WO2021217823A1 - 一种具有解酒功能的二氢杨梅素 - Google Patents
一种具有解酒功能的二氢杨梅素 Download PDFInfo
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- WO2021217823A1 WO2021217823A1 PCT/CN2020/096795 CN2020096795W WO2021217823A1 WO 2021217823 A1 WO2021217823 A1 WO 2021217823A1 CN 2020096795 W CN2020096795 W CN 2020096795W WO 2021217823 A1 WO2021217823 A1 WO 2021217823A1
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- WIPO (PCT)
- Prior art keywords
- dihydromyricetin
- alcohol
- animal
- experiment
- test
- Prior art date
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- KJXSIXMJHKAJOD-LSDHHAIUSA-N (+)-dihydromyricetin Chemical compound C1([C@@H]2[C@H](C(C3=C(O)C=C(O)C=C3O2)=O)O)=CC(O)=C(O)C(O)=C1 KJXSIXMJHKAJOD-LSDHHAIUSA-N 0.000 title claims abstract description 60
- KQILIWXGGKGKNX-UHFFFAOYSA-N dihydromyricetin Natural products OC1C(=C(Oc2cc(O)cc(O)c12)c3cc(O)c(O)c(O)c3)O KQILIWXGGKGKNX-UHFFFAOYSA-N 0.000 title claims abstract description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 title claims abstract description 12
- 230000000694 effects Effects 0.000 title claims abstract description 10
- 208000007848 Alcoholism Diseases 0.000 claims abstract description 12
- 201000007930 alcohol dependence Diseases 0.000 claims abstract description 12
- 238000002360 preparation method Methods 0.000 claims abstract description 6
- 239000003814 drug Substances 0.000 claims abstract description 5
- 229940079593 drug Drugs 0.000 claims abstract description 5
- 235000013305 food Nutrition 0.000 claims abstract description 5
- -1 flavone compound Chemical class 0.000 claims abstract description 4
- 230000002075 anti-alcohol Effects 0.000 claims description 10
- 229930003935 flavonoid Natural products 0.000 claims description 6
- 235000017173 flavonoids Nutrition 0.000 claims description 6
- 150000002215 flavonoids Chemical class 0.000 claims description 3
- 230000036541 health Effects 0.000 claims description 3
- 206010067125 Liver injury Diseases 0.000 claims description 2
- 230000001476 alcoholic effect Effects 0.000 claims description 2
- 231100000753 hepatic injury Toxicity 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 abstract description 3
- 208000022309 Alcoholic Liver disease Diseases 0.000 abstract description 2
- 102000027484 GABAA receptors Human genes 0.000 abstract description 2
- 108091008681 GABAA receptors Proteins 0.000 abstract description 2
- 108010024636 Glutathione Proteins 0.000 abstract description 2
- WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical compound O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 abstract description 2
- 210000004185 liver Anatomy 0.000 abstract description 2
- 229940118019 malondialdehyde Drugs 0.000 abstract description 2
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 abstract 1
- 229930003944 flavone Natural products 0.000 abstract 1
- 235000011949 flavones Nutrition 0.000 abstract 1
- 210000003494 hepatocyte Anatomy 0.000 abstract 1
- 210000004295 hippocampal neuron Anatomy 0.000 abstract 1
- 230000007863 steatosis Effects 0.000 abstract 1
- 231100000240 steatosis hepatitis Toxicity 0.000 abstract 1
- 150000003626 triacylglycerols Chemical class 0.000 abstract 1
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 abstract 1
- 241001465754 Metazoa Species 0.000 description 38
- 238000012360 testing method Methods 0.000 description 29
- 238000002474 experimental method Methods 0.000 description 21
- 239000000126 substance Substances 0.000 description 17
- 241000699670 Mus sp. Species 0.000 description 11
- 238000010171 animal model Methods 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 230000037396 body weight Effects 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 230000006978 adaptation Effects 0.000 description 6
- 239000008227 sterile water for injection Substances 0.000 description 6
- 206010019133 Hangover Diseases 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 230000035622 drinking Effects 0.000 description 5
- 238000003860 storage Methods 0.000 description 5
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000003305 oral gavage Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 241000218998 Salicaceae Species 0.000 description 2
- 241000555745 Sciuridae Species 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 238000009395 breeding Methods 0.000 description 2
- 230000001488 breeding effect Effects 0.000 description 2
- 230000008034 disappearance Effects 0.000 description 2
- 239000003651 drinking water Substances 0.000 description 2
- 235000020188 drinking water Nutrition 0.000 description 2
- 238000003304 gavage Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000028527 righting reflex Effects 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- MSTDXOZUKAQDRL-UHFFFAOYSA-N 4-Chromanone Chemical compound C1=CC=C2C(=O)CCOC2=C1 MSTDXOZUKAQDRL-UHFFFAOYSA-N 0.000 description 1
- 241000345998 Calamus manan Species 0.000 description 1
- 241000221017 Euphorbiaceae Species 0.000 description 1
- 241000220485 Fabaceae Species 0.000 description 1
- 208000012671 Gastrointestinal haemorrhages Diseases 0.000 description 1
- 108010068370 Glutens Proteins 0.000 description 1
- 241001115514 Myricaceae Species 0.000 description 1
- 241000270295 Serpentes Species 0.000 description 1
- 241001122767 Theaceae Species 0.000 description 1
- 241000219094 Vitaceae Species 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 230000003064 anti-oxidating effect Effects 0.000 description 1
- 230000001775 anti-pathogenic effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 208000030304 gastrointestinal bleeding Diseases 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- 235000021312 gluten Nutrition 0.000 description 1
- 235000021021 grapes Nutrition 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 210000005229 liver cell Anatomy 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 206010036067 polydipsia Diseases 0.000 description 1
- 235000012950 rattan cane Nutrition 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011076 safety test Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- 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
- 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
- A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
-
- 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
Definitions
- This application relates to the field of medical technology, in particular to a flavonoid compound with anti-alcoholic function, namely dihydromyricetin.
- Drinking culture as a part of our country's social culture, has already penetrated into the daily lives of many people. Drinking in moderation can promote blood circulation, relieve dampness and relieve pain, and relax the mood. However, excessive drinking can easily lead to drunkenness or acute alcoholism, which greatly harms health. Acute alcoholism caused by heavy drinking has become one of the diseases with the highest incidence during holidays. The development of safe and efficient hangover products has attracted more and more attention from the society.
- Dihydromyricetin molecular formula: C 15 H 12 O 8 , relative molecular mass: 320.25, chemical structure: (2R,3R)-3,5,7-trihydroxy-2-(3,4,5-trihydroxybenzene Yl)chroman-4-one.
- Dihydromyricetin is white needle-like crystals with a melting point of 245 ⁇ 246°C. Low solubility in room temperature and cold water, easily soluble in methanol, ethanol and acetone, very slightly soluble in ethyl acetate, hardly soluble in chloroform and petroleum ether.
- Dihydromyricetin can be prepared by mixing the raw materials of rattan tea with a certain concentration of ethanol in proportion and filtering, and then decoloring, concentrating, and crystallization of the extract, drying, crushing, and storing in aluminum bag packaging.
- Dihydromyricetin is widely present in plants of the genus Snake grapes, as well as in plants of the Myricaceae, Rhododendronaceae, Garciniaceae, Euphorbiaceae, Oliveaceae, Leguminosae, Salicaceae and Salicaceae. Previous studies have confirmed that dihydromyricetin has various pharmacological effects such as anti-oxidation, anti-tumor, anti-pathogenic microorganisms and regulating blood lipids.
- This application provides a new use of flavonoids, especially dihydromyricetin.
- flavonoids in the preparation of food, health care products or medicines with anti-alcoholic effect.
- the anti-alcohol effect is to resist alcoholism, resist alcohol dependence, prevent alcoholic liver damage, shorten the sobering time, and increase the tolerance to alcohol.
- the flavonoid compound is dihydromyricetin.
- the dosage of dihydromyricetin is 1-5000mg/kg. Further, it is 350 to 1050 mg/kg.
- Dihydromyricetin has a good hangover function, can increase the expression of GABAARs a4 subunits in hippocampus and neurons, and play a role in resisting alcoholism and alcohol dependence. Dihydromyricetin can also effectively prevent the reduction of liver gluten caused by alcohol. Glutathione depletion and malondialdehyde increase, reduce triglyceride content, reduce the degree of fatty degeneration of liver cells, and have a better prevention and treatment of alcoholic liver injury.
- Test substance Dihydromyricetin
- test substance 4°C, dry and dark
- Solvent sterile water for injection
- test substance Preparation of test substance: Weigh the test substance of the required quality, add sterile water for injection to prepare it to the required concentration, and mix well before administration.
- Animal numbering method Each squirrel cage is equipped with an identification card with information such as experiment number, experiment group, experimenter's name, animal breed and gender, and the mouse is marked with a line at the base of the tail.
- Food and drinking water SPF rats and mice growth and reproduction feed Co60 sterilized during the adaptation period, purchased from Beijing Keyao Xieli Feed Co., Ltd. High-pressure sterilized filtered water was used for experimental animal water.
- Animal selection and fasting The animals used in the experiment will remain healthy. The animals eat and drink freely during the experiment.
- mice in Vehicle group was from 22.38 ⁇ 0.66g at the beginning of the experiment to 27.43 ⁇ 1.31g at the end of the experiment. The body weight increased steadily during the experiment.
- the body weight of animals in the dihydromyricetin 3500mg/kg and dihydromyricetin 5000mg/kg groups increased steadily, and compared with the vehicle group, there was no statistically significant difference (p>0.05), see Table 3.
- the animal After a single oral administration of the test substance dihydromyricetin 3500mg/kg and 5000mg/kg, the animal has no visible abnormality with the naked eye, and the body weight steadily increases, so the MTD value of the test substance is 5000mg/kg.
- Test substance Dihydromyricetin
- test substance 4°C, dry and dark
- Solvent sterile water for injection
- test substance Preparation of test substance: Weigh the test substance of the required quality, add sterile water for injection to prepare to the required concentration, and mix well before administration
- Animal numbering method Each squirrel cage is equipped with an identification card with information such as experiment number, experiment group, experimenter's name, animal breed and gender, and the mouse is marked with a line at the base of the tail.
- Food and drinking water SPF rats and mice growth and reproduction feed Co60 sterilized during the adaptation period, purchased from Beijing Keyao Xieli Feed Co., Ltd. High-pressure sterilized filtered water was used for experimental animal water.
- Animal selection and fasting The animals used in the experiment will remain healthy. The animals eat and drink freely during the experiment.
- mice After the adaptation period, 40 experimental animals were divided into 4 groups, half male and half male. After fasting for 12 hours, the test substance was given by oral gavage according to body weight. The drunkenness rate (disappearance of righting reflex) and mortality of mice were observed to find out The amount and time required for the mice to gavage the stomach for the mice with the righting reflex disappeared and without death. Table 4 shows the alcohol gavage situation.
- test substance and control reagent were given by oral gavage according to their body weight. Time to disappearance of normal reflection), drunkenness rate and mortality rate.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Addiction (AREA)
- Polymers & Plastics (AREA)
- Mycology (AREA)
- Food Science & Technology (AREA)
- Nutrition Science (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Botany (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Toxicology (AREA)
- Gastroenterology & Hepatology (AREA)
- Epidemiology (AREA)
- Pediatric Medicine (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
黄酮类化合物特别是二氢杨梅素在制备具有解酒作用的食品、保健品或药品中的应用。其优点表现在：二氢杨梅素具有良好的解酒功能。二氢杨梅素能增加海马和神经元GABAARs a4亚基的表达，发挥抵抗酒精中毒和酒精依赖性作用，二氢杨梅素还能够有效阻止因酒精导致的肝脏还原型谷胱甘肽耗竭和丙二醛升高，降低甘油三酯含量，减轻肝细胞脂肪变性程度，具有较好的预防和治疗酒精性肝损伤效果。
Description
本申请涉及医药技术领域，尤其是涉及一种具有解酒功能的黄酮化合物，即二氢杨梅素。
饮酒文化作为我国社会文化的一部分，早已渗透到很多人群的日常生活之中。适量地饮酒能够促进血液循环、散湿止痛、放松心情等。但是过量饮酒容易导致醉酒或急性酒精中毒，极大的危害身体健康。重度饮酒导致的急性酒精中毒已经成为节假日发病率最高的疾病之一。安全、高效的解酒制品的开发越来越受社会重视。
二氢杨梅素，分子式：C
15H
12O
8，相对分子质量：320.25，化学结构：(2R,3R)-3,5,7-三羟基-2-(3,4,5-三羟基苯基)苯并二氢吡喃-4-酮。二氢杨梅素为白色针状结晶，熔点为245～246℃。常温和冷水中溶解度较低，易溶于甲醇、乙醇及丙酮，极微溶于醋酸乙酯，难溶于氯仿、石油醚。二氢杨梅素可以通过如下方法制备：将藤茶原料与一定浓度的乙醇按比例混合后过滤，将提取液进行脱色、浓缩、结晶等工序后，烘干，粉碎，以铝袋包装封口保存。
二氢杨梅素广泛存在于蛇葡萄科蛇葡萄属植物中，也存在于杨梅科、杜鹃科、藤黄科、大戟科、橄榄科、豆科、山榄科及柳科等植物中。既往研究证实 二氢杨梅素具有抗氧化、抗肿瘤、抗病原微生物及调血脂等多方面的药理作用。
发明内容
本申请提供黄酮类化合物，尤其是二氢杨梅素的一种新用途。
本申请采用下述技术方案：
黄酮类化合物在制备具有解酒作用的食品、保健品或药品中的应用。
所述解酒作用为抵抗酒精中毒，抵抗酒精依赖性作用，防治酒精性肝损伤，缩短醒酒时间，增加对酒精的耐受能力。
所述黄酮类化合物为二氢杨梅素。二氢杨梅素的用量为1～5000mg/kg。进一步地，为350～1050mg/kg。
本申请的有益效果如下：
二氢杨梅素具有良好的解酒功能，能增加海马和神经元GABAARs a4亚基的表达，发挥抵抗酒精中毒和酒精依赖性作用，二氢杨梅素还能够有效阻止因酒精导致的肝脏还原型谷胱甘肽耗竭和丙二醛升高，降低甘油三酯含量，减轻肝细胞脂肪变性程度，具有较好的预防和治疗酒精性肝损伤效果。
为使本申请的目的、技术方案和优点更加清楚，下面将结合本申请具体实施例对本申请技术方案进行清楚、完整地描述。显然，所描述的实施例仅是本申请一部分实施例，而不是全部的实施例。基于本申请中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本申请保护的范围。
实施例1：安全性试验
1.试验目的
观察二氢杨梅素对ICR小鼠的急性毒性作用
2.试剂及材料相关信息
受试物：二氢杨梅素
受试物储存条件：4℃，干燥避光
其他试剂：灭菌注射用水
来源：广东爱希德药业有限公司
性状：无色透明液体
规格：500ml/瓶
储存条件：RT
3.药物配制
溶剂：灭菌注射用水
受试物配制：称取所需质量的受试物，加入灭菌注射用水配制至所需浓度，给药前混匀。
4.实验动物饲养
动物品种和品系：ICR小鼠
级别：SPF级
性别：雌雄各半
来源：上海斯莱克实验动物有限责任公司
实验动物质量合格证号：20170005014935
实验动物生产许可证号：SCXK(沪)2017-0005
动物数量：订购雌雄各15只，共30只用于实验
实验开始时动物年龄：6～10w
实验开始时动物体重：20g±20％
适应环境时间：4天，与实验时相同饲养条件
动物编号方式：每个鼠笼均佩挂有实验编号、实验组别、实验人员姓名、动物品种和性别等信息的身份卡片，小鼠用尾根部画线标号。
环境：动物房环境保持温度23±2℃，湿度40～70％，12小时明暗交替。动物每笼5只饲养，每周更换两次垫料(玉米芯垫料，苏州埭川商贸有限公司)。
食物和饮水：适应期饲喂SPF大小鼠生长繁殖饲料Co60灭菌，购自北京科澳协力饲料有限公司。实验动物用水采用高压灭菌过滤水。
动物选择和禁食：用于实验的动物将保持健康状况。实验过程中动物自由饮食和饮水。
5.试验方法
适应期过后，30只实验动物分为3组，雌雄各半，禁食12h后根据体重分 别经口灌胃给予溶剂对照或受试物，给药情况如表1所示。观察给药后动物临床症状，有异常记录。并观察给予前和给予后第1，3，5，7天称量动物体重。实验结束动物采用吸入过量CO
2方法安乐死。
表1 急性毒性受试物及对照试剂给予情况
试验结果
1)死亡率
动物在试验期间均未表现出肉眼可见明显异常，死亡率为0，如表2所示。
表2 单次经口灌胃给予受试物二氢杨梅素对小鼠死亡率(％)的影响(n＝10，％)
2)体重
Vehicle组小鼠体重从实验开始时的22.38±0.66g到实验结束时体重为27.43±1.31g。实验期间体重稳定升高。二氢杨梅素3500mg/kg和二氢杨梅素5000mg/kg组动物体重稳定升高，且与vehicle组相比无统计学的显著性差异(p>0.05)，见表3。
表3 单次经口灌胃给予受试物二氢杨梅素对小鼠体重(g)的影响(n＝10，
)
结论
单次经口灌胃给予受试物二氢杨梅素3500mg/kg和5000mg/kg后，动物无肉眼可见明显异常，体重稳定升高，所以受试物的MTD值为5000mg/kg。
实施例2：有效性试验
1.试验目的
验证二氢杨梅素能否有效的解酒
2.试剂及材料相关信息
受试物：二氢杨梅素
受试物储存条件：4℃，干燥避光
其他试剂：
1)灭菌注射用水
来源：广东爱希德药业有限公司
性状：无色透明液体
规格：500ml/瓶
储存条件：RT
2)酒
品牌：红星二锅头
规格：500ml/瓶
储存条件：RT
3.药物配置
溶剂：灭菌注射用水
受试物配制：称取所需质量的受试物，加入灭菌注射用水配制至所需浓度，给药前混匀
4.试验动物饲养
动物品种和品系：ICR小鼠
级别：SPF级
性别：雌雄各半
来源：上海斯莱克实验动物有限责任公司
实验动物质量合格证号：20170005014935
实验动物生产许可证号：SCXK(沪)2017-0005
动物数量：订购雌雄各50只，共100只用于实验
实验开始时动物年龄：6～10w
实验开始时动物体重：20g±20％
适应环境时间：4天，与实验时相同饲养条件
动物编号方式：每个鼠笼均佩挂有实验编号、实验组别、实验人员姓名、动物品种和性别等信息的身份卡片，小鼠用尾根部画线标号。
环境：动物房环境保持温度23±2℃，湿度40～70％，12小时明暗交替。动物每笼5只饲养，每周更换两次垫料(玉米芯垫料，苏州埭川商贸有限公司)。
食物和饮水：适应期饲喂SPF大小鼠生长繁殖饲料Co60灭菌，购自北京科澳协力饲料有限公司。实验动物用水采用高压灭菌过滤水。
动物选择和禁食：用于实验的动物将保持健康状况。实验过程中动物自由饮食和饮水。
5.试验方法
1)试验1
适应期过后，40只实验动物分为4组，雌雄各半，禁食12h后根据体重分别经口灌胃给予受试物，观察小鼠醉酒率(翻正反射消失)及死亡率，找出小鼠翻正反射消失且无死亡所需要的小鼠灌胃酒量和时间，灌酒情况如表4所示。
表4 醉酒试验灌酒情况
试验结果
如表5所示，第二组动物在18ml/kg的剂量下，动物醉酒率100％，动物死亡率0％，适合解酒试验剂量。
表5 醉酒试验结果
2)试验2
60只实验动物分为3组，雌雄各半，禁食12h后根据体重分别经口灌胃给予受试物和对照试剂，如表6所示，灌酒10小时后观察小鼠醒酒时间(翻正反射消失时间)、醉酒率及死亡率。
表6 解酒试验受试物和对照试剂给予情况
试验结果如表7所示，灌酒10h后观察，二氢杨梅素1050mg/kg剂量组醒酒时间(214min)显著低于对照组(324min)，具有统计学差异。所以二氢杨梅素具有很好的解酒效果。
在解酒试验中，1050mg/kg剂量组有一只小鼠死亡，尸检发现胃肠出血严重致死，推测死亡小鼠可能为弱病鼠，与入组的99只动物差异较大，故剔除此动物数据。
表7 解酒试验数据
以上所述仅为本申请的实施例而已，并不用于限制本申请。对于本领域技术人员来说，本申请可以有各种更改和变化。凡在本申请的精神和原理之内所作的任何修改、等同替换、改进等，均应包含在本申请的权利要求范围之内。
Claims (9)
- 黄酮类化合物在制备具有解酒作用的食品、保健品或药品中的应用。
- 如权利要求1所述的应用，其特征在于，所述解酒作用为抵抗酒精中毒。
- 如权利要求1所述的应用，其特征在于，所述解酒作用为抵抗酒精依赖性作用。
- 如权利要求1所述的应用，其特征在于，所述解酒作用为预防或治疗酒精性肝损伤。
- 如权利要求1所述的应用，其特征在于，所述解酒作用为缩短醒酒时间。
- 如权利要求1所述的应用，其特征在于，所述解酒作用为增加对酒精的耐受能力。
- 如权利要求1所述的应用，其特征在于，所述黄酮类化合物为二氢杨梅素。
- 如权利要求7所述的应用，其特征在于，二氢杨梅素的用量为1～5000mg/kg。
- 如权利要求8所述的应用，其特征在于，二氢杨梅素的用量为350～1050mg/kg。
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| CN101007797A (zh) * | 2007-01-12 | 2007-08-01 | 广东药学院 | 一种从枳椇子中提取二氢杨梅素的方法 |
| CN103355713A (zh) * | 2012-04-06 | 2013-10-23 | 刘畅 | 一种速效解酒养胃饮品 |
| CN104127406A (zh) * | 2014-08-12 | 2014-11-05 | 浙江大学 | 一种二氢杨梅素在制备肝脏细胞氧化损伤的抑制剂中的应用 |
| CN104522639A (zh) * | 2014-12-10 | 2015-04-22 | 甘肃陇神戎发药业股份有限公司 | 一种防醉、解酒、保肝的制剂及其制备工艺 |
| CN107007813A (zh) * | 2017-05-27 | 2017-08-04 | 云南德彩堂生物医药科技有限公司 | 一种高效解酒护肝组合物，其制备方法和应用 |
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| CN106491582A (zh) * | 2015-09-06 | 2017-03-15 | 中国科学院上海生命科学研究院 | 含二氢杨梅素的抗醉制剂及其用途 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101007797A (zh) * | 2007-01-12 | 2007-08-01 | 广东药学院 | 一种从枳椇子中提取二氢杨梅素的方法 |
| CN103355713A (zh) * | 2012-04-06 | 2013-10-23 | 刘畅 | 一种速效解酒养胃饮品 |
| CN104127406A (zh) * | 2014-08-12 | 2014-11-05 | 浙江大学 | 一种二氢杨梅素在制备肝脏细胞氧化损伤的抑制剂中的应用 |
| CN104522639A (zh) * | 2014-12-10 | 2015-04-22 | 甘肃陇神戎发药业股份有限公司 | 一种防醉、解酒、保肝的制剂及其制备工艺 |
| CN107007813A (zh) * | 2017-05-27 | 2017-08-04 | 云南德彩堂生物医药科技有限公司 | 一种高效解酒护肝组合物，其制备方法和应用 |
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