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WO2008069604A1 - Composition comprenant l'extrait végétal mixte de aralia cordata thunb. et cimicifuga heracleifolia kom. pour la prévention et le traitement de l'inflammation et de la douleur - Google Patents

Composition comprenant l'extrait végétal mixte de aralia cordata thunb. et cimicifuga heracleifolia kom. pour la prévention et le traitement de l'inflammation et de la douleur Download PDF

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Publication number
WO2008069604A1
WO2008069604A1 PCT/KR2007/006331 KR2007006331W WO2008069604A1 WO 2008069604 A1 WO2008069604 A1 WO 2008069604A1 KR 2007006331 W KR2007006331 W KR 2007006331W WO 2008069604 A1 WO2008069604 A1 WO 2008069604A1
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Prior art keywords
disease
extract
pain
test
inflammatory disease
Prior art date
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Ceased
Application number
PCT/KR2007/006331
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English (en)
Inventor
Do-Young Choi
Jea-Dong Lee
Hyungin Yang
Myung Chul Yoo
Jeong-Eun Huh
Dong-Suk Park
Yong-Hyeon Back
Kyoung Soo Kim
Yong-Baik Cho
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SK Chemicals Co Ltd
Whan In Pharm Co Ltd
Kyung Hee University
Original Assignee
SK Chemicals Co Ltd
Whan In Pharm Co Ltd
Kyung Hee University
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Publication of WO2008069604A1 publication Critical patent/WO2008069604A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • 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
    • A61K36/237—Notopterygium
    • 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)
    • A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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)
    • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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

  • the present invention relates to a composition comprising the mixed herbal extract of
  • NOS nitric oxide synthase
  • PGs prostaglandin
  • COX cyclooxygenase
  • Araliacordata THUNB belonged to Araliaceae has been reported to contain various essential oils such as limonene, sabinene, myrcene, humeulene etc. and Cimicifuga heracleifolia Kom has been reported to contain cimifugine, salicylic acid, tannin, resin, caffeic acid, ferulic acid, cimitin, alkaloid, isoferulic acid etc. (Chung B.
  • the present inventors have confirmed that the extract of mixed herbs withAraliacordata THUNB ⁇ ndCimicifugaheracleifolia Kom shows potent antiinflammatory effect through various experiments, i.e., the several analgesic animal test using ICR mouse such as radiation-induced tail flick analgesia test, acetic acid-induced writhing test, hot plate test, formalin analgesia test, paw pressure analgesia test, etc.; several anti-inflammatory animal test such as croton oil-induced ear edema test, arachidonic-induced ear edema test, etc; and the inhibition test on specific arthritis such as the inhibition effect on the dissociation of glycoaminoglycan (GAG), a proteoglycan and type II collagen in chondrocyte and cartilage tissue etc, therefore, it can be used as the effective and safe therapeutics or health care food for treating and preventing inflammatory disease, specifically, arthritic disease, and pain disease.
  • the present invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising the extract of mixed herbs with AraliacordataTHUNB. and Cimicifugaheracleifolia Kom., as an active ingredient for the treatment and prevention of inflammatory disease, specifically, arthritic diseases by way of inhibiting cartilage dissociation, and pain disease.
  • the present invention also provides a use of the extract of mixed herbs with Aralia cordataTHUNB. and Cimicifiigaheracleifolia Kom., for the preparation of therapeutic agent for the treatment and prevention of inflammatory disease, specifically, arthritic diseases by way of inhibiting cartilage dissociation, and pain disease in a mammal or human.
  • the present invention also provides a method of treating or preventing inflammatory disease, specifically, arthritic diseases, and pain disease in a mammal or human in need thereof comprising administering to said mammal or human with an effective amount of the extract of mixed herbs with AraliacordataTHUNB. and Cimicifuga heracleifolia Kom., together with a pharmaceutically acceptable carrier thereof.
  • the present invention also provides a health care food or food additives comprising the extract of mixed herbs with AraliacordataTHUNB. and Cimicifuga heracleifolia Kom for the prevention and alleviation of inflammatory disease, especially, arthritic diseases, and pain disease.
  • a pharmaceutical composition comprising the extract of mixed herbs with Aralia cordata THUNB. and Cimicifuga heracleifolia Kom., as an active ingredient for the treatment and prevention of inflammatory disease, specifically, arthritic diseases by way of inhibiting cartilage dissociation, and pain disease.
  • mixed herbs comprises the combined herbs with Aralia cordata THUNB. and Cimicifuga heracleifolia Kom., with the mixed ratio (WAV) of 0.1-10:1, preferably, 0.5-5:1, more preferably, 1-2:1, most preferably, 1:1.
  • WAV mixed ratio
  • extract defined herein includes “the extract”soluble in water and Cl to C4 lower alcohol such as methanol, ethanol, butanol etc. or the mixture thereof, preferably, the mixture solvent of water and ethanol, more preferably, the mixture solvent of 20-80% ethanol.
  • inflammatory disease includes arthritic diseases such as degenerative arthritis, osteoarthritis, rheumatid arthritis and the like, asthma, irritable colon syndrome, shock by endotoxin or Crohn's disease etc., preferably, osteoarthritis or rheumatid arthritis.
  • pain disease includes acute pain, chronic pain, arthralgia, neuropathic pain, pain after surgery, migraine, neuropathy, or nervous damage, preferably, acute pain or chronic pain.
  • the present invention also provided a use of the extract of mixed herbs with Aralia cordata THUNB. and Cimicifuga heracleifolia Kom., for the preparation of therapeutic agent for the treatment and prevention of inflammatory disease, specifically, arthritic diseases by way of inhibiting cartilage dissociation, and pain disease in a mammal or human.
  • the present invention also provided a pharmaceutical composition
  • a pharmaceutical composition comprising the extract of mixed herbs with Aralia cordata THUNB. and Cimicifuga heracleifolia Kom., and a pharmaceutically acceptable carrier thereof as an active ingredient for treating and preventing inflammatory disease, specifically, arthritic diseases by way of inhibiting cartilage dissociation, and pain disease.
  • the inventive extract of mixed herbs with AraliacordataTHUNB. and Cimicifuga heracleifolia Kom, of the present invention may be prepared by the process comprising the steps: combining the dried herbs of Araliacordata THUNB. and Cimicifuga heracleifolia Kom with appropriate mixture ratio of 0.1-10:1, preferably, 0.5-5:1 (WAV); mixing the herbs with 1 to 20-fold, preferably, approximately 5 to 15-fold volume of distilled water, Cl to C4 lower alcohols such as ethanol, methanol etc.
  • the inventive extract of mixed herbs with Aralia cordata THUNB. and Cimicifuga heracleifolia Kom prepared by above-described method shows potent anti-inflammatory effect through various experiments, i.e., the several analgesic animal test using ICR mouse such as radiation-induced tail flick analgesia test, acetic acid- induced writhing test, hot plate test, formalin analgesia test, paw pressure analgesia test, etc; several anti-inflammatory animal test such as croton oil-induced ear edema test, arachidonic-induced ear edema test, etc; and the inhibition test on specific arthritis such as the inhibition effect on the dissociation of glycoaminoglycan (GAG), a proteoglycan and type II collagen in chondrocyte and cartilage tissue etc.
  • GAG glycoaminoglycan
  • the present invention there are provided a pharmaceutical composition
  • a pharmaceutical composition comprising the inventive extract of mixed herbs with Aralia cordata THUNB. and Cimicifuga heracleifolia Kom prepared by above-described method and a pharmaceutically acceptable carrier thereof as an active ingredient for treating and preventing inflammatory disease, especially, arthritic disease, and pain disease.
  • the inventive composition for treating and preventing inflammatory disease, especially, arthritic disease, and pain disease may comprise the above-described extract as 0.1 - 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, pro- pylhydroxy 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, poly
  • 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 extract or 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 0.1 to 1000mg/kg, preferably, 1 to 100 mg/kg by weight/day of the inventive extract 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 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 intra-cerebroventricular injection.
  • a health care food or food additives comprising the extract of mixed herbs with Aralia cordata THUNB. and Cimicifuga heracleifolia Kom for the prevention and alleviation of inflammatory disease, especially, arthritic diseases, and pain disease.
  • the health care food of the present invention comprises the above-described extract as 0.01 to 80 %, preferably 1 to 50 % by weight based on the total weight of the composition.
  • the health care food of the present invention can be contained in health food, health beverage etc, and may be used as powder, granule, tablet, chewing tablet, capsule, beverage etc.
  • the health care food of the present invention comprises the above-described extract as 0.01 to 80 %, preferably 1 to 50 % by weight based on the total weight of the composition.
  • the food additive of the present invention can be contained in health food, health beverage etc., and may be used as powder, granule, tablet, chewing tablet, capsule, beverage etc.
  • the present invention provide a composition of the health food beverage for the prevention and improvement of arthritic diseases adding 0.01 to 80 % the above- described extract by weight, 0.001 to 5 % amino acids by weight, 0.001 to 2 % vitamins by weight, 0.001 to 20 % sugars by weight, 0.001 to 10 % organic acids by weight and proper amount of sweetener and flavors.
  • examples of addable food comprising the above described extract of the present invention are various food, beverage, gum, vitamin complex, health improving food and the like, and can be used as power, granule, tablet, chewing tablet, capsule or beverage etc.
  • the extract of the present invention will be able to prevent and alleviate arthritic disease by way of adding to child and infant food, such as modified milk powder, modified milk powder for growth period, modified food for growth period.
  • the above-described composition therein can be added to food, additive or beverage, wherein, the amount of above described extract in food or beverage may generally range from about 0.1 to 80w/w %, preferably 1 to 50 w/w % of total weight of food for the health food composition and 1 to 30 g, preferably 3 to 10 g on the ratio of 100 ml of the health beverage composition.
  • the health beverage composition of present invention contains above described extract 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, cyc- lodextrin; and sugar alcohol such as xylitol, and erythritol etc.
  • natural deodorant such as taumatin, stevia extract such as levaudioside A, 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.
  • the inventive composition may additionally comprise one or more than one of organic acid, such as citric acid, fumaric acid, adipic acid, lactic acid, malic acid; phosphate, such as phosphate, sodium phosphate, potassium phosphate, acid pyrophosphate, polyphosphate; natural anti-oxidants, such as polyphenol, catechin, ⁇ - tocopherol, rosemary extract, vitamin C, green tea extract, licorice root extract, chitosan, tannic acid, phytic acid etc.
  • organic acid such as citric acid, fumaric acid, adipic acid, lactic acid, malic acid
  • phosphate such as phosphate, sodium phosphate, potassium phosphate, acid pyrophosphate, polyphosphate
  • natural anti-oxidants such as polyphenol, catechin, ⁇ - tocopherol, rosemary extract, vitamin C, green tea extract, licorice root extract, chitosan, tannic acid, phytic acid etc.
  • the extract of mixed herbs with Aralia cordata THUNB. and Cimicifuga her- acleifolia Kom of the present invention shows potent anti-inflammatory and anti-pain effect through various experiments, i.e., the several analgesic animal test using ICR mouse such as radiation-induced tail flick analgesia test, acetic acid-induced writhing test, hot plate test, formalin analgesia test, paw pressure analgesia test, etc; several antiinflammatory animal test such as croton oil-induced ear edema test, arachidonic- induced ear edema test, etc; and the inhibition test on specific arthritis such as the inhibition effect on the dissociation of glycoaminoglycan (GAG), a proteoglycan and type II collagen in chondrocyte and cartilage tissue etc.
  • GAG glycoaminoglycan
  • Seoul was cut into small pieces with the size of about 1.0 cm, mixed with 1.5 liter of 70% ethanol (v/v) and the mixture was subjected to reflux extraction for 4 hours.
  • Example 1 preparation of the extract of mixed herbs with Aralia cordata
  • Tail flick test was performed by the procedure according to the method disclosed in the literature as follows (Shaw FZ et ah, Brain Res., 911 (2), pplO5-115, 2001).
  • mice Male ICR mice (Orientbio Inc., Japan) weighing from 20 to 25g were acclimated to the experimental environment for several days and each test group consists of 8 mice. The test samples were administrated to the mice orally and 1 hour after the treatment, infrared ray was irradiated on the center of its tail. Then, the time until the mice showed an avoid response was measured and the relative inhibitory rate (%) based on the inhibitory effect of positive control (celecoxib®) was calculated. The result was shown in following Table 1.
  • the inventive extract of the present invention (AC extract) showed more potent inhibitory effect on the pain induced by radiation in animal model than the extract of each simple herb.
  • Acetic acid induced writhing analgesia test [79] [80] In order to determine the analgesic activity of the inventive extract of the present invention, acetic acid -induced writhing analgesia test was performed by the procedure according to the method disclosed in the literature as follows (B.A. Whittle, Brit. J. Pharmacol. Chemother., 22. , pp246-253, 1964).
  • mice Male ICR mice (Orientbio Inc., Japan) weighing from 20 to 25g were acclimated to the experimental environment for several days and each test group consists of 8 mice. The test samples were administrated to the mice orally and 1 hour after the treatment, 0.7% acetic acid (v/v in DW) was administrated to the mice intrapritoneally to induce pain. From 5 minutes after the treatment, the writhing frequency of the mice was recorded for 10 minutes and the relative inhibitory rate (%) based on the inhibitory effect of positive control (celecoxib®) was calculated. The result was shown in following Table 2.
  • the inventive extract of the present invention (AC extract) showed more potent inhibitory effect on the pain induced by acetic acid in animal model than the extract of each simple herb.
  • Hot plate test In order to determine the analgesic activity of the inventive extract of the present invention, hot plate test was performed by the procedure according to the method disclosed in the literature as follows (Lanhers et al., Planta Medica, 58. , ppl 17-123, 1992).
  • mice Male ICR mice (Orientbio Inc., Japan) weighing from 20 to 25g were acclimated to the experimental environment for several days and each test group consists of 8 mice. The test samples were administrated to the mice orally and 1 hour after the treatment, the mice were placed on the hot plate heated at 55 0 C. The time until the mice licked its sole or leaped was measured and the relative inhibitory rate (%) based on the inhibitory effect of positive control (celecoxib®) was calculated. The result was shown in following Table 3.
  • the inventive extract of the present invention (AC extract) showed more potent inhibitory effect on the pain in animal model than the extract of each simple herb.
  • mice Male ICR mice (Orientbio Inc., Japan) weighing from 20 to 25g were acclimated to the experimental environment for several days and each test group consists of 8 mice. The test samples were administrated to the mice orally and 1 hour after the treatment, 10% formalin (Sigma, USA) solution was administrated to the left hind legs of mice subcutaneously. The time that the mice licked the sole of its foot, from 5 minutes after the injection (1 st phase) and from 15 minutes to 20 minutes after the injection (2 nd phase), was measured and the relative inhibitory rate (%) based on the inhibitory effect of positive control (celecoxibs® was calculated. The result was shown in following Table 4.
  • the inventive extract of the present invention (AC extract) showed more potent inhibitory effect on the pain induced by formalin in animal model than the extract of each simple herb.
  • Paw pressure analgesia test In order to determine the analgesic activity of the inventive extract of the present invention, paw pressure analgesia test was performed by the procedure according to the method disclosed in the literature as follows (Randall LO and Selitto JJ, Arch. Int. Pharmacodyn., JJJ., pp409-419. 1957).
  • mice Male SD mice (Orientbio Inc., Japan) weighing from 180 to 20Og were acclimated to the experimental environment for several days and each test group consists of 8 mice. The test samples were administrated to the mice orally and 1 hour after the treatment, 2% carrageenan (Sigma, USA) was administrated to the mice subcutaneously to induce pain. From 3 hours after the treatment, the weight of inflamed area when the mice showed avoidance response was recorded by analgesic meter (Ugobasile, Italy) and the relative inhibitory rate (%) based on the inhibitory effect of positive control (celecoxib®) was calculated. The result was shown in following Table 5.
  • the inventive extract of the present invention (AC extract) showed more potent inhibitory effect on the pain induced by 2% carrageenan in animal model than the extract of each simple herb.
  • Croton oil-induced ear oedema test Croton oil induces to various inflammatory responses such as rash, swelling, blister etc on the spread surface when spread on skin.
  • croton oil induced ear oedema test was performed by the procedure according to the method disclosed in the literature as follows (Gabor M, Mouse ear in- dlammation models and their pharmacological applications, Published by Akademiai kiado, Budapest, pp24-28, 2000).
  • Male ICR mice (Orientbio Inc., Japan) weighing from 20 to 25g were acclimated to the experimental environment for several days and each test group consists of 6 mice.
  • mice were fed to the mice orally and 1 hour after the treatment, 2.5% croton oil dissolved in acetone was spread on the inside and outside of the mice's right ear to induce edema.
  • the mice were died with the over-dose of ether and then the level of ear edema was determined by speed-transformation method using a thickness gauge (Patrick et al., Toxicol. Appl. Pharmacol., 81_ , pp476-1985).
  • the relative inhibitory rate (%) based on the inhibitory effect of positive control (celecoxib®) was calculated. The result was shown in following Table 6.
  • the inventive extract of the present invention (AC extract) showed more potent inhibitory effect on the ear-edema induced by croton oil in animal model than the extract of each simple herb.
  • Arachidonic acid-induced ear oedema test [122] Arachidonic acid, a precursor of prostaglandin is a main etiological substance that induces platelet aggregation, arteriosclerosis, heart disease and inflammation etc.
  • arachidonic acid- induced ear oedema test was performed by the procedure according to the method disclosed in the literature as follows (Gabor M, Mouse ear indlammation models and their pharmacological applications, Published by Akademiai kiado, Budapest, pp24-28, 2000).
  • mice Male ICR mice (Orientbio Inc., Japan) weighing from 20 to 25g were acclimated to the experimental environment for several days and each test group consists of 6 mice. The test samples were administrated to the mice orally and 1 hour after the treatment, 50mg/ml of arachidonic acid dissolved in acetone was spread on the inside and outside of the mice s right ear to induce edema. One hour after the occurrence of edema, the mice were died with the over-dose of ether and then the level of ear edema was determined by speed-transformation method using a thickness gauge (Patrick et al., Toxicol. Appl. Pharmacol., &1 > pp476-1985). The relative inhibitory rate (%) based on the inhibitory effect of positive control (celecoxib®) was calculated. The result was shown in following Table 7.
  • the inventive extract of the present invention (AC extract) showed more potent inhibitory effect on the ear-edema induced by arachidonic acid in animal model than the extract of each simple herb.
  • the medium was replaced with new medium containing 5% inactivated fetal bovine serum with heat treatment, 1OmM HEPES and 100 unit/ml of penicillin-streptomycin. 30mg of the articular tissue was transferred to 48-well plates and each test sample was treated therewith. 1 hour after the incubation, 5ng/ml of IL-Ia was added to the medium to induce inflammation and further incubated at 37 0 C for 3 days. Then, the upper layer was collected and transferred to new medium to incubate for 25 days further. The culture supernatant in the medium was gathered at the 3rd day, 7th day, 14th day and 28th day respectively and stored at -20 0 C.
  • the GAG concentration in the culture medium of cartilage tissue prepared in Experimental Example 3-1 was measured by determining the amount of poly anionic substance produced by the reaction with Blyscan dye solution. Chondroitin sulfate was used as a standard. 50 microliter of each test sample in respective group was mixed with 500microliter of Blyscan dye solution and then was reacted for 30 minutes at room temperature. The solution was centrifuged with the speed of 12000 rpm for 10 minutes.
  • the inventive extract of the present invention (AC extract) showed more potent inhibitory effect on the GAG dissociation than the extract of each simple herb.
  • Acute toxicity test of oral administration was performed by using four- weeks-old ICR mouse (Orientbio, Japan) according to method disclosed in the literature (Haschek WM and Rousseaux CG, Handbook of toxicologic pathology, Published by Academic press, Inc,. New York, pp293-295, 1991).
  • the inventive extract of the present invention dissolved in water was administrated orally to each group consisting of 5 mice in a dose of 5g/kg/10ml. After administration, the mortality of the mice and clinical symptom, body weight change was observed and hematologic test and hematological biochemistry test was performed. Whether abdominal organ and thoracic organ is abnormal was observed with the naked eye by an autopsy.
  • Tablet preparation was prepared by mixing above components and entabletting. [165]
  • Capsule preparation was prepared by mixing above components and filling gelatin capsule by conventional gelatin preparation method. [172]
  • Injection preparation was prepared by dissolving the components in 2 ml ample and sterilizing by conventional injection preparation method. [179]
  • Vitamin B6 0.5mg
  • Health beverage preparation was prepared by dissolving active component, mixing, stirred at 85 0 C for 1 hour, filtered and then filling all the components in 2000 ml ample and sterilizing by conventional health beverage preparation method.
  • the extract of mixed herbs with Ar alia cor data THUNB. and Cimicifugaheracleifolia Kom of the present invention shows potent antiinflammatory and anti-pain effect through various experiments, i.e., the several analgesic animal test using ICR mouse such as radiation-induced tail flick analgesia test, acetic acid-induced writhing test, hot plate test, formalin analgesia test, paw pressure analgesia test, etc; several anti-inflammatory animal test such as croton oil- induced ear edema test, arachidonic-induced ear edema test, etc; and the inhibition test on specific arthritis such as the inhibition effect on the dissociation of gly- coaminoglycan (GAG), a proteoglycan and type II collagen in chondrocyte and cartilage tissue etc.
  • GAG gly- coaminoglycan

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Abstract

La présente invention concerne une composition comprenant l'extrait végétal mixte de Aralia cordata THUNB. et Cimicifuga heracleifolia Kom. Comme ingrédient actif pour prévenir et traiter l'inflammation et la douleur. L'extrait de la présente invention présente un effet anti-inflammatoire et anti-douleur efficace dans différentes expériences. Ainsi, il peut être utilisé comme agent thérapeutique ou aliment santé sûr et efficace pour traiter et prévenir l'inflammation, en particulier une maladie arthritique, et la douleur.
PCT/KR2007/006331 2006-12-08 2007-12-06 Composition comprenant l'extrait végétal mixte de aralia cordata thunb. et cimicifuga heracleifolia kom. pour la prévention et le traitement de l'inflammation et de la douleur Ceased WO2008069604A1 (fr)

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KR10-2006-0124410 2006-12-08
KR1020060124410A KR100830553B1 (ko) 2006-12-08 2006-12-08 독활 및 승마 혼합생약추출물을 포함하는 염증관련 질환예방 및 치료용 조성물

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US20120190882A1 (en) * 2009-06-21 2012-07-26 Lai Hung Cindy Yang Efficient isolation of cimiracemate a, and methods of use
CN103977049A (zh) * 2014-05-12 2014-08-13 成都中医药大学 食用土当归总有机酸的新用途
WO2017172648A1 (fr) * 2016-03-26 2017-10-05 Sirbal Ltd. Nanoformulations à base de plantes permettant de traiter le psoriasis et d'autres affections cutanées

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KR102634898B1 (ko) 2015-11-06 2024-02-08 주식회사 제뉴원사이언스 시호, 승마, 백작약 및 목향 혼합 추출물을 함유하는 염증성 장질환의 예방 및 치료용 약학 조성물

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20120190882A1 (en) * 2009-06-21 2012-07-26 Lai Hung Cindy Yang Efficient isolation of cimiracemate a, and methods of use
US8633332B2 (en) * 2009-06-21 2014-01-21 Purapharm Company Limited Efficient isolation of cimiracemate A, and methods of use
CN103977049A (zh) * 2014-05-12 2014-08-13 成都中医药大学 食用土当归总有机酸的新用途
WO2017172648A1 (fr) * 2016-03-26 2017-10-05 Sirbal Ltd. Nanoformulations à base de plantes permettant de traiter le psoriasis et d'autres affections cutanées
US11344598B2 (en) 2016-03-26 2022-05-31 Sirbal Limited Herbal nanoformulations for treating psoriasis and other skin conditions

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