WO2005067954A1 - Composition pharmaceutique comprenant l'extrait de sorbus amurensis koehne pour traiter ou prevenir les maladies du systeme cerebrovasculaire - Google Patents

Composition pharmaceutique comprenant l'extrait de sorbus amurensis koehne pour traiter ou prevenir les maladies du systeme cerebrovasculaire Download PDF

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Publication number
WO2005067954A1
WO2005067954A1 PCT/KR2004/002316 KR2004002316W WO2005067954A1 WO 2005067954 A1 WO2005067954 A1 WO 2005067954A1 KR 2004002316 W KR2004002316 W KR 2004002316W WO 2005067954 A1 WO2005067954 A1 WO 2005067954A1
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extract
sorbus
amurensis
koehne
pharmaceutical composition
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PCT/KR2004/002316
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English (en)
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Ho Sub Lee
Dae Gill Kang
Tae Oh Kwon
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Ho Sub Lee
Dae Gill Kang
Tae Oh Kwon
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Publication of WO2005067954A1 publication Critical patent/WO2005067954A1/fr

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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)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B61—RAILWAYS
    • B61B—RAILWAY SYSTEMS; EQUIPMENT THEREFOR NOT OTHERWISE PROVIDED FOR
    • B61B1/00—General arrangement of stations, platforms, or sidings; Railway networks; Rail vehicle marshalling systems
    • B61B1/02—General arrangement of stations and platforms including protection devices for the passengers
    • 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
    • A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
    • A23L2/52—Adding ingredients
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • 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
    • 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
    • E—FIXED CONSTRUCTIONS
    • E01—CONSTRUCTION OF ROADS, RAILWAYS, OR BRIDGES
    • E01F—ADDITIONAL WORK, SUCH AS EQUIPPING ROADS OR THE CONSTRUCTION OF PLATFORMS, HELICOPTER LANDING STAGES, SIGNS, SNOW FENCES, OR THE LIKE
    • E01F1/00—Construction of station or like platforms or refuge islands or like islands in traffic areas, e.g. intersection or filling-station islands; Kerbs specially adapted for islands in traffic areas
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F16—ENGINEERING ELEMENTS AND UNITS; GENERAL MEASURES FOR PRODUCING AND MAINTAINING EFFECTIVE FUNCTIONING OF MACHINES OR INSTALLATIONS; THERMAL INSULATION IN GENERAL
    • F16B—DEVICES FOR FASTENING OR SECURING CONSTRUCTIONAL ELEMENTS OR MACHINE PARTS TOGETHER, e.g. NAILS, BOLTS, CIRCLIPS, CLAMPS, CLIPS OR WEDGES; JOINTS OR JOINTING
    • F16B5/00—Joining sheets or plates, e.g. panels, to one another or to strips or bars parallel to them
    • F16B5/02—Joining sheets or plates, e.g. panels, to one another or to strips or bars parallel to them by means of fastening members using screw-thread

Definitions

  • the present invention relates to the extract of Sorbus amurensis having treating and preventing activity for cerebrovascular disease.
  • Background Art [2]
  • EDRF endothelium-derived relaxing factor
  • NO Nitric Oxide
  • Nitric oxide is formed by hydrolyzing L-arginine substrate by the action of nitric oxide synthase (NOS) and is reproduced in vascular endothelial cell.
  • NOS nitric oxide synthase
  • bNOS, nNOS, NOS I brain type NOS
  • iNOS, NOS II inducible NOS
  • ecNOS, eNOS, NOS III endothelium
  • Endothelium-derived relaxing factor is synthesized and released at normal state in endothelial cell and the synthesis and the release of them are promoted by various agonists such as acetylcholine, histamine, substance P, isopropanol etc.
  • Sorbus amurensis KOEHNE belonged to Malvaceae is distributed in South-Eastern area of Korea .
  • the cortex of the plant has been prescribed as a cough remedy and a restorative till now (Chung B. S. and Shin M. K.; HyangyakDaesacheon, Youngrimsa., pp618, 1998).
  • Some of the ingredients were isolating from Sorbus genus plant, i.e., lupeol and luepnone a triterpene compound from Korean sorbus plant(SorbM5 amurensis) Lee S. M., and Lee C. K, Analytical Science & Technology, 12 (2).
  • the present invention provides a pharmaceutical composition comprising the crude extract or non-polar solvent soluble extract of Sorbus amurensis KOEHNE, as an active ingredient for the treatment and prevention of cerebrovascular disease by relaxing endothelial cell.
  • Above described crude extract comprises the extract prepared by extracting plant material with water, lower alcohols such as methanol, ethanol, preferably methanol and the like, or the mixtures thereof.
  • Above described non-polar solvent soluble extract can be prepared by extracting above crude extract with non-polar solvent, for example, hexane, ethyl acetate or dichloromethane, preferably ethyl acetate.
  • the present invention also provides a use of above extract for the preparation of pharmaceutical composition to treat and prevent cerebrovascular disease.
  • the present invention also provides a health care food or food additives comprising above extract for the prevention or alleviation of cerebrovascular disease.
  • a pharmaceutical composition comprising the crude extract or non-polar solvent soluble extract of Sorbus amurensis KOEHNE, as active ingredients for the treatment and prevention of cerebrovascular disease by relaxing endothelial cell.
  • the term 'crude extract' disclosed herein comprises the extract prepared by extracting plant material with water, lower alcohols such as methanol, ethanol, preferably methanol and the like, or the mixtures thereof.
  • the term 'non-polar solvent soluble extract' disclosed herein can be prepared by extracting above crude extract with non-polar solvent, for example, hexane, ethyl acetate or dichloromethane, preferably ethyl acetate.
  • the term 'cerebrovascular disease' disclosed herein comprises various brain diseases such as transient ischemic attack (TIA), thrombotic cerebral infarction, hemodynamic cerebral infarction, hiatal infarxtion, cerebral hemorrhage hypertension and the like.
  • TIA transient ischemic attack
  • thrombotic cerebral infarction thrombotic cerebral infarction
  • hemodynamic cerebral infarction thrombotic cerebral infarction
  • hiatal infarxtion atal infarxtion
  • cerebral hemorrhage hypertension and the like.
  • the pharmaceutical composition of the present invention can contain about 0.01 ⁇ 50 % by weight of the above extract based on the total weight of the composition.
  • the health care food of the present invention comprises the above extract as 0.01 to 80 %, preferably 1 to 50 % by weight based on the total weight of the composition.
  • Above health care food can be contained in health care food, health beverage etc, and may be used as powder, granule, tablet, chewing tablet, capsule, beverage etc.
  • An inventive crude extract or non-polar solvent soluble extract of Sorbus amurensis KOEHNE may be prepared in accordance with the following preferred embodiment.
  • the inventive crude extract of Sorbus amurensis KOEHNE can be prepared by follows; Sorbus amurensis KOEHNE is dried, cut, crushed and mixed with 5 to 25-fold, preferably, approximately 10 fold volume of distilled water, lower alcohols such as methanol, ethanol, butanol and the like, or the mixtures thereof, preferably methanol; the solution is treated with the solvent at the temperature ranging from 20 to 100 ° C, preferably from 60 to 100 ° C, for the period ranging from 1 to 24 hours with extraction method by the extraction with hot water, cold water, reflux extraction, or ultra- sonication extraction with 1 to 5 times, preferably 2 to 3 times, consecutively; the residue is filtered to obtain the supernatant to be concentrated with rotary evaporator, at the temperature ranging from 20 to 100 ° C, preferably from 50 to 70 ° C and then dried by vacuum freeze-drying, hot air-drying or spray drying to obtain dried crude extract powder of Sorbus amurensis
  • polar solvent soluble and non-polar solvent soluble extract of present invention can be prepared by following procedure; the crude extract prepared by above step, is suspended in water, and then is mixed with 1 to 100-fold, preferably, 1 to 5-fold volume of non polar solvent such as ethyl acetate, chloroform, hexane and the like; the non-polar solvent soluble layer is collected to obtain non-polar solvent soluble extract of the present invention and remaining polar solvent soluble layer is collected to obtain polar solvent soluble extract of the present invention which is soluble in water, lower alcohols, or the mixtures thereof.
  • non polar solvent such as ethyl acetate, chloroform, hexane and the like
  • a pharmaceutical composition comprising the crude extract or non-polar solvent soluble extract of Sorbus amurensis KOEHNE prepared by above preparation method for the treatment and prevention of cerebrovascular disease as active ingredients.
  • the inventive composition for treating and preventing vascular contraction by inhibiting NO production may comprises above extracts as 0.01 ⁇ 50 % by weight based on the total weight of the composition.
  • 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 ). [37] Hereinafter, the following formulation methods and excipients are merely exemplary and in no way limit the invention.
  • 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 extract varies depending on the condition and the weight of the subject, severity, drug form, route and a 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 10 g/kg, preferably, 1 to 3 g/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 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, rec tally or by intravenous, intramuscular, subcutaneous, intra- cutaneous, intrathecal, epidural or intracerebroventricular injection.
  • the present invention provide a composition of the health care food beverage for the prevention and improvement of cerebrovascular disease adding above described extracts 0.01 to 80 % by weight, amino acids 0.001 to 5 % by weight, vitamins 0.001 to 2 % by weight, sugars 0.001 to 20 % by weight, organic acids 0.001 to 10 % by weight, sweetener and flavors of proper amount.
  • examples of addable food comprising above extracts 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 improve cerebrovascular disease by adding to child and infant food, such as modified milk powder, modified milk powder for a growth period, modified food for a growth period.
  • 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 care 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, cy- clodextrin; 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 py- rophosphate, polyphosphate; natural anti-oxidants, such as polyphenol, catechin, alpha -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 py- rophosphate, polyphosphate
  • natural anti-oxidants such as polyphenol, catechin, alpha -tocopherol, rosemary extract, vitamin C, green tea extract, licorice root extract, chitosan, tannic acid, phytic acid etc
  • the above extract of Sorbus amurensisKOEHNE may be 20 to 90 % high concentrated liquid, power, or granule type.
  • the above extract of Sorbus amurensisKOEHNE can comprise additionally one or more than one of lactose, casein, dextrose, glucose, sucrose and sorbitol.
  • Inventive extract of the present invention have no toxicity and adverse effect therefore; they can be used with safe.
  • FIG. 56 shows the vascular relaxing activity according to respective solvent soluble extract, i.e., soluble n-hexane soluble extract, ethylacetate soluble extract and n- butanol extract of Sorbus amurensis KOEHNE for 100 ?g/ml ;
  • Fig 2 shows the vascular relaxing activity according to each concentration of n- butanol soluble extract of Sorbus amurensis KOEHNE.
  • n -hexane soluble fraction was evaporated in vacuo to give 11.7g of n-hexane soluble extract of Sorbus amurensis KOEHNE.
  • n -butanol soluble fraction and water-soluble fraction were respectively evaporated in vacuo to give 17.2g of n-butanol soluble extract and 12.4g of water-soluble extract of Sorbus amurensis KOEHNE.
  • Phenylephrine HC1, L-NAME (Nitroarinine methyl ester), methylene blue, CDQ, indomethacin, glibenclamide, TEA, verapamil, atropine, propranolol and )ohimbine etc were procured from Sigma Chemical Co. (St. Louis, USA) and Y-27632 2HC1 ( tr ⁇ ns-4-[(lR)-l-aminoethyl]-N-4-pyridinylcyclohexane carboxamide dihydrochloride) and Zaprinast (2-(2-propyloxyphenyl)-8-azapurin-6-one) were from Tocris Cookson Ltd. (Bristol, Great Britain).
  • the thoracic aortas were rapidly and carefully dissected and placed into ice-cold Krebs solution (pH 7.4) containing 118 mmol/L NaCl, 4.7 mmol/L KCl, 1.1 mmol/L MgSO , 4 1.2 mmol/L KH PO , 1.5 mmol/L CaCl , 25 mmol L NaHCO , and 10 mmol/L 2 4 2 3 Glucose.
  • the aortas were performed in free of connective tissue and fat, and then cut into rings having width of approximately 3 mm. All dissecting procedures were performed with extreme care to protect the endothelium from inadvertent damage.
  • endothelial layer was mechanically removed by gently rubbing the luminal surface of the aortic ring back and forth several times with plastic tubing. Endothelial integrity or functional removal was verified by the presence or absence, respectively, of the relaxant response to 3 x 10 M acetylcholine on phenylephrine (3 x 10 M) contracted vessels.
  • the aortic rings were suspended by means of two L-shape stainless-steel wires inserted into lumen in a tissue bath containing Krebs solution (pH 7.4) at 37 ° C, while being continuously bubbled with 95% O -5% CO .
  • the baseline load placed on the 2 2 aortic rings was 2.0 g, and the changes in isometric tension were recorded using a force-displacement transducer (Grass FT 03, Quincy, MA, USA) connected to a Grass polygraph recording system (Model 7E).
  • the aortic rings were contacted with phenylephrine (3 x 10 M) to obtain maximal response.
  • acetylcholine (Ach) (10 - 10 M) was performed as a positive control in endothelium- intact aortic rings contracted by 3 x 10 M phenylephrine.
  • the rings were then exposed to various drugs for 30 min, and then aortic relaxation was carried out by cumulative addition of n-butanol extract of Sorbus amurensis KOEHNE.
  • DMSO dimethylsulfoxide
  • Fig 1 shows the vascular relaxing activity according to respective solvent soluble extract.
  • the extract i.e., soluble n-hexane soluble extract, ethylacetate soluble extract and n-butanol extract of Sorbus amurensis KOEHNE shows potent relaxing activity on endothelial cell by 395 + 1.5%, 71.1 + 4.15%, and 57.8 + 6.2%, in respective concentration of 100 ?g/ml respectively, which shows that ethylacetate soluble extract shows most potent activity among them.
  • Fig 2 shows the vascular relaxing activity of various concentration of n- butanol soluble extract of Sorbus amurensis KOEHNE, which shows that the relaxing activity of endothelial cell in dose dependent manner.
  • those activities were disappeared by removing vascular endothelial cell or inhibiting NO system, therefore, it is confirmed that n-butanol soluble extract shows relaxing activity of n-butanol soluble extract of Sorbus amurensis KOEHNE is dependent on the endothelial cell and NO system.
  • mice mean body weight 25 + 5g
  • Sprague- Dawley rats 235 + lOg, Jung-Ang Lab Animal Inc.
  • test sample or solvents 0.2 ml, i.p.
  • mice mean body weight 25 + 5g
  • Sprague- Dawley rats 235 + lOg, Jung-Ang Lab Animal Inc.
  • test sample or solvents 0.2 ml, i.p.
  • I wder 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. [114] Preparation of injection
  • Injection preparation was prepared by dissolving active component, controlling pH to about 7.5 and then filling all the components in 2 ml ample and sterilizing by conventional injection preparation method.
  • Preparation of liquid 120] Dried powder of Example 1 0.1 ⁇ 80g 121] Sugar 5 ⁇ 10g
  • Liquid preparation was prepared by dissolving active component, filling all the components and sterilizing by conventional liquid preparation method.
  • Preparation of health care food 129] Extract of Example 1 lOOOmg 130] Vitamin mixture optimum amount 131] Vitamin A acetate 70?g 132] Vitamin E l.Omg 133] Vitamin B 0.13mg 134] Vitamin B 0.15mg 2 135] Vitamin B 0.5mg 6 136] Vitamin B 0.2 ?g 12
  • Vitamin C lOmg 138] Biotin 10 ?g 139] Amide nicotinic acid 1.7mg 140] Folic acid 50 ?g 141] Calcium pantothenic acid 0.5mg 142] Mineral mixture optimum amount 143] Ferrous sulfate 1.75mg 144] Zinc ⁇ ride 0.82mg 145] Magnesium carbonate 25.3mg [146] Monopotassium phosphate 15mg
  • 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 1000 ml ample and sterilizing by conventional health beverage preparation method.
  • the crude extract or non-polar solvent soluble extract of Sorbus amurensis KOEHNE show potent relaxing activity of vascular endothelial cell by increasing the synthesis of endothelium-derived NO, therefore, it can be used as the therapeutics or health care food for treating and preventing cerebrovascular disease.

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Abstract

Cette invention se rapporte à une composition comprenant l'extrait brut de Sorbus amurensis KOEHNE, comme principes actifs pour le traitement et la prévention des maladies cérébrovasculaires. Ces extraits ont une puissante action relaxante des cellules endothéliales vasculaires par accroissement de l'endothélium dérivé de la production de NO, ils peuvent par conséquent servir d'agents thérapeutiques ou d'alicament pour traiter et prévenir les maladies cérébrovasculaires.
PCT/KR2004/002316 2004-01-14 2004-09-10 Composition pharmaceutique comprenant l'extrait de sorbus amurensis koehne pour traiter ou prevenir les maladies du systeme cerebrovasculaire WO2005067954A1 (fr)

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KR1020040002641A KR100637263B1 (ko) 2004-01-14 2004-01-14 정공피 추출물을 포함하는 뇌혈관계 질환의 예방 및치료를 위한 약학조성물
KR10-2004-0002641 2004-01-14

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KR20220000069A (ko) * 2020-06-25 2022-01-03 연세대학교 산학협력단 뇌 염증 및 퇴행성 뇌 질환의 예방 또는 치료용 조성물

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