올 추출물 24.00g을 얻었고 이를 다시 동결 건조하여 건조된 분말 24g 을 얻었다. 동결 건조한 분말을 -80℃ 냉동고(deep freezer)에 보관하고, 실험 시 증류수에 녹여 사용하였다.100g of dried Geumeunhwa (Gyeongdong Market, Daedeok Clinic, Seoul) is made into powder using a home mixer, and it is heated to 3 times for 6 hours at 100 ℃ while reflux cooling by adding 800ml of 80% ethanol solution. Extracted. Filtration was performed with cotton wool and the filtrate was concentrated under reduced pressure on a 40 ° C. water bath to obtain 24.00 g of ethanol extract, which was freeze-dried again to obtain 24 g of dried powder. The freeze-dried powder was stored in a -80 ° C freezer (deep freezer), and was used by dissolving in distilled water during the experiment.
실시예 2. 금은화 조추출물 제조예 2 Example 2 Preparation of Crude Crude Extract 2
건조한 금은화(경동시장, 대덕한의원, 서울) 100g을 정량하여 가정용 분쇄기로 1분간 마쇄하여 분말로 만들고 여기에 1000㎖의 80% 메탄올을 가하여 95℃ 수욕 상에서 환류냉각하면서 6시간씩 3회 반복하여 가열 추출하였다. 실온으로 식힌 후 여과하고 그 박을 80% 메탄올로 세척하여 여액이 1000㎖되게 하고 45℃ 수욕 상에서 감압 농축하여 메탄올 추출물 24g을 얻었다. Weigh 100g of dried Geumhwahwa (Gyeongdong Market, Daedeok Medical Center, Seoul) and grind it for 1 minute in a domestic grinder to make powder. Add 1000ml of 80% methanol and heat it three times for 6 hours while refluxing in a 95 ℃ water bath. Extracted. After cooling to room temperature, the mixture was filtered and the foil was washed with 80% methanol to make the filtrate 1000 ml, and concentrated under reduced pressure on a 45 ° C. water bath to obtain 24 g of methanol extract.
실시예 3. 금은화 클로로포름가용추출물 제조Example 3 Preparation of Gold Coated Chloroform Soluble Extract
실시예 2의 금은화 조추출물 2g 을 증류수 1000 ㎖에 현탁 시킨 다음, 클로로포름 1000 ㎖와 혼합한 후 진탕하여, 클로로포름 불용성층(상층)과 클로로포름 가용성층(하층)으로 분획하고 클로로포름 가용부를 수집하였다. 상층(물층)과 동일한 부피의 클로로포름 용매를 상기한 방법과 동일한 방법으로 5회 반복하여 용액의 색이 옅어질 때까지 최대한으로 클로로포름층에 용해가 가능한 물질을 얻어낸 후, 대형농축기(EYELA사, 모델명 N-11, 일본)를 사용하여 클로로포름 용매를 제거한 후, 건조상태의 금은화 클로로포름 가용 추출물 1.01 g을 수득하였다.2 g of the sterile gold extract of Example 2 was suspended in 1000 ml of distilled water, mixed with 1000 ml of chloroform, and then shaken to separate the chloroform insoluble layer (upper layer) and the chloroform soluble layer (lower layer), and the chloroform soluble portion was collected. The same volume of chloroform solvent as the upper layer (water layer) was repeated five times in the same manner as described above to obtain a substance that can be dissolved in the chloroform layer as much as possible until the color of the solution became light, followed by a large concentrator (EYELA, model name). N-11, Japan) was used to remove the chloroform solvent, and then 1.01 g of dried sterile chloroform soluble extract was obtained.
실시예 4. 금은화 에틸아세테이트 가용추출물 제조Example 4 Preparation of Gold Coated Ethyl Acetate Soluble Extract
실시예 3의 금은화 클로로포름 가용 추출물을 제외한 상층(물층)에 에틸아세테이트 1000㎖를 가한 후 진탕하여, 에틸아세테이트 불용성층(하층)과 에틸아세테이트 가용성층(상층)으로 분획하고 에틸아세테이트 가용부를 수집하였다. 하층(물층)과 동일한 부피의 에틸아세테이트 용매를 상기한 방법과 동일한 방법으로 5회 반복하여 용액의 색이 옅어질 때까지 최대한으로 에틸아세테이트층에 용해가 가능한 물질을 얻어낸 후, 대형농축기(EYELA사, 모델명 N-11, 일본)를 사용하여 에틸아세테이트 용매를 제거한 후, 건조상태의 금은화 에틸아세테이트 가용 추출물 0.81 g을 수득하였다.1000 ml of ethyl acetate was added to the upper layer (water layer) except for the gold chloroform soluble extract of Example 3, followed by shaking. The mixture was partitioned into an ethyl acetate insoluble layer (lower layer) and an ethyl acetate soluble layer (upper layer), and the ethyl acetate soluble part was collected. The same volume of ethyl acetate solvent as the lower layer (water layer) was repeated five times in the same manner as described above to obtain a substance that can be dissolved in the ethyl acetate layer as much as possible until the color of the solution becomes light. , Model name N-11, Japan) was used to remove the ethyl acetate solvent, and then 0.81 g of a soluble extract of dried gold silver ethyl acetate was obtained.
실시예 5. 금은화 부탄올가용추출물 및 수가용추출물 제조Example 5 Preparation of Gold Coated Butanol Soluble Extract and Soluble Extract
실시예 4의 금은화 에틸아세테이트 가용 추출물을 제외한 하층(물층)에 부탄올 1000 ㎖를 가한 후 진탕하여, 부탄올 불용성층(하층)과 부탄올 가용성층(상층)으로 분획하고 부탄올 가용부를 수집하였다. 하층(물층)과 동일한 부피의 부탄올 용매를 상기한 방법과 동일한 방법으로 5회 반복하여 용액의 색이 옅어질 때까지 최대한으로 부탄올층에 용해가 가능한 물질을 얻어낸 후, 대형농축기(EYELA사, 모델명 N-11, 일본)를 사용하여 부탄올 용매를 제거한 후, 건조상태의 금은화 부탄올 가용 추출물 3.85 g 및 금은화 수가용추출물 19.00 g을 수득하였다.1000 ml of butanol was added to the lower layer (water layer) except for the soluble extract of ethyl acetate ethyl acetate of Example 4, followed by shaking. The mixture was partitioned into a butanol insoluble layer (lower layer) and a butanol soluble layer (upper layer), and a butanol soluble portion was collected. The same volume of butanol solvent as the lower layer (water layer) was repeated five times in the same manner as described above to obtain a substance that can be dissolved in the butanol layer as much as possible until the color of the solution becomes light. Then, a large concentrator (EYELA, model name) N-11, Japan) was used to remove the butanol solvent, to obtain 3.85 g of dried gold-silver butanol soluble extract and 19.00 g of gold-silver water-soluble extract.
실시예 6. 금은화 각 용매분획의 TLC 크로마토그래피Example 6 TLC Chromatography of Each Solvent Fraction
상기 실시예 1 내지 5에서 수득한 5가지 용매 추출물을 사용하여 박층 크로마토그래피(Thin layer chromatography, TLC)를 수행하였다.Thin layer chromatography (TLC) was performed using the five solvent extracts obtained in Examples 1 to 5.
박층 크로마토그래피(TLC)의 전개용매는 클로로포름:메탄올:물(30:10:1)의 혼합용매를 사용하였고, UV 254nm 및 365nm에서 각각 아니스 알데히드 (anisaldehyde) 및 10% 황산용액을 사용하여 탐지하였다(도 1 및 도 2 참조). Thin layer chromatography (TLC) was used as a solvent for a mixed solvent of chloroform: methanol: water (30: 10: 1), and was detected using anisealdehyde and 10% sulfuric acid solution at UV and 254 nm and 365 nm, respectively. (See FIGS. 1 and 2).
TLC상에서 관측한 클로로포름 분획은 다른 분획에 비해 비교적 복잡한 양상을 보이고 있다. 우선 UV에서 탐지되는 성분은 적고 아니스알데히드 발색시약으로 발색한 결과, 테르페노이드(Terpenoid, 발색:blue)과 스테로이드(발색:green)계통의 화합물들이 주요 화합물로 존재할 것으로 판단되었다. 그리고 10% H2SO4 발색시약으로 발색한 결과, 스테로이드(발색:red) 계통 화합물들을 관측하여 CHCl3 분획에는 테르페노이드와 스테로이드 계통의 화합물로 구성되어있음을 알 수 있었다.The chloroform fraction observed on TLC shows a relatively complex aspect compared to other fractions. First, there were few components detected in the UV and the color was developed with an anisealdehyde coloring reagent. As a result, it was determined that compounds of terpenoid (Terpenoid, blue) and steroid (Color: green) exist as the main compounds. As a result of color development with 10% H 2 SO 4 colorant, the steroid (red) compounds were observed to show that the CHCl 3 fraction was composed of terpenoids and steroid compounds.
참고예 1. 뇌 MAO-A의 효소활성 측정Reference Example 1. Measurement of Enzyme Activity of Brain MAO-A
1-1. 효소원의 제조1-1. Preparation of Enzyme Source
랫트를 에테르(ether)를 가한 마취병에서 마취시키고 개복하여 좌심실로부터 채혈을 하여 실혈시키고 즉시 두개골을 절개하여 뇌를 적출하였다. 적출된 뇌를 0.01M PBS(phosphate buffered saline, pH 7.0)로 세척하고 습중량 1g당 9㎖의 차가운 0.25M 수크로즈(sucrose) 용액을 가하여 터렉스 디스퍼서(Turrax disperser)로 1분간 분쇄하여 균질화(homogenate) 하였다. 이 균질액을 4℃에서 700×g로 20분간 원심분리하고 그 상등액을 취하여 다시 18,000×g로 20분간 고속 원심분리 하였다. 상등액을 버리고 펠렛을 중량 1g당 PBS 5㎖에 현탁 시켜 효소원으로 사용하였다.Rats were anesthetized in ether-doped anesthesia, opened, and blood was drawn from the left ventricle. The extracted brain was washed with 0.01 M PBS (phosphate buffered saline, pH 7.0), and homogenized by grinding for 1 minute with a Turex disperser with 9 ml of cold 0.25 M sucrose solution per 1 g of wet weight. (homogenate). The homogenate was centrifuged at 700 x g for 20 minutes at 4 ° C, the supernatant was taken and again centrifuged at 18,000 x g for 20 minutes at high speed. The supernatant was discarded and the pellet was suspended in 5 ml of PBS per 1 g of weight to use as an enzyme source.
1-2. 효소활성측정1-2. Enzyme Activity Measurement
상기에서 제조한 효소원 0.5㎖를 시험관에 넣고 기질용액으로 1.0mM 세로토닌(세로토닌, Sigma사) 용액 0.5㎖를 가하고 37.5℃ 항온조에서 90분간 반응시켰다. 반응 후, 95℃ 수욕 상에서 3분간 가열하여 반응을 중단시킨 후 즉시 700×g로 원심분리하고 상등액 1.0㎖를 취하여 미리 준비한 앰버라이트 칼럼(Amberlite CG-50, H+form, 0.6×4㎝, Sigma사)에 부어 넣었다. 증류수로 수지를 충분히(40㎖ 이상) 세척한 후 4 N 초산용액 3㎖를 수지에 부어 넣고, 이때 용출액을 시험관에 받아 277nm에서 흡광도를 측정하였다. 따로 반응 개시점 대신 반응 종말점에서 기질용액을 넣은 보정군을 시험군과 함께 실행하였다. 각 실험군의 대조군을 기준으로 하여 온도변화와 약물투여에 따른 효소 활성의 변화를 정해진 수식에 따라 계산하였다(유시용, 서울대학교 대학원 박사학위논문, 1988).0.5 ml of the enzyme source prepared above was placed in a test tube, and 0.5 ml of a 1.0 mM serotonin (Serotonin, Sigma) solution was added as a substrate solution, and the reaction was carried out for 90 minutes in a 37.5 ° C thermostat. After the reaction, the reaction was stopped by heating in a 95 ° C. water bath for 3 minutes, and immediately centrifuged at 700 × g, and 1.0 ml of the supernatant was prepared in advance for an Amberlite column (Amberlite CG-50, H + form, 0.6 × 4 cm, Sigma). 4) poured into. After sufficiently washing the resin with distilled water (40 ml or more), 3 ml of 4 N acetic acid solution was poured into the resin, and the eluate was received in a test tube and the absorbance was measured at 277 nm. Separately, the correction group with the substrate solution at the reaction end point instead of the reaction start point was performed with the test group. The change of enzyme activity according to temperature change and drug administration was calculated according to the defined formula based on the control group of each experimental group (Yoo-Yong Yoo, Ph.D. dissertation, Seoul National University, 1988).
참조예 2. 간 MAO-B의 효소활성 측정Reference Example 2 Determination of Enzyme Activity of Liver MAO-B
2-1. 효소원의 제조2-1. Preparation of Enzyme Source
랫트의 간 미토콘드리아(mitochondria) 분획을 상법에 따라 분리하여 효소원으로 사용하였다. 즉, 에테르 병에서 마취 시킨 랫트를 즉시 복개하고 좌심실에서 채혈하여 실혈시킨 후 간을 적출하여 0.01M PBS(phosphate buffered saline, pH 7.0)에 씻고, 습 중량 1g당 0.25M 수크로즈 용액 5㎖를 가하여 터렉스 디스퍼서(Turrax disperser)로 1분간 분쇄하여 균질화 하였다. 이 균질액을 즉시 4℃에서 700×g로 20분간 원심분리 하였다. 상등액을 취하여 다시 18,000×g에서 20분 고속원심분리하고 상등액을 버리고 가라앉은 펠렛을 PBS 5㎖에 현탁 시켜 효소원으로 사용하였다.Liver mitochondria fractions of rats were separated according to the conventional method and used as an enzyme source. In other words, rats anesthetized in ether bottles were immediately subjected to blood collection in the left ventricle, blood was drawn, livers were extracted and washed in 0.01M PBS (phosphate buffered saline, pH 7.0), and 5 ml of 0.25M sucrose solution was added per 1 g of wet weight. The mixture was ground and homogenized for 1 minute with a Turrax disperser. This homogenate was immediately centrifuged at 700 x g for 20 minutes at 4 ° C. The supernatant was taken and again centrifuged at 18,000 × g for 20 minutes. The supernatant was discarded, and the pellet was suspended and suspended in 5 ml of PBS to use as an enzyme source.
2-2. 효소활성측정2-2. Enzyme Activity Measurement
맥웬 등의 방법(McEwen, C. M., et al., J. Lab. Clin. Med., 62, pp766-776, 1963)에 준하였다. 즉, 효소원 0.5㎖와 기질용액으로 4.0mM 벤질아민·HCl(benzylamine·HCl, Sigma사) 용액 0.5㎖를 시험관에 넣고 37.5℃ 항온조에서 90분간 계속 반응시켰다. 반응을 중지시키기 위하여 60% 과염소산(perchloric acid) 0.2㎖씩을 가하고 동시에 시클로헥산(cyclohexane) 4㎖를 가하여 진탕시킨 후 700×g로 20분간 원심분리 하여 시클로헥산층을 취하였다. 이 시클로헥산층을 242 nm에서 흡광도를 측정하였다. 따로 MAO-A에서와 마찬가지로 보정군을 시험군과 함께 실행하였다. 각 실험군의 대조군을 기준으로 하여 온도변화와 약물투여에 따른 효소 활성의 변화를 정해진 수식에 따라 계산하였다.McWen et al. (McEwen, CM, et al., J. Lab. Clin. Med. , 62 , pp766-776, 1963). That is, 0.5 ml of 4.0 mM benzylamine HCl (benzylamine HCl, Sigma) solution was added to the test tube with 0.5 ml of enzyme source and substrate solution, and the reaction was continued for 90 minutes in a 37.5 ° C. thermostat. To stop the reaction, 0.2 ml of 60% perchloric acid was added each time, 4 ml of cyclohexane was added thereto, followed by shaking, followed by centrifugation at 700 × g for 20 minutes to obtain a cyclohexane layer. The absorbance of this cyclohexane layer was measured at 242 nm. Separately, the calibration group was run with the test group as in MAO-A. Based on the control group of each experimental group, the change in enzyme activity according to the temperature change and drug administration was calculated according to a prescribed formula.
참조예 3. 혈중 LDH의 효소활성 측정Reference Example 3 Determination of Enzyme Activity of Blood LDH
혈중 LDH 효소활성은 시그마사에서 판매하는 어세이 키트(assay kit)를 사용하여 측정하였다(Sigma diagnostics® Lactate dehydrogenase(LD-L) (Procedure No. 228-UV). 실험동물로부터 채혈한 혈액을 즉시 3000 rpm에서 15분 원심 분리하여 혈장을 취하여 -80℃ 냉동고에 보관한 것을 냉장 온도에서 해동한 후 1 ㎖의 시약이 담긴 30℃ 큐벳에 50㎕를 가하고 조심스럽게 섞어준다. 일정한 온도가 유지되는 챔버가 장착된 스펙트로포토메터(spectrophotometer)에서 30초 후에 340 nm에서의 흡광도를 측정하고(초기 흡광도) 정확히 60초 후에 흡광도를 측정한다. 60초 후에 측정한 흡광도를 최종 흡광도로 한다. 측정된 최종 흡광도에서 초기흡광도를 빼준 값 (ΔA/분)을 분당 변화된 흡광도로 계산하고 효소활성은 다음의 수학식 1로부터 얻었다. LDH 1 단위(unit)는 효소활성 측정 조건에서 분당 NADH 1몰(mole)을 생성하도록 촉매 하는 효소의 활성으로 정의하였다. Serum LDH enzymatic activity was measured using an assay kit sold by Sigma (Sigma diagnostics® Lactate dehydrogenase (LD-L) (Procedure No. 228-UV). Centrifuge for 15 minutes at 3000 rpm, take the plasma, thaw it in a freezer at 50 ° F, add 50 μl to a 30 ° C. cuvette containing 1 ml of reagent, and mix carefully. The absorbance at 340 nm is measured (initial absorbance) after 30 seconds on a spectrophotometer equipped with the absorbance after 60 seconds, and the absorbance measured after 60 seconds is taken as the final absorbance. The value obtained by subtracting the initial absorbance at (ΔA / min) was calculated as the changed absorbance per minute and the enzyme activity was obtained from Equation 1. LDH 1 unit is NADH 1 per minute under the enzyme activity measurement conditions. It was defined as the activity of the enzyme that catalyzes to produce a (mole).
ΔA/분 = 340 nm에서의 분당 흡광도의 변화Change in absorbance per minute at ΔA / min = 340 nm
TV = 전체 반응 혼합액 부피 (1.05 ㎖) TV = total reaction mixture volume (1.05 ml)
SV = 시료 부피 (0.05 ㎖) SV = sample volume (0.05 ml)
LP = 빛의 길이(light path, 1 ㎝) LP = light path (1 cm)
참조예 4. 혈중 락테이트 함량 측정Reference Example 4. Determination of Blood Lactate Content
혈중 락테이트 함량은 시그마사의 키트 시약(Sigma kit reagent, Sigma diagnostics® Lactate (Procedure No. 735))을 이용하여 측정하였다. 실험동물로부터 채혈한 혈액을 즉시 3000 rpm에서 15분 원심 분리하여 혈장을 취하여 -80℃ 냉동고에 보관한 것을 냉장 온도에서 해동한 후 1 ㎖의 시약이 담긴 일정하게 30℃로 유지되는 큐벳에 10㎕를 가하고 10분 동안 인큐베이션 하였다. 혈장 샘플 대신 락테이트 표준품 용액을 농도별로 가하여 같은 방법으로 측정한 표준품과 함께 블랭크(blank)를 기준으로 하는 540 nm에서의 흡광도를 측정한다. 락테이트 표준품 용액을 농도별로 가하여 캘리브래이션 커브(calibration curve)를 작성하였으며 다음의 수학식 2를 이용하여 혈액 중의 락테이트 함량을 계산하였다.Blood lactate content is determined by Sigma kit reagent (Sigma diagnostics®). Lactate (Procedure No. 735)). The blood collected from the experimental animals was immediately centrifuged at 3000 rpm for 15 minutes, and the plasma was taken and stored in a freezer at -80 ° C. After thawing at the refrigeration temperature, 10 µl in a constant 30 ° C cuvette containing 1 ml of reagent. Was added and incubated for 10 minutes. Lactate standard solution is added instead of the plasma sample by concentration to measure the absorbance at 540 nm on a blank basis with the standard measured in the same manner. A calibration curve was prepared by adding lactate standard solutions by concentration, and lactate content in blood was calculated using Equation 2 below.
참조예 5. 통계처리Reference Example 5. Statistics Processing
실험결과는 SAS 통계프로그램을 이용하였으며(SAS User's Guide, Statistics, 6th edition, SAS Institute Inc., Cary, NC, U.S.A., 1988), 스튜던트 t-테스트(Student's t-test)를 사용하여 유의차 검정을 하였다. 모든 통계는 95% 수준에서 유의성을 검정하였다.Experimental results were evaluated using SAS statistical program (SAS User's Guide, Statistics, 6th edition, SAS Institute Inc., Cary, NC, USA, 1988), and the Student's t-test was used to test the significance difference. It was. All statistics tested significance at the 95% level.
참고예 6. 단백질 정량Reference Example 6. Protein Quantitation
단백질 함량은 우혈청알부민(bovine serum albumin)을 표준물질로 사용하고, 브래드포드 방법(Bradford's method)를 이용하여 측정하였다(Daniel, M.B and Stuart, J.E., Protein Methods. Wiley-Liss, N.Y. U.S.A., 1990).Protein content was measured using bovine serum albumin as a standard and Bradford's method (Daniel, MB and Stuart, JE, Protein Methods. Wiley-Liss, NYUSA, 1990). .
실험예 1. 금은화 추출물의 시험관내 MAO 저해활성Experimental Example 1. In vitro MAO inhibitory activity
금은화의 각 용매별 추출물이 시험관내 MAO-A 및 MAO-B의 활성에 미치는 영향을 알아보았다.The effects of extracts for each solvent of gold silver on the activity of MAO-A and MAO-B in vitro were investigated.
실시예 2 내지 5의 각 추출물들을 10㎎/㎖ 농도의 용액이 되도록 증류수로 녹이고, 이 액을 원액으로 1(10㎎/㎖), 1/2(5㎎/㎖), 1/4(2.5㎎/㎖) 희석액을 검액으로 사용하였다. 효소활성 측정은 참조예 1 및 2의 방법에 따라 제조된 뇌 MAO-A 및 간 MAO-B의 효소원을 사용하여 측정하였다. Each extract of Examples 2 to 5 was dissolved in distilled water to a solution of 10 mg / ml concentration, and this solution was used as a stock solution (1 (10 mg / ml), 1/2 (5 mg / ml), 1/4 (2.5). Mg / ml) diluent was used as the sample solution. Enzyme activity was measured using enzyme sources of brain MAO-A and liver MAO-B prepared according to the methods of Reference Examples 1 and 2.
각 분획의 활성 측정 결과 얻어진 IC50값과 전체 활성도(total activity) 및 특이활성도(specific activity)를 계산하여 표 1에 요약하였다.IC 50 values, total activity and specific activity obtained from the activity measurement of each fraction were calculated and summarized in Table 1.
실시예 2의 금은화 메탄올 추출물은 시험관내에서 MAO-A 및 MAO-B의 효소활성을 현저히 저해하는 것으로 나타났다. 메탄올 추출물의 MAO-A 및 MAO-B에 대한 IC50 값은 각각 0.60㎎/㎖과 1.50㎎/㎖이었다.Methanol extract of Example 2 was shown to significantly inhibit the enzymatic activity of MAO-A and MAO-B in vitro. IC 50 values for MAO-A and MAO-B of methanol extracts were 0.60 mg / ml and 1.50 mg / ml, respectively.
금은화는 MAO 저해성분에 대한 연구가 지금까지 보고 된 바가 없으므로 활성 성분에 대한 구체적인 성분연구를 시도할 목적으로 상법에 따라 용매 추출한 각 추출물들을 대상으로 효소활성에 대한 저해효과를 측정하였다.Since no studies on MAO inhibitors have been reported until now, gold and silver coins have been evaluated for their inhibitory effects on enzyme activity in each solvent-extracted extract according to the conventional method.
클로로포름 추출물에서 가장 강력한 MAO-A 및 MAO-B에 대한 저해활성이 확인되었으며 클로로포름 가용추출물의 MAO-A 및 MAO-B에 대한 IC50 값은 각각 0.15㎎/㎖과 1.03㎎/㎖이었다.The strongest inhibitory activity against MAO-A and MAO-B was identified in the chloroform extract, and the IC 50 values for MAO-A and MAO-B of the chloroform soluble extract were 0.15 mg / ml and 1.03 mg / ml, respectively.
에틸아세테이트 가용 추출물의 경우도 비교적 높은 농도에서 MAO-A에 대한 저해활성을 나타내 IC50 값이 0.72㎎/㎖으로 나타났으며 MAO-B에 대한 저해활성은 IC50 값이 1.04㎎/㎖으로 나타났다.The ethyl acetate soluble extract showed an inhibitory activity against MAO-A at a relatively high concentration, with an IC 50 value of 0.72 mg / ml and an inhibitory activity against MAO-B with an IC 50 value of 1.04 mg / ml. .
부탄올 가용추출물도 MAO-A 및 MAO-B에 대해 비교적 강한 저해활성을 나타냈으며 각각의 IC50 값은 각각 1.60㎎/㎖과 1.05㎎/㎖이었다.Butanol soluble extract also showed relatively strong inhibitory activity against MAO-A and MAO-B, and the respective IC 50 values were 1.60 mg / ml and 1.05 mg / ml, respectively.
물 가용추출물의 경우는 MAO-A에 대한 저해활성은 확인되지 않았으며 MAO-B에 대한 저해활성이 약하게 확인되었다. MAO-B에 대한 IC50 값은 4.40㎎/㎖이었다.In the case of water soluble extract, the inhibitory activity against MAO-A was not confirmed and the inhibitory activity against MAO-B was weakly confirmed. The IC 50 value for MAO-B was 4.40 mg / ml.
실험예 2. 금은화 메탄올 추출물이 체내 MAO 활성에 미치는 영향 : 시료의 경구 투여 Experimental Example 2. Effects of Methanol Extracts on MAO Activity in Body: Oral Administration of Samples
2-1. 실험동물 준비 및 금은화 추출물 경구투여2-1. Preparation of experimental animals and oral administration of gold and silver extract
5주령의 스프라구 도올리(Sprague Dawley, SD)계 웅성 흰쥐를 (주)바이오제노믹스사에서 공급받아 온도 23±3℃, 습도 50±10%, 12시간 주기로 조명을 조절하는 동물 사육실에서 일반 고형 사료와 물을 자유롭게 공급하면서 2~4주간 적응시킨 후 실험에 이용하였다. Sprague Dawley (SD) male rats, 5 weeks of age, are supplied by Biogenomes Co., Ltd. Adapted for 2-4 weeks with free feeding of feed and water, it was used for the experiment.
SD계 랫트 6마리를 한 군으로 하여 12시간 전에 절식시킨 동물에게 금은화 추출물을 경구투여하고 랫트의 뇌와 간의 MAO-A 및 MAO-B의 활성 변화를 측정하였다. 실시예 1의 동결 건조한 금은화 조추출물 10㎎을 증류수 1㎖에 녹이고 이 액을 실험 12시간 내지 하루 전에 절식시킨 동물에게 전날 오후와 실험 당일 2시간 전에 2회에 걸쳐 4㎖씩 경구투여하고, 2시간 경과한 후 희생시켰으며, 대조군에는 같은 조건으로 증류수 4㎖씩을 경구투여 하였다. 금은화 투여량은 시료 건조 중량으로 동물 체중 당 0.3g/㎏되는 양으로 사람 하루 용량 18-20g/60㎏에 해당하는 양이다.Six rats of SD rats were treated orally with gold silver extracts for 12 hours before fasting, and the activity changes of MAO-A and MAO-B in the brain and liver of rats were measured. 10 mg of the lyophilized sterling silver extract of Example 1 was dissolved in 1 ml of distilled water, and the solution was fasted orally to the animal fasted 12 hours to one day before the experiment and 2 times 4 ml two times before the afternoon and the day of the experiment. After the passage of time, sacrifice was performed, and 4 ml of distilled water was orally administered to the control group under the same conditions. The gold and silver dosage is 0.3 g / kg per animal body weight in the dry weight of the sample, corresponding to a human daily dose of 18-20 g / 60 kg.
2-2. 금은화 경구투여에 의한 랫트의 뇌 MAO-A와 간 MAO-B의 효소활성 변화2-2. Changes in Enzyme Activity of Brain MAO-A and Liver MAO-B in Rats Treated with Gold Silver Oral
대조군 및 본 발명의 금은화 투여군에서 뇌와 간을 적출하여 참조예 1 및 2의 방법을 따라 모노아민산화효소(MAO-A 및 MAO-B)를 준비하고, MAO-A 및 MAO-B의 효소활성을 측정하였다.Brain and liver were extracted from the control group and the gold-silver group of the present invention to prepare monoamine oxidases (MAO-A and MAO-B) according to the methods of Reference Examples 1 and 2, and the enzyme activity of MAO-A and MAO-B. Was measured.
도 3의 결과와 같이, 금은화 추출물 대신 증류수를 투여한 대조군의 효소활성을 기준으로 비교해 보면 MAO-A는 금은화 추출물에 의해서 통계적으로 유의한 정도는 아니지만 효소활성이 증가되는 것으로 나타났으며, MAO-B는 효소활성이 감소하는 경향을 나타냈다. As shown in FIG. 3, MAO-A was shown to increase the enzyme activity, although not statistically significant, by MAG-A in comparison with the enzymatic activity of the control group administered distilled water instead of the goldsmith's extract. B showed a tendency to decrease enzymatic activity.
실험예 3. 트래드밀 운동 및 수영에 의한 랫트의 MAO 활성, LDH 활성 및 락테이트 함량 변화 측정Experimental Example 3 Measurement of MAO Activity, LDH Activity and Lactate Content Changes of Rats by Treadmill Exercise and Swimming
3-1. 실험동물용 운동장치3-1. Exercise device for laboratory animals
실험용 운동장치로는 속도와 시간을 임의로 조절할 수 있는 랫트 한 마리용 트레드밀(treadmill)을 특수 제작하여(정도산업) 사용하였으며 수영의 경우 지름 40㎝, 높이 50㎝의 수조를 이용하여 수온을 30℃로 유지하면서 한 마리씩 따로 강제 수영을 하도록 하였다.As an experimental exercise device, a treadmill for a single rat that can arbitrarily adjust the speed and time was used (Jeong Ind.). For swimming, the water temperature is 30 ℃ using a 40cm diameter and 50cm height tank. Forced to swim one by one while maintaining a separate.
3-2. 실험동물3-2. Laboratory animals
5주령의 스프라그 도올리(Sprague Dawley, SD)계 웅성 흰쥐를 (주)바이오제노믹스사에서 공급받아 온도 23 ± 3℃, 습도 50 ± 10%, 12시간 주기로 조명을 조절하는 동물 사육실에서 일반 고형 사료와 물을 자유롭게 공급하면서 2~4주간 적응시킨 후 실험에 이용하였다. Sprague Dawley (SD) male rats, 5 weeks of age, are supplied by Biogenomes Co., Ltd. Adapted for 2-4 weeks with free feeding of feed and water, it was used for the experiment.
3-3. 실험동물의 운동3-3. Experimental Animal Movement
a. 예비운동 - 본 운동을 시작하기 일주일 전 미리 동물 사육실에서 2주간 적응시킨 동물을 대상으로 5m/5분을 시작으로 매일 운동속도와 시간을 증가시키면서 트레드밀 예비운동을 하였으며 최종일의 운동조건은 10m/8분이었다. 수영 예비운동은 30℃의 수조에서 매일 3분씩 강제 수영을 하도록 하였으며 최종일까지 운동조건의 변동은 없었다. 예비운동 중 운동능력이 현저히 낮은 동물은 제외시키고 평균 이상의 운동 능력을 보인 동물만을 본 실험을 위한 동물로 선정하였다. a. Preliminary Exercise -Treadmill preliminary exercise was performed every day starting from 5m / 5 minutes for the animals adapted for 2 weeks in the animal breeding room one week before the start of the exercise, increasing the speed and time of the day. It was minutes. The preliminary swimming exercise was forced to swim for 3 minutes every day in a 30 ℃ water bath, and there was no change in exercise conditions until the last day. Animals with significantly lower motor abilities during preliminary exercise were excluded, and only animals showing above-average motor abilities were selected for the experiment.
b. 본 운동 - 일주일간 예비운동을 거쳐 선정된 동물을 5그룹으로 나누어 2 그룹의 동물은 트레드밀 운동 (Tm, n=6, 10m/10분), (Th, 15m/10분), 그룹으로 2 그룹은 수영 운동(Sm, n=6, 3분), (Sh, 5분)그룹으로 분류하고 나머지 한 그룹은 대조군(n=6) 으로 분류하였다. 트레드밀 운동 그룹은 매일 정해진 속도의 런닝머신(running machine)에서 10분씩 운동을 하였으며, 수영 그룹은 30℃의 수조에서 각각 3분 혹은 5분씩 강제로 수영을 하게 하였다. b. Main Movement -After a week of preliminary exercise, the selected animals were divided into 5 groups, and the 2 groups animals were treadmill exercises (Tm, n = 6, 10m / 10 minutes), (Th, 15m / 10 minutes), and 2 groups. Were classified into swimming exercise (Sm, n = 6, 3 minutes), (Sh, 5 minutes) group, and the other group was classified as control group (n = 6). The treadmill exercise group exercised for 10 minutes on a running machine at a fixed speed every day, and the swimming group was forced to swim for 3 or 5 minutes in a 30 ° C water bath, respectively.
3-4. 운동에 의한 랫트 MAO의 활성 변화 측정3-4. Measurement of activity change in rat MAO by exercise
상기와 같이 일반 실험실 조건에서 적응시킨 SD계 랫트 6 마리를 한 군으로 하여 일주일 동안 예비운동을 통해 운동에 적응시키고 그룹을 나누어 다시 일주일 동안 본 운동을 시킨 후, 운동을 하지 않은 그룹을 대조군으로 운동 직후(0분), 운동 후 5분(5분), 30분 후(30분), 1시간 후(60분)에 각 동물의 뇌와 간에서 각각 MAO-A와 MAO-B의 활성 변화를 측정하였다. Six rats adapted to the general laboratory conditions as described above were adapted to exercise through a preliminary exercise for one week and divided into groups to perform the main exercise for another week, and then the non-exercised group was exercised as a control group. Immediately (0 minutes), 5 minutes (5 minutes), 30 minutes (30 minutes) and 1 hour (60 minutes) after exercise, the changes in the activity of MAO-A and MAO-B in the brain and liver of each animal Measured.
a. 트레드밀 운동을 한 랫트의 뇌 MAO-A의 효소활성 변화 a. Changes in Enzyme Activity of Brain MAO-A in Treadmill Exercise Rats
상기와 같이 트레드밀 운동을 한 그룹에 속하는 랫트의 뇌에서 MAO-A의 활성 변화를 측정한 결과는 도 4와 같다. As described above, the result of measuring the change in activity of MAO-A in the brain of rats belonging to the treadmill exercise group is shown in FIG. 4.
도 4에서 보는 바와 같이 운동을 한 후 동물의 뇌 MAO-A 효소활성은 운동 직후부터 운동을 하지 않은 동물에 비해 현저히 낮아지는 것으로 확인되었다. 이 결과는 한의학의 기미론을 체내 MAO 활성의 변화로 설명하려는 시도로 행해진 열성 병증모델 운동시의 MAO-A의 활성 변화와 일치하는 결과이므로, 동물이 신체적인 스트레스에 노출되었을 때 뇌에서 MAO-A의 활성이 일정 기간동안 감소하는 것을 확인할 수 있는 결과이다. 이는 또한 운동을 전후한 스트레스에 대한 반응으로 신경전달물질인 세로토닌의 농도가 급속히 변화하며 강한 신체 훈련을 시킨 동물의 뇌 조직에서 세로토닌의 농도와 세로토닌 모듈린 조직의 농도가 증가하며 이 기전에 따라 다양한 운동처방이 가능하다는 사실을 MAO 활성의 변화로서 설명할 수 있는 결과이기도 하다. As shown in FIG. 4, the brain MAO-A enzyme activity of the animals after exercise was found to be significantly lower than that of animals that did not exercise immediately after exercise. This result is consistent with the change in the activity of MAO-A during exercise in recessive model attempts to explain the clinic of oriental medicine as a change in the body's MAO activity. The result is that the activity of A decreases over a period of time. In addition, the concentration of serotonin, a neurotransmitter, changes rapidly in response to stress before and after exercise, and the concentration of serotonin and serotonin-modulin tissue increases in brain tissues of animals with strong physical training. The fact that exercise prescription is possible can be explained by the change of MAO activity.
한편 트레드밀 운동 속도를 10m/분과 15m/분으로 두 그룹으로 나누어 실험을 진행하였는데 운동을 하지 않은 그룹과는 95% 수준에서 통계적인 유의차를 보이는 반면 운동 속도를 달리한 두 그룹 간의 유의적인 차이는 발견할 수 없었다.On the other hand, the experiment was conducted by dividing the treadmill exercise speed into two groups of 10m / min and 15m / min, and there was a statistically significant difference at 95% compared to the group without exercise, while the significant difference between the two groups I couldn't find it.
b. 트레드밀 운동을 한 랫트의 간 MAO-B의 효소활성 변화 b. Changes of Enzyme Activity of Liver MAO-B in Rats Treadmilled
트레드밀 운동 후 동물의 간에서 측정한 MAO-B의 활성변화를 도 5에 나타냈다. 운동을 한 후 동물의 간 MAO-B 효소활성은 운동 직후부터 운동을 하지 않은 동물에 비해 현저히 증가되는 것으로 확인되었다. 이 결과는 한의학의 기미론을 체내 MAO 활성의 변화로 설명해 보려는 시도로 행해진 열성 병증모델 운동 시의 MAO-B의 활성 변화를 관찰하는 연구 결과에서도 발견된 사실이며 MAO-A와는 달리 동물이 신체적인 스트레스에 노출되었을 때 간에서 MAO-B의 활성은 일정 기간동안 증가된 상태를 유지하는 것을 확인 할 수 있었다. 한편 트레드밀 운동 속도를 10m/분과 15m/분으로 두 그룹으로 나누어 실험을 진행하였는데 MAO-A와는 달리 증가된 상태를 유지하는 경향은 같았지만 10m/분의 속도로 달렸던 그룹에 비해 15m/분의 속도로 달렸던 그룹의 효소활성이 현저히 증가하였다. 두 그룹 간에 이러한 유의적인 차이가 나타나는 것으로 보아 운동의 강도에 따라 더욱 민감한 변화를 나타내는 효소 타입은 MAO-B인 것을 알 수 있었다.The activity change of MAO-B measured in the liver of the animal after the treadmill exercise is shown in FIG. After exercise, hepatic MAO-B enzyme activity was found to be significantly increased compared to non-exercise animals immediately after exercise. These findings were also found in the study of observing changes in MAO-B activity during the exercise of febrile conditions in an attempt to explain the traditional theory of oriental medicine as a change in the body's MAO activity. When exposed to stress, MAO-B activity in the liver was found to remain elevated for a period of time. On the other hand, the experiment was carried out by dividing the treadmill movement speed into two groups of 10m / min and 15m / min. Unlike MAO-A, the treadmill movement speed was 15m / min. The enzymatic activity of the group that was run significantly increased. This significant difference between the two groups suggests that MAO-B is the type of enzyme that is more sensitive to the intensity of exercise.
c. 수영운동한 랫트의 뇌 MAO-A의 효소활성 변화c. Changes in Enzyme Activity of Brain MAO-A in Rats Swimming
상기와 같이 수영으로 운동을 시킨 그룹의 랫트의 뇌에서 MAO-A의 활성 변화를 측정한 결과는 도 6과 같다. As described above, the result of measuring the change in the activity of MAO-A in the brain of the rats exercised by swimming as described above is shown in FIG. 6.
도 6에서 보는 바와 같이 운동을 한 후 동물의 뇌 MAO-A 효소활성은 운동 직후부터 운동을 하지 않은 동물에 비해 현저히 낮아지는 것으로 확인되었다. 이 결과는 트레드밀 운동 시보다 훨씬 급격한 변화양상을 보임으로서 동물이 신체적인 스트레스에 노출되었을 때 뇌에서 MAO-A의 활성의 변화 양상을 관찰할 수 있는 좋은 보기가 될 것으로 생각한다. 이는 또한 운동을 전후한 스트레스에 대한 반응으로 신경전달물질인 세로토닌의 농도가 급속히 변화하며 강한 신체 훈련을 시킨 동물의 뇌 조직에서 세로토닌의 농도와 세로토닌 모듈린 조직 의 농도가 증가하며 이 기전에 따라 다양한 운동처방이 가능하다는 사실을 MAO 활성의 변화로서 설명할 수 있는 결과이기도 하다. 한편 수영을 하는 시간을 3분과 5분으로 달리하여 두 그룹으로 나누어 실험을 진행하였는데 3분 동안 수영을 한 그룹이 수영을 하지 않은 그룹과 95% 수준에서 통계적 유의차를 보이며 활성 변화를 나타낸 반면 5분 동안 수영한 그룹의 경우에는 대조그룹과 큰 차이를 보이지 않는 결과를 나타내, 이후 실험에서는 3분 동안 수영하는 그룹을 대조그룹으로 하여 실험을 진행하면서 효소활성 변화를 다시 확인하였다.As shown in FIG. 6, the brain MAO-A enzyme activity of the animals after exercise was found to be significantly lower than that of animals that did not exercise immediately after exercise. This result shows a much more rapid change than the treadmill exercise, and it is a good example to observe the change of MAO-A activity in the brain when the animal is exposed to physical stress. In addition, the concentration of serotonin, a neurotransmitter, changes rapidly in response to stress before and after exercise, and the concentration of serotonin and serotonin modulatory tissue increases in brain tissues of animals with strong physical training. The fact that exercise prescription is possible can be explained by the change of MAO activity. On the other hand, the experiment was divided into two groups with 3 minutes and 5 minutes of swimming time, and the group that had been swimming for 3 minutes showed a statistically significant difference at 95% level compared to the group that did not swim, while the change in activity was 5 In the case of swimming for a minute, the group showed no significant difference with the control group, and in the subsequent experiment, the change of enzyme activity was confirmed again while the experiment was performed using the swimming group for 3 minutes as a control group.
d. 수영운동한 랫트의 간 MAO-B의 효소활성 변화 d. Changes of Enzyme Activity of Liver MAO-B in Swimmers
수영 후 랫트의 간에서 측정한 MAO-B의 활성변화를 도 7에 나타냈다. The activity change of MAO-B measured in liver of rat after swimming is shown in FIG. 7.
수영 운동을 한 후 동물의 간 MAO-B 효소활성은 운동 직후부터 운동을 하지 않은 동물에 비해 현저히 증가되는 것으로 확인되었다. 이 결과는 트레드밀 운동 후의 효소활성 변화와 일치하는 경향을 보이며 변화 양상은 MAO-A 같은 곡선을 나타내는 것으로 확인되었다. MAO-A와는 달리 동물이 신체적인 스트레스에 노출되었을 때 간에서 MAO-B의 활성은 운동 시간에 따른 변화가 관찰되었으며 세 그룹 간에 통계적인 유의차가 발견되었다. After swimming exercise, hepatic MAO-B enzyme activity of the animals was found to be significantly increased compared to the animals that did not exercise immediately after exercise. This result shows a tendency to coincide with the change of enzyme activity after treadmill exercise, and the change pattern shows MAO-A-like curve. Unlike MAO-A, when the animal was exposed to physical stress, the activity of MAO-B in the liver changed with exercise time and statistically significant differences were found among the three groups.
3-5. 운동에 의한 랫트의 혈중 LDH 활성 및 락테이트 함량 변화 측정3-5. Measurement of LDH Activity and Lactate Content in Rats by Exercise
일반 실험실 조건에서 적응시킨 SD계 랫트 6 마리를 한 군으로 하여 일주일 동안 예비운동을 통해 운동에 적응시키고 그룹을 나누어 다시 일주일 동안 본 운동을 시킨 후 운동을 하지 않은 그룹을 대조군으로 운동 직후(0분), 운동 후 5분(5분), 30분 후(30분), 1시간 후(60분)에 각 동물에서 채혈한 혈액을 3000rpm에서 15분 원심 분리하여 얻은 혈장을 -80℃ 냉동고에 보관하였다가 혈중 LDH 활성의 변화와 락테이트 함량의 변화를 측정하였다.Six SD rats adapted under normal laboratory conditions were used as a group to adapt to exercise through preliminary exercise for one week, then divided into groups for another week, and then the non-executed group was immediately used as a control group (0 min. 5 minutes (5 minutes), 30 minutes (30 minutes), and 1 hour (60 minutes) after exercise, the blood obtained from each animal was centrifuged at 3000 rpm for 15 minutes and stored in a -80 ° C freezer. Changes in blood LDH activity and lactate content were measured.
a. 트레드밀 운동을 한 랫트의 혈중 LDH 효소활성 변화a. Changes of LDH Enzyme Activity in Blood of Treadmill Exercise Rats
트레드밀 운동 후 동물의 혈액에서 측정한 LDH의 활성변화를 도 8에 나타냈다. 운동을 한 후 동물의 혈중 LDH 효소활성은 운동 직후부터 운동을 하지 않은 동물에 비해 현저히 증가되는 것으로 확인되었다. 이 결과는 간 MAO-B의 변화양상과 같은 경향을 갖는 것으로 나타난다는 흥미로운 사실을 알게 되었다. LDH는 동물체 내에서 락테이트를 분해하거나 합성하는 가역적 활성을 갖는 효소로서 무산소 운동을 할 때 간으로부터 락테이트를 분해하여 에너지 대사전구 물질인 피루브산(pyruvate)을 생성하면서 동물체가 사용하는 에너지 형태 중 하나인 NADH를 생산하는 효소이다. 혈액 중에서도 LDH는 글루코스 부족 시 락테이트를 분해하여 에너지를 생산하는 기능을 나타내지만 운동 중 근육에서 LDH는 락테이트를 합성함으로서 무산소 운동 중 근육 내의 락테이트 농도를 높여 근육의 피로를 알리는 지표로 알려져 있다. 운동 속도를 10m/분과 15m/분으로 두 그룹으로 나누어 운동했을 때 트레드밀 운동 후 동물의 혈액에서 측정한 LDH 효소활성은 운동을 하지 않은 동물에 비해 현저히 증가하였으며 운동의 강도에 따른 변화는 크지 않았으나 두 그룹 모두 약 한 시간 동안 증가된 상태를 유지하고 있는 것으로 나타났다.8 shows changes in the activity of LDH measured in the blood of the animals after the treadmill exercise. After exercise, the blood LDH enzyme activity of the animals was found to be significantly increased compared to the animals that did not exercise immediately after exercise. It is interesting to note that this result appears to have the same tendency to change in liver MAO-B. LDH is an enzyme with reversible activity that degrades or synthesizes lactate in an animal.It is one of the forms of energy that animals use while producing anabolic pyruvate, an energy metabolic precursor that breaks down lactate from the liver during anoxic exercise. Is an enzyme that produces NADH. Among the blood, LDH has a function of producing energy by decomposing lactate in the case of glucose deficiency, but LDH synthesizes lactate in muscle during exercise, which is known as an indicator of muscle fatigue by increasing lactate concentration in muscle during anaerobic exercise. . When the exercise speed was divided into two groups, 10m / min and 15m / min, the LDH enzyme activity measured in the blood of animals after treadmill exercise was significantly increased compared to the non-exerciseed animals. Both groups remained elevated for about an hour.
b. 트레드밀 운동을 한 랫트의 혈중 락테이트 함량 변화b. Changes in Blood Lactate Content in Rats Treadmilled
트레드밀 운동 후 동물의 혈액에서 측정한 락테이트의 함량 변화를 도 9에 나타냈다. 운동을 한 후 동물의 혈중 락테이트 함량은 운동 후 30분부터 운동을 하지 않은 동물에 비해 아주 약간 증가되는 것으로 확인되었다. 이 결과는 간 MAO-B의 변화양상이나 혈중 LDH 효소활성과 같은 변화 경향을 갖는 것이다. 젖산(Lactic acid)은 무산소 운동을 할 때 근육에서는 락테이트가 합성됨으로서 락테이트 농도를 높여 근육의 피로를 알리는 지표물질로 알려져 있다. 간에서 분해 되어 에너지 대사 전구물질인 피루브산(pyruvate)을 생성하면서 동물체가 사용하는 에너지 형태 중 하나인 NADH를 생산하거나 글리코겐(glycogen)으로 저장되는 물질이다. 런닝머신의 속도를 10m/분과 15m/분으로 두 그룹으로 나누어 운동했을 때 트레드밀 운동 후 동물의 혈액에서 측정한 락테이트 농도는 운동을 하지 않은 동물과 비교했을 때 큰 차이를 보이지는 않았다. 오히려 운동 직후에는 아주 약간 감소하는 경향이다가 약하게 증가하는 것으로 나타났으나 두 그룹 모두 약 한 시간 이내에 정상 수준을 회복하였다.The change in the lactate content measured in the blood of the animals after the treadmill exercise is shown in FIG. 9. After the exercise, the blood lactate content of the animals was found to increase only slightly compared to the animals that did not exercise from 30 minutes after the exercise. This result is indicative of changes in liver MAO-B and changes in blood LDH enzyme activity. Lactic acid is known as an indicator of muscle fatigue by increasing lactate concentration by synthesizing lactate in muscles during anaerobic exercise. It breaks down in the liver to produce an energy metabolic precursor, pyruvate, which produces NADH, one of the energy forms used by animals, or is stored as glycogen. When the treadmill speed was divided into two groups of 10m / min and 15m / min, the lactate concentration measured in the blood of the animals after the treadmill exercise was not significantly different from that of the non-exercised animal. Rather, they tended to decrease slightly after exercise and then increase slightly, but both groups returned to normal within about an hour.
c. 수영운동한 랫트의 혈중 LDH 효소활성 변화c. Changes in LDH Enzyme Activity in Blood of Swimming Rats
수영 후 동물의 혈액에서 측정한 LDH의 활성변화를 도 10에 그림으로 나타냈다. 수영을 한 후 동물의 혈중 LDH 효소활성은 운동 직후부터 운동을 하지 않은 동물에 비해 현저히 증가되는 것으로 확인되었다. 이 결과는 간 MAO-B의 변화양상과 같은 경향을 갖는 것으로 나타났으며 효소활성의 변화 양상이 유사한 곡선으로 나타난다는 흥미로운 사실을 알게 되었다. 운동시간을 3분과 5분으로 두 그룹으로 나누어 수영했을 때 수영 후 동물의 혈액에서 측정한 LDH 효소활성은 운동을 하지 않은 동물에 비해 현저히 증가하였으며 운동의 강도에 따라 유의적인 차이를 나타내고 두 그룹 모두 약 한 시간 후에는 정상 상태로 회복되는 것으로 나타났다. 운동의 지표효소인 LDH의 활성이 MAO-A와 MAO-B의 활성과 유사한 변화양상을 갖는다는 사실을 확인함으로써 운동 중 체내 MAO활성 변화를 조절하는 물질을 운동능력향상과 스트레스개선을 위한 식품 소재로 이용할 수 있는 근거로 제시할 수 있을 것으로 생각한다.The activity change of LDH measured in the blood of the animal after swimming is shown in FIG. 10. After swimming, the blood LDH enzyme activity of the animals was found to be significantly increased compared to the animals that did not exercise immediately after exercise. The results showed the same trends as the changes in hepatic MAO-B, and it was interesting to note that the changes in the activity of enzymes appeared in similar curves. When swimming was divided into two groups of 3 minutes and 5 minutes, the LDH enzyme activity measured in the blood of the animals after swimming was significantly increased compared to the non-exercised animals, and there was a significant difference according to the intensity of exercise. After about an hour, it returned to normal. By confirming that the activity of LDH, an index marker of exercise, has a similar pattern of activity of MAO-A and MAO-B, foods for improving exercise ability and stress improvement were identified as substances controlling the change of MAO activity in the body during exercise. We think that we can suggest on basis to be able to use.
d. 수영 운동한 랫트의 혈중 락테이트 함량 변화d. Changes in Blood Lactate Content in Rats Swimmers
수영 후 동물의 혈액에서 측정한 락테이트의 함량변화를 도 11에 나타냈다. 수영을 한 후 동물의 혈중 락테이트 함량은 수영 직후에는 운동을 하지 않은 동물에 비해 현저히 증가하였으나 운동 후 30분을 전후 하여 정상 상태를 회복하는 것으로 확인되었다. 이 결과는 간 MAO-B의 변화양상이나 혈중 LDH 효소활성과 같은 경향을 갖는 것을 알게 되었다. 운동 시간을 3분과 5분으로 두 그룹으로 나누어 운동했을 때 수영 직후부터 수영 30분 후 까지는 95% 수준에서 두 그룹 간에 유의적인 락테이트 함량 차이를 보였으나 한 시간이 경과하자 모든 그룹에서 정상적인 상태를 회복하였다.The change in the lactate content measured in the blood of the animals after swimming is shown in FIG. 11. The blood lactate content of the animals after swimming was significantly increased compared to the animals without exercise immediately after swimming, but it was confirmed that the normal state was restored about 30 minutes after the exercise. This result was found to have a tendency such as changes in liver MAO-B and LDH enzyme activity in blood. When exercise was divided into two groups of 3 minutes and 5 minutes, there was a significant difference in lactate content between the two groups at the 95% level from just after swimming to 30 minutes after swimming. Recovered.
실험예 4. 금은화 경구투여 후 운동에 의한 랫트 MAO의 활성, 혈중 LDH 활성 및 혈중 락테이트 함량 변화에 미치는 영향 측정Experimental Example 4. Determination of the effect of exercise on rat MAO activity, blood LDH activity and blood lactate content after oral administration
상기 실험예 3의 방법과 동일하게, 일반 실험실 조건에서 적응시킨 SD계 랫트 6 마리를 한 군으로 하여 일주일 동안 점진적인 예비운동을 통해 운동에 적응시키고 그룹을 나누어 다시 일주일 동안 본 운동을 시키면서 금은화 추출물을 실험예 2-1의 방법에 따라 일주일 간 경구로 투여하고 운동 직후(0분), 운동 후 5분(5분), 30분 후(30분), 1시간 후(60분)에 각 동물의 뇌와 간에서 각각 MAO-A와 MAO-B의 활성 변화를 측정하였다. 또한 채혈한 혈액을 3000rpm에서 15분 원심 분리하여 얻은 혈장을 -80℃ 냉동고에 보관하였다가 혈중 LDH 활성의 변화와 락테이트 함량의 변화를 측정하였다. 운동 후의 체내 효소활성 변화를 관찰한 실험 결과 3분 동안 수영을 한 동물의 체내 효소활성 변화율이 가장 현저하게 변하는 것으로 확인 되었으므로 금은화 투여가 운동에 의한 동물의 체내 효소활성 변화를 측정하는 본 실험에서는 운동의 종류를 3분 수영으로 통일하여 실시하였다. 대조군은 운동을 하고 금은화 추출물 대신 증류수를 경구로 투여한 동물군 이었으며 공시험군은 운동을 하지 않고 증류수를 경구 섭취한 동물군 이었다. In the same manner as in Experiment 3, 6 SD rats adapted to general laboratory conditions were used as a group to adapt to exercise through gradual preliminary exercise for one week, and divided into groups to perform the exercise for another week. Following the method of Experiment 2-1, the animals were orally administered for one week, immediately after exercise (0 minutes), after 5 minutes (5 minutes), after 30 minutes (30 minutes), after 1 hour (60 minutes) of each animal. Changes in activity of MAO-A and MAO-B were measured in the brain and liver, respectively. Plasma obtained by centrifuging the collected blood for 15 minutes at 3000rpm was stored in a freezer at -80 ° C and the changes in blood LDH activity and lactate content were measured. As a result of observing the change of enzyme activity in the body after exercise, it was found that the rate of change of enzyme activity in the animal swimming for 3 minutes was most remarkably changed. The kind was carried out by unifying by 3 minutes swimming. The control group was a group of animals who exercised and orally administered distilled water instead of gold silver extract, and the blank group was a group of animals who orally consumed distilled water without exercise.
a. 수영운동한 랫트의 뇌 MAO-A의 효소활성 변화a. Changes in Enzyme Activity of Brain MAO-A in Rats Swimming
각 동물의 뇌에서 MAO-A의 활성 변화를 측정한 결과는 도 12와 같다. 도 12에서 보는 바와 같이 운동 직후부터 운동을 하지 않은 동물에 비해 현저히 낮아지는 뇌 MAO-A 효소활성은 금은화 추출물을 투여한 동물에서 운동을 하지 않은 동물과 같은 수준으로 회복되어 있는 것을 확인할 수 있었다. 이 결과로부터 금은화 추출물이 동물의 체내에서 MAO-A의 활성을 증가시킴으로서 운동으로 인한 동물체 내의 스트레스 조건에서 활성이 현저히 저하된 효소활성을 원 상태로 회복한 것으로 추정할 수 있었다. 이 결과는 한의학적으로 한성약물로 분류되는 금은화 추출물의 효소활성 증가 결과가 한의학의 기미론을 체내 MAO 활성의 변화로 설명하려는 시도로 행해진 동물실험에서 운동 시 한성약물에 의한 MAO-A의 활성 변화와 일치하는 결과이고 이는 또한 운동을 전후한 스트레스에 대한 반응으로 신경전달물질인 세로토닌의 농도가 급속히 변화하며 강한 신체 훈련을 시킨 동물의 뇌 조직에서 세로토닌의 농도와 세로토닌 모듈린 조직의 농도가 증가하며 이 기전에 따라 다양한 운동처방이 가능하다는 사실을 MAO 활성의 변화로서 설명할 수 있는 결과이기도 하다.As a result of measuring the change in the activity of MAO-A in the brain of each animal is shown in FIG. As shown in FIG. 12, the brain MAO-A enzyme activity, which is significantly lower than that of the non-exercise animal immediately after the exercise, was recovered to the same level as the non-exercised animal in the animal treated with the extract. From these results, it was estimated that the extract of gold sterling increased the activity of MAO-A in the body of the animal, thereby restoring the enzymatic activity of which activity was significantly reduced under stress conditions in the animal body due to exercise. This result is related to the change in the activity of MAO-A caused by the use of herbal medicine during exercise in the animal experiments in which the increase in the enzymatic activity of the gold and silver extracts, which are classified as oriental medicine, was attempted to explain the mimetics of oriental medicine as the change of the MAO activity in the body This is also in agreement with the pre and post-exercise stress, which results in a rapid change in the concentration of the neurotransmitter serotonin and an increase in the levels of serotonin and serotonin-modulin tissue in brain tissues of animals with strong physical training. The fact that various exercise prescriptions are possible according to the mechanism can be explained as a change in MAO activity.
b. 수영운동한 랫트의 간 MAO-B의 효소활성 변화b. Changes of Enzyme Activity of Liver MAO-B in Swimmers
수영 후 동물의 간에서 측정한 MAO-B의 활성변화를 도 13에 나타냈다. 운동 직후부터 운동을 하지 않은 동물에 비해 현저히 증가되는 뇌 MAO-B 효소활성은 금은화 추출물을 투여한 동물에서 운동을 하지 않은 동물과 같은 수준으로 거의 완전히 회복되는 것을 확인할 수 있었다. 이 결과로부터 금은화 추출물이 동물의 체내에서 MAO-B의 활성을 감소시킴으로서 운동으로 인한 동물체 내의 스트레스 조건에서 활성이 현저히 증가된 MAO-B 효소활성을 원 상태로 회복시킨 것이다. 이 결과는 MAO-A에 대한 금은화 추출물의 영향을 관찰한 도 12와 마찬가지로 눈에 띄게 확실한 변화 양상을 나타냄으로서 경구로 투여한 금은화 추출물이 뇌에서 뿐 아니라 간에서도 MAO 활성에 적극적으로 영향을 미치고 있다는 사실을 확인한 것이다. 따라서 금은화 추출물이 운동능력을 향상시키고 스트레스를 개선할 수 있는 식품의 소재로 활용 가능하다. The activity change of MAO-B measured in the liver of the animal after swimming is shown in FIG. 13. Significantly increased brain MAO-B enzymatic activity immediately after exercise was almost completely restored to the same level as the non-exercised animal in the animal treated with the extract. From these results, the extract was reduced MAO-B activity in the body of the animal to restore the MAO-B enzyme activity significantly increased activity under stress conditions in the animal body due to exercise. As shown in Fig. 12, which observed the effect of the sterling silver extract on MAO-A, the results showed that the orally administered sterling silver extract actively influenced MAO activity in the liver as well as in the brain. I confirmed the fact. Therefore, the extract of gold and silver can be used as a food material that can improve exercise ability and improve stress.
이 결과는 한성(cold) 및 열성스트레스(heat stress) 상태에 있는 동물에게 약물을 경구투여하고 효소활성의 변화를 관찰한 실험에서 확인된 결과와 같은 경향을 나타내는 것으로 확인되었다. 즉 한성약물을 경구투여하고 한성 및 열성스트레스를 유발시킨 경우 열성스트레스에 의해 감소된 MAO-A의 활성을 현저히 증가시킴으로서 병증의 개선효과를 기대하게 하는 반면, 한성 스트레스(cold stress) 유발 시에도 MAO-A의 효소활성은 증가되어 기론에 의한 한의학의 약리학적 해석이 MAO 활성 변화로 설명될 수 있음을 확인한 저자 등의 이전 실험 결과와 일치되는 결과임을 알 수 있었다(황금희 등, 대한본초학회지 14(1), pp1-14, 1999).This result was confirmed to show the same tendency as the results confirmed in the experiments in which oral administration of drugs and changes in enzyme activity to animals in cold and heat stress conditions. In other words, when oral administration of Hansung Pharm and causing Hanseong and recessive stress significantly increased the activity of MAO-A decreased by the recessive stress, the expectation of the improvement of the condition was expected, while MAO was induced even when cold stress was induced. The enzyme activity of -A was increased, which is consistent with the results of previous experiments by the authors who confirmed that the pharmacological interpretation of oriental medicine can be explained by the change in MAO activity (Hwang, Geum-Hee et al., Korean Journal of Herbal Medicine 14 ( 1) , pp 1-14, 1999).
c. 수영운동한 랫트의 혈중 LDH 효소활성 변화c. Changes in LDH Enzyme Activity in Blood of Swimming Rats
수영 후 동물의 혈액에서 측정한 LDH의 활성변화를 도 14에 나타냈다. 수영을 한 후 운동 직후부터 대조군에 비해 현저히 증가되었다가 약 한 시간이 경과했을 때 정상 수준으로 회복되는 것으로 확인된 동물의 혈중 LDH 효소활성은 금은화 추출물을 경구 투여한 실험동물 군에서 활성저하가 현저히 나타나 운동 후 한 시간까지 대조군과 같은 상태를 유지하고 있는 것으로 나타났다. 이 결과로부터 운동과 금은화 추출물 경구투여 동물에서 LDH의 변화 양상이 간 MAO-B의 변화양상과 같은 경향을 갖는다는 흥미로운 사실을 확인할 수 있었고 이러한 사실로부터 MAO에 대하여 저해활성을 갖는 금은화가 운동이나 신체의 스트레스로부터 회복을 촉진하는 활성을 갖는 것을 확인하였다.The activity change of LDH measured in the blood of the animal after swimming is shown in FIG. 14. Blood LDH enzyme activity in the animals found to increase significantly compared to the control group after swimming and to return to normal levels after about one hour was significantly decreased in the experimental animals group orally administered with the silver leaf extract. It appeared to remain in the same state as the control until one hour after exercise. From these results, it was found that the change of LDH tends to be the same as the change of hepatic MAO-B in oral exercise and gold silver extract oral animals. It was confirmed to have an activity that promotes recovery from stress.
d. 수영운동한 랫트의 혈중 락테이트 함량 변화d. Changes in Blood Lactate Content in Rats Swimming
수영 후 동물의 혈액에서 측정한 락테이트의 함량변화를 도 15에 나타냈다. 수영을 한 후 운동 직후부터 대조군에 비해 현저히 증가되는 것으로 확인된 동물의 혈중 락테이트 함량은 금은화 추출물을 경구 투여한 실험동물 군에서 대조군보다 낮은 상태를 유지하고 있는 것으로 확인되었다. 금은화 추출물 경구투여 동물에서 활성 저하가 지속되는 것으로 나타난 LDH 변화 양상이 락테이트 레벨의 패턴 변화와 일치하는 결과를 나타내는 것을 확인하였다. 이러한 사실로부터 MAO에 대하여 저해활성을 갖는 금은화가 운동이나 신체의 스트레스로부터 회복을 촉진하는 활성을 갖는 것을 확인할 수 있었다.Figure 15 shows the change in the lactate content measured in the blood of the animal after swimming. The blood lactate content of the animals that were found to be significantly increased compared to the control group immediately after the exercise after swimming was found to be lower than that of the control group in the experimental animal group administered orally with the sterling silver extract. It was confirmed that the pattern of LDH change that was shown to persist in activity in oral administration of gold silver extract extract showed consistent with the pattern change of lactate level. From these facts, it was confirmed that gold and silver coins having inhibitory activity against MAO have an activity of promoting recovery from exercise or physical stress.
실험예 5. 급성독성 시험Experimental Example 5. Acute Toxicity Test
ICR계 마우스(20±5 g, 바이오제노믹스)와 스프라그 도올리 랫트(235±10 g, 바이오제노믹스)를 사용하여 금은화 추출물의 급성독성 시험을 실시하였다. ICR계 마우스와 스프라그-도올리 랫트를 각각 10마리씩 4군으로 나누어 본 발명의 금은화 추출물을 각각 250, 500 및 1000 ㎎/㎏의 용량으로 경구 투여한 후 2주간 독성여부를 관찰한 결과 3군 모두에서 사망한 예가 한 마리도 없었고 외견상 대조군과 별다른 증상을 찾아볼 수 없었다.The acute toxicity test of the extract was conducted using ICR mice (20 ± 5 g, Biogenomes) and Sprague dooli rats (235 ± 10 g, Biogenomes). ICR-based mice and Sprague-Dawley rats were divided into four groups of 10 animals each, and the gold and silver extracts of the present invention were orally administered at doses of 250, 500, and 1000 mg / kg, respectively. No deaths occurred in all cases and no symptoms were apparent from the control group.
급성독성 시험 결과 금은화 메탄올 추출물의 경우 LD50이 1000 ㎎/㎏ 이상이었으며, 금은화 에탄올 추출물 역시 LD50이 1000 ㎎/㎏ 이상이었다. 또한 그 투여 가능 용량인 2000 ㎎/㎏에서 사망 예를 전혀 관찰할 수 없었으며, 체중 증가, 사료 섭취량 등에서 전혀 유의한 이상을 발견할 수 없었다. 따라서 금은화 추출물의 경우 안전한 약물임을 알 수 있었다.For the acute toxicity test results honeysuckle methanol extract LD 50 was more than 1000 ㎎ / ㎏, honeysuckle extract, ethanol was also LD 50 is more than 1000 ㎎ / ㎏. In addition, no mortality was observed at the dose of 2000 mg / kg, and no significant abnormality was found in weight gain and feed intake. Therefore, it was found that the gold coins extract is a safe drug.
하기에 상기 조성물의 제제 예를 설명하나, 이는 본 발명을 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Examples of the formulation of the composition are described below, but are not intended to limit the present invention but to explain in detail only.
제제예 1. 정제의 제조 Formulation Example 1 Preparation of Tablet
실시예 1 조추출물................................. 200 ㎎Example 1 Crude Extract ... 200 mg
유당 .............................................. 100 ㎎Lactose 100 mg
전분............................................... 100 ㎎Starch ......................................... 100 mg
스테아린산 마그네슘 ............................... 적 량Magnesium Stearate ...............
상기의 성분을 혼합하고 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조하였다.The tablets were prepared by mixing the above components and tableting according to a conventional method for producing tablets.
제제예 2. 캡슐제의 제조 Formulation Example 2 Preparation of Capsule
실시예 1 조추출물 ............................... 100 ㎎Example 1 Crude Extract ......................................... 100 mg
유당 ............................................ 50 ㎎Lactose ...... 50 mg
전분 ............................................ 50 ㎎Starch ............................ 50 mg
탈크 ............................................ 2 ㎎Talc ........................................ 2 mg
스테아린산 마그네슘 ............................ 적 량Magnesium Stearate ...............
상기의 성분을 혼합하고 통상의 캡슐제의 제조방법에 따라서 젤라틴 캡슐에 충전하여 캡슐제를 제조하였다.The capsules were prepared by mixing the above components and filling the gelatin capsules according to a conventional method for preparing capsules.
제제예 3. 액제의 제조 Formulation Example 3 Preparation of Liquid
실시예 1 조추출물 ........................... 1000 ㎎Example 1 Crude Extract ..................... 1000 mg
설탕 ........................................... 20 gSugar ........................... 20 g
이성화당 ....................................... 20 gIsomerized sugar ......................................... 20 g
레몬향 ......................................... 적량Lemon scent .........................
정제수를 가하여 전체 100 ㎖으로 맞추었다.Purified water was added to adjust the total volume to 100 ml.
상기의 성분을 통상의 액제의 제조방법에 따라서 혼합하고 100 ㎖ 의 갈색병에 충전하고 멸균시켜서 액제를 제조하였다.The above-mentioned components were mixed according to a conventional method for preparing a liquid solution, filled into a 100 ml brown bottle, and sterilized to prepare a liquid solution.
또한 하기와 같은 방법으로 스포츠 기능성 음료, 건강기능식품 및 건강기능음료를 제조하였다.In addition, sports functional drinks, health functional foods and health functional drinks were prepared in the following manner.
제제예 4. 스포츠 음료Formulation Example 4 Sports Drink
실시예 1 조추출물 ........................... 1000 ㎎Example 1 Crude Extract ..................... 1000 mg
시트르산 ...................................... 0.375 gCitric acid ............... 0.375 g
비타민 C ....................................... 0.075 gVitamin C ..................... 0.075 g
염화나트륨...................................... 0.125 gSodium Chloride ............... 0.125 g
염화칼륨........................................ 0.125 gPotassium chloride ..................................... 0.125 g
락트산칼슘..................................... 0.3 gCalcium Lactate ... 0.3 g
탄산마그네슘.................................... 5 mgMagnesium Carbonate ......................................... 5 mg
글루탐산나트륨.................................. 0.015 gSodium Glutamate ......................................... 0.015 g
향료..............................................적량Spices ..............................
정제수를 가하여 전체 250 ㎖으로 맞추었다.Purified water was added to adjust the total volume to 250 ml.
상기의 성분을 통상의 음료의 제조방법에 따라서 혼합하고 250 ㎖ 의 캔에 충전하여 스포츠 음료를 제조하였다.The above ingredients were mixed according to a conventional beverage production method and filled into 250 ml of can to prepare a sports drink.
제제예 5. 건강기능식품의 제조Formulation Example 5 Preparation of Health Functional Food
실시예 1 조추출물........................... 1000 ㎎Example 1 Crude extract ..................... 1000 mg
비타민 혼합물 .............................. 20 gVitamin Blend ............... 20 g
비타민 A 아세테이트......................... 70 ㎍Vitamin A Acetate ............... 70 μg
비타민 E ................................... 1 ㎎Vitamin E ......................... 1 mg
비타민 B1 .................................. 0.13 ㎎Vitamin B1 ..................................... 0.13 mg
비타민 B2 .................................. 0.15 ㎎Vitamin B2 ..................... 0.15 mg
비타민 B6 .................................. 0.5 ㎎Vitamin B6 ......................................... 0.5 mg
비타민 B12 ................................. 0.2 ㎍Vitamin B12 ................................. 0.2 μg
비타민 C ................................... 10 ㎎Vitamin C ......................................... 10 mg
비오틴 ..................................... 10 ㎍Biotin .......................... 10 μg
니코틴산아미드 ............................. 1.7 ㎎Nicotinic Acid Amide ......................................... 1.7 mg
엽산 ....................................... 50 ㎍Folic acid ......................................... 50 μg
판토텐산 칼슘 ............................... 0.5 ㎎Calcium Pantothenate ......................................... 0.5 mg
무기질 혼합물 ............................... 적량Mineral mixture ...............
황산제1철 ................................... 1.75 ㎎Ferrous Sulfate ............... 1.75 mg
산화아연 .................................... 0.82㎎Zinc Oxide ......................................... 0.82mg
탄산마그네슘 ................................ 25.3 ㎎Magnesium Carbonate ......................................... 25.3 mg
제1인산칼륨 .................................. 15 ㎎Potassium monophosphate ......................................... 15 mg
제2인산칼슘 .................................. 55 ㎎Dicalcium Phosphate ............... 55 mg
구연산칼륨 ................................... 90 ㎎Potassium Citrate ......................................... 90 mg
탄산칼슘 ..................................... 100 ㎎Calcium Carbonate ... 100 mg
염화마그네슘 ................................. 24.8 ㎎Magnesium Chloride ................................. 24.8 mg
상기 비타민 및 미네랄 혼합물의 조성비는 비교적 건강식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강기능식품 제조 방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강기능식품 조성물 제조에 사용할 수 있다.Although the composition ratio of the vitamin and mineral mixture is a composition suitable for a relatively healthy food in a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional health functional food production method. The granules may be prepared and used for preparing the nutraceutical composition according to a conventional method.
제제예 6. 건강기능음료의 제조Formulation Example 6 Preparation of Health Functional Drink
실시예 1 조추출물........................... 1000 ㎎Example 1 Crude extract ..................... 1000 mg
구연산...................................... 100 ㎎Citric Acid ..................... 100 mg
올리고당 ................................... 100 gOligosaccharide ......................................... 100 g
매실농축액 ................................. 2 gPlum concentrate ..................... 2 g
타우린 ..................................... 1 gTaurine ..................................... 1 g
정제수를 가하여 전체 ....................... 900㎖Purified water is added.
통상의 건강음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간동안 85℃에서 교반 가열한 후, 만들어진 용액을 여과하여 멸균된 2ℓ 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관한 다음 본 발명의 건강기능음료 조성물 제조에 사용한다.After mixing the above components in accordance with a conventional healthy beverage production method, and stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed sterilization and then refrigerated and stored in the present invention It is used to prepare a health functional beverage composition.
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.
본 발명은 금은화의 추출물은 시험관내 실험에서 MAO 효소활성을 강력히 저해하였고, 랫트에 경구 투여하고 운동한 후의 MAO-A 효소 정상화 효과, MAO-B 효소 저해효과, LDH 효소 저해 효과 및 락테이트 함량 감소효과를 나타냄을 밝힘으로서, 모노아민 산화효소 저해제, 항우울제 또는 우울증, 파킨슨씨병, 알츠하이머씨병을 위한 의약품 및 피로회복, 스트레스 해소 및 운동기능향상에 효과적인 스포츠용 기능성 식음료 뿐만 아니라 건강기능식품으로 이용가능하다.In the present invention, the extract of gold and silver coins strongly inhibited the MAO enzyme activity in the in vitro experiment, the normalization effect of MAO-A enzyme, MAO-B enzyme inhibition, LDH enzyme inhibition effect and lactate content after oral administration and exercise in rats It can be used as monoamine oxidase inhibitors, antidepressants or medicines for depression, Parkinson's disease, Alzheimer's disease, as well as sports functional foods and beverages that are effective for fatigue recovery, stress relief and motor function. .
도 1 은 본 발명의 금은화의 각 용매별 분획의 박층크로마토그램으로, 254mn UV에서 아니스 알데히드 용액을 사용하여 탐지한 것이고,1 is a thin layer chromatogram of each solvent fraction of the gold and silver of the present invention, which is detected by using an anise aldehyde solution at 254mn UV,
도 2 는 본 발명의 금은화의 각 용매별 분획의 박층크로마토그램으로, 365mn UV에서 10% 황산 용액을 사용하여 탐지한 것이고,Figure 2 is a thin layer chromatogram of each solvent fraction of the gold and silver of the present invention, it was detected using a 10% sulfuric acid solution at 365mn UV,
도 3 은 본 발명의 금은화 추출물을 랫트에 경구투여하였을 때 MAO-A 및 MAO-B의 활성정도의 변화를 나타낸 도이고,Figure 3 is a diagram showing the change in the activity of MAO-A and MAO-B when oral administration of the gold silver extract of the present invention to rats,
도 4 는 트레드밀 운동 후 랫트의 뇌에서의 MAO-A 효소 활성변화를 나타낸 도이고, 4 is a diagram showing the change of MAO-A enzyme activity in the brain of the rat after treadmill exercise,
도 5 는 트레드밀 운동 후 랫트의 간에서의 MAO-B 효소 활성변화를 나타낸 도이고, 5 is a diagram showing the change of MAO-B enzyme activity in the liver of the rat after treadmill exercise,
도 6 은 수영 후 랫트의 뇌에서의 MAO-A 효소 활성변화를 나타낸 도이고, 6 is a diagram showing the change of MAO-A enzyme activity in the brain of the rat after swimming,
도 7 은 수영 후 랫트의 간에서의 MAO-B 효소 활성변화를 나타낸 도이고, Figure 7 is a diagram showing the change in MAO-B enzyme activity in the liver of the rat after swimming,
도 8 은 트레드밀 운동 후 랫트의 혈중 락테이트 탈수소효소(LDH) 활성변화를 나타낸 도이고,8 is a diagram showing changes in lactate dehydrogenase (LDH) activity in rats after treadmill exercise,
도 9 는 트레드밀 운동 후 랫트의 혈중 락테이트 함량변화를 나타낸 도이고,9 is a diagram showing the change in blood lactate content of rats after treadmill exercise,
도 10 은 수영 후 랫트의 혈중 LDH 효소 활성변화를 나타낸 도이고,10 is a diagram showing the change in blood LDH enzyme activity of the rat after swimming,
도 11 은 수영 후 랫트의 혈중 락테이트 함량변화를 나타낸 도이고,11 is a diagram showing the change in blood lactate content of rats after swimming,
도 12 는 금은화 추출물을 경구투여한 랫트를 수영시킨 후, 뇌의 MAO-A 효소 활성변화를 나타낸 도이고,12 is a diagram showing the change in the MAO-A enzyme activity of the brain after swimming rats orally administered with the gold silver extract,
도 13 은 금은화 추출물을 경구투여한 랫트를 수영시킨 후, 간의 MAO-B 효소 활성변화를 나타낸 도이고,Figure 13 is a diagram showing the change in liver MAO-B enzyme activity after swimming rats orally administered gold silver coin extract,
도 14 는 금은화 추출물을 경구투여한 랫트를 수영시킨 후, 혈중 LDH 효소 활성변화를 나타낸 도이고,14 is a diagram showing the change in LDH enzyme activity in the blood after swimming rats orally administered with the gold silver extract,
도 15 는 금은화 추출물을 경구투여한 랫트를 수영시킨 후, 혈중 락테이트 함량변화를 나타낸 도이다.15 is a diagram showing the change in lactate content in the blood after swimming orally administered rats with gold silver extract.
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KR20210008608A (en) | 2019-07-15 | 2021-01-25 | 박경호 | Composition comprising extract of Lonicera japonica and Eucalpytus sp. for preventing or treating of cognitive dysfunction |
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