WO2013147419A1 - A composition comprising the compound isolated from chrysanthemum indicum for treating or preventing cerebrovascular system involved anxiety and the use thereof - Google Patents

A composition comprising the compound isolated from chrysanthemum indicum for treating or preventing cerebrovascular system involved anxiety and the use thereof Download PDF

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Publication number
WO2013147419A1
WO2013147419A1 PCT/KR2013/001279 KR2013001279W WO2013147419A1 WO 2013147419 A1 WO2013147419 A1 WO 2013147419A1 KR 2013001279 W KR2013001279 W KR 2013001279W WO 2013147419 A1 WO2013147419 A1 WO 2013147419A1
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Prior art keywords
anxiety
glucuronide
extract
system involved
chrysanthemum indicum
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PCT/KR2013/001279
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English (en)
French (fr)
Inventor
Soo-mi Choi
Jae-Won Kwon
Jae-Yoon Kim
Seung-Min Choi
Jin-Woo Lee
Jong-Gil Choi
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Yd Life Science Co., Ltd
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Publication of WO2013147419A1 publication Critical patent/WO2013147419A1/en

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    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • 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
    • 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)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • 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)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A61K36/287—Chrysanthemum, e.g. daisy
    • 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
    • A61P25/22—Anxiolytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine

Definitions

  • the present invention relates to a composition comprising the compounds isolated from Chrysanthemum indicum for treating or preventing cerebrovascular system involved anxiety and the use thereof.
  • Anxiety includes unpleasant or unstable feeling as well as the physical syndrome caused thereby, for example, enhanced autonomic nerve system such as palpitation, heart pounding, increase of heart pressure, hard sweating, hyperreflexia, mydriasis, trembling, gastrointestinal disorder, nocturia etc and abnormal behavior syndrome such as hypersensitiveness, hovering etc and it is basic response when human body is willing to adapt to unfamiliar environment (Argyropoulos S. V. et al., Pharmacol. Ther . 88 , pp213-227, 2000).
  • enhanced autonomic nerve system such as palpitation, heart pounding, increase of heart pressure, hard sweating, hyperreflexia, mydriasis, trembling, gastrointestinal disorder, nocturia etc and abnormal behavior syndrome such as hypersensitiveness, hovering etc and it is basic response when human body is willing to adapt to unfamiliar environment (Argyropoulos S. V. et al., Pharmacol. Ther . 88 , pp213-227
  • the anxiety disorder includes various disorders such as posttraumatic stress disorder (PTSD), obsessive compulsive disorder, social phobia, Pan-anxiety disorder etc. and relates to the other psychological disease such as depression, drug abuse etc.
  • PTSD posttraumatic stress disorder
  • obsessive compulsive disorder social phobia
  • Pan-anxiety disorder relates to the other psychological disease such as depression, drug abuse etc.
  • social phobia and pan-anxiety disorder cause widespread human suffering. Since anxiety is a normal psychological response, it could not completely be treated and the anxiety disorder frequently accompanies depression resulting in severe abuse diseases such as alcohol dependence.
  • the conveniently available representative anti-depressants are benzodiazepine drug such as diazepam, oxazepam, prazepam, lorazepam, alprazolam, helazepam, clonazepam etc, which are used for sedative and sleep indneer.
  • the benzodiazepine drug increases the affinity of GABA (gammaamino butyric acid) and opens the adjacent Cl-channel more frequently and increases the penetrability.
  • GABA gammaamino butyric acid
  • it has disadvantages, for example, habituation, addictiveness, the demand for strict management of medical doctor and various adverse actions such as dizziness, locomotor ataxia, orthostatic hypotension, respiratory suppression, headache, chronic sleep disturbance, liver disease etc (Mary J. Mycek et al., Pharmacology 2 nd Ed. Lipincott Williams & Wilkins, pp89-93, 2000).
  • the present invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising acacetin-7-O-glucuronide or luteolin-7-O-glucuronide isolated from an extract of Chrysanthemum indicum showing tranquilizing activity as an active ingredient in an effective amount to treat or prevent cerebrovascular system involved anxiety.
  • the present invention also provides a use of acacetin-7-O-glucuronide or luteolin-7-O-glucuronide isolated from an extract of Chrysanthemum indicum showing tranquilizing activity for the manufacture of pharmaceutical composition to treat or prevent cerebrovascular system involved anxiety.
  • the present invention also provides a health functional food comprising acacetin-7-O-glucuronide or luteolin-7-O-glucuronide isolated from an extract of Chrysanthemum indicum showing tranquilizing activity for the prevention or alleviation of cerebrovascular system involved anxiety.
  • a pharmaceutical composition comprising an acacetin-7-O-glucuronide or luteolin-7-O-glucuronide isolated from an extract of Chrysanthemum indicum showing tranquilizing activity, as an active ingredient in an effective amount to treat or prevent cerebrovascular system involved anxiety.
  • the present invention to provide a pharmaceutical composition
  • a pharmaceutical composition comprising an acacetin-7-O-glucuronide or luteolin-7-O-glucuronide isolated from an extract of Chrysanthemum indicum showing tranquilizing activity as an active ingredient and pharmaceutically acceptable carrier, diluents or adjuvants to treat or prevent cerebrovascular system involved anxiety.
  • cerebrovascular system involved anxiety includes panic disorder, obsessive compulsive disorder, social phobia, posttraumatic stress disorder (PTSD), pan-anxiety disorder depression, preferably, pan-anxiety disorder depression.
  • extract ’ disclosed herein includes water fraction removing non-polar solvent soluble fraction which can be prepared by; extracting Chrysanthemum indicum with polar solvent such as water, C1-C4 lower alcohol such as methanol, ethanol, butanol etc or the mixture thereof, preferably, water to afford crude extract at 1 st step; and suspending the crude extract in water and fractionating the suspended extract into non-polar solvent selected from hexane, ethylacetate, chloroform, dichloromethane, preferably, ethylacetate to afford non-polar solvent soluble extract and water fraction removed with non-polar solvent soluble fraction.
  • polar solvent such as water, C1-C4 lower alcohol such as methanol, ethanol, butanol etc or the mixture thereof, preferably, water to afford crude extract at 1 st step
  • non-polar solvent selected from hexane, ethylacetate, chloroform, dichloromethane, preferably, ethylacetate to afford non-polar solvent
  • An inventive compounds isolated from Chrysanthemum indicum may be prepared in accordance with the following preferred embodiment.
  • the inventive compound can be transformed into their pharmaceutically acceptable salt and solvates by the conventional method well known in the art.
  • acid-addition salt thereof formed by a pharmaceutically acceptable free acid thereof is useful and can be prepared by the conventional method.
  • the salts are precipitated by the water-miscible organic solvent such as methanol, ethanol, acetone or acetonitrile to prepare acid addition salt thereof and further the mixture of equivalent amount of compound and diluted acid with water or alcohol such as glycol monomethylether, can be heated and subsequently dried by evaporation or filtrated under reduced pressure to obtain dried salt form thereof.
  • organic acid or inorganic acid can be used as a free acid of above-described method.
  • organic acid such as methan sulfonic acid, p -toluensulfonic acid, acetic acid, trifluoroacetic acid, citric acid, maleic acid, succinic acid, oxalic acid, benzoic acid, lactic acid, glycolic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carbonylic acid, vanillic acid, hydroiodic acid and the like, and inorganic acid such as hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, tartaric acid and the like can be used herein.
  • the pharmaceutically acceptable metal salt form of inventive compound may be prepared by using base.
  • the alkali metal or alkali-earth metal salt thereof can be prepared by the conventional method, for example, after dissolving the compound in the excess amount of alkali metal hydroxide or alkali-earth metal hydroxide solution, the insoluble salts are filtered and remaining filtrate is subjected to evaporation and drying to obtain the metal salt thereof.
  • sodium, potassium or calcium salt are pharmaceutically suitable and the corresponding silver salt can be prepared by reacting alkali metal salt or alkali-earth metal salt with suitable silver salt such as silver nitrate.
  • the pharmaceutically acceptable salt of the compound comprise all the acidic or basic salt which may be present at the compounds, if it does not indicated specifically herein.
  • the pharmaceutically acceptable salt of the present invention comprise the salt of hydroxyl group such as the sodium, calcium and potassium salt thereof; the salt of amino group such as the hydrogen bromide salt, sulfuric acid salt, hydrogen sulfuric acid salt, phosphate salt, hydrogen phosphate salt, dihydrophosphate salt, acetate salt, succinate salt, citrate salt, tartarate salt, lactate salt, mandelate salt, methanesulfonate(mesylate) salt and p -toluenesulfonate (tosylate) salt etc, which can be prepared by the conventional method well known in the art.
  • the inventive compounds isolated from Chrysanthemum indicum can be prepared by the procedure comprising the steps consisting of; adding 0.05 to 0.3-fold, preferably, 0.1 to 0.2-fold volume of polar solvent such as water, C1-C4 lower alcohol such as methanol, ethanol, butanol etc or the mixture thereof, preferably, water to Chrysanthemum indicum ; extracting with extraction method by the reflux extraction, or ultra-sonication extraction, preferably, reflux extraction for the period ranging from 0.5 to 10 hours, preferably, 2 to 5 hours, at the temperature ranging from 50 to 120°C, preferably, 80 to 100°C; subjecting the solution with filtering to obtain the supernatant to be concentrated with rotary evaporator, at the temperature ranging from 35 to 45°C; drying to obtain dried inventive crude extract powder of Chrysanthemum indicum at 1 st step; suspending said crude extract in distilled water and adding organic-solvent soluble extract which can be extracted with organic solvent such as hex
  • a pharmaceutical composition comprising an acacetin-7-O-glucuronide or luteolin-7-O-glucuronide isolated from an extract of Chrysanthemum indicum prepared by the abovedescribed preparation method as an active ingredient in an effective amount to treat or prevent cerebrovascular system involved anxiety.
  • the pharmaceutical composition of the present invention can contain about 0.01 ⁇ 50 % by weight of the above compound based on the total weight of the composition.
  • the present inventor found that acacetin-7-O-glucuronide or luteolin-7-O-glucuronide isolated from an extract of Chrysanthemum indicum increased the time spent in open arm or closed arm and the number of open arm entries in elevated plus-maze test and the compounds have potent treating activity of cerebrovascular system involved anxiety.
  • the inventive composition for treating and preventing cerebrovascular system involved anxiety may comprises the above compound as 0.01 ⁇ 50 % by weight based on the total weight of the composition.
  • the inventive composition may additionally comprise conventional carrier, adjuvants or diluents in accordance with a using method well known in the art. It is preferable that said carrier is used as appropriate substance according to the usage and application method, but it is not limited. Appropriate diluents are listed in the written text of Remington’s Pharmaceutical Science (Mack Publishing co, Easton PA).
  • composition according to the present invention can be provided as a pharmaceutical composition containing pharmaceutically acceptable carriers, adjuvants or diluents, e.g., lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starches, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, polyvinyl pyrrolidone, water, methylhydroxy benzoate, propylhydroxy benzoate, talc, magnesium stearate and mineral oil.
  • pharmaceutically acceptable carriers e.g., lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starches, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, polyvinyl
  • the formulations may additionally include fillers, anti-agglutinating agents, lubricating agents, wetting agents, flavoring agents, emulsifiers, preservatives and the like.
  • the compositions of the invention may be formulated so as to provide quick, sustained or delayed release of the active ingredient after their administration to a patient by employing any of the procedures well known in the art.
  • compositions of the present invention can be dissolved in oils, propylene glycol or other solvents that are commonly used to produce an injection.
  • suitable examples of the carriers include physiological saline, polyethylene glycol, ethanol, vegetable oils, isopropyl myristate, etc., but are not limited to them.
  • the extract of the present invention can be formulated in the form of ointments and creams.
  • compositions containing present composition may be prepared in any form, such as oral dosage form (powder, tablet, capsule, soft capsule, aqueous medicine, syrup, elixirs pill, powder, sachet, granule), or topical preparation (cream, ointment, lotion, gel, balm, patch, paste, spray solution, aerosol and the like), or injectable preparation (solution, suspension, emulsion).
  • oral dosage form prowder, tablet, capsule, soft capsule, aqueous medicine, syrup, elixirs pill, powder, sachet, granule
  • topical preparation cream, ointment, lotion, gel, balm, patch, paste, spray solution, aerosol and the like
  • injectable preparation solution, suspension, emulsion
  • composition of the present invention in pharmaceutical dosage forms may be used in the form of their pharmaceutically acceptable salts, and also may be used alone or in appropriate association, as well as in combination with other pharmaceutically active compounds.
  • the desirable dose of the inventive compound of the present composition varies depending on the condition and the weight of the subject, severity, drug form, route and period of administration, and may be chosen by those skilled in the art. However, in order to obtain desirable effects, it is generally recommended to administer at the amount ranging from 0.0001 to 100 mg/kg, preferably, 0.001 to 10 mg/kg by weight/day of the inventive extract or compounds of the present invention. The dose may be administered in single or divided into several times per day. In terms of composition, the amount of inventive extract or compound should be present between 0.01 to 50% by weight, preferably 0.5 to 40% by weight based on the total weight of the composition.
  • composition of present invention can be administered to a subject animal such as mammals (rat, mouse, domestic animals or human) via various routes. All modes of administration are contemplated, for example, administration can be made orally, rectally or by intravenous, intramuscular, subcutaneous, intracutaneous, intrathecal, epidural or intracerebroventricular injection.
  • inventive compound of the present invention also can be used as a main component or additive and aiding agent in the preparation of various functional health food and health care food.
  • a functional health food comprising an acacetin-7-O-glucuronide or luteolin-7-O-glucuronide isolated from an extract of Chrysanthemum indicum for the prevention or alleviation of cerebrovascular system involved anxiety.
  • a functional health food defined herein “the functional food having enhanced functionality such as physical functionality or physiological functionality by adding the compound of the present invention to conventional food to prevent or improve cerebrovascular system involved anxiety in human or mammal.
  • It is the other object of the present invention to provide a health care food comprising an acacetin-7-O-glucuronide or luteolin-7-O-glucuronide isolated from an extract of Chrysanthemum indicum , together with a sitologically acceptable additive for the prevention or alleviation of cerebrovascular system involved anxiety.
  • a health care food defined herein “the food containing the compound of the present invention showing no specific intended effect but general intended effect in a small amount of quantity as a form of additive or in a whole amount of quantity as a form of capsule, pill, tablet etc.
  • a sitologically acceptable additive any substance the intended use which results or may reasonably be expected to result-directly or indirectly-in its becoming a component or otherwise affecting the characteristics of any food” for example, thickening agent, maturing agent, bleaching agent, sequestrant, humectant, anti-caking agent, clarifying agents, curing agent, emulsifier, stabilizer, thickner, bases and acid, foaming agents, nutrients, coloring agent, flavoring agent, sweetner, preservative agent, antioxidant, etc, which shall be explained in detail as follows.
  • direct additive a substance that becomes part of the food in trace amounts due to its packaging, storage or other handling.
  • Health foods can be contained in food, health beverage, dietary therapy etc, and may be used as a form of powder, granule, tablet, chewing tablet, capsule, beverage etc for preventing or improving of cerebrovascular system involved anxiety.
  • above described compound can be added to food or beverage for prevention and improvement of cognitive function disorder.
  • the amount of above described compound in food or beverage as a functional health food or health care food may generally range from about 0.01 to 100 w/w % of total weight of food for functional health food composition.
  • the preferable amount of the compound of the present invention in the functional health food, health care food or special nutrient food may be varied in accordance to the intended purpose of each food, it is preferably used in general to use as an additive in the amount of the extract or compound of the present invention ranging from about 0.01 to 5% in food such as noodles and the like, from 40 to 100% in health care food on the ratio of 100% of the food composition.
  • the health beverage composition of present invention contains above described extract or compound as an essential component in the indicated ratio
  • the other component can be various deodorant or natural carbohydrate etc such as conventional beverage.
  • natural carbohydrate are monosaccharide such as glucose, fructose etc; disaccharide such as maltose, sucrose etc; conventional sugar such as dextrin, cyclodextrin; and sugar alcohol such as xylitol, and erythritol etc.
  • natural deodorant such as taumatin, stevia extract such as levaudiosideA, glycyrrhizin et al., and synthetic deodorant such as saccharin, aspartam et al.
  • the amount of above described natural carbohydrate is generally ranges from about 1 to 20 g, preferably 5 to 12 g in the ratio of 100 ml of present beverage composition.
  • the other components than aforementioned composition are various nutrients, a vitamin, a mineral or an electrolyte, synthetic flavoring agent, a coloring agent and improving agent in case of cheese, chocolate et al., pectic acid and the salt thereof, alginic acid and the salt thereof, organic acid, protective colloidal adhesive, pH controlling agent, stabilizer, a preservative, glycerin, alcohol, carbonizing agent used in carbonate beverage et al.
  • the other component than aforementioned ones may be fruit juice for preparing natural fruit juice, fruit juice beverage and vegetable beverage, wherein the component can be used independently or in combination.
  • the ratio of the components is not so important but is generally range from about 0 to 20 w/w % per 100 w/w % present composition.
  • Examples of addable food comprising aforementioned extract therein are various food, beverage, gum, vitamin complex, health improving food and the like.
  • Inventive compound of the present invention has no toxicity and adverse effect therefore; they can be used with safe.
  • the inventive compounds showed potent increasing effect on the time spent in open arm or closed arm and the number of open arm entries in elevated plus-maze test. Therefore it can be used as the therapeutics or health food for treating or preventing cerebrovascular system involved anxiety with safe.
  • Fig. 1 shows the effect of LG compound on the time spent in open arm or closed arm and the number of open arm entries in elevated plus-maze test (data was expressed as percentage, *: P ⁇ 0.05, **: P ⁇ 0.01);
  • Fig. 2 shows the effect of AG compound on the time spent in open arm or closed arm and the number of open arm entries in elevated plus-maze test (data was expressed as percentage, *: P ⁇ 0.05, **: P ⁇ 0.01).
  • acacetin-7-O-glucuronide or luteolin-7-O-glucuronide compound was determined by comparing the physicochemical property with the data disclosed in already-known literature (Lee et al., 2002, Arch. Pharm. Res ., 25 , pp842-850; Gulluce et al., 2012, Food Chem ., 130 , pp248-263).
  • mice Male ICR mouse weighing 23-30g purchased from Samtaco Co. was bred with mice per cage and let to freely access to water and feed.
  • the cage was kept with following condition maintaining the temperature of 21 ⁇ 1°C and the relative humidity of 55 ⁇ 5% under the regularly controlled light/dark condition with an interval of 12 hours.
  • mice were accustomed with the environment for 1 week before the experiment.
  • mice 1 hour before the experiment, various concentration of AG and LG (7.5mg, 15, and 30 mg/kg) prepared in Example was orally administrated into the mice as a test group.
  • Lexapro ® (20mg/kg, p.o.) was administrated as a positive control group and the identical volume of distilled water was orally administrated as a negative control group.
  • the groups consist of 10 mice respectively.
  • the elevated plus-maze consists of cross-shaped maze positioned on the bottom at the height of 50cm wherein two opposite passages (length: 30cm, width: 5cm) among four passages is opened and the other two passages were surrounded with 15cm tall of wall.
  • the central platform (longitude: 5cm, width: 5cm) was set and video-tracking system (luminosity: 24 ⁇ 7 lux)was equipped at the central ceiling to record the behavior of the mice. The mouse was placed at the central area and the line of mouse sight is directed to outside of open arm.
  • mice The mouse was voluntarily allowed to stay at open arm or closed arm and the behavior of mice for 5 min including (1) the time spent in open arm or closed arm, (2) the number of open arm entries etc was recorded automatically by a videotracking system (EthoVision ® , Noldus Information Technology, Wageningen, The Netherlands).
  • LG treatment group showed similar anti-anxiety efficacy to positive control group (20mg/kg) in respect to the time spent in open arm or closed arm and the number of open arm entries as shown in Fig. 1.
  • the acute toxicity test was performed by administrating inventive compounds to ICR mice (male, 6 weeks, Orient Bio Inc., www.orient.co.kr).
  • the inventive compounds were orally administrated to the mice and the symptoms of mice were observed for 3 days. After administrating the compound, all the clinical changes i.e., mortality, clinical signs, body weight changes was observed and blood test such as haematological test and hematological biochemistry test was performed. The abnormal changes of abdominal organ and thoracic organ were observed after autopsy.
  • inventive compounds of the present invention was potent and safe substance in oral administration.
  • Powder preparation was prepared by mixing above components and filling sealed package.
  • Tablet preparation was prepared by mixing above components and entabletting.
  • Tablet preparation was prepared by mixing above components and filling gelatin capsule by conventional gelatin preparation method.
  • Injection preparation was prepared by dissolving active component, controlling pH to about 7.5 and then filling all the components in 2ml ample and sterilizing by conventional injection preparation method.
  • Liquid preparation was prepared by dissolving active component, filling all the components and sterilizing by conventional liquid preparation method.
  • Health beverage preparation was prepared by dissolving active component, mixing, stirred at 85°C for 1 hour, filtered and then filling all the components in 1000ml ample and sterilizing by conventional health beverage preparation method.
  • the inventive compounds i.e., acacetin-7-O-glucuronide and luteolin-7-O-glucuronide isolated from an extract of Chrysanthemum indicum increased the time spent in open arm or closed arm and the number of open arm entries in elevated plus-maze test, Therefore, it can be used as the therapeutics or health food for treating or preventing cerebrovascular system involved anxiety without adverse action.

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PCT/KR2013/001279 2012-03-29 2013-02-19 A composition comprising the compound isolated from chrysanthemum indicum for treating or preventing cerebrovascular system involved anxiety and the use thereof WO2013147419A1 (en)

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