WO2012033329A2 - Composition contenant un extrait d'oenanthe javanica en tant qu'ingrédient actif pour la prévention ou le traitement de troubles de l'apprentissage ou de troubles de la mémoire, et procédé pour la préparer - Google Patents
Composition contenant un extrait d'oenanthe javanica en tant qu'ingrédient actif pour la prévention ou le traitement de troubles de l'apprentissage ou de troubles de la mémoire, et procédé pour la préparer Download PDFInfo
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- WO2012033329A2 WO2012033329A2 PCT/KR2011/006591 KR2011006591W WO2012033329A2 WO 2012033329 A2 WO2012033329 A2 WO 2012033329A2 KR 2011006591 W KR2011006591 W KR 2011006591W WO 2012033329 A2 WO2012033329 A2 WO 2012033329A2
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- extract
- memory
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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)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
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- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Definitions
- the present invention relates to a composition for preventing or treating learning ability or memory impairment containing buttercup extract as an active ingredient, and a method of manufacturing the same. More specifically, acetylcholine in a buttercup, in particular field parsley, is used for food. Esterase (AChE) to inhibit the activity, or to extract the active ingredient that can prevent or treat learning or memory impairment is to use as a pharmaceutical composition or health functional food.
- AChE Esterase
- Buttercup is called root root, root root, and swimming, and it grows throughout Korea, and it is a savory vegetable that is widely distributed from the temperate zone to the tropics such as Sakhalin Island, yearly China, Japan, Southeast Asia, Oceania, etc. .
- Buttercups are divided into paddy buttercups and field buttercups according to the cultivation method.
- Paddy parsley is a hollow parsley that is cultivated by trapping water in paddy fields from the beginning to harvest. Buttercup is initially grown hydroponicly like paddy field but is cultivated after draining water. It is called field buttercup because it is cultivated in the state of the field, and the inside of the stem is not empty and the contents are full.
- buttercup parsley parsley is effective for jaundice, gynecology, headache or vomiting after drinking.
- the buttercup contains flavonoids and cholin essential oils.
- Quinoline-based alkaloids include rutamin, r-pagarin, and coumarin, and these ingredients help to protect against liver, antimutation and antioxidant activity.
- it is known to have an excellent effect on the treatment of high blood pressure as well as the removal of hangover after drinking.
- dementia is a degenerative disorder characterized by brain disorders such as cell death and memory loss, which is estimated to occur in about 10% of people over 65 years old and about 50% of elderly people over 80 years old. do. As the aging population has recently increased, the incidence rate is expected to increase more rapidly. Therefore, dementia has become a serious social and economic problem in modern society.
- Alzheimer's dementia There are various causes of dementia, which can be divided into Alzheimer's disease, vascular dementia, other alcoholism, trauma, and dementia resulting from Parkinson's disease. Since Alzheimer's dementia is present in more than half of patients with dementia, research on dementia has been focused on Alzheimer's dementia.
- Alzheimer's dementia The pathogenesis of Alzheimer's dementia is unclear, but to date, decreased acetylcholine function in the central nervous system, deposition in brain cells of senile plaques based on amyloid beta (A ⁇ ) protein, or cells It is known to be closely related to the appearance of a neurofibrillary tangle mainly composed of external superphosphorylated tau protein.
- a ⁇ amyloid beta
- the existing treatment for dementia is an acetylcholinease inhibitor that can inhibit the activity of acetylcholine esterase (AchE), an enzyme of acetylcholine, or acetylcholine synthesis that can maintain acetylcholine at a constant level.
- AchE acetylcholine esterase
- Substances such as precursors and acetylcholine receptor activators (Receptor agonist) are the majority.
- tacrine, aricept and galantamine, acetylcholine synthetic precursors are lecitin and acetylcholine.
- Receptor activators include RS-86, nicotine, and the like.
- the present invention aims to provide a pharmaceutical composition which is obtained from natural products, has little toxicity and side effects, has a strong anticholinesterase effect, and prevents or treats learning or memory impairment.
- the present invention is to provide a health functional food that is obtained from natural products, has little toxicity and side effects, has a strong anticholinesterase effect and improves learning ability or memory.
- the present invention is characterized by a pharmaceutical composition for the prevention or treatment of learning disorders or memory disorders using the buttercup extract as an active ingredient.
- the buttercup is characterized in that it is a field buttercup.
- the pharmaceutical composition for preventing or treating learning disorders or memory disorders of the present invention is characterized by being for oral administration.
- the extract is characterized in that the extract is available in a solvent selected from a lower alcohol having 1 to 4 carbon atoms, or an aqueous solution of the lower alcohol.
- the aqueous alcohol solution is characterized by being an aqueous alcohol solution having a mixing ratio of lower alcohol of 10 to 95 (v / v)%.
- the method of preparing a buttercup extract for preventing or treating learning disorders or memory disorders according to the present invention is mixed with a lower alcohol aqueous solution having 1 to 4 carbon atoms of 20 to 200 times the dry buttercup weight, and extracted for 4 to 20 hours at 50 to 90 ° C. Characterized in that.
- the lower alcohol aqueous solution is 50 to 80 (v / v)% ethanol aqueous solution, and extracted with the ethanol aqueous solution, the extract is ethyl acetate Or it is characterized in that the extraction with butanol.
- the present invention provides a health functional food for improving learning ability or memory with the buttercup extract as an active ingredient.
- the buttercup is characterized in that the field buttercup.
- the health functional food is characterized in that the powder, granules, tablets, capsules or beverage form.
- Buttercup extract according to the present invention is a natural-derived extract with little side effects or toxicity significantly inhibits the activity of acetylcholinesterase (AChE), and prevents memory impairment by administration of scopolamine, a drug that induces dementia or memory loss. It has the effect of preventing and shows the effect of treating memory disorders caused by alcohol or stress.
- AChE acetylcholinesterase
- AChE acetylcholinesterase
- Figure 2 is a graph comparing the inhibition rate of acetylcholinesterase activity of the re-extracted extract extracted from the alcohol extract of buttercup with various solvents.
- Figure 3 is a graph comparing the inhibition rate of acetylcholinesterase activity of paddy field extract and field buttercup extract.
- the present invention provides a composition that is effective in inhibiting the activity of acetylcholinesterase (AChE) and improving learning ability or memory in buttercups, a pharmaceutical composition for preventing or treating learning disorders or memory disorders, or health functional foods for improving learning ability or memory. Is to use.
- AChE acetylcholinesterase
- Buttercup in the present invention belongs to the asteraceae scientific name Umbelliferaceae ( Ostericum coreanum ), Oenanthe stonilifera ( Oenanthe stonilifera ), Oenanthe javanica ( Oenanthe javanica ), etc., preferably Crab is Korean parsley.
- Buttercup can be used both as water parsley, which is usually hydroponicly grown in paddy fields, and field parsley, called fire parsley, which is grown in the field.However, the field buttercup has the inhibitory activity of acetylcholinesterase (AChE) compared to the paddy field. It is more preferable at the point that it is excellent and the effect of preventing memory damage by a drug is excellent.
- AChE acetylcholinesterase
- a lower alcohol having 1 to 4 carbon atoms, or an aqueous solution of the lower alcohol may be used.
- the lower alcohol having 1 to 4 carbon atoms for example, methanol, ethanol, butanol, propanol, isopropanol and the like can be used, and preferably ethanol is used.
- An aqueous aqueous solution of)%, more preferably an aqueous alcohol solution having 50 to 80 (v / v)% is used.
- the extract is extracted with an aqueous ethanol solution having 50 to 80 (v / v)%, and the extract is extracted with ethyl acetate or butanol as an extract, which is excellent in inhibiting activity of acetylcholinesterase (AChE). It is advantageous in that.
- Buttercup extract of the present invention may be prepared by an extraction method such as stirring extraction, reflux cooling extraction, cold needle extraction, ultrasonic extraction or supercritical extraction using the solvent,
- composition comprising the buttercup extract of the present invention as an active ingredient can be used for the prevention and treatment of Alzheimer's dementia, vascular dementia, other alcoholism, trauma, Parkinson's disease, dementia or cognitive dysfunction, especially Alzheimer's disease. Suitable for the treatment of dementia.
- composition of the present invention includes the buttercup extract in an amount of 0.1 to 50% by weight based on the total weight of the composition.
- composition as described above is not necessarily limited thereto, and may vary according to the condition of the patient and the type and extent of the disease.
- composition comprising the buttercup extract of the present invention as an active ingredient may further comprise suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions.
- compositions comprising the buttercup extract according to the present invention as an active ingredient, oral formulations, such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, and sterile injectable solutions, respectively, according to conventional methods
- Carriers, excipients and diluents which may be used in the form of a formulation, which may be included in the composition containing the extract as an active ingredient, 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 Can be mentioned.
- Solid preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and the solid preparations may include at least one excipient such as starch, calcium carbonate, sucrose in the extract. ) Or lactose, gelatin and the like are mixed. In addition to simple excipients, lubricants such as magnesium styrate talc are also used. Oral liquid preparations include suspending agents, liquid solutions, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. .
- Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories.
- 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 of the present invention vary depending on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration and the duration, and may be appropriately selected by those skilled in the art.
- the composition of the present invention is preferably administered at 0.01 mg / kg to 10 g / kg, preferably 1 mg / kg to 1 g / kg based on the solid content of the buttercup extract. Administration may be administered once a day or may be divided several times. Therefore, the above dosage does not limit the scope of the present invention in any aspect.
- composition of the present invention can be administered to mammals such as rats, mice, livestock, humans, etc. by various routes. All modes of administration can be expected, for example by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection. Especially preferably, the buttercup extract of the present invention is superior in preventing memory damage compared to intraperitoneal administration.
- the present invention provides a dietary supplement comprising a buttercup extract and a food supplement acceptable food supplement additive exhibiting a learning or memory enhancing effect.
- composition comprising the buttercup extract of the present invention as an active ingredient includes, for example, various foods, beverages, gums, teas, vitamin complexes, health supplements, and the like, and are powders, granules, tablets, capsules, or beverages. Available in form.
- Buttercup extract itself of the present invention is a drug that can be used with confidence even when taken for a long time for the purpose of prevention because there is little toxicity and side effects.
- the amount of the extract is generally based on solids, health functional food in the form of powder, granules, tablets, capsules, etc. of the present invention.
- the amount of the extract in the case of can be added in an amount of 0.01 to 15% by weight of the total food weight
- a health functional food in the form of a beverage can be added in a ratio of 0.02 to 10 g, preferably 0.3 to 1 g based on 100 ml of the beverage.
- the health functional food of the beverage form of the present invention contains the extract as an essential ingredient in the ratio indicated, and there are no special limitations in the liquid component, and it may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. Can be.
- natural carbohydrates are conventional monosaccharides such as disaccharides such as glucose and fructose, such as maltose, sucrose and the like, and polysaccharides such as dextrin, cyclodextrin and the like.
- Sugars and sugar alcohols such as xylitol, sorbitol, and erythritol.
- natural flavoring agents such as, tauumatin, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used.
- the proportion of natural carbohydrates is generally about 1-20 g, preferably about 5-12 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 adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like.
- the 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.
- Extracts of ethanol aqueous solution of baeknyeon fruit, pomegranate, citron, fig, fresh vinegar, jujube and paddy parsley 70 (v / v)% were prepared to compare the inhibitory activity of acetylcholinesterase.
- Each ethanol aqueous solution extract was extracted with 10 ml of dry sample 600 ml of ethanol (ethanol content 70 (v / v)%) without reflux at 60 °C for 8 hours, filtered to remove the residue 50 to 60 mmHg and 30 The resultant was evaporated to concentration under the condition of 40 to 40 ° C., and the resultant concentrate was hot-air dried to obtain an ethanol extract powder.
- DMSO dimethyl sulfoxide
- buffer I 100 mM phosphate
- Blank was added with saline instead of enzyme.
- acetylthiocholine iodine solution it was also confirmed that a slight non-specific reaction does not appear when measuring the ethanol extract powder and enzyme activity.
- baeknyeoncho fruit, pomegranate and citron extract showed 8 to 11% inhibition of acetylcholinesterase activity, but the non-parsley extract exhibited an activity inhibition rate of 23.5%, more than 2 times, fig, fresh vinegar and jujube Inhibition rate of the enzyme activity of the extract was less than 5%.
- the inhibition rate of acetylcholinesterase activity of the non-parsley hot water extract powder and the alcohol extract powder was measured by the method of Experimental Example 1, and compared with DHED added to 37.8 ⁇ M as a positive control group, the results are shown in Table 1. .
- the AChE activity experiment was repeated five times to test the significance of the results by a one-way ANOVA test.
- the inhibition rate of acetylcholinesterase activity of each fraction extract was measured by the method of Experimental Example 1 and is shown in FIG. 2.
- ethyl acetate and butanol extract showed the greatest inhibition rate of enzyme activity, and the active ingredient which inhibits acetylcholinesterase activity of the buttercup extract by E-alcohol extraction was considered to be in ethyl acetate layer or butanol layer. It became.
- Non- buttercup extract powder and field buttercup extract powder were added at a concentration of 500 ⁇ g / ml, DHED was added at a concentration of 100 ⁇ M as a positive control group, and the inhibition rate of acetylcholinesterase activity was measured by the method of Experimental Example 1 and is shown in FIG. 3.
- the field buttercup extract was prepared by the same extraction method, and even though the same concentration was used, it was confirmed that it was more than two times higher than the inhibition rate of the enzyme activity of the non buttercup extract, and showed the same level of inhibition of enzyme activity as the DHED of 50 ⁇ M.
- the experimental instrument is a shuttle box (50 ⁇ 15 ⁇ 40 cm) with an electric grid floor.
- the box is divided into partition doors and forms a room of 25 ⁇ 15 cm.
- noise and noise 60 dB or less, and whether the learning and memory impairment impaired by scopolamine in rats can be treated through the administration of Paddy Buttercup and Field Buttercup extract of Experiment 4 I looked at it.
- the memory loss of the scopolamine-administered group was obvious.
- the memory reduced by scopolamine was restored by tacrine, an anticholinesterase that was previously used as a dementia drug.
- the recovery of memory lowered by scopolamine was more effective in the field buttercups than in the field buttercups, and the memory recovery effect of the field buttercups was better than that of tacrine.
- the therapeutic effect of memory-lowering memory was carried out for 4 weeks.
- Alcohol was intraperitoneally administered at a 2.5 g / kg dose daily.
- Doses of field buttercup extract were orally administered at 10 mg / kg and the positive control linoleic acid at 10 mg / kg for 4 weeks.
- the Y-maze test was performed after 4 weeks of administration.
- the Y-maze test is a test method for verifying spatial perception, consisting of three arms of the same size and a black plastic maze. Each arm consists of 80 ⁇ 35 ⁇ 15 cm and each arm maintains the same angle. The rat is placed at the end of the arm and allowed to move freely for 10 minutes. Record the order in which the rat enters each arm. Scores are given when three different arms are selected in succession. These scores (% of alternation) are shown in Table 4 by comparing the groups.
- 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.
- the above ingredients are mixed and filled into gelatin capsules to prepare capsules.
- the amount of the above ingredient is prepared per ampoule (2 ml).
- each component is added and dissolved in purified water, lemon flavor is added to the mixture, and then the above ingredients are mixed, purified water is added to adjust the total amount to 100 ml, and then filled in a brown bottle.
- the solution is prepared by sterilization.
- Vitamin B6 0.5 mg
- composition ratio of the vitamin and mineral mixture is a composition suitable for a relatively healthy food in a preferred embodiment
- the compounding ratio 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.
- composition ratio is a composition that is relatively suitable for the preferred beverage in a preferred embodiment
- the composition ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.
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Abstract
La présente invention concerne une composition contenant un extrait d'Oenanthe javanica en tant qu'ingrédient actif pour la prévention ou le traitement de troubles de l'apprentissage ou de troubles de la mémoire, et un procédé pour la préparer. Plus particulièrement, la présente invention concerne une composition qui peut être utilisée comme composition pharmaceutique ou alicament et qui est préparée par extraction d'un ingrédient actif à partir d'Oenanthe javanica, qui est une herbe comestible, l'ingrédient actif exerçant la fonction de prévention de l'activation de l'acétylcholinestérase (AChE), ou la fonction de prévention ou de traitement de troubles de l'apprentissage ou de troubles de la mémoire.
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CN201180043211.8A CN103153322B (zh) | 2010-09-08 | 2011-09-07 | 含有水芹菜提取物作为有效成分的学习能力或记忆力障碍预防或治疗用组合物及其制造方法 |
Applications Claiming Priority (2)
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KR20100087923 | 2010-09-08 | ||
KR10-2010-0087923 | 2010-09-08 |
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WO2012033329A2 true WO2012033329A2 (fr) | 2012-03-15 |
WO2012033329A3 WO2012033329A3 (fr) | 2012-06-28 |
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PCT/KR2011/006591 WO2012033329A2 (fr) | 2010-09-08 | 2011-09-07 | Composition contenant un extrait d'oenanthe javanica en tant qu'ingrédient actif pour la prévention ou le traitement de troubles de l'apprentissage ou de troubles de la mémoire, et procédé pour la préparer |
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KR (1) | KR101280421B1 (fr) |
CN (1) | CN103153322B (fr) |
WO (1) | WO2012033329A2 (fr) |
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CN108570058B (zh) * | 2018-06-05 | 2019-06-28 | 南阳师范学院 | 一种从水芹菜提取的联苯型木脂素化合物及其方法和用途 |
KR102296347B1 (ko) * | 2019-11-27 | 2021-09-01 | 강원대학교산학협력단 | 천연물 복합 추출물을 유효성분으로 함유하는 허혈성 뇌혈관 질환 예방용 조성물 |
KR20210147707A (ko) | 2020-05-29 | 2021-12-07 | 좋은영농조합법인 | 미나리 추출물을 포함하는 숙취 해소 및 예방용 조성물 |
Citations (3)
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KR20000009588A (ko) * | 1998-07-27 | 2000-02-15 | 한수길 | 안지오텐신 ⅰ전환효소 저해제 |
KR20010097307A (ko) * | 2000-04-21 | 2001-11-08 | 이인수 | 미나리 추출물을 함유하는 폐암예방 및 전이억제용식이조성물 |
KR20030085771A (ko) * | 2002-05-01 | 2003-11-07 | 메디코룩스(주) | 미나리 추출물을 함유하는 미백조성물 |
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CN1187076C (zh) * | 2003-02-26 | 2005-02-02 | 包头市千年健药物研究开发有限公司 | 一种治疗老年痴呆的药物及其制备方法 |
-
2011
- 2011-09-07 KR KR1020110090830A patent/KR101280421B1/ko active IP Right Grant
- 2011-09-07 WO PCT/KR2011/006591 patent/WO2012033329A2/fr active Application Filing
- 2011-09-07 CN CN201180043211.8A patent/CN103153322B/zh not_active Expired - Fee Related
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20000009588A (ko) * | 1998-07-27 | 2000-02-15 | 한수길 | 안지오텐신 ⅰ전환효소 저해제 |
KR20010097307A (ko) * | 2000-04-21 | 2001-11-08 | 이인수 | 미나리 추출물을 함유하는 폐암예방 및 전이억제용식이조성물 |
KR20030085771A (ko) * | 2002-05-01 | 2003-11-07 | 메디코룩스(주) | 미나리 추출물을 함유하는 미백조성물 |
Non-Patent Citations (2)
Title |
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HAN, Y.-Q. ET AL.: 'In vivo and in vitro anti-hepatitis B virus activity of total phenolics from Oenanthe javanica' JOURNAL OF ETHNOPHARMACOLOGY vol. 118, no. 1, June 2008, pages 148 - 153 * |
YANG, X.-B. ET AL.: 'Antidiabetic effect of Oenanthe javanica flavone' ACTA PHARMACOLOGICA SINICA vol. 21, no. 3, March 2000, pages 239 - 242 * |
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Publication number | Publication date |
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WO2012033329A3 (fr) | 2012-06-28 |
KR101280421B1 (ko) | 2013-07-01 |
CN103153322B (zh) | 2015-10-07 |
KR20120026010A (ko) | 2012-03-16 |
CN103153322A (zh) | 2013-06-12 |
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