WO2011115416A2 - Fraction de sedum sarmentosum pour décomposer l'alcool et soulager la gueule de bois - Google Patents

Fraction de sedum sarmentosum pour décomposer l'alcool et soulager la gueule de bois Download PDF

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WO2011115416A2
WO2011115416A2 PCT/KR2011/001815 KR2011001815W WO2011115416A2 WO 2011115416 A2 WO2011115416 A2 WO 2011115416A2 KR 2011001815 W KR2011001815 W KR 2011001815W WO 2011115416 A2 WO2011115416 A2 WO 2011115416A2
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alcohol
fraction
ethyl acetate
sedum
extract
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PCT/KR2011/001815
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Korean (ko)
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WO2011115416A3 (fr
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성창근
모은경
김승미
양선아
이청하
조현호
김현호
이승엽
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(주)대덕바이오
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/41—Crassulaceae (Stonecrop family)
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A61P25/32—Alcohol-abuse
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/334—Foods, ingredients or supplements having a functional effect on health treating the effects of consuming alcohol, narcotics or other addictive behavior, e.g. treating hangover or reducing blood alcohol levels
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps

Definitions

  • the present invention relates to a solvent fraction of Sedum sarmentosum having alcohol decomposition and hangover ability, which has an effect of promoting the activity of alcohol degrading enzymes ADH (Alcohol dehydrogenase) and ALDH (Acetaldehyde dehydrogenase). It is to provide a functional food useful to improve side effects.
  • Korea's alcohol consumption is among the highest in the world, and the socioeconomic and health consequences of alcohol use are enormous, with deaths caused by liver cancer and cirrhosis being the leading cause of death for Koreans.
  • Excessive alcohol consumption affects almost every part of the body and is reported to cause many diseases, including liver disease, gastritis, pancreatitis, high blood pressure, stroke, diabetes, and heart disease.
  • the average drinking time for adults over 20 years old is about 8 days a month, about 11 days for men and about 4 days for women.
  • the frequency of intoxication was about 4.7% at least once a week, about 10.7% at 1 to 3 times a month, and about 13.2% at 1 to 3 times a month.
  • modern people consume excessive amounts of alcohol that they cannot afford in the human body, and side effects such as thirst, general boredom, fatigue, memory loss, bloating, indigestion, vomiting diarrhea and vitamin deficiency Many suffer from the phenomenon and the risk of alcoholism is increasing that much.
  • This hangover phenomenon is known to be caused by the action of acetaldehyde and alcohol accumulated in the liver cells and the body.
  • acetaldehyde is a representative chemical that causes headaches after drinking alcohol, and WHO has warned of its toxicity.
  • Ethanol the main ingredient of alcohol
  • ADH alcohol dehydrogenase
  • ADH aldehyde dehydrogenase
  • Acetaldehyde the first metabolite of ethanol, has been found to be a major cause of alcoholic liver disorders due to its high reactivity and toxicity.
  • Acetaldehyde interferes with the respiration of mitochondria, a cellular energy production organ, inhibits oxidative phosphorylation, binds to membrane proteins and collagen proteins to produce antibodies, immunologically cytotoxic, and inhibits the release of hepatocellular secreted proteins. It has been found to do.
  • acetaldehyde promotes collagen synthesis of myofibroblast, causing hepatic fibrosis and degeneration of hepatocytes, and reacting with macromolecules in vivo to form adducts.
  • triglycerides may accumulate in the liver by alcohol ingested by the human body. It is known that fatty acid oxidation by alcohol acts as an important factor of triglyceride accumulation, rather than increasing fatty acid accumulation in liver. Accumulation of triglycerides in the liver reflects metabolic disorders in the liver, and continued triglyceride accumulation may eventually lead to fibrosis and damage to liver cells. As a result of this alcohol metabolism, many fatty acids are made and fat accumulates in the liver, which is called alcoholic fatty liver. The alcoholic fatty liver is often progressed to chronic liver disease, and 10-15% of alcoholic hepatitis and 8-20% of cirrhosis have been reported to be related to alcoholic fatty liver.
  • ALDH a major enzyme involved in the oxidation of aldehydes, including aldehydes, is widely distributed in many organs and tissues, including the liver, kidneys, heart, and stomach, and is also present in cytosol, mitochondria, and microsomal, showing broad substrate specificities. It has the character of a drug metabolism enzyme that can respond to.
  • ALDH has type ⁇ which initiates oxidation even at low concentration of aldehyde and type I which does not work if acetaldehyde does not have high concentration, but Asians generally have slow acetaldehyde oxidation due to lack or lack of type ⁇ ALDH and thus oxidation Unexpected toxic effects of acetaldehyde and ethanol will interfere with normal metabolism, and you will feel various hangovers.
  • Korean Patent Publication No. 2003-70232 is a composition for relieving hangover and antioxidant action containing sesame oil extract
  • Korean Patent Registration No. 721644 is a functional food for hangover elimination
  • Korean Patent Registration No. 787633 is a brown rice as a substrate.
  • sedum is a perennial plant with dicotyledon Rosales Sedum, also called donnamul, Dot herbs, moisture seconds. It is excellent for removing hangovers and protects the liver. It stimulates appetite, clears blood, has bactericidal, anti-inflammatory, and detoxification effects. It is rich in vitamin C, as well as various nutrients such as phosphate and calcium. It is also effective in oriental medicine, and it has been used as a remedy for bites of paracetamol, detoxification, jaundice, bruises, cirrhosis, snakes, etc. It is effective and has recently been shown to lower cholesterol levels, making it a good food for men as well as menopausal women.
  • the Korean patent registration No. 660175 is a hangover cure beverage composition consisting of hot water extracts of cedar mugwort, hydrangea (root), root vegetable, old root and seed powder. Is disclosed.
  • the present inventors are studying natural products having the activity of ADH (Alcohol dehydrogenase) and ALDH (Acetaldehyde dehydrogenase), the ethanol ethyl acetate fraction promotes the activity of ADH (Alcohol dehydrogenase) and ALDH (Acetaldehyde dehydrogenase) to break down alcohol and hangover.
  • the present invention was completed after confirming that there was an elimination effect.
  • the problem to be solved by the present invention is to provide a dolmul fraction with alcohol decomposition and hangover ability.
  • Another problem to be solved of the present invention is to provide a functional health food composition for alcohol degradation and hangover relief by providing an effect of promoting the activity of ADH (Alcohol dydrogenase) and ALDH (Acetaldehyde dehydrogenase).
  • the present invention provides ethanol ethyl acetate solvent fraction having the ability to decompose and hangover.
  • the sedum extract of the present invention includes extracts available in fresh juice, ethanol, methanol or 50-100% aqueous alcohol solution thereof.
  • the extract of the sedum of the present invention is a dried and powdered sedum of about 1 to 20 times (v / w), preferably 2 to 10 times (v / w) lower alcohol having 1 to 4 carbon atoms or their 1 to 5 times, preferably by extraction method such as hot water extraction, reflux cooling extraction, ultrasonic extraction for about 1 hour to 2 days, preferably 2 hours to 1 day at an extraction temperature of 20 to 100 °C with an aqueous alcohol solution of After repeating 2 to 3 times to obtain the extract, the resultant was filtered under reduced pressure and the filtered extract was mixed and concentrated under reduced pressure at 20 to 100 ° C., preferably at 50 to 70 ° C., using a rotary vacuum concentrator to remove the solvent. Crude extract which is a soluble extract according to the lower alcohol of 4 or an alcohol aqueous solution thereof can be obtained.
  • composition of the present invention comprises 0.01 to 50% by weight of the extract or fraction based on the total weight of the composition.
  • compositions comprising the sedum extract or fraction of the present invention may further comprise a suitable carrier, excipient or diluent according to conventional methods.
  • Carriers, excipients and diluents that may be included in the compositions of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
  • composition comprising the extract according to the present invention is formulated in the form of an oral dosage form such as powder, granule, tablet, capsule, suspension, emulsion, syrup, aerosol, external preparation, suppository or sterile injectable solution, respectively according to a conventional method.
  • an oral dosage form such as powder, granule, tablet, capsule, suspension, emulsion, syrup, aerosol, external preparation, suppository or sterile injectable solution, respectively according to a conventional method.
  • it may be prepared using diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, etc. which are commonly used.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid preparations include at least one excipient such as starch, calcium carbonate, sucrose, lactose, gelatin in the extract or fraction.
  • Liquid preparations for oral use include suspensions, solvents, emulsions, and syrups.
  • various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included.
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations and suppositories.
  • non-aqueous solvent and suspending agent propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used.
  • base of the suppository witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.
  • compositions containing extracts or fractions of the sedum of the present invention can be used in a variety of food and beverages for alcohol decomposition and hangover relief.
  • Foods to which the extracts or fractions of the present invention may be added include various foods, for example, beverages, gums, teas, vitamin complexes, dietary supplements, and the like, pills, powders, granules, acupuncture tablets, capsules or It can be used in the form of a drink.
  • the amount of the extract in the food or beverage in general, may be added to 0.01 to 15% by weight of the total food weight in the case of the health food composition of the present invention, 0.02 to 10g, preferably based on 100ml for the health beverage composition It may be added at a ratio of 0.3 to 1g.
  • the health beverage composition of the present invention has no particular limitation on the liquid component except for containing the extract as an essential ingredient in the indicated ratio, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks.
  • natural carbohydrates examples include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; Polysaccharides such as dextrin, cyclodextrin; Conventional sugars such as and the like and sugar alcohols such as xylitol, sorbitol, and erythritol.
  • natural flavoring agents tacumatin, stevia extract, etc.
  • synthetic flavoring agents saccharin, aspartame, etc.
  • the proportion of said 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.
  • the composition of the present invention includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, coloring and neutralizing agents (such as cheese and chocolate), pectic acid and salts thereof, alginic acid and its Salts, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like.
  • compositions of the present invention may also contain pulp for the production of natural fruit juices and fruit juice beverages and vegetable beverages. These components can be used independently or in combination.
  • the proportion of such additives is not so critical but is generally selected from the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.
  • Sedum ethyl acetate fraction of the present invention has the effect of promoting the activity of ADH and ALDH, liver enzymes involved in alcohol metabolism, thirst, systemic malaise, fatigue, memory loss, bloating, indigestion, vomiting Diarrhea, vitamin deficiency, etc. can improve the hangover.
  • the ethanol ethyl acetate fraction can quickly break down ethanol into acetic acid, the final metabolite by activating ADH and ALDH, the liver enzymes involved in alcohol metabolism, thereby reducing liver damage from alcohol intake. It can help to improve diseases caused by alcohol consumption such as stroke, esophagitis and diabetes.
  • Figure 1 shows the results of ADH and ALDH activity analysis of solvent extracts, solvent fractions, water extracts and fresh juice of sedum.
  • Figure 2a shows the effect of the solvent extracts, solvent fractions, water extracts and juice of sedum on ethanol oxidation.
  • Figure 2b shows the effect on acetaldehyde oxidation in solvent extracts, solvent fractions, water extracts and juice of sedum.
  • Figure 3a shows the effect on the ethanol degradation of the ethyl acetate fraction of dolgi.
  • Figure 3b shows the effect on the acceleration of acetaldehyde decomposition of the ethyl acetate fraction of dolgi.
  • Figure 4 shows the effect on the expression of ADH and ALDH ⁇ of solvent extracts, solvent fractions and juice of dolgi.
  • Washed and dried Sedum sarmentosum 100 g of dried pulverized pulverized powder with 0.5 L of methanol three times at 45 ° C for 3 hours, shaken for 24 hours, extracted and filtered Concentration gave 30 g of methanol extract. 0.5 liter of water was added to the methanol extract, the mixture was suspended, and 0.5 mL of hexane was added twice. The hexane layer was separated, and the hexane layer was concentrated under reduced pressure to obtain a hexane fraction.
  • Table 1 shows the results of measuring ADH and ALDH activity of the sedum extract.
  • the methanol extract of Example 1 showed 70% and 90% ADH and ALDH activity, respectively, and the hexane fraction of methanol extract showed 30% and 50% ADH and ALDH activity, respectively.
  • ALDH activity was 250% and 300%, and butanol fractions showed ADH and ALDH activity of 90% and 80%.
  • the ethanol extract of Example 2 and these fractions showed similar activities as in Example 1, but showed particularly good ADH and ALDH activity in the ethyl acetate fractions of Examples 1 and 2.
  • the ethyl acetate fraction of the alcohol extract of dolmen according to the present invention had an excellent effect of promoting ADH and ALDH activity compared to methanol extract, hexane fraction, butanol fraction, water extract and fresh dolmul juice (see FIG. 1).
  • the rats used in the experiment were sprague-dawley male rats (6 weeks old, body weight 180 ⁇ 200g) purchased from Daehan Biolink, and were used after adaptive breeding for 7 days.
  • the breeding temperature was 22 ⁇ 2 °C and lighting time was 12 hours ( 8: 00 ⁇ 20: 00), and solid feeds (super feed) and water were freely provided up to 12 hours before the experiment.
  • Methanol extract, hexane fraction, ethyl acetate fraction, butanol fraction, fresh dolmul juice and water extracts were anesthetized with ether after the time of sacrifice of the orally administered experimental animals, and then opened, blood was collected from the posterior vena cava and the liver was extracted. Blood was left at room temperature for 40 minutes to aggregate the blood cells and centrifuged (MX-301, TOMY Tech, USA) using a centrifuge at 4 °C 3000rpm for 10 minutes to obtain a serum. After liver was taken over, the remaining blood was sufficiently removed with 0.9% physiological saline, and the saline was removed using filter paper. The extracted liver was rapidly frozen with liquid nitrogen and stored at -80 ° C (used in Experimental Example 3). ).
  • Alcohol and acetaldehyde concentrations were measured in blood using serum separated from the blood of the rats using an alcohol and acetaldehyde analysis kit, and the resulting NADH was measured at 340 nm using an UV spectrophotometer.
  • the results for the ethanol oxidation ability of fresh dolmul juice and each dolmul solvent extract is expressed in relative concentration to the control.
  • the doldol ethyl acetate fraction according to the present invention has an excellent effect of lowering the concentration of alcohol and acetaldehyde in blood as compared to the raw dolmul juice and other solvent fractions.
  • the dolmul ethyl acetate fraction according to the present invention has an excellent effect of lowering ethanol and acetaldehyde concentration.
  • RT-PCR Reverse Transcriptase-Polymerase Chain Reaction
  • the first step was to use RT kit to (1) activate 10 minutes at 30 °C, (2) 60 minutes at 45 °C, and (3) After inactivation at 95 ° C. for 5 minutes to synthesize cDNA, the experiment was carried out using the cDNA synthesized in step 1 in two steps, and PCR was performed using a PCR kit ( Premix Taq TM Hot Start version, TaKaRa Bio, Japan). 2) PCR products for each gene were obtained and confirmed by electrophoresis on 1.2% agarose gel mixed with 0.05% EtBr (Ethidum Bromide). An electrophoretic marker was used 100bp ladder maker (iNtRON, Korea).
  • ADH and ALDH expression of dolmul methanol extract and dolmul butanol fraction were similar to the control, ADH expression of dolmul hexane fraction was similar to the control and ALDH ⁇ expression was lower than the control.
  • the expression level of ADH and ALDH ⁇ was shown to be high, and the ethanol extract of dolnamul showed higher expression levels of ADH and ALDH ⁇ than the control and fresh greens.
  • the ethanol ethyl acetate fraction according to the present invention has an excellent effect of promoting ADH and ALDH activity compared to fresh dolmul juice and other solvent fractions.
  • Acute toxicity test was performed using 6-week-old SPF SD rats as follows. Two animals per group were dissolved in the doldol ethyl acetate fraction of the present invention and administered once orally at a dose of 1 g / kg / ml. After administration of the extract, mortality, clinical symptoms, and changes in body weight were observed. Hematological and hematological examinations were performed. Necropsy was performed to observe abdominal and thoracic organ abnormalities. As a result, no significant clinical symptoms or dead animals were noted in all animals treated with the test substance, and no toxic changes were observed in weight changes, blood tests, blood biochemical tests, and autopsy findings.
  • dolna ethyl acetate fraction according to the present invention did not show a toxicity change in all rats up to 5,000 mg / kg, the minimum lethal dose (LD 50 value) orally administered was determined to be more than 5,000 mg / kg safe substance.
  • the above ingredients are mixed and filled in an airtight cloth to prepare a powder.
  • tablets are prepared by tableting according to a conventional method for preparing tablets.
  • each component is added to the purified water to dissolve it, and lemon flavor is added thereto, then the above ingredients are mixed, adjusted to 100 ml by adding purified water, and then filled into a brown bottle and sterilized to prepare a liquid solution. do.
  • Vitamin E 1.0mg
  • Vitamin B6 0.5mg
  • composition ratio of the above-mentioned vitamin and mineral mixtures is composed of relatively suitable ingredients suitable for health foods in a preferred formulation example, but the compounding ratios may be arbitrarily modified, and the above ingredients are mixed according to a conventional health food manufacturing method.
  • the granules may be prepared and used for preparing a health food composition according to a conventional method.
  • the resulting solution is filtered and obtained in a sterilized 2 L container, sealed and sterilized and then refrigerated and stored in the present invention for the preparation of healthy beverage compositions.
  • composition ratio is a composition suitable for a preferred beverage in a preferred formulation example
  • the compounding ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and use purpose.

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Abstract

La présente invention porte sur une fraction de Sedum sarmentosum qui possède une excellente propriété de décomposition de l'alcool et de soulagement de la gueule de bois. Une fraction d'acétate d'éthyle de l'extrait alcoolique de Sedum sarmentosum facilite les activités de l'ADH et de l'ALDH, qui sont des enzymes du foie associées au métabolisme de l'alcool, et donc soulage les symptômes de la gueule de bois tels que la soif, une faiblesse générale, la fatigue ou autres, qui sont les effets secondaires provoqués par l'absorption d'alcool. L'activation de l'ADH et de l'ALDH permet à l'éthanol d'être rapidement décomposé en acide acétique, qui est le produit final du métabolisme de l'alcool, réduisant ainsi les lésions hépatiques provoquées par l'absorption d'alcool et améliore la résistance à un grand nombre de maladies provoquées par l'absorption d'alcool.
PCT/KR2011/001815 2010-03-15 2011-03-15 Fraction de sedum sarmentosum pour décomposer l'alcool et soulager la gueule de bois WO2011115416A2 (fr)

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KR1020100022893A KR100976241B1 (ko) 2010-03-15 2010-03-15 알코올분해 및 숙취해소용 돌나물 분획물
KR10-2010-0022893 2010-03-15

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KR102106757B1 (ko) 2013-11-29 2020-05-06 주식회사 젬백스앤카엘 난소 동결 보존용 펩티드 및 이를 포함하는 조성물
CN106344597A (zh) * 2016-08-18 2017-01-25 滨州医学院 垂盆草苷在制备预防或治疗急性肺损伤和肺纤维化的药物中的应用
KR102230958B1 (ko) * 2019-06-05 2021-03-23 한국 한의학 연구원 수분초를 유효성분으로 포함하는 뼈 성장 촉진용 조성물

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CN111297935A (zh) * 2019-12-20 2020-06-19 河南省医药科学研究院 一种垂盆草提取物及其制备方法和应用

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