KR101059282B1 - Composition for the prevention and treatment of drug addiction and withdrawal symptoms containing gold and silver extract as an active ingredient - Google Patents
Composition for the prevention and treatment of drug addiction and withdrawal symptoms containing gold and silver extract as an active ingredient Download PDFInfo
- Publication number
- KR101059282B1 KR101059282B1 KR1020090000631A KR20090000631A KR101059282B1 KR 101059282 B1 KR101059282 B1 KR 101059282B1 KR 1020090000631 A KR1020090000631 A KR 1020090000631A KR 20090000631 A KR20090000631 A KR 20090000631A KR 101059282 B1 KR101059282 B1 KR 101059282B1
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- KR
- South Korea
- Prior art keywords
- extract
- gold
- silver
- composition
- drug addiction
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/35—Caprifoliaceae (Honeysuckle family)
- A61K36/355—Lonicera (honeysuckle)
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/334—Foods, ingredients or supplements having a functional effect on health treating the effects of consuming alcohol, narcotics or other addictive behavior, e.g. treating hangover or reducing blood alcohol levels
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
Abstract
본 발명은 금은화추출물을 유효성분으로 함유하는 조성물에 관한 것으로서, 구체적으로 본 발명의 금은화 추출물은 약물 중독의 지표로 사용되는 보행성 활동량(locomotor activity)의 감소효과뿐만 아니라, 뇌의 측핵과 선조체에서의 신경활성 지표인 c-Fos 발현을 급격히 감소시킴을 확인함으로써, 상기 조성물은 약물 중독 및 금단증상의 예방 및 치료를 위한 약학조성물 또는 건강기능식품으로 유용하게 이용될 수 있다.The present invention relates to a composition containing the sterling silver extract as an active ingredient, specifically, the sterling silver extract of the present invention, as well as the effect of reducing locomotor activity used as an indicator of drug addiction, in the nucleus and striatum of the brain By confirming the rapid reduction of c-Fos expression, which is an indicator of neuronal activity, the composition may be usefully used as a pharmaceutical composition or health functional food for the prevention and treatment of drug addiction and withdrawal symptoms.
금은화, 보행성 활동량, c-Fos, 코카인, 금단증상 Gold Silver Coins, Gait Activity, c-Fos, Cocaine, Withdrawal Symptoms
Description
본 발명은 금은화추출물을 유효성분으로 함유하는 약물 중독 및 금단증상의 예방 및 치료용 약학조성물 또는 건강기능식품에 관한 것이다.The present invention relates to a pharmaceutical composition or health functional food for the prevention and treatment of drug addiction and withdrawal symptoms containing gold and silver extract as an active ingredient.
[문헌 1] Einhorn, L.C., et al., Electrophysiological effect of cocaine in the mesoaccumbens dopamine system:studies in the ventral tegmental area, J Neurosci., 8(1), pp 100-112, 1988Einhorn, LC, et al., Electrophysiological effect of cocaine in the mesoaccumbens dopamine system: studies in the ventral tegmental area, J Neurosci., 8 (1) , pp 100-112, 1988
[문헌 2] Wiechman BE., et al., Pharmacol. Biochem. Behav., 15(3), pp.425-433, 19812 Wiechman BE., Et al., Pharmacol. Biochem. Behav ., 15 (3) , pp. 425-433, 1981
[문헌 3] Parada A., et al., Neuropharmacology, 39(9), pp.1645-1652, 2000Parada A., et al., Neuropharmacology , 39 (9) , pp. 1645-1652, 2000
[문헌 4] Pontieri FE., et al., Natl. Acad. Sci. USA., 92, pp.12304-12308, 19954 Pontieri FE., Et al., Natl. Acad. Sci. USA. , 92 , pp.12304-12308, 1995
[문헌 5] Kuczenski R., et al., J. Neurosci., 11(9), pp.2703-2712, 1991Kuczenski R., et al., J. Neurosci ., 11 (9) , pp.2703-2712, 1991
[문헌 6] 박종희 저, 한약백과도감(하), 도서출판 신일상사, p.654-655, 2002[Document 6] Park, Jong-Hee Author, Encyclopedia of Herbal Medicine (Ha), Book Publishing Company, Il-il, p.654-655, 2002
[문헌 7] 문태철 외 7인, 금은화 플라보노이드성분의 항염증작용, 대한약학회, 약학회지, 43(1), pp.117-123, 1999[Reference 7] Moon Tae-Chul et al. 7, Anti-inflammatory activity of gold and silver flavonoids, Korean Journal of Pharmacy, Journal of Pharmacy, 43 (1) , pp.117-123, 1999
[문헌 8] 박욱연 외 2인, 한약재 추출물의 항균효과 검색, 한국식품영양과학회, 한국식품영양학회지, 한국영양식량학회지, 21(1), pp.91-96, 1992[Document 8] Park, Uk-Yeon et al. 2, Antimicrobial Effect of Medicinal Herb Extracts, Korean Society of Food Science and Nutrition, Korean Society of Food Science and Nutrition, 21 (1) , pp.91-96, 1992
[문헌 9] Karasinska JM., et al., Eur Neurosci., 22(7), pp.1741-1750, 20059, Karasinska JM., Et al., Eur Neurosci ., 22 (7) , pp.1741-1750, 2005
[문헌 10] Jang EY, et al., Eur J Pharmacol., 587(1-3), pp.124-128, 200810 Jang EY, et al., Eur J Pharmacol., 587 (1-3) , pp. 124-128, 2008
[문헌 11] 이형철 외, 동의병리학회지, 15(4), pp543-547, 2001[Reference Document 11] Hyung-Chul Lee et al., Journal of Oriental Pathology , 15 (4) , pp543-547, 2001
과학문명의 발달과 급진하는 경제사회에 따른 현대인들의 잇따른 스트레스로 인해 약물 중독의 확산은 가장 중요한 현대 사회문제 중의 하나이다. 약물이란 질병을 예방, 치료하는데 사용되는 물질을 지칭하며, 신체기능의 변화를 일으키는 물질을 말한다. 이러한 약물의 남용은 부정적인 측면에서 신체적, 정신적, 사회적으로 자기 파괴의 문제를 발생시킨다. 약물 중독은 아편이나 신경안정제 또는 알코올과 같은 약물에 대한 신체적인 반응을 지칭한다. 이러한 약물 중독은 내성, 금단증상 및 습관화의 현상을 가지는데, 약물의 사용으로 인한 통제력 상실을 의미하기도 한다. 최근의 약물남용은 청소년, 여성 약물남용자의 증가로 인한 세계적으로 심각한 정신질환중의 하나로서, 중독성 약물에 대한 치료제의 개발은 시급한 현실이다. The spread of drug addiction is one of the most important modern social problems due to the development of scientific civilization and the stress of modern people due to the rapid economic society. Drug refers to a substance used to prevent or treat a disease, and refers to a substance that causes a change in physical function. Abuse of these drugs raises the problem of self-destruction both physically, mentally and socially on the negative side. Drug addiction refers to a physical reaction to drugs such as opiates, neurostabilizers or alcohol. Drug addiction has symptoms of tolerance, withdrawal symptoms and habituation, which can mean loss of control due to drug use. Recent drug abuse is one of the world's most serious mental illnesses caused by the increasing number of adolescents and female drug abusers. The development of drugs for addictive drugs is urgently needed.
이러한 약물 중독의 해결책으로 여러 가지 사회정책 및 치료, 재활을 위한 프로그램이 이루어지고 있지만, 근본적인 치료대책으로서 한계점을 가지고 있다.As a solution of drug addiction, various social policies, treatments, and rehabilitation programs are being implemented, but they have limitations as a fundamental treatment measure.
코카인 (cocaine), 암페타민 (amphetamine), 모르핀 (morphine), 니코틴(nicotine), 대마초, 카페인(caffeine) 등과 같은 중독성 약물들은 행동방식 중 행동적 민감화 (Behavioral sensitization)현상을 유발하는데 행동적 민감화란 적은 양의 중독성 약물을 반복적 또는 간헐적으로 투여하면 보행성 활동량(locomotor activity)과 상동적 행동(stereotypy)이 점진적으로 증가하는 현상으로, 활동량의 점차적인 증가가 유도발달되는 상태인 발달 단계(Development = induction of sensitization)와 일단 발달된 활동량이 비교적 장기간 유지되는 상태인 발현 단계 (expression of sensitization)로 나타나게 되는데, 이러한 현상을 담당하는 신경적 근저(neural substrate)는 중추 신경계내 중뇌 변연 도파민계(mesolimbic dopamine pathway)로 도파민 신경세포와 그 표적영역인 측좌핵(NAc, nucleus accumbens)과 선조체(striatum)인 것으로 알려져 있으며(Einhorn, L.C., et al., Electrophysiological effect of cocaine in the mesoaccumbens dopamine system:studies in the ventral tegmental area, J Neurosci., 8(1), pp 100-112, 1988), 중독성 약물들은 약물투여에 따른 보행성 활동량을 증가시킨다고 알려져 있어(Wiechman BE., et al., Pharmacol. Biochem. Behav., 15(3), pp.425-433, 1981), 보행성 활동량은 주요한 약물 중독의 지표로 사용되고 있다. Addictive drugs such as cocaine, amphetamine, morphine, nicotine, cannabis, caffeine, etc., cause behavioral sensitization in behavior. Repeated or intermittent doses of an addictive drug gradually increase locomotor activity and homotypy, a developmental phase in which a gradual increase in activity is induced. of sensitization and the expression of sensitization, which is a state where activity is developed for a relatively long time, and the neural substrate responsible for this phenomenon is the mesolimbic dopamine pathway in the central nervous system. Dopamine neurons and their target regions, the nucleus accumbens (NAc) and striatum. (Einhorn, LC, et al., Electrophysiological effect of cocaine in the mesoaccumbens dopamine system: studies in the ventral tegmental area, J Neurosci., 8 (1) , pp 100-112, 1988). It is known to increase the amount of walking activity following administration (Wiechman BE., Et al., Pharmacol. Biochem. Behav ., 15 (3) , pp.425-433, 1981). Is being used.
코카인은 약물강화효과를 통하여 탐닉현상이 생기는데, 이러한 행동적 변화에 영향을 주는 요인이 도파민 (Dopamine, DA) 신경전달계의 활성화로서, 특히 코카인 투여로 인한 보상 및 강화작용은 복측 피개 영역 (Ventral tegmental area, VTA)의 A10 신경 (A10 neuron)에서 기시하여 측핵 (Nucleus accumbens)으로 투사되는 중뇌 변연계가 중요한 역할을 맡고 있다고 알려져 있다(Einhorn, L.C., et al., Electrophysiological effect of cocaine in the mesoaccumbens dopamine system:studies in the ventral tegmental area, J Neurosci., 8(1), pp 100-112, 1988).Cocaine is induced through drug-intensifying effects. The factor affecting this behavioral change is the activation of the dopamine (DA) neurotransmitter. In particular, cocaine administration compensates and strengthens the ventral tegmental area. The midbrain limbic system, originating in the A10 neuron of the area (VTA) and projecting into the nucleus accumbens, is known to play an important role (Einhorn, LC, et al., Electrophysiological effect of cocaine in the mesoaccumbens dopamine system). : studies in the ventral tegmental area, J Neurosci., 8 (1) , pp 100-112, 1988).
최근의 연구들을 보면 코카인의 투여로 인하여 약물 중독과 관련이 있는 측핵 및 선조체 등의 도파민성 신경세포의 투사부위에서 신경활성의 지표라고 알려진 초기 유전자 c-Fos (Immediate early gene c-Fos)의 단백인 c-Fos발현이 증가되었 다는 보고가 있다. 실험동물에 반복적으로 도파민 D1 수용체 효능제인 SKF-38393를 투여한 경우, 보행성 활동량과 신경활성도의 지표인 c-Fos 의 발현이 증가되었다. 또한 도파민의 길항물질인 SCH 23390을 투여한 결과, 코카인에 의한 보행성 활동량이 줄어들었다 (Parada A., et al., Neuropharmacology, 39(9), pp.1645-1652, 2000). 추가로 생체내 (In vivo) 미세투석법 (Microdialysis)을 이용하여 관찰한 실험에서 약물 중독과 관련있는 부위인 선조체 및 측핵에서 코카인 투여로 인한 도파민의 농도는 현저하게 증가하였으며 (Pontieri FE., et al., Natl. Acad. Sci. USA., 92, pp.12304-12308, 1995), 이는, 보행성 활동량이 증가를 보임으로써, 생화학적인 측면인 도파민과 행동학적인 측면인 보행성 활동량이 상관관계가 있음을 보여주는 실험적인 증거를 제시하였다 (Kuczenski R., et al., J. Neurosci., 11(9), pp.2703-2712, 1991). In a recent study due to the administration of cocaine, known as indicators of neuronal activity in drug addiction and related cheukhaek and projected areas of the striatum, including dopaminergic neurons of the early gene cF os (Immediate early gene cF os ) protein, c of There are reports of increased fos expression. Repeated administration of SKF-38393, a dopamine D1 receptor agonist, to experimental animals increased the expression of c-Fos, an indicator of gait activity and neuronal activity. In addition, the administration of dopamine antagonist SCH 23390 resulted in a decrease in ambulatory activity caused by cocaine (Parada A., et al., Neuropharmacology , 39 (9) , pp.1645-1652, 2000). In addition, in the experiments observed using in vivo microdialysis, the concentration of dopamine due to cocaine administration in the striatum and the nucleus, which are related to drug intoxication, increased significantly (Pontieri FE., Et. al., Natl. Acad. Sci. USA. , 92 , pp . 12304-12308, 1995), which showed an increase in gait activity, correlating dopamine, a biochemical aspect, and gait activity, a behavioral aspect. Experimental evidence has been shown to show that there is (Kuczenski R., et al., J. Neurosci ., 11 (9) , pp.2703-2712, 1991).
따라서 약물의 중독성에 관여하는 신경기전의 규명이야말로 약물중독치료에 궁극적인 해답을 줄 수 있을 것이다.Therefore, the identification of neural mechanisms involved in drug addiction may be the ultimate solution to drug addiction treatment.
인동(忍冬, Lonicerae Caulis et Folium)은 인동과의 인동덩굴 (Lonicera japonica Thunberg)의 줄기 또는 엽(葉)이 붙은 줄기를 건조한 것으로 추운 겨울에도 넝쿨이 살아서 시들지 않기 때문에 붙여졌다. Lonicerae Caulis et Folium is a dry stem or lobe of Lonicera japonica Thunberg, which is attached because the vine does not live and wither in cold winter.
일반적으로, 금은화는 인동과의 인동덩굴 또는 그 변종의 꽃봉오리 부분을 나타내며, 본초강목(本草綱目)에는 경(莖; 줄기), 엽(葉; 잎) 및 화(花; 꽃) 모두 사용한다고 하였으나, 임상적으로 등(藤), 엽(葉) 보다 꽃(금은화)이 효능이 좋기 때문에 지금은 대부분 꽃만을 사용하게 되으며, 금은화란 이름은 처음 피는 꽃이 흰색이지만 차차 노랗게 변해서 붙여진 이름으로 인동화(忍冬花), 이화(二花), 은화(銀花), 쌍화(雙花), 금화(金花), 금등화(金藤花), 금은등(金銀藤), 원앙등(鴛鴦藤), 로사등(鷺藤), 노옹수(老翁須), 좌전등(左纏藤), 금채고(金釵股), 통영초(通靈草) 및 밀통등(蜜桶藤)이라는 다양한 이름으로 불리우며, 특징은 특이한 냄새가 있고 맛은 달고 성질은 차다. 성분으로는 루테올린(luteolin) 및 이노시톨(inositol)이 약 1%가 함유되어 있으며 이외에 사포닌(saponin), 탄닌(tannin) 및 로니세린(lonicerin, =luteolinrhamnoglucoside)을 함유하며(박종희 저, 한약백과도감(하), 도서출판 신일상사, p.654-655, 2002), 효능으로는 이질, 열독으로 인한 피부 조직 괴사, 유선염, 대장염, 위궤양, 방광염, 인후염, 편도선염, 기관지염, 결막염 및 부스럼, 유행성 이하선염으로 인한 고열, 화농성 감염증의 효과가 있으며, 약리작용은 항균작용, 항염증작용, 해열작용, 백혈구 탐식작용 증가, 중추신경 흥분작용, 혈청 콜레스테롤 강하, 궤양 예방효과 등이 보고되어 있으나(문태철 외 7인, 금은화 플라보노이드성분의 항염증작용, 대한약학회, 약학회지, 43(1), pp.117-123, 1999; 박욱연 외 2인, 한약재 추출물의 항균효과 검색, 한국식품영양과학회, 한국식품영양학회지, 한국영양식량학회지, 21(1), pp.91-96, 1992), 상기 문헌 어디에도 금은화추출물이 약물 중독 및 금단증상에 효과적이라는 어떠한 개시도 된 바가 없다.In general, gold and silver coins represent the bud part of the genus Phosphorus or its variety, and both the stem, the leaves, and the flowers are used for the herbaceous cortex. However, clinically, flowers (gold and silver) are more effective than 藤, 藤 (leaf), so now they mostly use only flowers. The name of gold and silver is the name of the first blooming flower, but gradually changed to yellow. Inhwahwa, Ewha, Silver, Ssanghwa, Geumhwa, Geumdeunghwa, Geumeundeung, Mandarin Lamp Various names such as 藤, Rosa lanterns, Noh Onsu, left front lantern, Geumchaego, Tongyeongcho and Tongtong, etc. It has a peculiar smell and tastes sweet and cold. It contains about 1% of luteolin and inositol, and contains saponin, tannin, and lonicerin (luteolinrhamnoglucoside). (Bottom), Shinil Trading Co., p.654-655, 2002), the effect is dysentery, skin tissue necrosis due to heat poisoning, mastitis, colitis, gastric ulcer, cystitis, sore throat, tonsillitis, bronchitis, conjunctivitis and mumps, mumps It has high fever and purulent infectious diseases, and its pharmacological effects are antimicrobial, anti-inflammatory, antipyretic, leukocyte phagocytosis, central nervous system excitability, serum cholesterol drop, and ulcer prevention effects (Mt. the anti-inflammatory effect of flavonoid components honeysuckle, of Pharmacy, about Journal, 43 (1), pp.117-123, 1999; antimicrobial effect of the two, other medicinal herb extracts bakukyeon search, Korea Food Research, Korean Journal of Nutrition, Food Science and Nutrition Korea, 21 (1), pp.91-96, 1992), supra anywhere honeysuckle extract drug addiction and also not been any initiation of effective withdrawal symptoms.
이에 본 발명자들은 금은화추출물이 약물 중독의 지표로 사용되는 보행성 활동량의 감소효과뿐만 아니라, 뇌의 측핵과 선조체에서의 신경활성 지표인 c-Fos 발현을 급격히 감소시킴을 확인함으로써, 약물 중독 및 금단증상의 치료 효과를 확인 하여 본 발명을 완성하였다.Therefore, the present inventors confirmed that gold and silver extract extracts not only the effect of reducing the amount of gait activity used as an indicator of drug addiction, but also dramatically decreases c-Fos expression, which is an indicator of neuronal activity in the nucleus and striatum of the brain. The present invention was completed by confirming the therapeutic effect of the symptoms.
상기 목적을 달성하기 위하여, 금은화추출물을 유효성분으로 함유하는 약물 중독 및 금단증상의 예방 및 치료용 약학조성물을 제공한다.In order to achieve the above object, it provides a pharmaceutical composition for the prevention and treatment of drug addiction and withdrawal symptoms containing a gold coin extract as an active ingredient.
또한 본 발명은, 금은화추출물을 유효성분으로 함유하는 약물 중독 및 금단증상의 예방 및 개선용 건강기능식품을 제공한다.In another aspect, the present invention provides a dietary supplement for the prevention and improvement of drug addiction and withdrawal symptoms containing gold and silver extract as an active ingredient.
본원에서 정의되는 금은화추출물은 물, C1 내지 C4의 저급 알콜 용매 또는 이들의 혼합 용매, 바람직하게는 물 및 에탄올 혼합 용매, 보다 바람직하게는 60 내지 100% 에탄올 혼합용매, 가장 바람직하게는 90 내지 100% 에탄올에 가용한 추출물을 포함한다.The sterling silver extracts as defined herein are water, lower alcohol solvents of C 1 to C 4 or mixed solvents thereof, preferably water and ethanol mixed solvents, more preferably 60 to 100% ethanol mixed solvents, most preferably 90 To extracts soluble in 100% ethanol.
본원에서 정의되는 약물은 코카인 (cocaine), 암페타민 (amphetamine), 모르핀 (morphine), 니코틴(nicotine), 대마초 또는 카페인(caffeine) 등이며, 바람직하게는 코카인임을 특징으로 포함한다.Drugs as defined herein are cocaine, amphetamine, morphine, nicotine, cannabis or caffeine, and the like, preferably characterized as being cocaine.
이하, 본 발명을 상세히 설명한다. Hereinafter, the present invention will be described in detail.
본 발명의 금은화추출물은 하기와 같이 제조될 수 있다.The gold coin extract of the present invention can be prepared as follows.
본 발명의 본 발명의 금은화를 음건하여 마쇄한 후, 금은화 중량의 약 1 내지 25배, 바람직하게는 약 5 내지 20배 분량의 물, C1 내지 C4의 저급 알콜 용매 및 이들의 혼합 용매, 바람직하게는 물 및 에탄올 혼합 용매, 보다 바람직하게는 60 내지 100% 에탄올 혼합용매로, 실온에서 약 10 내지 96시간, 바람직하게는 60 내지 80시간 동안 열수 추출, 냉침 추출, 환류 냉각 추출 또는 초음파 추출 등의 추출방법을 사용하여, 바람직하게는 냉침 추출한 후 수득한 추출액을 여과, 감압 농축 또는 건조하여 본 발명의 금은화추출물을 수득할 수 있다.After drying and crushing the gold and silver coins of the present invention, about 1 to 25 times, preferably about 5 to 20 times the amount of water, C 1 to C 4 lower alcohol solvents and mixed solvents thereof, Preferably hot water extraction, cold extraction, reflux cooling extraction or ultrasonic extraction with water and ethanol mixed solvent, more preferably 60-100% ethanol mixed solvent at room temperature for about 10-96 hours, preferably 60-80 hours Using an extraction method such as, preferably, the extract obtained after cold extraction is filtered, concentrated under reduced pressure or dried to obtain the gold coin extract of the present invention.
본 발명은 상기 제조방법으로 수득한 금은화추출물을 유효성분으로 함유하는 약물 중독 및 금단증상의 예방 및 치료용 약학조성물을 제공한다.The present invention provides a pharmaceutical composition for the prevention and treatment of drug addiction and withdrawal symptom, which contains the gold and silver extract obtained by the manufacturing method as an active ingredient.
본 발명의 조성물은, 조성물 총 중량에 대하여 상기 추출물을 0.02 내지 50% 중량으로 포함한다. The composition of the present invention comprises from 0.02 to 50% by weight of the extract relative to the total weight of the composition.
그러나 상기와 같은 조성은 반드시 이에 한정되는 것은 아니고, 환자의 상태 및 질환의 종류 및 진행 정도에 따라 변할 수 있다.However, the composition is not limited thereto, and may vary depending on the condition of the patient, the type of disease, and the progress of the disease.
본 발명의 금은화추출물을 포함하는 조성물은 약학적 조성물의 제조에 통상적으로 사용하는 적절한 담체, 부형제 및 희석제를 더 포함할 수 있다. The composition containing the gold coin extract of the present invention may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.
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 있으며, 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, 프로필히드록시벤 조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다. 제제화할 경우에는 보통 사용하는 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 또는 부형제를 사용하여 조제된다. 경구투여를 위한 고형제제에는 정제, 환제, 산제, 과립제, 캡슐제 등이 포함되며, 이러한 고형제제는 상기 추출물에 적어도 하나 이상의 부형제 예를 들면, 전분, 칼슘카보네이트(calcium carbonate), 수크로스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제된다. 또한 단순한 부형제 이외에 마그네슘 스티레이트 탈크 같은 윤활제들도 사용된다. 경구를 위한 액상제제로는 현탁제, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조제제, 좌제가 포함된다. 비수성용제, 현탁제로는 프로필렌글리콜 (propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 위텝솔(witepsol), 마크로골, 트윈 (tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 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. Carriers, excipients and diluents which may be used in combination with the extract, and which may be included in the composition comprising the extract 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, propylhydroxybenzate, talc, magnesium stearate and mineral oil. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and the solid preparations may include at least one excipient such as starch, calcium carbonate, sucrose in the extract. ) Or lactose, gelatin and the like are mixed. In addition to simple excipients, lubricants such as magnesium styrate talc are also used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
본 발명의 추출물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. 그러나 바람직한 효과를 위해서, 본 발명의 추출물은 1일 0.01 mg/kg 내지 10 g/kg으로, 바람직하게는 1 mg/kg 내지 1 g/kg으로 투여하는 것이 좋다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수 있다. 따라서 상기 투여량 은 어떠한 면으로든 본 발명의 범위를 한정하는 것은 아니다.Preferred dosages of the extracts of the present invention vary depending on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art. However, for the desired effect, the extract of the present invention is preferably administered at 0.01 mg / kg to 10 g / kg, preferably 1 mg / kg to 1 g / kg per day. The administration may be carried out once a day or divided into several doses. Therefore, the above dosage does not limit the scope of the present invention in any aspect.
본 발명의 조성물은 쥐, 생쥐, 가축, 인간 등의 포유동물에 다양한 경로로 투여될 수 있다. 투여의 모든 방식은 예상될 수 있는데, 예를 들면, 경구, 직장 또는 정맥, 근육, 피하, 자궁내 경막 또는 뇌혈관내(Intracerebroventricular) 주사에 의해 투여될 수 있다. The composition of the present invention may be administered to mammals such as rats, mice, livestock, humans, and the like in various routes. All modes of administration can be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or Intracerebroventricular injection.
또한, 본 발명은 금은화추출물을 유효성분으로 함유하는 약물 중독 및 금단증상의 예방 및 개선용 건강기능식품을 제공한다.The present invention also provides a dietary supplement for the prevention and improvement of drug addiction and withdrawal symptoms containing gold and silver extract as an active ingredient.
본원에서 정의되는 “건강기능식품”은 건강기능식품에 관한 법률 제6727호에 따른 인체에 유용한 기능성을 가진 원료나 성분을 사용하여 제조 및 가공한 식품을 의미하며, “기능성”이라 함은 인체의 구조 및 기능에 대하여 영양소를 조절하거나 생리학적 작용 등과 같은 보건 용도에 유용한 효과를 얻을 목적으로 섭취하는 것을 의미한다.As defined herein, "health functional food" means a food manufactured and processed using raw materials or ingredients having functional properties useful for the human body under the Health Functional Food Act No. 6767, and "functional" means It means ingestion for the purpose of obtaining useful effects on health use such as nutrient control or physiological action on structure and function.
본 발명의 추출물을 포함하는 조성물은 약물 중독 및 금단증상의 예방 및 개선을 위한 약제, 식품 및 음료 등에 다양하게 이용될 수 있다. 본 발명의 금은화추출물을 첨가할 수 있는 식품으로는, 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합제, 건강보조 식품류 등이 있고, 분말, 과립, 정제, 캡슐, 시럽제 또는 음료인 형태로 사용할 수 있다.The composition comprising the extract of the present invention can be used in various ways, such as drugs, foods and drinks for the prevention and improvement of drug addiction and withdrawal symptoms. Foods to which the gold and silver extract of the present invention may be added include, for example, various foods, beverages, gums, teas, vitamin complexes, health supplements, and the like, and are powders, granules, tablets, capsules, syrups or beverages. Can be used as
본 발명의 금은화추출물 자체는 독성 및 부작용은 거의 없으므로 예방 목적으로 장기간 복용 시에도 안심하고 사용할 수 있는 약제이다.The gold and silver extract of the present invention has little 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 약물 중독 및 금단증상의 예방 및 치료를 위한 목 적으로 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 15 중량%로 가할 수 있으며, 건강 음료 조성물은 100 ㎖를 기준으로 0.02 내지 10 g, 바람직하게는 0.3 내지 1 g의 비율로 가할 수 있다. The extract of the present invention may be added to food or beverage for the purpose of preventing and treating drug addiction and withdrawal symptoms. 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 15% by weight of the total food weight, the health beverage composition is 0.02 to 10 g based on 100 ml, preferably Can be added in a ratio of 0.3 to 1 g.
본 발명의 건강 음료 조성물은 지시된 비율로 필수 성분으로서 상기 추출물을 함유하는 것 외에 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 등의 디사카라이드, 예를 들어 말토스, 슈크로스 등의 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 20g, 바람직하게는 약 5 내지 12g이다.In addition to containing the extract as an essential ingredient in the indicated ratio, the health beverage composition of the present invention is not particularly limited in the liquid component and may contain various flavors or natural carbohydrates as additional ingredients, as in general beverages. Examples of the above-mentioned natural carbohydrates include monosaccharides such as disaccharides such as glucose and fructose such as maltose, sucrose and the like and polysaccharides such as dextrin, cyclodextrin and the like Sugar, 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 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 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 중진제(치즈, 초콜릿 등), 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 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 조합 하여 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 its Salts, 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 in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.
본 발명의 금은화추출물은 약물 중독의 지표로 사용되는 보행성 활동량의 감소효과뿐만 아니라, 뇌의 측핵과 선조체에서의 신경활성 지표인 c-Fos 발현을 급격히 감소시키는 효과를 나타내는 바, 약물 중독 및 금단증상의 예방 및 치료용 약학조성물 또는 건강기능식품으로 유용하게 사용될 수 있다.The gold and silver extract of the present invention not only reduces the amount of gait activity used as an indicator of drug addiction, but also shows an effect of rapidly decreasing c-Fos expression, which is an indicator of neuronal activity in the nucleus and striatum of the brain, drug addiction and withdrawal. It can be usefully used as a pharmaceutical composition or health functional food for the prevention and treatment of symptoms.
이하, 본 발명을 하기 참고예, 실시예 및 실험예에 의해 상세히 설명한다.Hereinafter, the present invention will be described in detail by the following reference examples, examples and experimental examples.
단, 하기 참고예, 실시예 및 실험예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 참고예, 실시예 및 실험예에 의해 한정되는 것은 아니다.However, the following reference examples, examples and experimental examples are merely to illustrate the invention, the content of the present invention is not limited by the following reference examples, examples and experimental examples.
참고예 1. 실험동물의 준비Reference Example 1. Preparation of Laboratory Animals
실험동물은 체중 250-260 g의 스프라그-다우리(Sprague-Dawley)계 수컷 랫트(효창사이언스)를 사용하였고, 대구한의대학교 동물사육실에서 일정한 조건(온도: 21± 2℃, 명암: 12시간 명암주기)에서, 사료와 음수의 자유로운 섭취가 가능하도록 하였으며, 실험시작 전까지 물과 먹이를 충분히 제공하며 실험시작 전에 실험동물을 3일 동안 하루에 10분씩 사전취급(Handling)한다.The experimental animals were Sprague-Dawley male rats (Hyochang Science) weighing 250-260 g. In the time-contrast cycle, free intake of feed and negative water was allowed, and sufficient water and food were provided before the start of the experiment, and the animals were handled for 10 minutes a day for 3 days before the start of the experiment.
참고예 2.Reference Example 2. 통계처리Statistical processing
보행성 활동량은 박스 내에서 수평이동거리(㎝)로 측정하였으며, 통계적 유의성은 SPSS 프로그램(Version 11.01)의 포스트 훅 터키 테스트(post hoc Turkey test)로 검정하여 p값이 0.05이하인 경우에 유의한 것으로 인정하였다.Pedestrian activity was measured by horizontal movement distance (cm) in the box, and statistical significance was tested by the SPSS program (Version 11.01) post hoc Turkey test. Admitted.
실시예 1. 금은화추출물의 제조 Example 1 Preparation of Gold Coin Extract
대구광역시에 위치한 대원약업사에서 구입하여 음건 세절한 금은화 3kg을 15ℓ용량의 95% 에탄올을 가하고, 상온(24℃)에서 72시간 동안 추출하여 수득한 추출액을 여과한 후, 감압농축기 (EYELA Co., Japan)로 감압 농축하여 금은화추출물 290g을 수득하였다(이하 “LJ"라 함).Purified from Daewon Pharmaceutical Co., Ltd. located in Daegu Metropolitan City, 3 kg of finely divided gold and silver coins were added with 15 L of 95% ethanol, and the extract was extracted for 72 hours at room temperature (24 ° C), and then filtered under reduced pressure (EYELA Co., Concentration under reduced pressure in Japan) to give 290 g of silver coin extract (hereinafter referred to as "LJ").
실험예 1. 약물 투여 후 행동적 민감성에 대한 금은화추출물의 효과Experimental Example 1.Effect of Gold Coin Extract on Behavioral Sensitivity after Drug Administration
급성 및 만성 약물 투여로 의한 행동적 민감성에 대한 상기 실시예 1의 금은화추출물의 효과를 확인하기 위하여 하기와 같이 코카인 투여 후 랫트의 보행성 활동량 변화에 대한 실험을 문헌에 기재된 방법을 응용하여 하기와 같은 방법으로 수행하였다(Karasinska JM., et al., Eur Neurosci., 22(7), pp.1741-1750, 2005).In order to confirm the effect of the sterling silver extract of Example 1 on the behavioral sensitivity due to acute and chronic drug administration, the experiment on the change in gait activity of rats after cocaine administration was applied as follows. The same method was performed (Karasinska JM., Et al., Eur Neurosci ., 22 (7) , pp.1741-1750, 2005).
1-1. 보행성 활동량의 측정 방법1-1. How to measure amount of walking activity
실험동물의 활동량은 비디오트랙킹(videotracking)을 이용하여 에토비젼 프 로그램(Ethovision program, Noldus Information Technology BV, Wageningen, Netherlands)으로 측정하였다. 상세하게는 가로, 세로, 높이가 40cm x 40cm x 45cm 인 검은색 무광택 아크릴 상자를 이용하여 실험동물의 수평 움직임을 추적하였으며, 9개 상자의 약 2.5 m 위에 디지털 카메라를 설치하여 이로부터 얻어진 화상을 컴퓨터에 전달하여 검은 배경에 흰색 피사체의 대조 원리를 이용함으로써 흰색 실험동물 상(Image)의 중심점을 초당 수 번 인식하는 방식으로 실험동물의 움직임을 따라 추적하여 실험동물의 움직임의 궤적을 데이터화하여 움직인 거리를 정량화하였다.The activity of the experimental animals was measured by an etovision program (Ethovision program, Noldus Information Technology BV, Wageningen, Netherlands) using videotracking. In detail, the horizontal movement of the test animal was tracked using a black matt acrylic box of 40 cm x 40 cm x 45 cm in width, length, and height, and the image obtained from the digital camera was installed on about 2.5 m of nine boxes. By using a contrasting principle of a white subject on a black background, it transfers it to a computer and recognizes the center point of the white experimental image several times per second. Phosphorus distance was quantified.
1-2. 보행성 활동량의 측정1-2. Measurement of ambulatory activity
상기 참고예 1에서 준비된 실험동물을 사육장에서 외부소음이 차단된 실험실로 옮겨 각각 무게를 측정한 후, 9개의 활동량 측정상자에 개별적으로 넣었다. 상자 내에서 60분간 적응시간을 거쳐 60분간 기저 활동량(baseline)을 측정한 후, 금은화추출물 25, 50, 및 100 mg/kg을 각각 1회 경구 투여하였으며, 대조군으로 2 ml/kg의 vehicle(70% PEG+1% Tween 80+10% EtOH)를 경구 투여하였다. Vehicle 또는 금은화 추출물을 경구투여하고, 60분 후 생리식염수 또는 코카인 20 mg/kg를 단회투여하고, 추가적으로 60분 동안 보행하여 박스 내에서 수평이동거리(cm)로 보행성 활동량을 측정하였다.The experimental animals prepared in Reference Example 1 were transferred to a laboratory where external noise was blocked in a kennel and weighed, respectively, and then placed in nine activity measuring boxes individually. After measuring baseline for 60 minutes in a box after 60 minutes of adaptation time, 25, 50, and 100 mg / kg of gold and silver extracts were orally administered once, and 2 ml / kg of vehicle (70) was used as a control. % PEG + 1% Tween 80 + 10% EtOH) was administered orally. Vehicle or gold silver extract was orally administered, after 60 minutes physiological saline or
그 실험결과, 표 1 및 도 1에서 나타내는 바와 같이, 정상군(vehicle투여 후 생리식염수 처치군)에선 1101.10 ± 305.47cm로, 대조군(vehicle 투여 후 코카인 처치군)에서 최고 20671.56 ± 1876.09cm 까지 증가한데 반하여, 금은화추출물 25, 50, 100 mg/kg 투여군의 경우 각각 9547.57 ± 1692.65cm, 11808.75 ± 2154.74cm, 5884.67 ± 1227.53cm로 증가하여 대조군에 비해 보행성 활동량이 감소하였으며, 특히, 금은화추출물 25, 100 mg/kg 투여군은 대조군에 비해 유의하게 감소되었음을 확인하였다(표 1 및 도 1 참조). As a result of the experiment, as shown in Table 1 and Figure 1, in the normal group (physiological saline treatment group after the vehicle administration) to 1101.10 ± 305.47 cm, increased to 20671.56 ± 1876.09 cm in the control group (cocaine treatment group after vehicle administration) On the contrary, in the 25, 50 and 100 mg / kg administration group, the amount of gait activity decreased compared to the control group, increasing to 9547.57 ± 1692.65 cm, 11808.75 ± 2154.74 cm and 5884.67 ± 1227.53 cm, respectively. It was confirmed that the mg / kg administration group was significantly reduced compared to the control group (see Table 1 and Figure 1).
또한, 도 2 또는 표 1에서 나타내는 바와 같이 정상적인 상태에서 금은화추출물을 투여한 후의 행동학적 변화가 일어나는지를 확인하기 위하여, 금은화추출물(금은화 단독투여군) 100 mg/kg를 경구투여 한 후, 생리식염수를 처치하고 추가적으로 60분 동안 보행성 활동량을 측정한 결과, 1419.03± 609.38 cm로 정상군과 비슷한 양상을 보여 정상상태에서는 별 다른 영향을 미치지 않은 것으로 확인되었다.In addition, as shown in FIG. 2 or Table 1, in order to check whether behavioral change occurs after administration of the gold leaf extract in a normal state, oral administration of 100 mg / kg of the gold leaf extract (gold leaf alone administration group), After 60 minutes of treatment, walking activity was measured for 1419.03 ± 609.38 cm, which was similar to that of the normal group.
1시간 보행성 활동량(cm)1 hour gait activity (cm)
실험예 2. 약물 투여에 의한 면역조직화학분석법을 이용한 c-Fos 발현에 대한 금은화추출물의 효과Experimental Example 2. Effect of sterling silver extract on c-Fos expression by immunohistochemical analysis by drug administration
상기 실시예 1에서 얻은 금은화추출물의 약물 투여에 의한 초기유전자 c-fos 발현을 확인하기 위하여 기존문헌에 기재된 방법을 응용하여 하기와 같은 실험을 하였다(Jang EY, et al., Eur J Pharmacol., 587(1-3), pp.124-128, 2008)In order to confirm the expression of the initial gene c-fos by drug administration of the sterling silver extract obtained in Example 1, the following experiment was applied by applying the method described in the existing literature (Jang EY, et al., Eur J Pharmacol., 587 (1-3) , pp.124-128, 2008)
실험당일 검사단계에서 금은화추출물 100 mg/kg 경구투여하고, 1시간 후 코카인 20 mg/kg을 복강 투여하여 그로부터 2 시간 뒤 소듐펜토바르비탈(sodium phentobarbital, 100 mg/kg)로 마취시킨 후, 심장을 통해 500 ml의 4% 파라포름알데하이드(paraformaldehyde, PFA)로 혈액을 관류시켜 뇌 조직을 고정시켰다. 뇌 조직을 꺼낸 후 10% 수크로스(sucrose)/4% PFA에 약 2시간 동안 고정시킨 다음, 20% 수크로스(sucrose)/PBS(phosphate buffer solution) 용액에 담근 후 하루 동안 4℃ 냉장 상태로 유지하였다. 그런 다음 -20℃상태에서 크라이오톰(cryotome; Shandon Cryotome, Thermo Fisher Scientific)으로 30 um두께로 뇌 조직을 절편하여 측핵 부위를 취하여 0.1% 아지드나트륨/완충용액(soduim azide/PBS)에 넣어 4℃에 보관하였다. On the day of the test, 100 mg / kg of gold and silver extract was orally administered, and after 1 hour, 20 mg / kg of cocaine was intraperitoneally administered, followed by anesthesia with sodium phentobarbital (100 mg / kg) after 2 hours. The brain tissue was fixed by perfusion with 500 ml of 4% paraformaldehyde (PFA). After removing the brain tissue, it was fixed in 10% sucrose / 4% PFA for about 2 hours, soaked in 20% sucrose / phosphate buffer solution (PBS) solution and refrigerated at 4 ° C for one day. Maintained. Then, the brain tissue was sectioned at 30 um with cryotome (Shandon Cryotome, Thermo Fisher Scientific) at -20 ° C, and the nucleus site was taken and placed in 0.1% sodium azide / PBS. Stored at ° C.
조직절편은 완충용액(PBS)에 3회 세척하여 2% Triton-X-100/PBS 용액에서 5분간 세포막의 지질을 제거하는 과정을 거친 후 3% BSA/PBS 용액으로 블록킹(blocking)하였다. 그리고 0.1% BSA/PBS 용액에 1:1000으로 희석된 1차 rabbit anti-Fos antibody (Santa cruz, CA, USA)를 이용하여 4℃에서 20시간 동안 반응시킨 후, 발색제로 DAB를 사용하여 c-Fos 단백질을 발현시켰다.Tissue sections were washed three times in buffer (PBS) to remove lipids from cell membranes for 2 minutes in 2% Triton-X-100 / PBS solution and then blocked with 3% BSA / PBS solution. After reacting with a primary rabbit anti-Fos antibody (Santa cruz, CA, USA) diluted 1: 1000 in 0.1% BSA / PBS solution at 4 ° C. for 20 hours, c- using DAB as a colorant was used. Fos protein was expressed.
실험결과, 도 3에서 나타내는 바와 같이 대조군에 비해 금은화추출물 100 mg/kg 투여군이 측핵과 선조체에서 신경활성지표인 c-Fos 유전자의 발현을 급격히 감소시켜 약물중독의 효과가 있음을 알 수 있다(도 3 참조). As a result, as shown in FIG. 3, the group treated with 100 mg / kg of gold and silver extracts significantly reduced the expression of the c-Fos gene, which is a neuronal activity marker, in the nucleus and striatum compared to the control group (FIG. 3). 3).
실험예 3. 급성독성실험Experimental Example 3. Acute Toxicity Test
상기 실시예 1에서 얻은 금은화추출물의 투여에 의한 독성을 확인하기 위하여 기존문헌에 기재된 방법을 응용하여 하기와 같은 실험을 하였다 (이형철 외, 동의병리학회지, 15(4), pp543-547, 2001).In order to confirm the toxicity by the administration of the sterling silver extract obtained in Example 1, the following experiment was applied by applying the method described in the existing literature (Hyung-Chul Lee et al., Journal of Oriental Pathology , 15 (4) , pp543-547, 2001) .
6 주령의 특정병원체부재 (Specific pathogen-free, SPF) SD계 랫트를 사용하여 급성독성실험을 실시하였다. 각 그룹당 2마리씩의 동물에 본 발명의 금은화추출물을 500 ㎎/㎏의 용량으로 1회 경구투여 하였다. 실험물질 투여 후 동물의 폐사여부, 임상증상 및 체중변화를 관찰하고 혈액학적 검사와 혈액생화학적 검사를 실시하였으며, 부검하여 육안으로 강장기와 흉강 장기의 이상여부를 관찰하였다.Acute toxicity test was performed using 6-week-old specific pathogen-free (SPF) SD rats. Two animals of each group were orally administered with the gold coin extract of the present invention at a dose of 500 mg / kg. After administration of the test substance, mortality, clinical symptoms, and changes in body weight were observed, and hematological and hematological examinations were performed.
그 결과, 실험 물질을 투여한 모든 동물에서 특기할 만한 임상증상이나 폐사된 동물은 없었으며, 체중변화, 혈액검사, 혈액생화학 검사 및 부검 소견 등에서도 독성변화는 관찰되지 않았다. As a result, no significant clinical symptoms or dead animals were noted in all animals treated with the test substance, and no toxic changes were observed in weight changes, blood tests, blood biochemical tests, and autopsy findings.
또한, 본 발명의 금은화추출물은 랫트에서 각각 500 ㎎/㎏ 까지도 독성변화를 나타내지 않았으며, 경구투여 최소치사량 (LD50)은 500 ㎎/㎏ 이상인 안전한 물질로 판단되었다. In addition, the gold and silver extract of the present invention did not show toxic changes up to 500 mg / kg in rats, respectively, and the minimum lethal dose (LD 50 ) was determined to be a safe substance of 500 mg / kg or more.
하기에 본 발명의 금은화추출물을 포함하는 조성물의 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.Hereinafter, an example of the preparation of the composition containing the gold coin extract of the present invention, but the present invention is not intended to limit it, but is intended to explain in detail only.
제제예 1. 산제의 제조Formulation Example 1 Preparation of Powder
금은화추출물(LJ) 20 mgGold Coin Extract (LJ) 20 mg
유당 100 mg
탈크 10 mg
상기의 성분들을 혼합하고 기밀포에 충진하여 산제를 제조한다.The above ingredients are mixed and filled in an airtight cloth to prepare a powder.
제제예 2. 정제의 제조Formulation Example 2 Preparation of Tablet
금은화추출물(LJ) 10 mgGold Coin Extract (LJ) 10 mg
옥수수전분 100 mg
유당 100 mg
스테아린산 마그네슘 2 mgMagnesium stearate 2 mg
상기의 성분들을 혼합한 후 통상의 정제 제조방법에 따라서 타정하여 정제를 제조한다.After mixing the above components and tableting according to the conventional tablet manufacturing method to prepare a tablet.
제제예 3. 캅셀제의 제조 Formulation Example 3 Preparation of Capsule
금은화추출물(LJ) 10 mgGold Coin Extract (LJ) 10 mg
결정성 셀룰로오스 3 mg3 mg of crystalline cellulose
락토오스 14.8 mgLactose 14.8 mg
마그네슘 스테아레이트 0.2 mgMagnesium Stearate 0.2 mg
통상의 캡슐제 제조방법에 따라 상기의 성분을 혼합하고 젤라틴 캡슐에 충전하여 캡슐제를 제조한다.According to a conventional capsule preparation method, the above ingredients are mixed and filled into gelatin capsules to prepare capsules.
제제예 4. 주사제의 제조Formulation Example 4 Preparation of Injection
금은화추출물(LJ) 10 mgGold Coin Extract (LJ) 10 mg
만니톨 180 mg180 mg mannitol
주사용 멸균 증류수 2974 mgSterile sterilized water for injection 2974 mg
Na2HPO4,12H2O 26 mgNa2HPO4,12H2O 26 mg
통상의 주사제의 제조방법에 따라 1 앰플당(2㎖) 상기의 성분 함량으로 제조한다.According to the conventional method for preparing an injection, the amount of the above ingredient is prepared per ampoule (2 ml).
제제예 5. 액제의 제조Formulation Example 5 Preparation of Liquid
금은화추출물(LJ) 20 mgGold Coin Extract (LJ) 20 mg
이성화당 10 g10 g of isomerized sugar
만니톨 5 g5 g of mannitol
정제수 적량Purified water
통상의 액제의 제조방법에 따라 정제수에 각각의 성분을 가하여 용해시키고 레몬향을 적량 가한 다음 상기의 성분을 혼합한 다음 정제수를 가하여 전체를 정제수를 가하여 전체 100㎖로 조절한 후 갈색병에 충진하여 멸균시켜 액제를 제조한다.After dissolving each component in purified water according to the usual method of preparing a liquid solution, adding lemon flavor appropriately, mixing the above components, adding purified water, adjusting the whole to 100 ml by adding purified water, and then filling into a brown bottle. The solution is prepared by sterilization.
제제예 6. 건강 식품의 제조Formulation Example 6 Preparation of Healthy Food
금은화추출물(LJ) 1000 ㎎Gold Silver Coconut Extract (LJ) 1000 mg
비타민 혼합물 적량Vitamin mixture proper amount
비타민 A 아세테이트 70 ㎍70 μg of Vitamin A Acetate
비타민 E 1.0 ㎎Vitamin E 1.0 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 ㎍0.2 μg of vitamin B12
비타민 C 10 ㎎
비오틴 10 ㎍10 μg biotin
니코틴산아미드 1.7 ㎎Nicotinic Acid 1.7 mg
엽산 50 ㎍50 μg folic acid
판토텐산 칼슘 0.5 ㎎Calcium Pantothenate 0.5mg
무기질 혼합물 적량Mineral mixture quantity
황산제1철 1.75 ㎎Ferrous Sulfate 1.75 mg
산화아연 0.82 ㎎0.82 mg of zinc oxide
탄산마그네슘 25.3 ㎎Magnesium carbonate 25.3 mg
제1인산칼륨 15 ㎎15 mg of potassium phosphate monobasic
제2인산칼슘 55 ㎎Secondary calcium phosphate 55 mg
구연산칼륨 90 ㎎Potassium citrate 90 mg
탄산칼슘 100 ㎎100 mg of calcium carbonate
염화마그네슘 24.8 ㎎Magnesium chloride 24.8 mg
상기의 비타민 및 미네랄 혼합물의 조성비는 비교적 건강식품에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 그 배합비를 임의로 변형 실시하여도 무방하며, 통상의 건강식품 제조방법에 따라 상기의 성분을 혼합한 다음, 과립을 제조하고, 통상의 방법에 따라 건강식품 조성물 제조에 사용할 수 있다.Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.
제제예 7. 건강 음료의 제조Formulation Example 7 Preparation of Healthy Drink
금은화추출물(LJ) 1000 ㎎Gold Silver Coconut Extract (LJ) 1000 mg
구연산 1000 ㎎
올리고당 100 g100 g of oligosaccharide
매실농축액 2 gPlum concentrate 2 g
타우린 1 gTaurine 1 g
정제수를 가하여 전체 900 ㎖Purified water was added to a total of 900 ml
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 건강음료 조성물 제조에 사용한다. The above components were mixed according to a conventional health drink manufacturing method, and the mixture was heated at 85 DEG C for about 1 hour with stirring, and the solution thus prepared was filtered to obtain a sterilized 2-liter container, which was sealed and sterilized, ≪ / RTI >
상기 조성비는 비교적 기호음료에 적합한 성분을 바람직한 실시예로 혼합 조성하였지만, 수요계층, 수요국가, 사용용도 등 지역적, 민족적 기호도에 따라서 그 배합비를 임의로 변형 실시하여도 무방하다.Although the composition ratio is a mixture of the components suitable for the preferred beverage as a preferred embodiment, the blending ratio may be arbitrarily varied according to the regional and national preferences such as the demand level, the demanding country, and the intended use.
[이 발명을 지원한 국가연구개발사업][National R & D project supporting this invention]
[과제고유번호] [Task unique number]
515-82-06593 515-82-06593
[부처명][Name of Buddha]
지식경제부 Ministry of Knowledge Economy
[연구사업명][Name of research project]
지역혁신센터 사업 Regional Innovation Center Project
[연구과제명][Name of Research Project]
뇌질환 치료를 위한 한방제제 및 천연물 신약개발 Development of Herbal Medicine and Natural Products for Treatment of Brain Disease
[주관기관][Host]
대구한의대학교 산학협력단 Daegu Haany University Industry-Academic Cooperation Foundation
[연구기간][Research period]
2008년 03월 01일 ~ 2009년 02월 28일 March 01, 2008 to February 28, 2009
도 1은 코카인 투여로 유도된 금은화 추출물의 보행성 활동량에 대한 효과를 나타낸 도이고,1 is a diagram showing the effect on the amount of gait activity of the gold coin extract induced by cocaine administration,
도 2은 금은화추출물(100 mg/kg)의 단독 투여 시 보행성 활동량에 대한 효과를 나타낸 도이며,2 is a view showing the effect on the amount of gait activity when administration of gold and silver coin extract (100 mg / kg),
도 3은 코카인 투여로 유도한 금은화추출물의 뇌의 측핵과 선조체 내 c-Fos 발현에 대한 효과를 나타내는 도이다.3 is a diagram showing the effect on the expression of c-Fos in the nucleus and striatum of the cerebral nucleus extract induced by cocaine administration.
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