KR100679319B1 - A pharmaceutical composition comprising the extract of dandelion for treating or preventing depression disease - Google Patents
A pharmaceutical composition comprising the extract of dandelion for treating or preventing depression disease Download PDFInfo
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- KR100679319B1 KR100679319B1 KR1020050067612A KR20050067612A KR100679319B1 KR 100679319 B1 KR100679319 B1 KR 100679319B1 KR 1020050067612 A KR1020050067612 A KR 1020050067612A KR 20050067612 A KR20050067612 A KR 20050067612A KR 100679319 B1 KR100679319 B1 KR 100679319B1
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- Prior art keywords
- extract
- dandelion
- present
- mao
- pharmaceutical composition
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- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
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Abstract
본 발명은 민들레 추출물을 포함하는 우울증 질환의 예방 및 치료를 위한 약학조성물에 관한 것으로서, 본 발명의 민들레 추출물은 우울증의 원인이 되는 MAO의 활성을 저해하여 항우울 효과를 나타내므로, 본 발명의 민들레 추출물을 포함하는 조성물은 우울증 질환의 예방 및 치료를 위한 의약품 또는 건강기능식품으로 유용하게 이용될 수 있다.The present invention relates to a pharmaceutical composition for the prevention and treatment of depressive diseases, including dandelion extract, the dandelion extract of the present invention exhibits an antidepressant effect by inhibiting the activity of MAO that causes depression, dandelion of the present invention The composition containing the extract may be usefully used as a pharmaceutical or nutraceutical for the prevention and treatment of depressive diseases.
MAO(monoamine oxidase; 모노아민 산화효소), 세로토닌(serotonin), 민들레(Traxacum mongolicum), 항우울제, 건강기능식품 MAO (monoamine oxidase), serotonin, dandelion (Traxacum mongolicum), antidepressants, health functional food
Description
도 1은 본 발명의 민들레 추출물을 경구 투여한 랫트의 MAO 활성 변화를 나타낸 것이고,Figure 1 shows the change in MAO activity of rats orally administered dandelion extract of the present invention,
도 2는 본 발명의 민들레 추출물을 경구 투여한 랫트의 뇌의 세로토닌 농도 변화를 나타낸 것이다.Figure 2 shows the serotonin concentration changes in the brain of rats orally administered dandelion extract of the present invention.
본 발명은 민들레 추출물을 포함하는 우울증 질환의 예방 및 치료를 위한 약학조성물에 관한 것이다.The present invention relates to a pharmaceutical composition for the prevention and treatment of depressive diseases comprising dandelion extract.
중추신경계에서 세로토닌(seretonin; 5-hydroxytryptamine, 5-HT)는 인식, 식이, 수면, 성적행동, 공격성, 분위기 등 많은 생리적 기능을 조절하는 신경전달물질로서 또는 신경조절물질로서 기능을 한다. 이러한 생리적인 기능 이외에도 충추신경계에서 세로토닌의 불균형으로 인하여 분노, 정신질환, 우울증과 같은 다양 한 정신장애와 행동장애의 질병이 유발되는 것으로 알려져 있다.In the central nervous system, serotonin (5-hydroxytryptamine, 5-HT) functions as a neurotransmitter or neuromodulator that regulates many physiological functions such as cognition, diet, sleep, sexual behavior, aggressiveness, and mood. In addition to these physiological functions, various disorders of mental and behavioral disorders such as anger, mental illness, and depression are known to be caused by serotonin imbalance in the nervous system.
우울증은 일명 '마음의 감기'라고 불리며 전체 성인의 10~20%가 경험할 수 있는 흔한 정신적 질환이다. 우울감 또는 슬픈 감정들은 일상생활에서 흔히 느낄 수 있는데, 병적인 우울증은 슬프거나 울적한 느낌이 기분상의 문제를 넘어 신체와 생각의 여러 부분에까지 영향을 미쳐서 개인이나 사회생활에 영향을 주기도 하며, 우울한 기분에 빠져 의욕을 상실한 채 무능감·고립감·허무감·죄책감·자살 충동 등에 사로 잡혀 심할 경우 자살 기도까지 이르는 질병이다.Depression, also known as a `` cold of mind, '' is a common mental illness that 10-20% of all adults may experience. Depression or sad feelings are common in everyday life. Morbid depression can affect one's personal and social life, as sad or depressed feelings affect not only the mood but also the body and thoughts. It is a disease that leads to suicide attempts when severely caught up in disability, isolation, guilt, guilt, and suicidal thoughts.
따라서, 우울증을 치료하기 위한 약물로서 세로토닌을 기질로 이용하는 효소인 MAO의 활성을 저해하는 저해제가 전통적으로 이용되어 왔다.Therefore, inhibitors that inhibit the activity of MAO, an enzyme that uses serotonin as a substrate, have traditionally been used as drugs for treating depression.
MAO(monoamine oxidase; 모노아민 산화효소)는 중추신경계나 말초조직 등 동물조직 중의 미토콘드리아에 널리 존재하면서, 신경전달물질이나 호르몬성 아민화합물(hormonal amines)의 대사를 관장하는 효소로서 하기와 같은 반응으로 아민화합물의 산화적 탈아미노화(deamination)를 촉매하여 신경전달물질과 식사와 장내 박테리아에 의해 유래 되는 호르몬성 아민을 분해한다.MAO (monoamine oxidase) is widely present in mitochondria in animal tissues such as the central nervous system and peripheral tissues, and is an enzyme that controls the metabolism of neurotransmitters and hormonal amines. It catalyzes the oxidative deamination of amine compounds to break down hormonal amines derived from neurotransmitters and food and gut bacteria.
[화학식 1][Formula 1]
MAO는 내인성 기질로서 카테콜아민(catecholamines)과 인돌알킬아민(indolealkylamines) 또는 그 유도체를 주로 이용하며 기질 특이성에 따라 세로토 닌, 노르에피네프린, 에피네프린(epinephrine)을 산화적으로 탈아미노화 시키는 A-형과 벤질아민(benzylamine), 페네틸아민(phenethylamine)의 산화를 촉매하는 B-형으로 나눌 수 있다.MAO mainly uses catecholamines and indolealkylamines or derivatives thereof as endogenous substrates, and A-type oxidative deamination of serotonin, norepinephrine and epinephrine depending on substrate specificity. It can be divided into B-type catalyzing the oxidation of benzylamine, phenethylamine.
상기 MAOIs(monoamine oxidase inhibitors)는 통상적으로 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). The monoamine oxidase inhibitors (MAOIs) are typically 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) , pp 180-94, 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) and have been used as drugs to treat Parkinson's disease (Danisi F., Geriatrics . 57 (3) , pp46-50, 2002; Ahlskog JE. Neurology . 60 (3) , pp381- ) . 9, 2003), as well as other causes of panic symptoms (Sheehan DV., J Clin. Psychiatry. , 63 Suppl 14, pp17-21, 2002), as drugs for treating attention deficit and impulsive hyperactivity in children. (Spencer TJ, et al., J Clin Psychiatry . 63 Suppl 12, pp 16-22, 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 MAOI의 기능이 연구되고 있어서 알츠하이머씨병(Alzheimer's disease)을 치료하는 강력한 후보물질로서 MAOI들의 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. 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, new MAOI functions are being studied, and new functions of MAOIs have been reported as potent candidates for the treatment of Alzheimer's disease (Sterling J, et al., J Med Chem. 21 ; 45 (24), pp5260-). 79, 2002) Pharmacotherapy for the eradication of Helicobacter pylori 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) (Brown BR. HIV Clin. , 14 (3) 1, pp5-8, 2002), modulating the effects of drugs treating alcoholic patients (Wing MK. Chemico-Biological Interactions, 130-132 pp919-930, 2001) It has also been applied to drug therapy to overcome 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).
그러나, 항우울제로 가장 흔하게 처방되고 있는 SSIRs(selective serotonin reuptake inhibitors) 약물은 신경전달물질인 세로토닌의 흡수를 조절하는 단일 기작 메커니즘(single-action mechanism) 항우울제로 기질 선택성으로 인하여 MAIOs나 TCAs(tricyclic antidepressants)보다 안정하고 내성이 강한 장점이 있지만, 세로토닌에 대한 선택성으로 인한 안전성 때문에 오히려 일부 환자에게는 항우울제로서의 효과를 나타내지 않는 단점이 지적되고 있다. 이로 인해 최근에는 세로토닌과 노르에피드린의 흡수를 함께 저해하는 새로운 이중 기작(dual-action) 항우울제가 새롭게 주목받고 있다.However, SSIRs (selective serotonin reuptake inhibitors) drugs, which are most commonly prescribed as antidepressants, are single-action mechanism antidepressants that regulate the uptake of the neurotransmitter serotonin. MAIOs or tricyclic antidepressants (TCAs) due to substrate selectivity There is a more stable and resistant advantage, but it is pointed out that some patients do not show an effect as an antidepressant due to safety due to selectivity for serotonin. As a result, recently, a new dual-action antidepressant agent that inhibits the absorption of serotonin and norepinephrine is attracting new attention.
상기 세로토닌-노르에피네프린 재흡수 억제제(SNRIs; serotonin-norepinephrine reuptake inhibitors) 항우울증 약물은 초기 다중 기작(multi-action) 항우울제의 부작용을 개선하고 SSRIs의 안정성과 내성을 갖추었으며 신속한 효과를 나타내는 장점이 있는 것으로 알려져 있다. 그러나 이에 대한 연구는 아직 초기 단계이고, 따라서 부작용이 적은 항우울제에 대한 지속적인 연구가 절실히 요구되고 있는 실정이다.The serotonin-norepinephrine reuptake inhibitors (SNRIs) antidepressant drugs have the advantages of improving the side effects of early multi-action antidepressants, having the stability and resistance of SSRIs, and exhibiting rapid effects. It is known. However, the research is still in its infancy, and thus, there is an urgent need for continuous research on antidepressants with low side effects.
한편, MAOIs는 MAO의 활성을 억제함과 동시에 교감성 아민과 세로토닌에 의해 영향을 받는 장기에 영향을 주며, 다른 효소의 작용을 억제하여 많은 약물의 간대사를 방해하는 문제가 있다. 또한, 과도한 중추자극으로 인하여 진전, 불면증, 발한 과다, 흥분, 경조증(hypomania)을 일으키기도 하며, 체위성 저혈압, 현훈, 두통 등을 유발하기도 한다.On the other hand, MAOIs inhibit the activity of MAO and at the same time affect the organs affected by sympathetic amines and serotonin, and there is a problem that interferes with the hepatic metabolism of many drugs by inhibiting the action of other enzymes. In addition, excessive central stimulation may cause tremors, insomnia, excessive sweating, excitement, hypomania, positional hypotension, dizziness, headaches, and so on.
민들레(Taraxacum mongolicum H. Mazz.)는 국화과(compositae)에 속한 다년초로 한방에서는 전초를 건조한 것을 봄과 여름에 꽃이 피기 전이나 후에 채취하여 청열해독, 소염, 이뇨의 목적으로 이용하는 포공영이라는 약물로 이용되어 왔다.Dandelion ( Taraxacum mongolicum H. Mazz.) Is a perennial herb belonging to the compositae, and it is a drug called pogongyoung, which is used for the purpose of clearing detoxification, anti-inflammatory, and diuresis by collecting dried flowers before or after flowering in spring and summer. Has been used.
또한, 어린잎을 나물로 이용하고 뿌리는 약용으로 하였다는 기록이 있으며(이창복, 대한식물도감, 향문사, 서울, 1999), 식품공전(한국식품공업협회, 식품공전, 문영사, 서울, 2001)에는 민들레의 어린순, 어린잎, 뿌리부위를 식품의 주원료로 이용할 수 있는 것으로 수록하고 있다. In addition, young leaves are used as herbs and roots are medicinal (Lee Chang-bok, Korea Plant Book, Hyangmunsa, Seoul, 1999), Food Code (Korea Food Industry Association, Food Code, Munyoungsa, Seoul, 2001) It contains young sprouts, young leaves and roots of dandelion as the main ingredients of food.
기타, 민들레는 신수본초에 수재 되어 있으며, 화한약 백과도감에는 소염, 항균, 이뇨, 유즙분비 촉진, 적출심장에 대하여 소량을 사용할 경우 흥분시키고 다량 사용 시에는 억제 작용을 나타내는 것으로 기록되어 있다. 항암효과(Ko SG, Koh SH, Jun CY, Nam CG, Bae HS, Shin MK., Biol Pharm Bull. 10:1604-1610, 2004), 위장관의 metaplasia와 atypical hyperplasia의 치료효과(Liu XR, Han WQ, Sun DR., Zhongguo Zhong Xi Yi Jie He Za Zhi. 10:602-603. 1992), 만성 B형 간염의 치료효과(Chen Z.Zhong Xi Yi Jie He Za Zhi. 2:71-74, 1990), antiviral action(Zheng M.Zhong Xi Yi Jie He Za Zhi. 1:39-41,1990) 등에 민들레 추출물과 민들레로부터 분리된 성분을 이용하여 보고되었다. In addition, dandelion is harvested in Sinsubon herb, and the encyclopaedia of the Chinese herbal medicine is reported to excite the anti-inflammatory, antibacterial, diuretic, milk secretion, and excitement when a small amount is used, and inhibits the use of a large amount. Anticancer effect (Ko SG, Koh SH, Jun CY, Nam CG, Bae HS, Shin MK., Biol Pharm Bull . 10 : 1604-1610, 2004), Gastrointestinal metaplasia and atypical hyperplasia (Liu XR, Han WQ , Sun DR., Zhongguo Zhong Xi Yi Jie He Za Zhi. 10 : 602-603.1992), Therapeutic Effect of Chronic Hepatitis B (Chen Z.Zhong Xi Yi Jie He Za Zhi. 2 : 71-74, 1990) and antiviral action (Zheng M. Zhong Xi Yi Jie He Za Zhi. 1 : 39-41,1990) have been reported using dandelion extracts and components isolated from dandelions.
그러나, 상기와 같이 다양한 활성 연구가 보고되고 있지만 민들레의 혈압조절작용이나 신경안정효과, 치매치료효과 내지는 항우울효과 등에 관한 보고는 거의 이루어지지 않고 있다.However, although various active studies have been reported as described above, few reports have been made on dandelion's blood pressure regulation, neurostable effect, dementia treatment or antidepressant effect.
이에 본 발명자는 기존의 항우울제들의 장단점을 고려하여 천연 물질로부터 세로토닌을 기질로 이용하는 MAO를 저해하는 활성과 그 작용 성분을 연구하던 중 본 발명의 민들레 추출물의 탁월한 MAO의 저해 활성을 확인함으로써 본 발명을 완성하였다. Accordingly, the present inventors have studied the present invention by confirming the excellent inhibitory activity of MAO of the dandelion extract of the present invention while studying the activity and inhibitory activity of MAO using serotonin as a substrate from natural substances in consideration of the advantages and disadvantages of existing antidepressants. Completed.
본 발명의 목적은 MAO의 활성을 저해하는 효과를 갖는 민들레 추출물을 포함하는 우울증의 치료 및 예방을 위한 약학조성물을 제공하는 것이다.An object of the present invention is to provide a pharmaceutical composition for the treatment and prevention of depression, including dandelion extract having an effect of inhibiting the activity of MAO.
상기 목적을 달성하기 위하여, 본 발명은 민들레 추출물을 유효성분으로 함유하는 우울증의 예방 및 치료용 약학조성물을 제공한다.In order to achieve the above object, the present invention provides a pharmaceutical composition for the prevention and treatment of depression containing dandelion extract as an active ingredient.
상기 추출물은 물 및 메탄올, 에탄올, 부탄올 등과 같은 C1 내지 C4의 저급알콜 및 이들의 혼합용매, 바람직하게는 메탄올 수용액에 가용한 추출물을 포함한다.The extract includes water and C 1 to C 4 lower alcohols such as methanol, ethanol, butanol and the like, and a mixture thereof, an extract available in an aqueous methanol solution.
이하, 본 발명을 상세히 설명한다.Hereinafter, the present invention will be described in detail.
본 발명의 민들레 추출물추출물은 하기와 같이 수득될 수 있다.Dandelion extract extract of the present invention can be obtained as follows.
본 발명의 민들레를 채집하여 건조하고 마쇄기로 분말화 한 후, 민들레 시료 중량의 약 2 내지 10배, 바람직하게는 약 5 내지 8배에 달하는 부피의 물 및 메탄올, 에탄올, 부탄올 등과 같은 C1 내지 C4의 저급 알콜의 극성용매 또는 이들의 약 1:0.1 내지 1:10의 혼합비를 갖는 혼합용매로, 바람직하게는 80% 메탄올 수용액을 가하여 환류냉각을 하면서 90 내지 100 ℃에서 6시간씩 3회 반복하여 가열추출한 다음, 탈지면으로 여과하고, 그 여액을 40 ℃의 수욕 상에서 감압 농축하여 얻은 에탄올 추출물을 다시 동결 건조하여 민들레 추출물을 수득할 수 있다.The dandelion of the present invention is collected, dried and pulverized with a crusher, and then has a volume of water up to about 2 to 10 times, preferably about 5 to 8 times the weight of the dandelion sample and C 1 to C, such as methanol, ethanol, butanol, and the like. Polar solvent of C 4 lower alcohol or a mixed solvent having a mixing ratio of about 1: 0.1 to 1:10, preferably 3 times at 90 to 100 ° C. for 3 hours with reflux cooling by adding 80% aqueous methanol solution After repeated heating and extraction, the resultant was filtered with cotton wool, and the filtrate was freeze-dried again by ethanol extract obtained by concentrating under reduced pressure on a water bath at 40 ℃ can obtain a dandelion extract.
본 발명은 상기의 제법으로 얻어진 민들레 추출물을 유효성분으로 함유하는 우울증 질환의 예방 및 치료용 약학조성물을 제공한다.The present invention provides a pharmaceutical composition for the prevention and treatment of depression disease containing dandelion extract obtained by the above method as an active ingredient.
또한, 민들레는 생약으로 사용되어 오던 약재로서 이로부터 추출된 본 발명의 추출물들 역시 독성 및 부작용 등의 문제가 없으므로, 예방을 목적으로 한 장기간 복용시에도 안심하고 사용할 수 있다.In addition, the dandelion has been used as a medicinal herb extracts of the present invention extracted from it also have no problems such as toxicity and side effects, so can be used with confidence even during long-term administration for the purpose of prevention.
본 발명에 따른 우울증 질환의 예방 및 치료용 약학조성물은, 조성물 총 중 량에 대하여 상기 추출물을 0.1 내지 50 중량%로 포함한다.The pharmaceutical composition for preventing and treating depressive diseases according to the present invention comprises 0.1 to 50% by weight of the extract based on the total weight of the composition.
본 발명의 추출물을 포함하는 약학조성물은 약학적 조성물의 제조에 통상적으로 사용하는 적절한 담채, 부형제 및 희석제를 더 포함할 수 있다.The pharmaceutical composition comprising the extract of the present invention may further comprise suitable tints, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.
본 발명의 추출물의 약학적 투여 형태는 이들의 약학적 허용가능한 염의 형태로도 사용될 수 있고, 또한 단독으로 또는 타 약학적 활성 화합물과 결합뿐만 아니라 적당한 집합으로 사용될 수 있다.Pharmaceutical dosage forms of the extracts of the present invention may be used in the form of their pharmaceutically acceptable salts, or may be used alone or in combination with other pharmaceutically active compounds, as well as in any suitable collection.
본 발명에 따른 추출물을 포함하는 약학조성물은, 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. 추출물을 포함하는 조성물에 포함될 수 있는 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에이스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로오스, 메틸 셀룰로오스, 미정질 셀룰로오스, 폴리비닐리롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 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), 수크로오스(sucrose) 또는 락토오스(lactose), 젤라틴 등을 섞어 조제된다. 또한, 단순한 부형제 이외에 마그네슘 스테아레이트, 탈크 같은 윤활제들도 사용된다. 경구 투여를 위한 액상 제제로는 현탁액, 내용액제, 유제, 시럽제 등이 해당되는데 흔히 사용되는 단순 희석제인 물, 리퀴드 파라핀 이외에 여러 가지 부형제, 예를 들면 습윤제, 감미제, 방향제, 보존제 등이 포함될 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. 좌제의 기제로는 웨텝솔(witepsol), 마크로골, 트윈(tween) 61, 카카오지, 라우린지, 글리세로제라틴 등이 사용될 수 있다.Pharmaceutical compositions comprising extracts according to the invention, 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 formulated and used. Carriers, excipients and diluents that may be included in the composition comprising the extract include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, aceitol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium Silicates, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, 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 such solid preparations may contain at least one excipient such as starch, calcium carbonate and sucrose in the extract. Or lactose, gelatin, or the like is mixed. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, liquid solutions, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oils such as olive oil, injectable esters 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 0.0001 내지 100 ㎎/㎏, 바람직하게는 0.001 내지 100 ㎎/㎏으로 투여하는 것이 좋다. 투여는 하루에 한번 투여할 수도 있고, 수회 나누어 투여할 수도 있다. 상기 투여량은 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 preferred effect, the extract of the present invention is preferably administered at 0.0001 to 100 mg / kg, preferably 0.001 to 100 mg / kg per day. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect.
본 발명은 우울증 질환의 예방 효과를 나타내는 상기 추출물 및 식품학적으로 허용 가능한 식품보조 첨가제를 포함하는 건강기능식품을 제공한다.The present invention provides a health functional food comprising the extract and a food acceptable food supplement additive exhibiting a prophylactic effect of depression disease.
민들레 추출물을 첨가할 수 있는 식품으로는 예를 들어, 각종 식품류, 음료, 껌, 차, 비타민 복합제, 건강 기능성 식품류 등이 있다.Examples of the food to which the dandelion extract can be added include various foods, beverages, gums, teas, vitamin complexes, and health functional foods.
또한, 우울증 질환의 예방 효과를 목적으로 식품 또는 음료에 첨가될 수 있다. 이때, 식품 또는 음료 중의 상기 추출물의 양은 전체 식품 중량의 0.01 내지 15 중량%로 가할 수 있으며, 건강 음료 조성물은 100 ㎖를 기준으로 0.02 내지 5 g, 바람직하게는 0.3 내지 1 g의 비율로 가할 수 있다.It may also be added to foods or beverages for the purpose of preventing depressive diseases. At this time, the amount of the extract in the food or beverage may be added in 0.01 to 15% by weight of the total food weight, the health beverage composition may be added in a ratio of 0.02 to 5 g, preferably 0.3 to 1 g based on 100 ml. have.
본 발명의 건강 기능성 음료 조성물은 지시된 비율로 필수 성분으로서 상기 추출물을 함유하는 외에 다른 성분에는 특별한 제한이 없으며, 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등의 추가 성분을 함유할 수 있다. 상술한 천연 탄수화물의 예로는 모노사카라이드, 예를 들어 포도당, 과당 등; 디사카라이드, 예를 들어 말토오스, 수크로오스 등; 및 폴리사카라이드, 예를 들어 덱스트린, 시클로덱스트린 등과 같은 통상적인 당, 및 자일리톨, 솔비톨, 에리트리톨 등의 당알콜이다. 상술한 것 이외의 향미제로서 천연 향미제인 타우마틴, 스테비아 추출물, 예를 들어 레바우디오시드 A, 글리시르히진 등; 및 합성 향미제, 예를 들어 사카린, 아스파르탐 등을 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.The health functional beverage composition of the present invention is not particularly limited to other ingredients in addition to containing the extract as an essential ingredient in the indicated ratio, and may contain additional ingredients such as various flavoring agents or natural carbohydrates as in general beverages. . 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 a flavoring agent other than the above-mentioned, a natural flavoring agent, taumartin, a stevia extract, for example, rebaudioside A, glycyrrhizin, etc .; And synthetic flavoring agents such as saccharin, aspartame and the like. The proportion of such natural carbohydrates is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.
상기 외에 본 발명의 추출물은 여러 가지 영양제, 비타민, 광물(전해질), 합성 및 천연 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 추출물들은 천연 과일 쥬스 및 과일 쥬스 음료 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 독립적으로 또는 조합하여 사용할 수 있다. 이때, 첨가제의 비율은 그다지 중요하지는 않지만 본 발명의 추출물 100 중량부 당 0 내지 약 20 중량부의 범위에서 선택되는 것이 일반적이다.In addition to the above, the extract of the present invention has various nutrients, vitamins, minerals (electrolytes), synthetic and natural flavors, coloring and neutralizing agents (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective properties Colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like. In addition, the extracts of the present invention may contain flesh for the production of natural fruit juices and fruit juice beverages and vegetable beverages. These components can be used independently or in combination. At this time, the ratio of the additive is not very important, but is generally selected from the range of 0 to about 20 parts by weight per 100 parts by weight of the extract of the present invention.
이하, 본 발명을 하기 실시예 및 실험예에 의거하여 보다 구체적으로 설명한다.Hereinafter, the present invention will be described in more detail based on the following Examples and Experimental Examples.
단, 하기의 실시예 및 실험예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 이들에 한정되는 것은 아니다.However, the following Examples and Experimental Examples are merely illustrative of the present invention, but the content of the present invention is not limited thereto.
실시예 1. 민들레 추출물의 제조Example 1 Preparation of Dandelion Extract
1-1. 경구투여용 민들레 추출물1-1. Dandelion extract for oral administration
건조한 민들레 100 g을 마쇄기로 갈아 분말화 한 후, 80% 에탄올 용액을 800 ㎖ 가하고 환류 냉각을 하면서 100 ℃에서 6시간씩 3회 반복하여 가열추출한 다음 탈지면으로 여과하였다. 100 g of dry dandelion was ground and ground to a mill, followed by 800 ml of 80% ethanol solution and reflux cooling, followed by heat extraction three times at 100 ° C. for 6 hours, followed by filtration through cotton wool.
얻은 여액은 40 ℃의 수욕 상에서 감압 농축하여 수득한 에탄올 추출물 17.67 g을 다시 동결 건조하여 분말을 16 g 수득하였다. The obtained filtrate was freeze-dried again 17.67 g of the ethanol extract obtained by concentrating under reduced pressure on a water bath at 40 ℃ to obtain 16 g of a powder.
상기와 같이 수득된 민들레 추출물은 -80 ℃의 급속냉동고(deep freezer)에 보관하여 실험시 증류수에 녹여 사용하였다. The dandelion extract obtained as described above was stored in a deep freezer at -80 ° C and dissolved in distilled water during the experiment.
1-2. 민들레 메탄올 추출물1-2. Dandelion Methanol Extract
건조시킨 민들레 100 g을 마쇄하여 분말로 만들고, 여기에 80% 메탄올 용액을 가하여 95 ℃ 수욕 상에서 환류 냉각을 하면서 6시간 가열추출하였다.100 g of dried dandelion was ground to a powder, and 80% methanol solution was added thereto, followed by heating and extraction under reflux cooling on a 95 ° C. water bath for 6 hours.
실온으로 냉각시킨 후 여과하고, 그 박을 80% 메탄올 용액으로 세척하여 여 액이 1000 ㎖가 되도록 만든 다음 45 ℃ 수욕 상에서 감압 농축하여 메탄올 추출물 1500 ㎎을 수득하였다.After cooling to room temperature and filtration, the foil was washed with 80% methanol solution to make the filtrate to 1000 ml, and then concentrated under reduced pressure in a 45 ℃ water bath to give 1500 mg of methanol extract.
실험예 1. 시약 및 실험 준비Experimental Example 1. Reagents and Experimental Preparation
1-1. 시약1-1. reagent
본 발명에서 사용한 민들레는 서울 경동시장 소재 한약재 도매상에서 구입하여 사용하였으며, 효소활성 측정에 사용한 세로토닌, 벤질아민, 이온교환수지 Amberlite GC-50은 시그마 케미컬사(Sigma Chemical Co., St.Louis, MO, 미국) 제품을 사용하였다.The dandelion used in the present invention was purchased from a Chinese herbal medicine wholesaler in Gyeongdong Market, Seoul. Serotonin, benzylamine, and ion exchange resin Amberlite GC-50 used for measuring enzyme activity were manufactured by Sigma Chemical Co., St. Louis, MO. , USA) product was used.
기타, HPLC용 용매는 Merk사 제품을, 칼럼크로마토그래피용 용매 및 시료 추출용 용매는 국산 특급 시약을 구입하여 사용하였다.In addition, HPLC solvents were manufactured by Merk, and column chromatography and sample extraction solvents were purchased from domestic special reagents.
1-2. 실험동물1-2. Laboratory animals
5주령의 스프라그-도울리(Sprague-Dawely)계 웅성 흰쥐(랫트)를 (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 사용하였다.Sprague-Dawely male rats, 5 weeks old, are supplied from BIOGENOMICS Co., Ltd. to control lighting at a temperature of 23 ± 3 ℃, humidity of 50 ± 10%, and 12-hour cycle. Was used in the experiment after adapting for 2-4 weeks while freely supplying solid food and water.
실험예 2. 뇌 MAO-A의 활성 측정Experimental Example 2. Measurement of activity of brain MAO-A
2-1. 효소원 조제2-1. Enzyme source preparation
랫트를 에테르를 가한 마취 병에서 마취시켜 개복한 후, 좌심실로부터 채혈을 하여 실혈시키고, 즉시 두개골을 절개하여 뇌를 적출하였다. 적출된 뇌는 0.01 M 인산완충용액(phosphate buffered saline, PBS; pH 7)으로 세척하고, 습중량 1 g당 9 ㎖의 차가운 0.25 M 수크로오스 용액을 가하여 Turrax 균질기로 1분간 호모제네이트(homogenate) 하였다.The rats were anesthetized in an ether-doped anesthesia jar, and then opened, and blood was drawn from the left ventricle, and the skull was immediately dissected to extract the brain. The extracted brain was washed with 0.01 M phosphate buffered saline (PBS; pH 7), and 9 ml cold 0.25 M sucrose solution per 1 g of wet weight was added and homogenated for 1 minute with a Turrax homogenizer. .
상기 호모제네이트는 4 ℃에서 700×g으로 20분간 원심분리하고, 그 상등액을 취하여 다시 18,000×g으로 20분간 고속 원심분리한 다음, 상등액은 버리고 가라앉은 펠렛을 중량 1 g당 PBS 5 ㎖에 현탁시켜 효소원으로 사용하였다.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, and the supernatant was discarded and the pellet was submerged in 5 ml of PBS / g. Suspension was used as an enzyme source.
2-2. 효소활성 측정2-2. Enzyme Activity Measurement
상기에서 준비한 효소원 0.5 ㎖를 시험관에 넣고 기질 용액으로 0.1 mM 세로토닌 용액 0.5 ㎖를 가하여 37.5 ℃의 항온조에서 90분간 배양하였다. 95 ℃ 수욕 상에서 3분간 가열하여 반응을 중단시킨 후 즉시 700×g으로 원심분리하고, 상등액을 1.0 ㎖ 취하여 미리 준비한 Amberlite GC-50(H+form) 칼럼(0.6×4 ㎝)에 부어 넣었다. 증류수로 수지를 충분히 세척한 다음(40 ㎖ 이상), 4 N 초산용액 3 ㎖를 수지에 부어 넣고 이때 용출액을 시험관에 받아 277 ㎚에서 흡광도를 측정하였다.0.5 ml of the enzyme source prepared above was placed in a test tube, and 0.5 ml of 0.1 mM serotonin solution was added as a substrate solution, and then incubated for 90 minutes in a 37.5 ° C. thermostat. The reaction was stopped by heating for 3 minutes in a 95 ° C. water bath, and immediately centrifuged at 700 × g, 1.0 mL of the supernatant was poured into a previously prepared Amberlite GC-50 (H + form) column (0.6 × 4 cm). 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.
이와는 별도로 반응 개시점 대신 반응 종말점에서 기질 용액을 넣은 보정군을 실험군과 함께 실행하였으며, 각 실험군의 대조군을 기준으로 하여 온도 변화와 약물 투영에 따른 효소활성의 변화를 정해진 수식에 따라 계산하였다.Separately, the correction group with the substrate solution was added to the reaction end point instead of the reaction initiation point with the experimental group. Based on the control group of each experimental group, the change in the enzyme activity according to the temperature change and the drug projection was calculated according to a predetermined formula.
실험예 3. 간 MAO-B의 활성 측정Experimental Example 3 Determination of Activity of Liver MAO-B
3-1. 효소원 조제 3 -1. Enzyme source preparation
랫트의 간 미토콘드리아를 분획하기 위하여 랫트를 에테르를 가한 마취 병에서 마취시켜 개복한 후, 좌심실로부터 채혈을 하여 실혈시키고, 즉시 간을 적출하였다. 적출된 간은 0.01 M 인산완충용액(phosphate buffered saline, PBS; pH 7)으로 세척하고, 습중량 1 g당 9 ㎖의 차가운 0.25 M 수크로오스 용액을 가하여 Turrax 균질기로 1분간 호모제네이트(homogenate) 하였다.In order to fractionate the rat liver mitochondria, the rat was anesthetized in an anesthetic bottle to which ether was added, and then opened. The blood was collected from the left ventricle, and blood was immediately extracted. The extracted liver was washed with 0.01 M phosphate buffered saline (PBS; pH 7), and 9 ml cold 0.25 M sucrose solution per 1 g of wet weight was added and homogenated with a Turrax homogenizer for 1 minute. .
상기 호모제네이트는 4 ℃에서 700×g으로 20분간 원심분리하고, 그 상등액을 취하여 다시 18,000×g으로 20분간 고속 원심분리한 다음, 상등액은 버리고 가라앉은 펠렛을 중량 1 g당 PBS 5 ㎖에 현탁시켜 효소원으로 사용하였다.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, and the supernatant was discarded and the pellet was submerged in 5 ml of PBS / g. Suspension was used as an enzyme source.
3-2. 효소활성 측정3-2. Enzyme Activity Measurement
McWeen 등의 방법(McWeen, C. M., Cohen. J. R. and Cohen, J. D., An amine oxidase in normal human serum, J. Lab. Clin. Med., 62, 766-776, 1963)에 준하여 효소활성을 측정하였다.Enzyme activity was measured according to the method of McWeen et al. (McWeen, CM, Cohen. JR and Cohen, JD, An amine oxidase in normal human serum, J. Lab. Clin. Med. , 62 , 766-776, 1963).
효소원 0.5 ㎖와 기질 용액으로 4 mM 벤질아민-HCl 용액 0.5 ㎖를 시험관에 넣고 37.5 ℃ 항온조에서 90분간 배양한 후, 반응을 중지시키기 위하여 60% 과염소산 용액 0.2 ㎖씩을 가함과 동시에 시클로헥산 4 ㎖를 가하여 진탕시킨 다음 700×g으로 20분간 원심분리하고, 시클로헥산층을 취하여 242 ㎚에서 흡광도를 특정하였 다.0.5 ml of 4 mM benzylamine-HCl solution with 0.5 ml of enzyme source and substrate solution was added to the test tube and incubated in a 37.5 ° C. thermostat for 90 minutes, and then 0.2 ml of 60% perchloric acid solution was added to stop the reaction. After addition, the mixture was shaken and centrifuged at 700 × g for 20 minutes, and a cyclohexane layer was taken to determine absorbance at 242 nm.
보정군과 실험군을 함께 실시하였으며, 각 실험군의 대조군을 기준으로 하여 온도 변화와 약물 투여에 따른 효소활성의 변화를 정해진 수식에 따라 계산하였다.The correction group and the experiment group were carried out together, and the change in enzyme activity according to the temperature change and the drug administration was calculated according to the prescribed formula based on the control group of each test group.
실험예 4. 민들레 추출물의 경구 투여에 의한 MAO의 활성변화 측정Experimental Example 4. Determination of MAO activity by oral administration of dandelion extract
상기 실험예 1에서 준비한 랫트 6마리를 1군으로 하여 12시간 전에 절식시킨 후, 상기 실시예 1-1에서 수득한 민들레 추출물 분말을 경구 투여용 시료로서 사용하였다. 즉, 동결 건조한 민들레 분말 10 ㎎을 증류수 1 ㎖에 녹여서 실험 하루 전에 절식시킨 동물에게 전날 오후와 실험 당일 2시간 전에 2회에 걸쳐 4 ㎖씩 경구 투여하였다. 대조군에는 같은 조건으로 증류수 4 ㎖를 투여하였는데, 이때 양은 시료 건조 중량으로 동물 체중당 0.3 g/㎏에 해당되는 양으로, 사람으로는 12~20 g/60 ㎏에 해당된다.Six rats prepared in Experimental Example 1 were fasted 12 hours as a group, and the dandelion extract powder obtained in Example 1-1 was used as a sample for oral administration. That is, 10 mg of lyophilized dandelion powder was dissolved in 1 ml of distilled water and fasted orally administered to the animals fasted one day before the experiment, two times 4 ml two times before the afternoon and the day before the experiment. The control group was administered 4 ml of distilled water under the same conditions, in which the amount corresponds to 0.3 g / kg per animal body weight in the dry weight of the sample, and 12 to 20 g / 60 kg in humans.
경구 투여 2시간 후 해부하여 실험예 2 내지 3의 방법으로 MAO의 활성변화를 측정하고, 그 결과를 도 1에 나타내었다. After 2 hours of oral administration, it was dissected to measure the change in activity of MAO by the method of Experimental Examples 2 to 3, and the results are shown in FIG. 1.
도 1에서 확인할 수 있는 바와 같이, 민들레 추출물 대신 증류수를 투여한 대조군의 효소활성을 기준으로 비교해 볼 때, 통계적 유의차는 없지만 MAO-A는 민들레 추출물에 의해서 효소 활성이 증가하는 것으로 나타난 반면, MAO-B는 감소하는 경향을 나타내었다. As can be seen in Figure 1, when compared with the enzyme activity of the control group administered distilled water instead of dandelion extract, there is no statistically significant difference, while MAO-A appeared to increase the enzyme activity by the dandelion extract, MAO- B tended to decrease.
실험예 5. 민들레 추출물의 경구 투여에 의한 뇌의 세레토닌 함량변화 측정Experimental Example 5. Measurement of Serotonin Content in the Brain by Oral Administration of Dandelion Extract
상기 실험예 4에서 적출한 뇌 조직 중의 세레토닌의 함량을 측정하기 위하며, 랫트를 에테르를 가한 마취 병에서 마취시켜 개복한 후, 좌심실로부터 채혈을 하여 실혈시키고, 즉시 두개골을 절개하여 뇌를 적출하였다. 적출된 뇌는 0.01 M 인산완충용액(phosphate buffered saline, PBS; pH 7)으로 세척하고, 습중량 1 g당 9 ㎖의 차가운 0.25 M 수크로오스 용액을 가하여 Turrax 균질기로 1분간 호모제네이트(homogenate) 하였다.In order to measure the content of serotonin in the brain tissue extracted in Experimental Example 4, the rat was anesthetized in an anesthetic bottle to which ether was added, and then opened, and then blood was collected from the left ventricle. It extracted. The extracted brain was washed with 0.01 M phosphate buffered saline (PBS; pH 7), and 9 ml cold 0.25 M sucrose solution per 1 g of wet weight was added and homogenated for 1 minute with a Turrax homogenizer. .
상기 호모제네이트는 4 ℃에서 700×g으로 20분간 원심분리하고, 그 상등액을 취하여 다시 18,000×g으로 20분간 고속 원심분리한 다음, 상등액 1 ㎖를 즉시 -80 ℃의 냉동고에 보관하였다가 분석 시 0.1 ㎖의 4 M 아세트산칼륨 용액(potassuium acetate; H 7.4)를 가하여 녹인 후 4 ℃에서 10,000 rpm의 속도로 15분 동안 원심분리하였다. 상등액 50 ㎕를 취하여 HPLC 완충용액과 동량으로 희석한 후 HPLC 시료 조제용 필터로 여과하고, 여과액 중 10 ㎕를 분석에 이용하였다.The homogenate was centrifuged at 700 × g for 20 minutes at 4 ° C., the supernatant was taken, and then rapidly centrifuged at 18,000 × g for 20 minutes, and then 1 ml of the supernatant was immediately stored in a freezer at −80 ° C. for analysis. 0.1 ml of 4 M potassium acetate solution (potassuium acetate; H 7.4) was added thereto, dissolved, and centrifuged for 15 minutes at 10,000 rpm at 4 ° C. 50 µl of the supernatant was taken, diluted in the same amount with HPLC buffer, filtered through an HPLC sample preparation filter, and 10 µl of the filtrate was used for analysis.
분석에 사용된 HPLC는 gradient pump와 DAD detector가 부착된 Hewlett-Packardd 1100 System으로 100 ㎕ 루프(loop)를 이용하여 수동으로 주입(injection)하였다. 분석에 이용한 칼럼은 Capcellpack C18(1.0×250 ㎜)이며, 분석용매는 20 mM KH2PO/CHCN3 혼합용매를 80:20의 비율로 섞어 사용하였다. 이때, flow rate는 1 ㎖/분이며, 오븐의 온도는 40 ℃이고, retention time은 약 3.7분이며, 측정 파장은 254/360 ㎚였다.The HPLC used for analysis was manually injected using a 100 μl loop into a Hewlett-Packardd 1100 System equipped with a gradient pump and a DAD detector. The column used for analysis was Capcellpack C18 (1.0 × 250 mm), and the analytical solvent was used by mixing 20 mM KH 2 PO / CHCN 3 mixed solvent at a ratio of 80:20. At this time, the flow rate was 1 ml / min, the temperature of the oven was 40 ° C., the retention time was about 3.7 minutes, and the measurement wavelength was 254/360 nm.
효소활성에 사용한 세로토닌 용액은 세로토닌(5-TH) 10 ㎎을 50 % CH3CN 1 ㎖에 녹여 원액을 제조하고, 50 % CH3CN로 희석하여 0.1, 0.5, 1, 5, 10 ㎕/㎖가 되도록 검액을 조제하되, 모든 실험을 7회 반복하여 평균치를 구하고, 그 결과는 도 2에 나타내었다.Serotonin solution used for the enzyme activity of serotonin (5-TH) 10 ㎎ to 50% CH 3 CN to prepare a stock solution dissolved in 1 ㎖, and diluted with 50% CH 3 CN 0.1, 0.5 , 1, 5, 10 ㎕ / ㎖ Prepare the test solution to be, but all the experiments were repeated seven times to obtain the average value, the results are shown in FIG.
도 2에서 보여지는 바와 같이, 대조군의 뇌 조직 중 세로토닌의 함량은 19.2 ㎎/㎖인데 반해, 본 발명의 민들레 추출물을 경구 투여한 랫트의 경우 19.6 ㎎/㎖로 나타났다. 이는 MAO 저해 약물로 임상에서 항우울제로 이용되고 있는 deprenyl을 5 ㎎/㎏이 되도록 투여한 양성 대조군 25.7 ㎎/㎖과 비교하여 불 때, 통계적으로 유의한 변화는 아니나 세로토닌이 신경전달물질로서 작용하는 점을 고려하면 매우 중요한 변화이다.As shown in FIG. 2, the serotonin content in the brain tissue of the control group was 19.2 mg / ml, whereas the rats orally administered the dandelion extract of the present invention was 19.6 mg / ml. This is not a statistically significant change when compared to 25.7 mg / ml of the positive control group administered with 5 mg / kg of deprenyl, which is used as an antidepressant in clinical practice as an MAO inhibitor, but serotonin acts as a neurotransmitter. Considering this is a very important change.
실험예 6. 민들레 추출물의 시험관 내 MAO 활성변화 측정Experimental Example 6. Measurement of MAO activity change in vitro of dandelion extract
상기의 실시예 1-2에서 수득한 민들레 메탄올 추출물과 민들레 추출물의 용매별 분획물을 10 ㎎/㎖ 용액이 되도록 증류수로 녹이고, 이 용액을 원액으로 하되 1(10 ㎎/㎖), ½(5 ㎎/㎖), ¼(2.5 ㎎/㎖) 희석액을 검액으로 사용하여 실험예 2 내지 3의 방법에 준하여 효소활성을 측정하였다. Dissolve the dandelion methanol extract obtained in Example 1-2 and the solvent-specific fractions of the dandelion extract with distilled water to make a 10 mg / ㎖ solution, the solution was used as a stock solution 1 (10 ㎎ / ㎖), ½ (5 mg / Ml), ¼ (2.5 mg / ㎖) diluent was used as the test solution and the enzyme activity was measured in accordance with the method of Experimental Examples 2-3.
그 결과, 민들레 메탄올 추출물은 시험관 내에서 MAO-A 및 MAO-B의 활성을 현저하게 저해하는 것으로 나타났다. 이때 메탄올 추출물의 MAO-A 및 MAO-B에 대한 저해 활성은 ㎎/㎖ 농도에서 각각 73.0, 67.8 %였다. As a result, dandelion methanol extract was found to significantly inhibit the activity of MAO-A and MAO-B in vitro. At this time, the inhibitory activity of the methanol extract against MAO-A and MAO-B was 73.0 and 67.8% at the mg / ml concentration, respectively.
실험예 7. 통계처리Experimental Example 7. Statistical Processing
실험 결과는 SAS 통계프로그램을 이용하였으며, 스튜던트 t-테스트를 통하여 p가 0.05 이하인 경우 유의한 차이로 판정하였다.The experimental results were SAS statistical program, and was determined to be a significant difference when the p is less than 0.05 through the Student's t-test.
본 발명의 추출물을 포함하는 약학조성물의 제제예를 설명하나, 본 발명은 이를 한정하고자 함이 아닌 단지 구체적으로 설명하고자 함이다.One example of the formulation of the pharmaceutical composition comprising the extract of the present invention, but the present invention is not intended to limit it, but is intended to explain in detail.
제제예 1. 산제의 제조Formulation Example 1 Preparation of Powder
민들레 추출물 분말 20 ㎎Dandelion Extract Powder 20mg
유당 100 ㎎
탈크 10 ㎎
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
민들레 추출물 분말 10 ㎎Dandelion Extract Powder 10mg
옥수수 전분 100 ㎎100 mg corn starch
유당 100 ㎎
스테아린산 마그네슘 2 ㎎2 mg magnesium stearate
상기의 성분들을 혼합한 후 통상의 정제의 제조방법에 따라서 타정하여 정제를 제조한다.After mixing the above components, tablets are prepared by tableting according to a conventional method for preparing tablets.
제제예 3. 캅셀제의 제조Formulation Example 3 Preparation of Capsule
민들레 추출물 분말 10 ㎎Dandelion Extract Powder 10mg
결정성 셀룰로오스 3 ㎎3 mg of crystalline cellulose
락토오스 14.8 ㎎Lactose 14.8 mg
마그네슘 스테아레이트 2 ㎎Magnesium Stearate 2mg
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
민들레 추출물 분말 10 ㎎Dandelion Extract Powder 10mg
만니톨 180 ㎎Mannitol 180 mg
주사용 멸균 증류수 2794 ㎎Sterile distilled water for injection 2794 mg
Na2HPO4·12H2O 26 ㎎ Na 2 HPO 4 · 12H 2 O 26 ㎎
통상의 주사제의 제조방법에 따라 1 앰플(2 ㎖)당 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
민들레 추출물 분말 10 ㎎Dandelion Extract Powder 10mg
이성화당 10 g10 g of isomerized sugar
만니톨 5 g 5 g of mannitol
정제수 적당량Purified water
통상의 액제의 제조방법에 따라 정제수에 각각의 성분을 가하여 용해시키고, 레몬향을 적당량 가한 다음 상기의 성분을 혼합한 다음 정제수를 가하여 전체를 100 ㎖로 조절한 후 갈색병에 충진하여 멸균시켜 액제를 제조한다.According to the conventional method of preparing a liquid solution, each component is added and dissolved in purified water, lemon flavor is added to the appropriate amount, the above components are mixed, and then purified water is added to adjust the total amount to 100 ml, and then sterilized by filling in a brown bottle. To prepare.
제제예 6. 건강 음료의 제조Formulation Example 6 Preparation of Healthy Drink
민들레 추출물 분말 10 ㎎Dandelion Extract Powder 10mg
비타민 C 15 g15 g of vitamin C
비타민 E(분말) 100 g100 g of vitamin E (powder)
젖산철 19.75 gIron lactate 19.75 g
산화아연 3.5 g3.5 g of zinc oxide
니코틴산아미드 3.5 gNicotinamide 3.5 g
비타민 A 0.2 g0.2 g of vitamin A
비타민 B1 0.25 g0.25 g of vitamin B1
비타민 B2 0.3 g 0.3 g of vitamin B2
물 적당량Water
통상의 건강 음료 제조방법에 따라 상기의 성분을 혼합한 다음, 약 1시간 동안 85 ℃에서 교반 가열 후, 만들어진 용액을 여과하여 멸균된 2 ℓ의 용기에 취득하여 밀봉 멸균한 뒤 냉장 보관하여 본 발명에 따른 건강 음료 조성물 제조에 사용 한다.After mixing the above components according to a conventional healthy beverage production method, and then stirred and heated at 85 ℃ for about 1 hour, the resulting solution is filtered and obtained in a sterilized 2 L container, sealed sterilization and refrigerated and stored in the present invention To prepare a healthy beverage composition according to the invention.
상기 조성비는 비교적 기호 음료에 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 preferred beverage in a preferred embodiment, the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.
상술한 바와 같이, 본 발명의 민들레 추출물 및 비극성 용매 가용 추출물은 MAO의 활성을 저해시킴으로써 우울증을 완화하는 항우울 효과를 나타내므로, 우울증 질환의 예방 및 치료를 위한 약학조성물 또는 건강기능식품으로서 이용가능하다.As described above, the dandelion extract and the non-polar solvent soluble extract of the present invention exhibit an antidepressant effect to alleviate depression by inhibiting the activity of MAO, and thus can be used as a pharmaceutical composition or health functional food for the prevention and treatment of depression disease. Do.
Claims (4)
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