KR100990710B1 - Composition comprising herbal mixture extract as an active ingredient for prevention and treatment of alcohol dependence - Google Patents

Abstract

The present invention relates to a composition for the prevention and treatment of alcohol dependence using the mixed herbal medicine extract as an active ingredient, and more specifically to the prevention of alcohol dependence using the mixed herbal medicine extract including browning and earthworm having an anti- craving effect as an active ingredient and A therapeutic composition. The composition comprising the mixed herbal medicine extract of the present invention can be usefully used for the prevention and treatment of alcohol dependence by reducing the expression of POMC mRNA associated with spontaneous alcohol intake to prevent alcohol intake.

Description

Composition comprising herbal mixture extract as an active ingredient for prevention and treatment of alcohol dependence}

The present invention relates to a composition for the prevention and treatment of alcohol dependence using the mixed herbal medicine extract as an active ingredient, and more specifically to the prevention of alcohol dependence using the mixed herbal medicine extract including browning and earthworm having an anti- craving effect as an active ingredient and A therapeutic composition.

Alcohol dependence means that there is always an obsessive desire to drink continuously or periodically to avoid discomfort in the absence of alcohol and that causes various types of mental, physical and social disorders as a result of excessive alcohol intake.

According to the Korea Institute for Health and Social Affairs, in 2001, 26.1% of males, 10.5% of females, and 20.9% of all adults were alcohol dependent. This suggests that one in five adults is alcohol dependent, increasing social problems and costs.

In Oriental Medicine, in relation to alcohol dependence, Emperor Inchuchu (黄 병), 『Che hospital Furon』, 『Checho Kang-mok』, 『Cultivation of Bangshin-pyeon (增 輯 醫) Classical texts such as 方 新 』, etc. describe the dependence of alcohol dependence, mental symptoms, and physical symptoms, and in modern clinical practice, it is composed of Galgunju-tang (탕 根 解酒 湯) and Chang-za (자 子). Hajujigalang, Haeunji Galtang (견 酒 丸), Galhwa (Gulhwa) and Earth's Earth, Geunja, Gal Geun, Injin, Jinpi, Yanggang ), Seongjucheonggantang (醒酒 淸 肝 湯) consisting of Red Bongryong (赤 茯 笭) and Chodugu (豆寇 구) are used. Recently, various studies have been conducted on the effects of the herbal medicine on alcoholism.

Han-eun reported that GOT, GPT, and TG were significantly changed by administering Haejuji-galtang to alcohol-induced rats. Kyung Hee University Graduate School, p.44, 1992), Bang, Geunjuju-tang, Junjuhwan and Hajujigaltang, were administered to mice with alcoholism. The changes in motor incoordination by Rota-Rod and the transit time of T-maze in water were compared with those of the control group (Bye Hye-yeon, Hwang Eon-wan: 葛根 解酒 湯 合 酒 酒 丸 and Hajijigaltang). The Effects of Experimental Alcoholism on the Behavior of Mice, Journal of Oriental Neuropsychiatry, 5 (1): 93-101, 1994, Yeong-Jeun Lee, the root extract and its major extract, Dyeze, Syrian Golden Hams (Keung Wing-Ming, Vallee Bert L .: Daidzin and daidzein suppress free-choice ethanol intake by Syrian Golden hamsters, Proc. Natl. Acad. Sci, USA, pp. 10008-100012, 1993), Overstreet found that a mixture of root and citrus reticulata extract and root extract reduced alcohol intake in P rats, Fawn-Hooded rats (alcohol preferred rats) (Overstreet DH, Lee YW, Rezvani AH, Pei YH, Criswell HE, Janowsky DS: Suppression of alcohol intake after administration of the Chinese herbal medicine, NPI-028, and its derivatives, Alcohol Clin Exp Res, 20 (2): 221-227, 1996). , Giancarlo reported that Salvia miltiorrhiza extract inhibited the ethanol intake and preference of sP rats (Sardinian alcohol preferred rats) who prefer ethanol (Giancarlo Colombo, Roberta Agabio, Carla Lobina, Roberta Reali, Paolo Morazzoni, Ezio). Bomba rdelli and Gian Luigi Gessa: Salvia miltiorrhiza Extract Inhibits Alcohol Absorption, Preference, and Discrimination in sP Rats, Alcohol, 18 (1): 65-70, 1999), Reduction of Drinking Desire in Male Patients Recovered from 28 to 59 Years (Jong-Tae Yoon, Myung-Jung Kim, and Sung-Kon Kim: The Effect of Long-term Dose of Brown Root on Drinking Desire of Alcoholic Patients, Neuropsychiatric, 34 (6): 1937-1948 , 1995), Kim stated that reed does not raise blood alcohol levels in normal and alcohol-dependent patients (Kim Ji-hoon, Kim Myung-jeong, Kim Seong-gon, Park Je-min, and Young-in Chung: Long-term administration of radix puerariae on blood alcohol levels in normal adults). Impact, Neuropsychiatry, 35 (6): 1230-1235, 1996; Kim, Myung-Jung, Young-In Chung, Je-Min Park, Seong-Kon Kim, and Young-Gil Choi: The Effect of Brown Root on Blood Alcohol Concentration and Drinking Effect in Alcohol-Dependent Patients, Neuropsychiatric Medicine, 35 (6): 1236-1246, 1996). Kang et al. Reported that rooting reduces the desire for basic drinking and blocks the increase in alcohol cravings induced after drinking (Cheol-Joong, Kim Myung-Jung, Sung-Kon Kim, and In-Ju Kim: Effects of Browning on Alcohol Craving and Cerebral Local Blood Flow in Alcohol-Dependent Patients, Neuropsychiatry, 36 (5): 861-869, 1997).

The cause of alcohol dependence is that ethanol is an abnormality of neurotransmitter system including dopamine, and the reward system dysfunction causes ethanol resistance and strengthening, which eventually leads to alcohol cravings. Sanchis-Segura C, Grisel JE, Olive MF, Ghozland S, Koob GF, Roberts AJ, Cowen MS: Role of the Endogenous Opioid System on the Neuropsychopharmacological Effects of Ethanol: New Insights About an Old Question, Alcohol Clin Exp Res, 29 (8): 1522-1527, 2005). The alcohol-induced mechanism is a precursor of beta-endorphin, POMC (proopiomelanocortin), which plays an important role in the endogenous Opioid system (EOPS). This high, hypothalamus is known to increase the release of beta-endorphin, an endogenous opiate peptide. Increased beta endorphins are known to exhibit reinforc-ing effects by compensating EOPS by altering the binding sites of opioid receptors. In order to treat this alcoholic craving, it has been studied that drugs such as naltrexone act as opiate antagonists and reduce the craving. However, there have been limited studies on the efficacy of herbal medicines, but there is no research on the anti- longing mechanism.

Gal Geunjujutang used in the present invention was used in alcohol clinical trials in patients with alcoholism, Gal Geunjujuwon Wonbang (Dept. of Oriental Medicine Hospital, Kyung Hee University College of Oriental Medicine: Kyung Hee Oriental Medicine Prescription, Kyung Hee Medical Center, Seoul, p.533, 1997) To add the earth's potency of Haedogdogok.

The study on alcoholism of galgejuju-tang far-field was conducted to demonstrate the effects on the alcoholism of galgejuju-tang, Hajujigaltang, which consists of earth and gallium, and changes in ataxia due to the number of foot-steps, rearing, and Rota-Rod. In the study of the behavior of alcoholism mice such as the change of T-maze time in the water, the change in the number of foot-steps showed a significant decrease in Galgeju-tang in 8 hours compared to the control, and the change in the number of rearing was The treatment group showed significant change in 3 hours and 8 hours compared to the control group, and the Hajujigaltang group showed significant change in 8 hours. In the change of ataxia induced by Rota-Rod, the Galgeju-tang administration group showed significant relief at 8 hours, and the change in the number of successes of T-maze in the water tended to increase. Changes in the time of T-maze in water showed a significant decrease at 8 hours in the Galgeju-tang administration group (李 時珍: 本草綱目, 人民 衛生 出版社, 北京, pp.798, 862, 1277, 1577, 1558, 1718, 1982), after experimenting with experimental alcoholism in rats to investigate the effects of haejugaltang on alcoholism, the wall climbing time showed a significant increase in the haejugaltang in 5 and 8 hours compared to the control group (Han Kyung-seung) , Ji-Hyuk Kim, Eui-Whan Hwang: Haejigaltang, Danjuhwan, and Seongjucheonggantang, and their effects on experimental alcoholism, Graduate School of Kyung Hee University, p.44, 1992), have shown efficacy in alleviating the decline of spatial perception ability due to alcoholism.

Radix Puerariae is a root of the perennial deciduous plant of Leguminosae. The name is Pueraria thunbergiana B. The effects of reed roots include Haedogok, sweat sweating, presentation jinjin, Saengjinjigal, detoxification, and booster. Clinically, it has been widely used for colds, vomiting, measles, sputum, diarrhea, angina, hypertension, migraine, retinal artery occlusion, sudden elongation, and alcoholism.

The effect of long-term administration of carpal root on the alcoholic effect of male patients who were hospitalized due to alcohol dependence and recovered from acute alcoholism and withdrawal was divided into 4 groups for the treatment of carpal root and placebo for 4 weeks. Systolic blood pressure was significantly lower at 10, 30, 60, 90 minutes after drinking and diastolic blood pressure at 10, 30, 60, 90, 120 minutes after drinking. The systolic blood pressure before the rooting was significantly increased at 10 minutes after drinking and the diastolic blood pressure was 10, 30, and 60 minutes after drinking. The amount of exercise was significantly lower at 60, 90 minutes after drinking and the voice was significantly lower at 10, 30, 60, 90 minutes after drinking (Kim, Myung-Jung, Young-In Chung, Je-Min, Kim, Seong-Kon, and Young-Gil Choi). Effects of Roots on Blood Alcohol Concentration and Drinking Effects in Neuropsychiatry, 35 (6): 1236-1246, 1996).

Of the 28 to 59-year-old male patients recovering from acute alcoholism and withdrawal, the placebo group included 64 subjects with at least 4 out of 13 questions in the Short Michigan Alcoholism Screening Test and at least 2 out of 4 questions with CAGE. Randomly assigned to 3 groups of 2g dose group (1g for morning and evening) and 4g (2g each for morning and evening), and administered for 4 weeks daily to measure drinking desire using Likert Scale and VAS. In one study, there was a significant decrease in the desire for drinking in the group of the roots (Yong, Jong-Tae, Myung-Jung Kim, and Sung-Kon Kim: The effect of long-term administration on the drinking habits of alcoholic patients, Neuropsychiatric, 34 (6): 1937-1948, 1995).

In five patients who were hospitalized for alcoholism and recovered from acute poisoning and withdrawal symptoms, alcohol craving, anxiety, and mood were measured by VAS to assess the level of basic alcohol craving and to use SPECT (single photon emission computed tomography). Local blood flow in bilateral caudate head, bilateral thalamus, and bilateral orbital frontal lobe was measured to determine the effects of dry root granules on craving and brain local blood flow after alcohol intake. It is suggested that there is a significant association between the change in drinking desire and the change of local blood flow in the limbic system and striatum, especially the unknown nucleus. Sung-Gon Kim and In-Ju Kim: Alcohol Craving and Cerebral Soup in Alcohol-Dependent Patients Effect of changes in blood flow, nerve Psychiatry, 36 (5): 861-869, 1997).

Puerariae Flos composed mainly in the present invention dried flowers of the perennial deciduous tree (Pueraria thunbergiana B.) belonging to the legumes (Leguminosae), the efficacy of the poison is remarkable and the effect of the main symptoms (醒胃 止渴) It is widely used in the recovery of liver function by treating the symptoms such as drinking excessive, dry mouth, crisis damage (胃氣 損傷) in the clinical.

Studies on browning significantly reduced ethanol concentrations in the blood, brain and liver of rats. Tectorigenin and kaikasaponin III isolated from browning were free radicals in subacute alcoholic rats. By inhibiting the production enzymes to restore liver damage caused by alcohol, and involved in the alcohol metabolism enzyme system affected the detoxification effect. Kakkalide and its metabolites were found to inhibit blood alcohol concentrations in mice (Hyeok Han: Kakalide and its metabolites inhibited blood alcohol levels and metabolic enzymes in mice) Partial Separation and Purification, Graduate School of Kyunghee University, 2002) (Niiho Y, Yamazaki T, Nakajima Y, Itoh H, Takeshita T, Kinjo J, Nohara T .: Pharmacological studies on puerariae flos.: I. The effects of pu-erariae flos on alcoholic metabolism and spontaneous movement in mice, Yakugaku Zasshi, 109 (6): 424-431, 1989), Gall needles produced more neurons in the dentate gyrus of alcoholic rats (Seo Jung-cheol, Kim Lee-hwa, Rose Hyun, Kim Yeon-jeong, Jung Ho-ho, Kim Chang-joo, Kim Yeon-hee, Lim Baek-bin: Korean Journal of Acupuncture and Moxibustion, 18 (6): 206-214, 2001).

In addition, the earth, the main drug of the present invention, is a fruit or seed with a fleshy fruit stalk of Rhovenaceae (Hovenia dulcis T.), a plant of Rhamnaceae. , Haejudok, Tongryui (通 利 二 便) has the efficacy of mainly used to solve the detoxification. When Hoveno-dulinol of C17H16O8 was removed from the extracts of the larvae and administered to rats with alcohol, the enzyme activities of ADH and ALDH were increased (Hong Yuri, Kim Min Hee, Ahn Cheol, Lee Hyun Yong) , Jong-Dae Kim: Studies on the Physiological Activity of the Extracts of the Barley Tree, Journal of Agricultural Sciences, Kangwon National University, 11: 1-11, 2000), The Barley Tree Extract and Alder Extract Increase the Alcohol Degradation in Rats and Humans It has been reported that the addition of the extract of the bark tree after inducing hepatitis has a therapeutic effect on the hepatitis, and the extract of the bark tree has the effect of lowering the blood alcohol concentration of the alcohol-administered rats (Sang Wook Ahn, Kim Young Gil, Kim Min Hee, Lee Byung Ik, Lee, Sang-Ho, Hyuk-Il Hwang, Baek-Hyun Lee, and Hyong-Yong Lee: Comparison of liver detoxification and alcohol degradability of bark and alder extract, 韓國 藥用 作物 學會 誌, 7 (4): 263-268, 1999). Healthy drinks developed as hangover-relieving beverages were taken orally 30 minutes before and after alcohol administration, and blood and acetaldehyde levels were measured at 1 and 5 hours after ingestion. Health drink lowered alcohol concentration by 48% and acetaldehyde concentration by 36% (Kang, Seong-hee, Kim, Sung-moon, Kim, Jin-hyun: Increased alcohol-degrading effect by acid hydrolysis of extracts of barberry, Korean Journal of Biotechnology and Bioengineering, 20 (2): 129- 132, 2005). To test the effect of the Earth's water extract on ethanol-addicted rats' learning ability, divided into two groups: normal, 25% ethanol-controlled group, and sample-administered group administered with earth-water extract and ethanol. After administering the drug, the experiment was conducted three times a day with a straight line and the T-maze experiment was performed three times a day for three days from the next day. The time required to reach the target point was significantly shortened by learning in the control group, and the control group significantly decreased the learning ability due to the decline of memory, but in the case of the sample group continuously administered the water extract of the earth, the learning ability was significantly decreased due to ethanol poisoning. Recovery (Lim Jong Pil, Choi Hoon, Song Jung Mo: Effect of Earthling on Learning Ability of Rats Addicted to Ethanol, 韓國 藥用 作物 學會 誌, 11 (3): 232-235, 2003). Bark, throat, and fruit extracts of the bark tree decreased blood alcohol concentration, and hot water extracts decomposed alcohol by increasing the activity of alcohol dehydrogenase (Lim Jong-Pil, Choi Hoon, Song Jung-Mo: Effect of Earthling on the Learning Ability of Ethanol-addicted Rats, 11 (3): 232-235, 2003). As a result of experiments in rats and alders extracts of rats and humans, it was found that there was alcohol degradation in the body. And 42% for the mixture. In addition, the effects of alcohol degradation could be confirmed by enhancing ADH and ALDH enzyme activity when administered to mice and humans (Kim Young-gil, Lee Sang-ho, Kwon Hyuk-il, Hwang-baek, Lee Hyun-yong, Ahn Sang-uk, Kim Min-hoe, Lee Byung-ik: Liver Detoxification and Alcohol Degradation in the Body, 韓國 藥用 作物 學會 誌, 7 (4): 263-268, 1999).

Hyangbuja is a dried root of the perennial herbaceous cyperus ro-tundus L. belonging to the Cyperaceae family. It is effective for self-sealing, landscaping pain, etc. Treats cramps and dysmenorrhea. In the study to investigate the effects of flavor extracts on methamphetamine and nicotine dependence, depression, and anxiety and the association between cannabinoid receptors and sigma receptors as therapeutic drugs, the extracts of perfume extracts were found to be effective through the effects of CB₁ and σ₁ receptor antagonism or agonistic effects. It was judged to have a therapeutic effect on drug addiction, depression and anxiety (Jung, Min Sook: Effect of Hyangbuja Extract on methamphetamine and nicotine dependence, Graduate School of Chonbuk National University, 2006).

Looking at the above simple rice research, brown root, brown hair, earth, and Hyangbuja are considered to be important drugs for the treatment of alcohol dependence by Galgeju-tang, and the remaining drugs such as Yanggang, hawthorn, tree (Chinese quince), baekrye, jirye, Efficacy and other related studies of the dermis, bleeding, and ginseng are shown in Table 1 below.

origin efficacy Research contents Yanggang Dry root of Alpinia officinarum H., a perennial plant belonging to the Zingiberaceae family Warmth, wind Hepatitis therapies that bind HBs antigens in hepatitis vaccines. Sansa Dried fruits of the hawthorn (Crataegus pinnatifida B.) belonging to the Rosaceae News (消食 積), wild fish blood (散 瘀血) Study on prevention of hyperlipidemia and liver damage on alcohol Neck and Dried fruit of the mature leaves of Chaenomeles sinensis K., a deciduous shrub belonging to the Rosaceae family West muscle activity, hua hua Study of free radical scavenging activity test of Chinese herbal medicine (compared with existing antioxidants)
Gosam Dry roots of the perennial herb, Sophora flavescens AIT, belonging to the legume family passion
Humidity
Geopung
Insecticide Inhibitory Effect on the Increase of C-fos Positive Peptides Increased by XO / HX
Regeneration Effect of NIH 3T3 Fibroblasts Damaged by Cadmium Toxicity dermis Dried skin of mature fruit of Citrus unshiu Markovich, a subfamily of Rutaceae, and related plant Selfishness,
Humidity Changes in Colonic Transport, Dead Action, and Small Intestine Transport Basement Dried young fruits of the Pancirus trifoliata R. belonging to the Rutaceae Fertility costs, Saddam droplets Changes in Colonic Transport, Dead Action, and Small Intestine Transport Ejection Root Root of Curcuma zedoariar Rosc, a Perennial Root Plant of the Zingiberaceae Family Sputum, tong, hwahwa, jitong Study on Analgesic Effect of Homemade Alcoholic Herbal Acupuncture Whiteness Dried rhizome of Atractylodes japonica K. belonging to Compositae Bobby Wing, Humidity, 中 中 Pharmacological action of air conditioners, anti-diarrheal drugs, diuretics, blood pressure enhancers, anti-inflammatory drugs

The existing Galgunju-tang does not contain gallium and tertiary, and has revealed alcohol degrading ability, but there is no research on the effects of genetic factors of alcohol dependence.

On the other hand, high alcohol preference is known to increase the expression level of hypothalamic POMC mRNA and alcohol increases the production of beta-endodolphin in the hypothalamus (Dennis D. Rasmussen, Brian M. Boldt, Charles W. Wilkinson, and Dennis R. Mitton: Opiomelanocortin Gene Expression And Implications For Dependence, Relapse, And Deprivation Effect ALCOHOLISM: CLINICAL AND EXPERIMENTAL RESEARCH, 26 (4): 535-546, 2002). Beta endorphins are produced by the posttranslational processing (PTP) of POMC. POMC is a precursor required for the production of ACTH, beta-endorphin, α-, β-, γ-MSH and is expressed by leptin in the pituitary gland and hypothalamus. POMC produces various hormones that affect the secretion of GnRH and plays an important role in reproductive physiology. Since direct measurement of beta endorphins is technically very difficult, beta-endorphin-like peptide (PE-EPLP), POMC primary transcripts, and POMC mRNA are studied to study alcohol dependence. The measurement site is selected by measuring the arch nucleus of the hypothalamus of the brain, because there is a mechanism for synthesizing POMC in the hypothalamus.

In addition, alcohol is known to increase the activity of Endogenous Opioid system (EOPS), especially alcohol is known to increase POMC. When alcohol was administered, POMC mRNA was increased in the hypothalamus of alcohol-loving rats (P rats) compared to non-alcoholic rats (nP rats), and high spontaneous alcohol intake (Krishnan-Sarin S, Wand GS, Li XW, Portoghese PS, Froehlich JC: Ef-fect of mu opioid receptor blockade on alcohol intake in rats bred for high alcohol drinking, Pharmacol Biochem Behav, 59 (3): 627-635, 1998), 2 months old Comparison of POMC mRNA expression in male C57BL / 6 and DBA / 2 after alcohol consumption showed that C57BL / 6 mice were higher than DBA / 2 type (Jamensky NT, Gianoulakis C: Comparison of the Proopiomelanocortin and Proenkephalin Opioid Peptide Systems in Brain Regions of the Alcohol-Preferring C57BL / 6 and Alcohol-Avoiding DBA / 2 Mice, Alcohol, 18 (2-3): 177-187, 1999). In a study to investigate the effects of spontaneous alcohol intake on the brain beta-endorphin system of C57BL / 6 and DBA / 2, C57BL / 6 consumed significantly more alcohol than DBA / 2, and spontaneous alcohol intake was observed in the hypothalamus mRNA was increased. And beta endorphin-like peptide was significantly increased. However, DBA / 2 did not alter the activity of the beta-endorphin system (De Waele J, Gianoulakis C: Enhanced activity of the brain β-endorphin system by free-choice ethanol drinking in C57BL / 6 but not DBA / 2 mice, European Journal of Pharmacology, 258 (1-2): 119-129, 1994). Compared with ANA rats with low alcohol consumption and POMC mRNA expression, AA rats, which are characterized by high impulsive behavior, showed higher tendency in AA rats (Lindblom J, Wikberg JE, Bergstrom L: Alcohol-preferring AA rats). s-how a derangement in their central melanocortin signaling system, Pharmacol Biochem Behav, 72 (1-2): 491-496, 2002). In addition, AA rats contained 52% higher amounts of POMC mRNA in the arch nucleus than ANA rats, and proopiomelanocortin, proenkephalin, and prodinor were administered to ANA rats and AA rats through in situ hybridization. Comparing the pin mRNA, AA mice showed significantly higher proopiomelanocortin mRNA in the hypothalamic arch nucleus, proenkephalin mRNA in the frontal cortex, and prodinorphine mRNA in the medial dorsal cortex (Marinelli). PW, Kiianmaa K, Gianoulakis C: Opioid propeptide mRNA content and receptor density in the brains of AA and ANA rats, Life Scie-nces, 66 (20): 1915-1927, 2000). In clinical studies, blood was collected from 12 chronic alcoholics and 12 nonalcoholics, indicating a significant increase in POMC mRNA in chronic alcoholics (Rosenberger P, Muhlbauer E, Weissmuller T, Rommelspacher H, Sinha P). , Wernecke KD, Finckh U, Rettig J, Kox WJ, Spies CD: Decreased proopiomelanocortin mRNA in lymphocytes of chronic alcoholics after intravenous human corticotropin releasing factor injection, Alcohol Clin Exp Res, 27 (11): 1693-1700, 2003). Compared with alcoholism and POMC mRNA of control group, it was higher than control group in alcoholic lymphocytes (Winkler A, Schmidt LG, Rommelspacher H, Melzig MF: Quantification of proopiomelanocortin mRNA in peripheral lymphocytes of alcoholics, Alcohol, 15 (1) : 43-50, 1998).

Therefore, the present inventors have used the alcohol-dependent animal model C57BL / 6 mice, and the mixed herbal extracts including browning and sapphire reduced the alcohol consumption preference of the animal model and further improved the expression level of POMC mRNA, a precursor of beta endorphin. The present invention has been completed by identifying significant reductions.

An object of the present invention to provide a composition for the prevention and treatment of alcohol dependence using a mixed herbal extracts, such as browning and earth, which are natural ingredients without side effects.

In order to achieve the above object, the present invention comprises a brown root, browning, earth, yangbuja, Yanggang, hawthorn, Chinese quince, baekrye, fruit room, dermis, sessile and ginseng extracted with water, alcohol or a mixture thereof as a solvent. Provides a blended herbal extract.

In addition, the present invention provides a method for producing the mixed herbal medicine extract.

The present invention also provides a pharmaceutical composition for preventing and treating alcohol dependence containing the extract as an active ingredient.

In addition, the present invention provides a health food for preventing and improving alcohol dependence containing the extract as an active ingredient.

Hereinafter, the present invention will be described in detail.

The present invention provides mixed herbal medicine extracts including brown root, brownish root, earthworm, saengbuja, Yanggang, hawthorn, Chinese quince, baekchul, fruiting, dermis, extract and ginseng extracted with water, alcohol or a mixture thereof as a solvent.

The mixed herbal medicines preferably contain 2 to 30% by weight of each of the roots, brown roots, brown roots, earthworms, hyangbuja, Yanggang, hawthorn, Chinese quince, baekchul, fruiting, dermis, and extracts of ginseng. More preferably, 20% by weight, Yanggang, hawthorn, saengbuja and fruit fat, 5 to 12% by weight, baekchul, Chinese quince and red ginseng, 2 to 8% by weight and dermis and buds 2 to 6% by weight, but is not limited thereto. It is not.

Preferably, the alcohol is a C ₁ to C ₄ lower alcohol, but is not limited thereto, and the lower alcohol is preferably ethanol or methanol.

In addition,

1) At room temperature using a mixture of herbal medicines containing 2-30% by weight of brown root, brown hair, earth, saengbuja, Yanggang, hawthorn, throat, white peach, dermis, dermis, extract and red ginseng, using water, alcohol or mixtures thereof. Preparing an extract by shaking with heat;

2) It provides a method for producing a mixed herbal medicine extract consisting of the step of removing solids from the extract of step 1 and concentrating.

The mixed herbal medicine extract of the present invention is galvanized in the original root of Geunjuju-tang (Kyung Hee Oriental Medicine Hospital, Kyung Hee Oriental Medicine Hospital, Kyung Hee Medical Center, Seoul, p.533, 1997). And additionally containing the earth, characterized in that it comprises 2-30% by weight of brown root, browning, earth, hyangbuja, Yanggang, hawthorn, neck, white baekrye, fruit room, dermis, and ginseng.

To investigate the anti-craving effect and mechanism of the mixed herbal medicine extract of the present invention, an animal experiment was conducted using C57BL / 6 mice, which are alcohol-dependent animal models. C57BL / 6 mice, the animals used in this study, have high bioactivity, high incidence of hydrocephalus and eye abnormalities, and good hair loss for tumor cell transplantation, and high palatability for alcohol and morphine. (Meliska CJ, Bartke A, McGlacken G, Jensen RA: Ethanol, nicotine, am-phetamine, and aspartame consumption and preferences in C57BL / 6 and DBA / 2 mice, Pharmacol Biochem Behav, 50 (4): 619-626, 1995). In particular, C57BL / 6 was found to have a significantly higher difference in consumption of alcohol and nicotine freely consumed orally than similar species C3H / HeJ (Li XC, Karadsheh MS, Jenkins PM, Stitzel JA: Genetic correlation bet-ween the free-choice oral consumption of nicotine and alcohol in C57BL / 6JxC3H / HeJ F2 intercross mice, Behav Brain Res, 157 (1): 79-90, 2005). Alcohol preference (Bachmanov AA, Reed DR, Li X, Li S, Beauchamp GK, Tordoff MG: Voluntary ethanol consumption by mice: genome-wide analysis of quantitative trait loci and their interactions in a C57BL / 6ByJ x 129P3 / J F2 intercross, Genome Res, 12 (8): 1257-1268, 2002), and C57BL / 6 showed significantly higher alcohol intake and alcohol preference than DBA / 2, an alcohol-preferred mouse (Meliska CJ, Bartke A, McGlacken G). , Jensen RA: Ethanol, nicotine, am-phetamine, and aspartame consum ption and preferences in C57BL / 6 and DBA / 2 mice, Pharmacol Biochem Behav, 50 (4): 619-626, 1995). Thus, C57BL / 6 is an animal model that is widely used for the study of alcohol-dependent therapeutic drugs due to the spontaneous intake of alcohol and the preference for alcohol (Unwin JW, Taberner PV: Voluntary ethanol consumption after ethanol and acetaldehyde treatment in alcohol-preferring C57BL mice, Psych-opharmacology (Berl), 78 (4): 361-364, 1982).

In addition, in the present invention, a modified finite approach (limited access procedure) was used to be alcohol-dependently (Stromberg MF, Casale M, Volpicelli L, Volpicelli JR, O'BRIEN CP: A Comparison of the Effects of the Opioid Antagonists Naltrexone, Naltri-ndole, and β-Funaltrexamine on Ethanol Consumption in the Rat, Alcohol, 15 (4): 281-289, 1998). That is, three weeks old C57BL / 6 mice were stabilized for three weeks, and then two hours of alcohol intake was measured for two hours while the drug was administered for 10 days, and water intake was measured for the remaining 22 hours. The finite approach is suitable for the study of the effects of various pharmacological agents on alcohol consumption, compared to the 24h two-bottle choice technique, and sustained medicinal effects with short half-life drugs or intracranial infusion. It is effective for short-term drug research, and it can be applied to alcohol dependence research because it can measure various behavioral and genetic factors in alcohol consumption (Le AD, Ko J, Chow S, Quan B: Alcohol consumption by C57BL / 6, BALB / c, and DBA / 2 mice in a limited access paradigm, Pharmacol Biochem Behav, 47 (2): 375-378, 1994). In the present invention, a finite approach was applied for alcohol dependence. C57BL / 6 mice had a 10% alcohol intake of 3.3 g / kg for 2 hours immediately after the dependency period. This suggests that the alcohol consumption of alcohol-dependent animals compared with other studies is sufficient for alcohol consumption.

In a preferred embodiment of the present invention, the expression of POMC mRNA, a precursor of beta-endorphin, was determined to elucidate the mechanism of action on alcohol dependence of the mixed herbal extracts. The exact cause of alcohol dependence is not yet known, but beta-endorphin is known to have a large effect. Ethanol is known to increase the endogenous opioid peptide beta-endorphin and to alter the binding sites of opioid receptors, resulting in reinforcing effects beyond the Endogenous Opioid system (EOPS) (Blum K, Topel H: Opioid peptides and alcoholism: genetic deficiency and chemical management, Funct Neurol, 1 (1): 71-83, 1986; Topel H: Beta-endorphin genetics in the etiology of alcoholism, Alcohol, 5 (2): 159- 165, 1988; Gianoulakis C: The effect of ethanol on the biosynthesis and regulation of opioid peptides, Experientia, 45 (5): 428-435, 1989). Higher liking of alcohol is known to increase the expression of POMC mRNA in the hypothalamus and alcohol is known to increase the production of beta-endorphins in the hypothalamus (Dennis D. Rasmussen, Brian M. Boldt, Charles W. Wilkinson, and Dennis R. Mitton: Opiomelanocortin Gene Expression And Implications For Dependence, Relapse, And Deprivation Effect ALCOHOLISM: CLINICAL AND EXPERIMENTAL RESEARCH, 26 (4): 535-546, 2002). Beta endorphins are produced by the posttranslational processing (PTP) of POMC. POMC is a precursor required for the production of ACTH, beta-endorphin, α-, β-, γ-MSH and is expressed by leptin in the pituitary gland and hypothalamus. POMC produces various hormones that affect the secretion of GnRH and plays an important role in reproductive physiology. Since direct measurement of beta endorphins is technically very difficult, beta-endorphin-like peptide (PE-EPLP), POMC primary transcripts, and POMC mRNA are studied to study alcohol dependence. The measurement site is selected by measuring the arch nucleus of the hypothalamus of the brain, because there is a mechanism for synthesizing POMC in the hypothalamus.

POMC mRNA was measured to determine the therapeutic mechanism for the alcohol dependence of the mixed herbal medicine extract of the present invention, it was significantly lower in the 7-day administration group compared to the 1 day administration group Galgunjutang (Fig. 1). Alcohol is known to increase the activity of the Endogenous Opioid System (EOPS), especially alcohol, which is known to increase POMC. When alcohol was administered, POMC mRNA was increased in the hypothalamus of alcohol-loving rats (P rats) compared to non-alcoholic rats (nP rats), and high spontaneous alcohol intake (Krishnan-Sarin S, Wand GS, Li XW, Portoghese PS, Froehlich JC: Ef-fect of mu opioid receptor blockade on alcohol intake in rats bred for high alcohol drinking, Pharmacol Biochem Behav, 59 (3): 627-635, 1998), 2 months old Comparison of POMC mRNA expression in male C57BL / 6 and DBA / 2 after alcohol consumption showed that C57BL / 6 mice were higher than DBA / 2 type (Jamensky NT, Gianoulakis C: Comparison of the Proopiomelanocortin and Proenkephalin Opioid Peptide Systems in Brain Regions of the Alcohol-Preferring C57BL / 6 and Alcohol-Avoiding DBA / 2 Mice, Alcohol, 18 (2-3): 177-187, 1999). In a study to investigate the effects of spontaneous alcohol intake on the brain beta-endorphin system of C57BL / 6 and DBA / 2, C57BL / 6 consumed significantly more alcohol than DBA / 2, and spontaneous alcohol intake was observed in the hypothalamus mRNA was increased. And beta endorphin-like peptide was significantly increased. However, DBA / 2 did not alter the activity of the beta-endorphin system (De Waele J, Gianoulakis C: Enhanced activity of the brain β-endorphin system by free-choice ethanol drinking in C57BL / 6 but not DBA / 2 mice, European Journal of Pharmacology, 258 (1-2): 119-129, 1994). Compared with ANA rats with low alcohol consumption and POMC mRNA expression, AA rats, which are characterized by high impulsive behavior, showed higher tendency in AA rats (Lindblom J, Wikberg JE, Bergstrom L: Alcohol-preferring AA rats). s-how a derangement in their central melanocortin signaling system, Pharmacol Biochem Behav, 72 (1-2): 491-496, 2002). In addition, AA rats contained 52% higher amounts of POMC mRNA in the arch nucleus than ANA rats, and proopiomelanocortin, proenkephalin, and prodinor were administered to ANA rats and AA rats through in situ hybridization. Comparing the pin mRNA, AA mice showed significantly higher proopiomelanocortin mRNA in the hypothalamic arch nucleus, proenkephalin mRNA in the frontal cortex, and prodinorphine mRNA in the medial dorsal cortex (Marinelli). PW, Kiianmaa K, Gianoulakis C: Opioid propeptide mRNA content and receptor density in the brains of AA and ANA rats, Life Scie-nces, 66 (20): 1915-1927, 2000). In clinical studies, blood was collected from 12 chronic alcoholics and 12 nonalcoholics, indicating a significant increase in POMC mRNA in chronic alcoholics (Rosenberger P, Muhlbauer E, Weissmuller T, Rommelspacher H, Sinha P). , Wernecke KD, Finckh U, Rettig J, Kox WJ, Spies CD: Decreased proopiomelanocortin mRNA in lymphocytes of chronic alcoholics after intravenous human corticotropin releasing factor injection, Alcohol Clin Exp Res, 27 (11): 1693-1700, 2003). Compared with alcoholism and POMC mRNA of control group, it was higher than control group in alcoholic lymphocytes (Winkler A, Schmidt LG, Rommelspacher H, Melzig MF: Quantification of proopiomelanocortin mRNA in peripheral lymphocytes of alcoholics, Alcohol, 15 (1) : 43-50, 1998).

Taken together, Galgunju-tang can be interpreted to reduce the alcohol preference by lowering the expression of POMC mRNA, thereby reducing the effect of alcohol to prevent alcohol intake.

In addition, the present invention provides a pharmaceutical composition for preventing and treating alcohol dependence containing the mixed herbal medicine extract as an active ingredient.

The pharmaceutical composition of the present invention may further contain one or more active ingredients exhibiting the same or similar functions in addition to the mixed herbal medicine. The composition may be administered orally or parenterally during clinical administration and may be used in the form of a general pharmaceutical formulation. The compositions of the present invention can be administered in effective amounts through various routes of administration. The use together contains a pharmaceutically acceptable carrier. More specifically, pharmaceutically acceptable carriers can be any standard pharmaceutical carrier that can be used in known formulations such as sterile solutions, tablets, coated tablets and capsules. Typically, the carrier may contain excipients such as starch, milk, sugar, certain types of clays, gelatin, stearic acid, talc, vegetable oils or oils, gums, glycols, or other known excipients, and also flavors, pigment additives. And other ingredients. The formulation for administering the composition containing the mixed herbal extract of the present invention as an active ingredient may be administered by oral, intravenous, intramuscular, or transdermal administration in a conventional manner, but is not limited thereto. In actual clinical administration, it can be administered in a variety of oral and parenteral formulations, which are formulated using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrants, surfactants and the like that are commonly used. Solid form preparations for oral administration include tablets, pills, powders, granules and capsules, and the like form at least one excipient such as starch, calcium carbonate, sucrose or lactose. (lactose), gelatin, etc. are mixed and prepared. In addition to simple excipients, lubricants such as magnesium styrate talc are also used. Oral liquid preparations include suspensions, liquid solutions, emulsions, syrups, and the like, and may include various excipients such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents, water and liquid paraffin. In addition, the compositions of the present invention can be administered parenterally, and parenteral administration is by subcutaneous injection, intravenous injection or intramuscular injection. In order to formulate into a parenteral formulation, it is prepared in solution or suspension by mixing in water with a stabilizer or buffer, including the herbal composition, and formulated in a unit dosage form of ampoules or vials.

The dosage of the composition of the present invention is appropriately selected depending on the absorbency, inactivation rate, rate of excretion, the age, sex and condition of the patient, and the severity of the disease to be treated in the body, but generally once to three times a day. It can be administered in divided doses. When the mixed herbal medicine extract in the composition of the present invention as an active ingredient, the effective dose is 100 ~ 1,000 mg / kg / day, preferably 100 ~ 500 mg / kg / day. The exact amount, route of administration, and frequency of the agent can be readily determined according to the nature of the agent, the weight and condition of the subject to be administered, and the nature of the particular derivative to be used.

The compositions of the present invention can be used alone or in combination with methods using surgery, radiation therapy, hormone therapy, chemotherapy and biological response modifiers for the prevention and treatment of alcohol dependence.

The present invention also provides a health food for preventing and improving alcohol dependence containing the mixed herbal medicine extract as an active ingredient.

When the mixed herbal medicine extract of the present invention is used as a food, it may be added as it is or used with other food or food ingredients, and may be appropriately used according to a conventional method. The blending amount of the active ingredient can be suitably determined according to the purpose of its use (prevention, health or therapeutic treatment). In general, the mixed extract of the present invention may be added in an amount of 0.1 to 50% by weight, preferably 1 to 10% by weight based on the raw materials in the manufacture of food or beverage. The effective dose of the mixed extract of the present invention may be used in accordance with the effective dose of the pharmaceutical composition, but may be less than the above range in the case of long-term intake for the purpose of health and hygiene or for health control. It is evident that the component can be used in an amount above the range because there is no problem in terms of safety.

There is no particular limitation on the kind of food. Examples of the food to which the mixed extract may be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, beverages, teas, and drinks. Alcoholic beverages and vitamin complexes.

As described above, the composition comprising the mixed herbal medicine extract of the present invention can be usefully used for the prevention and treatment of alcohol dependence by preventing the intake of alcohol by reducing the expression of POMC mRNA associated with spontaneous alcohol intake.

Hereinafter, the present invention will be described in detail by Examples and Test Examples. However, the following Examples and Test Examples are only illustrative of the present invention, and do not limit the content of the present invention.

< Example  1> mix Herbal medicine  Extract (" Rooting Haejutang Manufacturing)

It is a newly formulated prescription made by adding 12 g of earth's earth to Geun-ju Hae-tang of Kyunghee Medical Center Oriental Medicine Hospital Kyunghee Medical Center (Kyung Hee Oriental Medicine Hospital, Kyung Hee Oriental Medicine Hospital, Kyung Hee Medical Center, Seoul, p.533, 1997). , 10 pouches (850 g) were applied in a single pouch (85 g) unit, and then frozen and dried in a powder state. The content and quantity of Galgeju-tang are shown in Table 2.

Composition and Quantity of Galgeju-tang Composition Scientific name Dose Rooting Puerariae radix 12.0 g Gala Puerariae flos 12.0 g Yanggang Alpiniae officinarum Rhizoma 8.0g Sansacho Crataegii Fructus 8.0g Hyangbuja Cyperi Rhizoma 8.0g Basement Aurantii immaturus Fructus 8.0g Whiteness Atractylodis macrocephalae Rhizoma 4.0g Tree (quince) Chaenomelis Fructus 4.0g Gosam Sophorae Radix 4.0g dermis Citri pericarpium 3.0 g Ejection Zedoariae Rhizoma 2.0 g Earth Hovenia semen 12.0 g Total amount 85.0 g

The mixture was mixed at a rate of 300 cc of water per medicinal herb, and then heated for 3 hours in a reflux condenser to obtain a primary warm water. This warm water was put into a rotary vacuum flask again and concentrated under reduced pressure to obtain a secondary stock solution. The second stock solution was again lyophilized into a solid extract. This was pulverized with a grinder to obtain 103.8 g of powder.

This translates into a daily intake of 345 mg / kg per kg of an adult (60 kg) and 8.6 mg / mouse (based on a 25g body weight).

<Example 2> low dose group (GHT-L)

Intake dose of the low dose group (GHT-L) Galgeju-tang is administered 17.2 mg / mouse (688 mg / kg) per day by administering the galgejuju-tang prepared in Example 1 at a concentration twice higher than the daily intake of the mouse ) Was administered.

<Example 3> Brown root haejutang high dose group (GHT-H)

The high dose group (GHT-H) of Galgunju-tang was administered at a concentration 10 times higher than the daily intake of mice to administer 86.0 mg / mouse (3450 mg / kg) per day.

<Comparative Example 1> Brown root soup without gallium and earth

Comparative example 1 was used as the root galgejutang which does not contain the existing browning and earth globe. Brown root haejutang of Comparative Example 1 was prepared in the same manner as in Example 1 except for the grinding and earth. Galgeunjutang of Comparative Example 1 was administered in a concentration 10 times higher than the daily intake of the mice in the same manner as the GHT-H group was administered 86.0mg / mouse (3450mg / kg) per day.

Experimental Example 1 Treatment Effect of Galgejujutang Alcohol Dependence

In order to determine the therapeutic effect of the alcohol dependence of Galgejujutang of the present invention, the following experiment was performed.

1. Experimental Animal

Three-week old C57BL / 6 male mice (Hyochang Science, Cod) were used as the test subjects. C57BL / 6 male mice were acclimated to the experimental environment by raising 5 animals per cage for 5 days (up to 5 days of the experiment) from the arrival date. Water and mouse compound feed (Samyang Oil Feed Co., Ltd., Seoul) was freely ingested for 24 hours.

A modified finite approach was then used for behavioral alcohol dependence of the subject mice. That is, by raising one mouse per cage, for a week (up to the 12th day of the experiment), only 10% (v / v) alcohol (Sigma St, Louis, MO, USA) was provided for 24 hours with food instead of water. Alcohol consumption was forced. During the next three weeks (up to the 33rd day of the experiment), only 10% (v / v) alcohol was provided for 2 hours between 2 pm and 4 pm daily, so that only alcohol intake was learned. The remaining 22 hours without alcohol provided water. All feeds were provided 24 hours. Contrast was adjusted every 12 hours from 06 to 18:00.

Drug administration was conducted for 10 days from the 38th day to the 47th day of the experiment. To this end, the mice were randomly administered 0.1 ml of water in the morning of the 38th day of the experiment, the first day of the drug administration. Was divided into a low dose administration group (688 mg / kg, Example 2) and a high dose administration group (3.450 g / kg, Example 3). All doses were orally administered at 0.1 ml irrespective of treatment groups, and each dose group was varied in concentration. Drug administration began at 12 am, two hours before the start of alcohol delivery. 10% (v / v) alcohol was provided without water provision for 2 hours between 2 pm and 4 pm. Twenty-two hours without alcohol were given water and feed was provided for all 24 hours.

2. Measurement of POMC mRNA Expression

C57 / BL6 male mice (Hyochang science, Daegu) adapted to the experimental environment were used as 5 subjects per cage for 5 days from the arrival date. The drug administration was compared with the high dose administration group (GHT-H), the mediator group, and the existing Galgeju-tang, which did not contain gallium and tertiary, which showed some significance as a result of drug treatment. The dosage was 0.1 ml of water in the mediator group, and the group treated with Galgeju-tang extract was divided into 3.45 g / kg administration group, which was a high dose treatment group, and the comparison group was administered 3.45 g / kg of the existing Galgejuju-tang. . All doses were orally administered at 0.1 ml regardless of the administration group. Drug administration was administered at 12 am, two hours before the start of alcohol delivery. In order to measure the expression level of POMC gene in the arcuate nucleus, each group was divided into mediator group and Galgeunju-tang high-dose group. The cervical nucleus of the hypothalamus of the brain was excised and used as a material for the experiment.

RNA was isolated immediately after cutting the arch nucleus of the hypothalamus of the brain. The RNA was separated into 700 μl of Trizol solution in the cut tissue and then finely ground. Subsequently, 200 µl of chloroform solution was added thereto, followed by centrifugation at 12,000 rpm, the supernatant was added to a new tube, 200 µl of isopropyl alcohol was added, and the mixture was allowed to stand overnight in a freezer, and then the supernatant was removed after centrifugation at 12,000 rpm. 700 μl of 75% ethanol was added thereto and centrifuged. After centrifugation, the supernatant was removed, the tube was completely dried, and RNA was extracted by adding 10-20 μl of DEPC solution. The extracted RNA was quantified using a spectrometer and used for RT-PCR.

The primers related to expression in the POMC were 436 bp in size to the forward primers (SEQ ID NO: 1: 5'-GAT TCT GCT ACA GTC GCT C-3 ') and reverse primers (SEQ ID NO: 2: 5'-GAA CTC TAG). GGG AAA GGC-3 ') was used by BIONICS. RT-PCR using RT-PCR kit (Promega Co. USA), 11 μl RNase-free water, 4 μl AMV / Tfl 5fl reaction buffer, 2 μl dNTP mixture, 1 μl forward and reverse primer, 25 mM After addition of 0.8 μl of MgSO ₄ , 0.4 μl of AMV reverse transcriptase, and 0.4 μl of Tfl DNA polymerase, 1 μl of template RNA was mixed, followed by reverse transcription at 45 ° C. for 45 minutes to synthesize primary strand cDNA. After preheating at 94 ° C. for 2 minutes, denaturation at 94 ° C. for 30 seconds, primer binding at 50 ° C. for 1 minute, and extension reaction at 40 ° C. for 1 minute were repeated 40 times and finally 72 ° C. After reacting for 7 minutes at RT-PCR to synthesize a second strand cDNA.

Upon completion of the PCR reaction, electrophoresis was performed on 2.0% agarose gel to confirm the amplification of RNA bands. The amplified RNA bands were measured by measuring the amount of each band with a density meter to measure the expression of POMC mRNA. The measurement result of POMC mRNA was tested using an independent t-test as an average comparative analysis of each group.

To evaluate the effect of galgejuju-tang on hypothalamic POMC mRNA expression, the mean values of the three groups were compared by measuring the POMC mRNA expression in the high dose group, mediator group and comparison group on day 1 and 7 after administration. As a result, there was no significant difference in the mean between the median group and the comparison group on the 1st and 7th day, but there was a significant difference between the high dose group of the galgeunjutang on the 1st and 7th day (p = 0.043) ( 1).

Alcohol is known to increase the activity of the Endogenous Opioid System (EOPS), especially alcohol, which is known to increase POMC. When alcohol was administered, POMC mRNA was increased in the hypothalamus of alcohol-loving rats (P rats) compared to non-alcoholic rats (nP rats), and high spontaneous alcohol intake (Krishnan-Sarin S, Wand GS, Li XW, Portoghese PS, Froehlich JC: Ef-fect of mu opioid receptor blockade on alcohol intake in rats bred for high alcohol drinking, Pharmacol Biochem Behav, 59 (3): 627-635, 1998), 2 months old Comparison of POMC mRNA expression in male C57BL / 6 and DBA / 2 after alcohol consumption showed that C57BL / 6 mice were higher than DBA / 2 type (Jamensky NT, Gianoulakis C: Comparison of the Proopiomelanocortin and Proenkephalin Opioid Peptide Systems in Brain Regions of the Alcohol-Preferring C57BL / 6 and Alcohol-Avoiding DBA / 2 Mice, Alcohol, 18 (2-3): 177-187, 1999). In a study to investigate the effects of spontaneous alcohol intake on the brain beta endorphin system of C57BL / 6 and DBA / 2, C57BL / 6 was significantly more alcoholic than DBA / 2, and spontaneous alcohol intake was observed in the hypothalamus of POMC mRNA. Increased. And beta endorphin-like peptide was significantly increased. However, DBA / 2 did not alter the activity of the beta-endorphin system (De Waele J, Gianoulakis C: Enhanced activity of the brain β-endorphin system by free-choice ethanol drinking in C57BL / 6 but not DBA / 2 mice, European Journal of Pharmacology, 258 (1-2): 119-129, 1994). Compared with ANA rats with low alcohol consumption and POMC mRNA expression, AA rats, which are characterized by high impulsive behavior, showed higher tendency in AA rats (Lindblom J, Wikberg JE, Bergstrom L: Alcohol-preferring AA rats). s-how a derangement in their central melanocortin signaling system, Pharmacol Biochem Behav, 72 (1-2): 491-496, 2002). In addition, AA rats contained 52% higher amounts of POMC mRNA in the arch nucleus than ANA rats, and proopiomelanocortin, proenkephalin, and prodinor were administered to ANA rats and AA rats through in situ hybridization. Comparing the pin mRNA, AA mice showed significantly higher proopiomelanocortin mRNA in the hypothalamic arch nucleus, proenkephalin mRNA in the frontal cortex, and prodinorphine mRNA in the medial dorsal cortex (Marinelli). PW, Kiianmaa K, Gianoulakis C: Opioid propeptide mRNA content and receptor density in the brains of AA and ANA rats, Life Scie-nces, 66 (20): 1915-1927, 2000). In clinical studies, blood was collected from 12 chronic alcoholics and 12 nonalcoholics, indicating a significant increase in POMC mRNA in chronic alcoholics (Rosenberger P, Muhlbauer E, Weissmuller T, Rommelspacher H, Sinha P). , Wernecke KD, Finckh U, Rettig J, Kox WJ, Spies CD: Decreased proopiomelanocortin mRNA in lymphocytes of chronic alcoholics after intravenous human corticotropin releasing factor injection, Alcohol Clin Exp Res, 27 (11): 1693-1700, 2003). Compared with alcoholism and POMC mRNA of control group, it was higher than control group in alcoholic lymphocytes (Winkler A, Schmidt LG, Rommelspacher H, Melzig MF: Quantification of proopiomelanocortin mRNA in peripheral lymphocytes of alcoholics, Alcohol, 15 (1) : 43-50, 1998).

Taken together, Galgunju-tang can be interpreted to reduce the alcohol preference by lowering the expression of POMC mRNA, thereby reducing the effect of alcohol to prevent alcohol intake.

1 shows POMC mRNA expression measurement results. *: Independent t-test (p = 0.043) of daily GHT-H group.

<110> University-Industry Cooperation Group of Kyung Hee University <120> Composition comprising herbal mixture extract as an active          ingredient for prevention and treatment of alcohol dependence <130> 7p-10-41 <160> 2 <170> KopatentIn 1.71 <210> 1 <211> 19 <212> DNA <213> Artificial Sequence <220> <223> Forward primer for POMC <400> 1 gattctgcta cagtcgctc 19 <210> 2 <211> 18 <212> DNA <213> Artificial Sequence <220> <223> Reverse primer for POMC <400> 2 gaactctagg ggaaaggc 18  

Claims (9)

1) mixed herbs comprising 10 to 15 parts by weight of reeds, browned and earthen seeds respectively, 5 to 10 parts by weight of Yanggang, Sansa, Hyangbu and Jisil, respectively, and 2 to 5 parts by weight of baekchul, neck, red ginseng, dermis and sesame seeds Preparing an extract by mixing water, alcohol or a mixture thereof in room temperature or by heating; 2) preparing a concentrate by concentrating under reduced pressure from the extract of step 1); And 3) Pharmacy for preventing and treating alcohol dependence, comprising a mixed herbal extract as an active ingredient, characterized in that to reduce the degree of expression of POMC mRNA prepared by the manufacturing method comprising the step of lyophilizing the concentrate of step 2) Composition. The pharmaceutical composition for preventing and treating alcohol dependence of claim 1, wherein the alcohol of step 1) is a C ₁ to C ₄ lower alcohol.  3. The pharmaceutical composition for preventing and treating alcohol dependence of claim 2, wherein the lower alcohol is ethanol or methanol. delete delete delete delete delete 1) mixed herbs comprising 10 to 15 parts by weight of reeds, browned and earthen seeds respectively, 5 to 10 parts by weight of Yanggang, Sansa, Hyangbu and Jisil, respectively, and 2 to 5 parts by weight of baekchul, neck, red ginseng, dermis and sesame seeds Preparing an extract by mixing water, alcohol or a mixture thereof in room temperature or by heating; 2) preparing a concentrate by concentrating under reduced pressure from the extract of step 1); And 3) lyophilized the concentrate of step 2), including the root, browning, earth, hyangbuja, Yanggang, hawthorn, neck, white, fruit room, dermis, extract and ginseng , Health food for preventing and improving alcohol dependence containing a mixed herbal extract as an active ingredient, characterized in that to reduce the expression level of POMC mRNA.

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