WO2023121314A1 - Utilisation d'un extrait de tubercule d'apios americana pour une protection contre une lésion hépatique alcoolique ou une lésion cérébrale alcoolique - Google Patents

Utilisation d'un extrait de tubercule d'apios americana pour une protection contre une lésion hépatique alcoolique ou une lésion cérébrale alcoolique Download PDF

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WO2023121314A1
WO2023121314A1 PCT/KR2022/020995 KR2022020995W WO2023121314A1 WO 2023121314 A1 WO2023121314 A1 WO 2023121314A1 KR 2022020995 W KR2022020995 W KR 2022020995W WO 2023121314 A1 WO2023121314 A1 WO 2023121314A1
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alcoholic
extract
disease
liver
composition
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PCT/KR2022/020995
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English (en)
Korean (ko)
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이준
이수은
남현화
서윤수
서영혜
문병철
이아영
류승목
김효선
김중선
이지혜
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한국한의학연구원
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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)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • 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
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • 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
    • 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
    • A23V2200/322—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the nervous system or on mental function
    • 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

Definitions

  • the present invention relates to the use of an Apios americana tuber extract for the protection of alcoholic liver damage or alcoholic brain damage, and more particularly, a composition for preventing alcoholic liver or brain damage using Apios americana tuber extract and protection against alcoholic liver or brain damage provides a way Additionally, the present invention provides a composition for preventing, improving, or treating alcoholic liver disease or brain nervous system disease using Apios americana tuber extract, and a method for preventing, improving or treating alcoholic liver disease or brain nervous system disease. Furthermore, the present invention provides a composition for relieving hangover and a method for relieving hangover using Apios americana tuber extract.
  • Alcohol is the cause of many diseases, from very mild symptoms to serious diseases that can lead to death.
  • the liver has detoxification and decomposition functions to detoxify drugs, toxic substances, alcohol, etc., but this detoxification function of the liver easily damages liver cells, which can cause drug-related, toxic, and alcoholic liver diseases.
  • Alcoholic liver disease can be largely divided into alcoholic fatty liver, alcoholic hepatitis, and alcoholic cirrhosis according to clinical symptoms, and usually occurs when 60-80 g of alcohol is consumed per day for about 10 years.
  • Alcoholic fatty liver is caused by the accumulation of cholesterol and triglycerides in the liver cells due to excessive alcohol intake. It can be recovered soon if you stop drinking, but if you continue to drink, it develops into hepatitis.
  • Alcoholic hepatitis is a state in which liver cell necrosis and inflammation occur, and it shows various symptoms such as fatigue, anorexia, weight loss, jaundice, fever, and right upper quadrant pain. About 40% of patients suffering from this develop alcoholic cirrhosis.
  • Alcoholic cirrhosis is a condition that cannot be restored to a normal liver, and shows various symptoms such as general fatigue, loss of appetite, ascites, esophageal varices, hemorrhage, hepatic encephalopathy, and coma. It is known that 50% of deaths due to end-stage liver disease are caused by alcohol.
  • alcohol induces morphological changes by causing loss of nerve cells by causing disorders in proliferation and differentiation of nerve cells, nerve development, and cell-to-cell interactions, and furthermore, causes cranial nerve disease due to death of nerve cells. do.
  • Acetylcholinesterase inhibitors and NMDA glutamate receptor blockers are currently being used to treat alcoholic brain disease, but they only have the effect of relieving symptoms rather than treating them, and the prevention and treatment of alcoholic brain disease are not clear. Therefore, the development of drugs with decisive effects is required.
  • chemotherapeutic agents developed and used for disease treatment often show side effects and toxicity due to long-term administration, so attention is focused on research to explore new treatments from natural products that can effectively treat diseases while being harmless to the human body.
  • Substances separated and purified from natural substances are relatively less toxic and are safe even when consumed for a long period of time compared to pharmaceuticals, so they have recently been in the limelight as therapeutic agents and therapeutic supplements for various diseases.
  • Korean Patent Publication No. 10-2018-0095193 discloses the anticancer activity of Apios americana extract
  • Korean Patent Publication No. 10-2015-0132616 discloses Apios extract or fermentation It has been disclosed that the extract exhibits an immune enhancing effect by increasing the gene or protein expression of NO, an immune enhancer, in RAW 264.7 cells.
  • the present inventors confirm that Apios americana Medikus tuber extract exhibits a protective effect against alcoholic liver damage and brain damage and can be used in combination for the prevention, improvement, or treatment of alcoholic liver disease and alcoholic brain disease. By confirming that it can be, the present invention was completed.
  • an object of the present invention is to provide a composition for protecting alcoholic liver damage or relieving hangover using Apios americana tuber extract.
  • a further object of the present invention is to provide a composition for preventing, improving or treating alcoholic liver disease.
  • a further object of the present invention is to provide a method for protecting alcoholic liver damage or relieving hangover and a method for preventing, improving or treating alcoholic liver disease using Apios americana tuber extract.
  • a further object of the present invention is to provide the use of Apios americana tuber extract in the preparation of a medicine or health functional food for protecting alcoholic liver damage or relieving hangover.
  • a further object of the present invention is to provide the use of Apios americana tuber extract in the preparation of a medicament or health functional food for the prevention, improvement or treatment of alcoholic liver disease.
  • Another object of the present invention is to provide a composition for protecting alcoholic brain damage using Apios americana tuber extract.
  • a further object of the present invention is to provide a composition for preventing, improving or treating alcoholic brain disorders.
  • a further object of the present invention is to provide a method for protecting alcoholic brain damage using Apios americana tuber extract and a method for preventing, improving or treating alcoholic brain disorders.
  • the present invention further aims to provide the use of Apios americana tuber extract in the preparation of a medicament or health functional food for the protection of alcoholic brain damage.
  • a further object of the present invention is to provide the use of Apios americana tuber extract in the preparation of a pharmaceutical or health functional food for the prevention, improvement or treatment of alcoholic brain disorders.
  • the present invention provides a composition for protecting alcoholic liver damage or relieving hangover, comprising an extract of Apios Americana tuber as an active ingredient.
  • the present invention provides a pharmaceutical composition for preventing or treating alcoholic liver disease and/or a health functional food composition for preventing or improving alcoholic liver disease comprising the above-described composition.
  • the present invention provides a method for protecting alcoholic liver damage or relieving hangover and preventing, improving or preventing alcoholic liver disease, comprising administering an effective amount of Apios Americana tuber extract to a subject in need thereof. provide a treatment method.
  • the present invention further provides the use of Apios Americana tuber extract in the preparation of a medicament or health functional food for protecting alcoholic liver damage or relieving hangover.
  • the present invention further provides the use of Apios Americana tuber extract in the preparation of a medicament or nutraceutical for preventing, ameliorating or treating alcoholic liver disease.
  • the extract may be extracted using water, C1 to C4 lower alcohol, or a mixture thereof as a solvent.
  • the extract may exhibit any one or more of the following effects (a) to (d):
  • the alcoholic liver disease may be any one or more selected from the group consisting of alcoholic fatty liver, alcoholic hepatitis, and alcoholic cirrhosis.
  • the composition for relieving hangover may be a health functional food composition.
  • the present invention also provides a composition for protecting against alcoholic brain damage comprising Apios Americana tuber extract as an active ingredient.
  • the present invention provides a pharmaceutical composition for preventing or treating alcoholic brain nervous system disease and/or a functional health food composition for preventing or improving alcoholic brain disease, comprising Apios Americana tuber extract as an active ingredient.
  • the present invention provides a method for protecting alcoholic brain damage or preventing, improving or treating alcoholic brain disease, comprising administering an effective amount of Apios Americana tuber extract to a subject in need thereof.
  • the present invention further provides the use of Apios Americana tuber extract in the manufacture of a medicament or nutraceutical for protection against alcoholic brain damage.
  • the present invention further provides the use of Apios Americana tuber extract in the manufacture of a medicament or health functional food for the prevention, improvement or treatment of alcoholic brain disorders.
  • the extract may be extracted using water, C1 to C4 lower alcohol, or a mixture thereof as a solvent.
  • the extract may exhibit any one or more of the following effects (a) to (c):
  • the alcoholic brain nervous system disease is alcohol intoxication, alcoholic amnesia, alcoholic dementia, alcoholic coma, Wernicke-Korsakoff syndrome, alcoholic neuropathy, marcia parvi - It may be any one or more selected from the group consisting of Marchiafava-Bignami disease (MBD), alcoholic cerebellar degeneration, and central pontine myelinolysis (CPM).
  • MBD Marchiafava-Bignami disease
  • CPM central pontine myelinolysis
  • composition containing the Apios americana extract according to the present invention exhibits a protective effect against alcohol-induced liver damage and brain damage, thereby preventing, improving or treating various alcoholic diseases such as alcoholic liver disease or alcoholic brain disease. provide effect.
  • it since it increases the mRNA expression of ADH1 and ALDH2 in liver tissue, it can be used as a hangover reliever.
  • Figure 1 shows the change in relative weight of liver tissue according to the administration of Apios americana tuber extract in a chronic alcohol-induced fatty liver mouse model (Con: normal control group; EtOH: ethanol-administered group; AP100: Apios americana tuber extract 100 mg/kg and AP200: Apios americana tuber extract 200 mg/kg administration group, *p ⁇ 0.05, ***p ⁇ 0.001 vs ethanol administration group).
  • Figure 2 shows the change in blood triglyceride concentration according to the administration of Apios americana tuber extract in a chronic alcoholic fatty liver induced mouse model (Con: normal control group; EtOH: ethanol administration group; AP100: Apios americana tuber extract 100 mg/kg and AP200: Apios americana tuber extract 200 mg/kg administration group, *p ⁇ 0.05 vs ethanol administration group).
  • Figure 3 shows the changes in AST and ALT levels in blood according to the administration of Apios americana tuber extract in a chronic alcoholic fatty liver induced mouse model (Con: normal control group; EtOH: ethanol administration group; AP100: Apios americana tuber extract 100 mg / kg administration group; and AP200: Apios americana tuber extract 200 mg/kg administration group, *p ⁇ 0.05, **p ⁇ 0.01, ***p ⁇ 0.001 vs ethanol administration group).
  • Figure 4 shows the changes in the mRNA expression levels of ADH1 and ALDH2 in liver tissue according to the administration of Apios americana tuber extract in a mouse model induced by chronic alcoholic fatty liver (Con: normal control group; EtOH: ethanol administration group; AP100: Apios americana group) Tuber extract 100 mg/kg administration group; and AP200: Apios americana tuber extract 200 mg/kg administration group, *p ⁇ 0.05 vs ethanol administration group).
  • Figure 5 is a photograph of H&E tissue staining observing the degree of fat deposition in liver tissue according to the administration of Apios americana tuber extract in a chronic alcoholic fatty liver induced mouse model (Con: normal control group; EtOH: ethanol-administered group; and AP100: Apios americana tuber extract 100 mg/kg administration group).
  • Figure 6 is a schematic diagram showing the design and timeline of mouse behavioral tests to confirm the protective effect of Apios americana extract against alcoholic brain damage.
  • Figure 8 shows the change in latency time to fail (latency time to fail) according to the administration of Apios americana tuber extract in the rotarod test (Con: normal control group; EtOH: ethanol administration group; AP100: Apios americana tuber extract 100 mg/kg administration group; and AP200: Apios americana tuber extract 200 mg/kg administration group, *p ⁇ 0.05, **p ⁇ 0.01, ***p ⁇ 0.001 vs ethanol administration group).
  • the present inventors confirmed that the tuber extract exhibits a protective effect against alcoholic liver damage and brain damage, and can be applied in combination to the prevention, improvement, or treatment of alcoholic liver disease and/or alcoholic brain disease.
  • a composition with a solution to the above problems was sought.
  • a first aspect of the present invention relates to the use of an Apios americana tuber extract that exhibits a protective effect against alcoholic liver damage.
  • the present invention provides a composition for protecting alcoholic liver damage or relieving hangover, comprising an Apios Americana tuber extract as an active ingredient.
  • Apios americana As used herein, the term "Apios americana ( Apios americana Medikus)" is a creeping perennial herb belonging to the legume family, and is also called Indian potato.
  • the part of Apios americana used in the composition of the present invention is an underground tuber, and the tuber of Apios americana can be purchased commercially or collected or cultivated in nature.
  • the Apios americana tubers may be dried through a conventional drying method such as natural drying or hot air drying.
  • extract refers to the Apios americana tuber, more preferably an extract obtained by extracting the dried Apios americana tuber, a diluted or concentrated liquid of the extract, a dried product obtained by drying the extract, It includes extracts of all formulations that can be formed using the extract itself and the extract, such as a refined product or a purified product of the extract, or a mixture thereof.
  • the extract of the present invention may be extracted from natural, hybrid or mutant plants of Apios americana, and may also be extracted from plant tissue culture.
  • the extract may be prepared by using hexane, chloroform, methylene chloride, ethyl acetate, acetone, C 1 to C 4 lower alcohol, water or a mixed solvent thereof as an extraction solvent, preferably It may be prepared by using C 1 to C 4 lower alcohol, water, or a mixed solvent thereof as an extraction solvent, but is not limited thereto.
  • the extract may be obtained by using ethanol as an extraction solvent.
  • a method for preparing the extract is not particularly limited, and may be extracted according to a method commonly used in the art.
  • Non-limiting examples of the extraction method include immersion extraction, hot water extraction, ultrasonic extraction, filtration, reflux extraction, and the like, which may be performed alone or in combination of two or more methods.
  • the Apios americana extract can be prepared by extracting dried tubers of Apios americana one or more times using the extraction solvent, obtained by concentrating the solvent extract under reduced pressure and then freeze-drying or spray-drying. It can be prepared as a dry extract.
  • composition of the present invention may contain Apios americana tuber fraction as an active ingredient for protection against alcoholic liver damage or hangover relief.
  • fraction refers to a result obtained by performing fractionation to separate a specific component or a specific component group from a mixture containing various components.
  • the fractionation method for obtaining the fraction is not particularly limited, and may be performed according to a method commonly used in the art.
  • a non-limiting example of the fractionation method is a method of obtaining a fraction from the extract by treating the extract obtained by extracting the dried Apios americana tuber with a predetermined solvent.
  • the solvent used to obtain the fraction may be hexane, chloroform, methylene chloride, ethyl acetate, acetone, C 1 to C 4 lower alcohol, water, or a mixed solvent thereof, but is not limited thereto. .
  • the protective effect of alcoholic liver damage according to the administration of Apios americana tuber extract was confirmed in a chronic alcoholic fatty liver induced mouse model.
  • FIGS. 1 to 5 in the Apios americana tuber extract administration group, alcohol-induced fat deposition in liver tissue was suppressed (FIG. 1 and FIG. 5), and blood triglyceride concentration and AST and ALT increased by alcohol It was confirmed that the levels decreased (FIG. 2 and FIG. 3), and the mRNA expression of ADH1 and ALDH2 in liver tissue decreased due to alcohol increased (FIG. 4). From this, it can be seen that Apios americana tuber extract protects the liver from liver damage caused by chronic alcohol intake, thereby exhibiting effects in preventing, improving, or treating alcoholic liver disease, as well as relieving hangovers.
  • the present invention provides a pharmaceutical composition for preventing or treating alcoholic liver disease comprising an extract of Apios Americana tuber as an active ingredient; And it provides a health functional food composition for preventing or improving alcoholic liver disease.
  • alcoholic liver disease means any liver disease resulting from alcoholic liver damage due to chronic alcohol intake.
  • the alcoholic liver disease may be any one or more selected from the group consisting of alcoholic fatty liver, alcoholic hepatitis, and alcoholic cirrhosis, but is not limited thereto.
  • the present invention further provides a health functional food composition for relieving a hangover comprising an Apios Americana tuber extract as an active ingredient.
  • the term “hangover” refers to a phenomenon in which discomfort, headache, or decline in mental and physical performance appear or persist after being intoxicated.
  • Ethanol absorbed into the body due to drinking is mainly metabolized in the liver, oxidized to acetate via acetaldehyde, and then discharged out of the body. It is known that ALDH acts in the decomposition/oxidation process of
  • ingested alcohol In the normal process of alcohol metabolism, ingested alcohol is absorbed in the stomach or small intestine, enters the bloodstream, and is transported to the liver. It can be decomposed into acetate and decomposed into carbon dioxide gas and water to be discharged out of the body.
  • the Apios americana tuber extract according to the present invention increases the mRNA expression of ADH1 and ALDH2 in liver tissue reduced by alcohol
  • Apios americana tuber extract A composition containing as an active ingredient increases the expression of ADH and / or ALDH mRNA in liver tissue to effectively remove hangover-causing substances, thereby reducing vomiting, nausea, dizziness, thirst, lethargy, headache, muscle pain, memory loss, heartburn, etc. It can improve hangover symptoms.
  • prevention means any action to suppress or delay the onset of a disease or condition. In the present invention, it means delaying the onset of alcoholic liver disease or suppressing the onset of alcoholic liver disease.
  • the term “improvement” refers to any action that improves or beneficially changes a disease or condition, and in the present invention means improving symptoms of alcoholic liver disease.
  • treatment refers to any action that delays, stops, or reverses the progression of a disease or condition, and in the present invention, alleviates, alleviates, or reduces the symptoms of alcoholic liver disease. It means to remove or reverse.
  • the present invention further provides a method for protecting alcoholic liver damage or relieving hangover and alcoholic liver disease, comprising administering an effective amount of Apios Americana tuber extract to a subject in need thereof. Preventive, ameliorative or therapeutic methods are provided.
  • the present invention further provides use of an Apios Americana tuber extract in the preparation of a medicament or health functional food for protecting alcoholic liver damage or relieving hangover.
  • the present invention further provides use of an Apios Americana tuber extract in the preparation of a medicament or nutraceutical for preventing, ameliorating or treating alcoholic liver disease.
  • Apios americana tuber fraction may be administered for the purpose of protecting alcoholic liver damage, relieving hangover and/or preventing, improving or treating alcoholic liver disease.
  • Apios americana tuber fraction may be included in drugs or health functional foods for protecting alcoholic liver damage or relieving hangover.
  • Apios americana tuber fraction may be included in a pharmaceutical or health functional food for preventing, improving or treating alcoholic liver disease.
  • a second aspect of the present invention relates to the use of an Apios americana tuber extract that exhibits a protective effect against alcoholic brain damage.
  • the present invention provides a composition for protecting against alcoholic brain damage comprising Apios Americana tuber extract as an active ingredient.
  • the description of the Apios americana tuber extract is the same as described above, so the description thereof is omitted.
  • composition of the present invention may contain Apios americana tuber fraction as an active ingredient for use in protecting against alcoholic brain damage.
  • composition according to the second aspect of the present invention since the description of the Apios americana tuber fraction is the same as described above, description thereof will be omitted.
  • the present invention provides a pharmaceutical composition for preventing or treating alcoholic brain nervous system disease comprising an Apios Americana tuber extract as an active ingredient; And it provides a health functional food composition for preventing or improving alcoholic ventricular border disease.
  • alcoholic brain nervous system disease includes all brain nervous system diseases that are directly induced by or indirectly related to alcohol intake, and the brain nervous system refers to the nervous system including the brain and spine. .
  • alcoholic cranial nervous system diseases are specifically alcoholism, alcoholic amnesia, alcoholic dementia, alcoholic coma, Wernicke-Korsakoff syndrome, alcoholic neuropathy, and Marchiafavi-Binami disease.
  • -It may be any one or more selected from the group consisting of Bignami disease (MBD), alcohol cerebellar degeneration, and central pontine myelinolysis (CPM), but is not limited thereto.
  • the "alcoholism” indicates toxicity by suppressing various parts of the brain by alcohol, and various symptoms appear depending on the concentration of alcohol in the blood. At first, it is a stage of pleasure, such as inability to concentrate and talk a lot, and then there is an excitement stage, such as numbness and talk, and discordance in motor functions, such as memory loss, confusion, and disorientation.
  • the "alcoholic amnesia” refers to a case in which a certain portion is not remembered partially (grayout) or completely (blackout) when drinking alcohol. It is related to the blood level of alcohol and can sometimes be confused with the passing out of alcohol, but it is characterized by the absence of loss of consciousness at all.
  • the alcoholic amnesia can lead to alcoholic dementia. Dementia is a disease in which various cognitive functions, including memory, gradually develop, causing problems in the ability to perform daily life.
  • the "alcoholic coma” is an internal medical emergency condition in which consciousness becomes blurred as the detoxification function of the liver is lowered and eventually loses consciousness.
  • the "Wernicke-Korsakoff syndrome” is a continuation of Korsakoff's syndrome after Wernicke encephalopathy (WE), in which different stages of a disease appear consecutively.
  • Wernicke's encephalopathy is an acute phase abnormal behavior syndrome characterized by eye movement disorders, mental state changes, and gait ataxia, and Korsakoff psychosis appears as Wernicke's encephalopathy improves.
  • the "alcoholic neuropathy” is a neurological disease that is particularly common in patients with chronic alcohol addiction. Usually, when it starts slowly, sensory abnormalities appear, and pain or motor function abnormalities may accompany it.
  • the "Marchiafava-Bignami disease (MBD)” is a kind of side effect caused by alcohol and is characterized by necrosis and atrophy of the corpus callosum. Clinically, it presents with speech difficulties, gait disturbance, disturbance of consciousness, convulsions, and disconnection syndrome with loss of corpus callosum.
  • the "alcoholic cerebellar degeneration” refers to ataxia, wide gait, eye movement disorder due to nodular lobe damage, severe coordination disorder caused by lower extremities, and the like. There is degeneration of Purkinje cells, and white matter atrophy is evident in the central lobe and the anterior folia of the vermis.
  • central pontine myelinolysis (CPM)
  • CCM central pontine myelinolysis
  • It is an acquired, symmetrical, non-inflammatory demyelinating disease of the base of the pons, which clinically results in decreased consciousness, dysphagia, dysarthria, ophthalmoplegia, facial paralysis, etc., and can develop into locked-in syndrome.
  • the composition of the present invention is also effective in improving depression caused by alcohol.
  • prevention refers to any action that suppresses or delays the onset of a disease or condition. In the present invention, it means delaying the onset of alcoholic brain nervous system disease or suppressing the onset of it.
  • the term "improvement” refers to any action that improves or beneficially changes a disease or condition, and in the present invention, refers to improving symptoms of alcoholic cranial nerve disease. .
  • treatment refers to any action that delays, stops, or reverses the progression of a disease or condition, and in the present invention, alleviates or alleviates the symptoms of alcoholic cranial nerve disease. or to eliminate, or to reverse.
  • the present invention further provides a method for protecting alcoholic brain damage and prevention of alcoholic brain disease, comprising administering an effective amount of Apios Americana tuber extract to a subject in need thereof, Improvement or treatment methods are provided.
  • the present invention further provides use of an Apios Americana tuber extract in the manufacture of a medicament or health functional food for protection against alcoholic brain damage.
  • the present invention further provides the use of Apios Americana tuber extract in the manufacture of pharmaceuticals or health functional foods for the prevention, improvement or treatment of alcoholic brain diseases.
  • Apios americana tuber fraction may be administered for the purpose of protecting alcoholic brain damage and/or preventing, improving or treating alcoholic liver disease.
  • Apios americana tuber fraction may be included in drugs or health functional foods for protecting alcoholic brain damage or relieving hangover.
  • Apios americana tuber fraction may be included in a drug or health functional food for preventing, improving or treating alcoholic brain disease.
  • the pharmaceutical composition according to the present invention can be prepared into a pharmaceutical formulation using methods well known in the art to provide rapid, sustained or delayed release of the active ingredient after administration to a mammal.
  • preparation of a dosage form it is preferable to mix or dilute the active ingredient with a carrier or to encapsulate it in a carrier in the form of a container.
  • the pharmaceutical composition of the present invention is formulated according to conventional methods into oral formulations such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories and sterile injection solutions. It may further include appropriate carriers, excipients and diluents commonly used in the preparation of the composition.
  • carriers that may be included in the pharmaceutical composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, and the like. When formulated, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations contain at least one excipient, for example, starch, calcium carbonate, sucrose, etc. ) or by mixing lactose and gelatin.
  • excipients for example, starch, calcium carbonate, sucrose, etc.
  • lubricants such as magnesium stearate and talc are also used.
  • Liquid preparations for oral use include suspensions, solutions for oral use, emulsions, syrups, etc., and various excipients such as wetting agents, sweeteners, aromatics, preservatives, etc. may be included in addition to water and liquid paraffin, which are commonly used simple diluents. there is.
  • Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried formulations, and suppositories.
  • Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents.
  • injectable esters such as ethyl oleate
  • witepsol, macrogol, tween 61, cacao butter, laurin paper, glycerogeratin and the like may be used as a base for the suppository.
  • the term "administration" means introducing the pharmaceutical composition of the present invention to a patient by any suitable method.
  • the administration method of the pharmaceutical composition according to the present invention is not particularly limited, and may follow a method commonly used in the art.
  • the administration method is not limited as long as it can reach the target tissue, but may be intraperitoneal administration, intravenous administration, intramuscular administration, subcutaneous administration, intradermal administration, oral administration, topical administration, or intranasal administration.
  • the pharmaceutical composition according to the present invention may be prepared in various formulations depending on the desired administration method.
  • the pharmaceutical composition of the present invention can be administered in a pharmaceutically effective amount.
  • the "pharmaceutically effective amount” means an amount sufficient to treat a disease with a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level is subject type and severity, age, sex, infected virus type, drug activity, drug sensitivity, time of administration, route of administration and excretion rate, duration of treatment, factors including drugs used concurrently, and other factors well known in the medical field.
  • a typical daily dose of the pharmaceutical composition according to the present invention can be appropriately selected by those skilled in the art, and can be administered once or divided into several times.
  • composition of the present invention may be administered daily or intermittently, and the number of administrations per day may be administered once or divided into 2 to 3 times.
  • composition of the present invention can be used alone or in combination with other drug treatments for the prevention, improvement, or treatment of alcoholic liver disease or brain nervous system disease. It is important to administer the amount that can obtain the maximum effect with the minimum amount without side effects in consideration of all the above factors, and can be easily determined by those skilled in the art.
  • the term "individual” refers to all animals, including humans, who have or are likely to develop alcoholic liver injury or alcoholic brain injury, more specifically, alcoholic liver disease or brain nervous system disease.
  • the animal may be not only humans but also mammals such as cattle, horses, sheep, pigs, goats, camels, antelopes, dogs, and cats that require treatment for similar symptoms, but are not limited thereto.
  • the term "food” refers to meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, tea, drinks, alcohol Beverages, vitamin complexes, health functional foods and health foods, etc., include all foods in a conventional sense.
  • the health functional food composition of the present invention includes forms such as pills, powders, granules, precipitates, tablets, capsules or liquids, and as foods to which the composition of the present invention can be added, for example, various foods, such as For example, there are beverages, chewing gum, tea, vitamin complexes, and health supplements.
  • the food auxiliary additives include food auxiliary additives common in the art, such as flavoring agents, flavoring agents, coloring agents, fillers, stabilizers, and the like.
  • natural carbohydrates examples include monosaccharides such as glucose, fructose, and the like; disaccharides such as maltose, sucrose and the like; and polysaccharides such as conventional sugars such as dextrins, cyclodextrins, and the like, and sugar alcohols such as xylitol, sorbitol, and erythritol.
  • natural flavors eg, rebaudioside A, glycyrrhizin, etc.
  • synthetic flavors sacharin, aspartame, etc.
  • the health functional food composition of the present invention is various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and fillers (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, and the like.
  • it may contain fruit flesh for the manufacture of natural fruit juice, fruit juice beverages and vegetable beverages. These components may be used independently or in combination.
  • the health supplement includes health functional food and health food.
  • the functional food is the same term as food for special health use (FoSHU), and is a medicine processed to efficiently display bioregulatory functions in addition to nutrient supply, and has high medical effect.
  • “function (sex)” means to obtain useful effects for health purposes such as regulating nutrients for the structure and function of the human body or physiological functions.
  • the food of the present invention can be prepared by a method commonly used in the art, and can be prepared by adding raw materials and ingredients commonly added in the art during the preparation.
  • the formulation of the food may also be prepared without limitation as long as the formulation is recognized as a food.
  • the health functional food composition of the present invention can be prepared in various types of formulations, and unlike general drugs, it has the advantage of not having side effects that may occur when taking drugs for a long time using food as a raw material.
  • the term "subject” includes any animal (eg, human, horse, pig, rabbit, dog, sheep, goat, non-human primate, cow, cat, guinea pig, or rodent), but It is not limited to this. These terms do not denote a specific age or gender. Thus, adult/adult and newborn subjects, whether female/female or male/male, as well as fetuses are intended to be included.
  • a patient refers to a subject suffering from a disease or disorder. The term patient includes human and veterinary subjects.
  • the effect of the Apios americana tuber extract or fraction and the composition including the route of administration, frequency of administration, dosage, etc. are the same as described above, so the description thereof will be omitted.
  • Apios Americana tuber used in the present invention was purchased from a farm in Sacheon, Gyeongsangnam-do. After pulverizing the dried Apios tubers, they were extracted by immersion or ultrasonic extraction at about 40 °C using 10 to 15 times the weight of the sample in 70% ethanol solvent. If necessary, hot water extraction was performed at about 100 ° C using a reflux extraction device. Each extract was filtered, concentrated with a vacuum concentrator, and lyophilized to remove remaining solvent and water, and then the finished extract was homogenized.
  • mice weighing 19 g or more were selected, and as shown in Table 1, they were divided into a normal control group, an ethanol-administered group, and a drug-administered group.
  • the ethanol-treated group and the drug-treated group were fed a Lieber-DeCarli liquid diet containing 5% ethanol for 10 days to chronically consume alcohol, and the normal control group was fed the same diet without ethanol.
  • the Apios americana extract prepared in Example 1 was orally administered to the drug administration group at a dose of 100 mg/kg and 200 mg/kg, respectively, at a fixed time every day.
  • high-dose (5 g/kg) ethanol was orally administered to the ethanol-administered group and the drug-administered group, sacrificed 9 hours later, and blood and organs were obtained through autopsy.
  • Relative weight of liver absolute weight of liver / body weight ⁇ 100
  • the relative weight of the liver increased significantly in the alcohol-administered group compared to the normal control group, but the relative weight of the liver decreased in a concentration-dependent manner in the Apios extract-administered group.
  • the Apios extract inhibits alcohol-induced fat deposition in liver tissue.
  • the concentration of triglyceride (TG) in the blood increases, which increases the risk of fatty liver and circulatory diseases. Therefore, by measuring the TG concentration in the blood obtained from each group, the hepatoprotective effect of treatment with Apios extract was confirmed. As a result, as confirmed in 2, the TG concentration of the alcohol-administered group was significantly increased compared to the normal control group, but the increased TG concentration due to alcohol administration was significantly decreased in the Apios extract-administered group.
  • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are enzymes that exist in liver cells and are released into the blood when liver cells are damaged, so the blood level increases. Liver function test is used as an indicator of Therefore, by measuring the levels of AST and ALT in the blood obtained from each group, the hepatoprotective effect of treatment with the Apios extract was confirmed. As a result, as confirmed in FIG. 3, the Apios extract reduced blood AST and ALT, which were increased due to alcohol, and showed statistically significant results when administered at 200 mg/kg.
  • Alcohol dehydrogenases (ADH) and acetaldehyde dehydrogenases (ALDH) are enzymes that play the most important role in the process of metabolizing alcohol and acetaldehyde, which are cytotoxic substances.
  • ADH and ALDH have several subclasses ( subclass), among which ADH1 and ALDH2 are the subclasses that play the most important roles, by measuring their mRNA expression levels, the liver protection effect and hangover relief effect according to Apios extract treatment were confirmed. As confirmed in 4, the Apios extract increased the mRNA expression of ADH1 and ALDH2 in the blood, which was reduced by alcohol, and showed statistically significant results when administered at 200 mg/kg.
  • liver histological examination H&E staining was performed to observe the degree of fat deposition and inflammatory changes in the liver. As a result, as shown in FIG. 5, it was confirmed that fat deposition in the liver tissue was improved in the group administered with 100 mg/kg of Apios extract compared to the alcohol-administered group.
  • mice of each group in Table 1 were evaluated for memory ability for fear situations experienced in a specific space.
  • CFC behavioral tests were performed as shown in FIG. 6 . Specifically, after putting the mouse into the chamber during the training session and allowing it to move around freely for 120 seconds, an electric shock was applied to the foot through the grid. After 24 hours, mice were placed in the same chamber during the test period and behavioral patterns were evaluated. The higher the memory capacity for space, the lower the movement due to fear, so it was judged that the lower the ambulatory move time, the lower the cognitive impairment.
  • the rotarod test was performed on the mice of each group in Table 1. As shown in Figure 6, 5 g / kg ethanol was orally administered on the morning of the 11th autopsy, and rotarod test was performed immediately before autopsy after 9 hours. First, after adapting the mouse for 30 seconds at a speed of 5 rpm in a rotating cylinder, the time until it fell from the cylinder to the floor was measured while increasing the speed from 5 rpm to 40 rpm for 300 seconds. The better the sense of balance and motor coordination, the longer the latency time to fail, so it was judged that the longer the latency time to fail, the more effective the cognitive impairment was.

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Abstract

La présente invention se rapporte à une utilisation d'un extrait de tubercule d'Apios americana pour une protection contre une lésion hépatique alcoolique ou une lésion cérébrale alcoolique, et plus particulièrement, fournit une composition destinée à la protection contre une lésion hépatique alcoolique ou une lésion cérébrale alcoolique et se rapporte à une méthode de protection contre une lésion hépatique alcoolique ou une lésion cérébrale alcoolique, chacune utilisant un extrait de tubercule d'Apios americana. En outre, la présente invention concerne une composition destinée à la prévention, au soulagement ou au traitement d'une maladie hépatique alcoolique ou d'une maladie du système nerveux cérébral et une méthode destinée à la prévention, au soulagement ou au traitement d'une maladie hépatique alcoolique ou d'une maladie du système nerveux cérébral, chacune utilisant un extrait de tubercule d'Apios americana. En outre, la présente invention concerne une composition destinée à soulager la gueule de bois et une méthode destinée à soulager la gueule de bois, chacune utilisant un extrait de tubercule d'Apios americana.
PCT/KR2022/020995 2021-12-21 2022-12-21 Utilisation d'un extrait de tubercule d'apios americana pour une protection contre une lésion hépatique alcoolique ou une lésion cérébrale alcoolique WO2023121314A1 (fr)

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KR20190020889A (ko) * 2017-08-22 2019-03-05 안동대학교 산학협력단 아피오스 추출물을 유효성분으로 함유하는 혈전증의 예방 또는 치료용 약학적 조성물 및 건강 기능 식품
KR20200145757A (ko) * 2019-06-19 2020-12-30 한국 한의학 연구원 아피오스 아메리카나 괴경 추출물의 분획물을 포함하는 알코올성 위염 예방, 개선 또는 치료용 조성물 및 이의 제조방법

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