EP2240191A2 - Composition comprising the extracts of lysimachia clethroides for prevention and treatment of cardiovascular diseases - Google Patents
Composition comprising the extracts of lysimachia clethroides for prevention and treatment of cardiovascular diseasesInfo
- Publication number
- EP2240191A2 EP2240191A2 EP08870585A EP08870585A EP2240191A2 EP 2240191 A2 EP2240191 A2 EP 2240191A2 EP 08870585 A EP08870585 A EP 08870585A EP 08870585 A EP08870585 A EP 08870585A EP 2240191 A2 EP2240191 A2 EP 2240191A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- extract
- prevention
- lysimachia clethroides
- treatment
- composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
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Classifications
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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)
-
- A—HUMAN NECESSITIES
- A47—FURNITURE; DOMESTIC ARTICLES OR APPLIANCES; COFFEE MILLS; SPICE MILLS; SUCTION CLEANERS IN GENERAL
- A47K—SANITARY EQUIPMENT NOT OTHERWISE PROVIDED FOR; TOILET ACCESSORIES
- A47K1/00—Wash-stands; Appurtenances therefor
- A47K1/08—Accessories for toilet tables, e.g. glass plates, supports therefor
- A47K1/09—Holders for drinking glasses, tooth brushes, hair brushes, or the like
-
- A—HUMAN NECESSITIES
- A46—BRUSHWARE
- A46B—BRUSHES
- A46B17/00—Accessories for brushes
- A46B17/06—Devices for cleaning brushes after use
- A46B17/065—Sterilising brushes; products integral with the brush for sterilising, e.g. tablets, rinse, disinfectant
-
- A—HUMAN NECESSITIES
- A47—FURNITURE; DOMESTIC ARTICLES OR APPLIANCES; COFFEE MILLS; SPICE MILLS; SUCTION CLEANERS IN GENERAL
- A47K—SANITARY EQUIPMENT NOT OTHERWISE PROVIDED FOR; TOILET ACCESSORIES
- A47K5/00—Holders or dispensers for soap, toothpaste, or the like
- A47K5/18—Holders or dispensers for soap, toothpaste, or the like for both soap and toothpaste or the like; in combination with holders for drinking glasses, toothbrushes, or the like ; Toothpaste dispensers; Dental care centers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
- A61L2/02—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using physical phenomena
- A61L2/08—Radiation
- A61L2/10—Ultra-violet radiation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
Definitions
- the present invention relates to a composition for prevention and treatment of cardiovascular diseases, which comprises an extract of Lysimachia clethroides, and health functional food products. More particularly, the invention is characterized by containing, as an active ingredient, an extract of Lysimachia clethroides which has an effect of treating and preventing cardiovascular diseases by directly inhibiting NAD(P)H oxidases to inhibit oxidative stress, and at the same time, activating en- dothelial-type nitric oxide synthase to thereby regulate the contraction and relaxation of vascular smooth muscle cells.
- NAD(P)H oxidases to inhibit oxidative stress
- activating en- dothelial-type nitric oxide synthase to thereby regulate the contraction and relaxation of vascular smooth muscle cells.
- Endothelial dysfunction is the main mechanism which indvces an extensive range of cardiovascular diseases, including hypertension, arteriosclerosis, hyperlipidemia, diabetes mellitus, obesity and the like (B runner H. et al., J. Hypertens., 2005, 23:233-246), since the discovery of abnormal relaxation of blood vessels in hypertensive patients in 1990 (Panza JA et al., New England Journal of Mededne, 323:22-27 ', 1990).
- Endothelial cells are epithelial cells lining along the cavities of blood vessels and lymph vessels, and their main function is to prodvce vasodilators and vasodilator mediators to regulate the vascular tone as well as the structure.
- a cardiovascular disease is a disease starting in the form of initial endothelial dysfunction and finally resulting in abnormality in the heart and vascular system.
- the name is a generic term for a group of abnormalities in the heart and blood vessels, including, but not limited to, arteriosclerosis, hypertension, hyperlipidemia, coronary artery diseases (heart attack), cerebrovascular diseases (stroke, dementia), peripheral vascular diseases, arrhythmia, cardiac failure, congestive heart diseases, myocardial diseases, and the like.
- ROS reactive oxygen species
- eNOS endothelial-type nitric oxide synthase
- Nitric oxide which is produced by endothelia-type nitric oxide synthase, is a potent vasorelaxant factor, and also plays a critical role in the overall homeostatic regulation of the cardiovascular system by inhibiting platelet aggregation, proliferation of vascular muscle cells, vascular adhesion of monocytes, and expression of arteriosclerosis-associated proteins (Ibrstermann et al., Circulation, 113:1708-1714, 2005).
- vascular smooth muscle cells vascular smooth muscle cells
- VSMC vascular smooth muscle cells
- regulation of lipoproteins having oxidizing power, and the like to thereby cause cardiovascular diseases [Lynch and Frei, J. Lipid Res., 34:1745-1753, 1993].
- NAD(P)H oxidases the increased generation of active oxygen species in the blood vessels due to NAD(P)H oxidases, is associated with the impaired function of endothelial nitric oxide (NO) in patients having clinical risk factors for atherosclerosis and coronary artery diseases.
- NO endothelial nitric oxide
- Lysimachia clethroides is a perennial plant of family Primulaceae and is a herbaceous perennial commonly growing in the sun. It grows to a height of 50 to 100 cm, and grows in the wild state over the whole land of Korea as well as in Japan, Manchuria and China. It is also known as gooseneck loosestrife, and is known to treat irregular menstruation and leucorrhea in women, infant weight loss, hydrops, dysentery, bruises, pain in the posterior ear, and the like. In private practices, the plant has been long used in the treatment of irregular menstruation, dysentery and bruises.
- NAD(P)H oxidase activity and vasorelaxant effect with a number of plant extracts, and finally confirmed the effects of potent inhibition of the activity of NAD(P)H oxidases, reduction of vascular oxidative stress, direct enhancement of the activity of endothelial-type nitric oxide synthase, relaxation of blood vessels and regulation of blood pressure, thus completing the present invention.
- the present invention was designed based on such discoveries as described above, and an object of the invention is to provide a composition for prevention and treatment of a cardiovascular disease, comprising an extract of Lysimachia clethroides as an active ingredient.
- Another object of the present invention is to provide a health functional food product for prevention of a cardiovascular disease, comprising an extract of Lysimachia clethroides as an active ingredient.
- composition for prevention and treatment of a cardiovascular disease of the present invention is characterized by containing an extract of Lysimachia clethroides as an active ingredient.
- the extract of Lysimachia clethroides is preferably extracted by using the leaves or the whole plant.
- the extract of Lysimachia clethroides is preferably extracted with a solvent selected from the group of water, a C -C lower alcohol, and a mixture thereof.
- the C -C lower alcohol is preferably methanol, ethanol or butanol.
- the extract of Lysimachia clethroides is preferably extracted with a 30 to 95 wt% aqueous solution of ethanol.
- the extract of Lysimachia clethroides be extracted with a solvent selected from the group of water, a C -C lower alcohol and a mixture thereof, and the extract be re-extracted with butanol.
- the extract of Lysimachia clethroides be extracted with a solvent selected from the group consisting of water, a C -C lower alcohol and a mixture thereof, and concentrated to obtain a crude extract, and the crude extract be suspended in water, and re-extracted with hexane, ethyl acetate and butanol in this order.
- the crude extract of Lysimachia clethroides is preferably obtained at 30 to 95 0 C.
- the crude extract and water be mixed and suspended at a volume ratio of 1:5 to 25
- hexane, ethyl acetate or butanol and the suspension be mixed and extracted at a volume ratio of 1:0.1 to 2.0.
- the butanol is preferably n-butanol.
- the extract of Lysimachia clethroides is characterized by having an NAD(P)H oxidase inhibitory activity.
- the extract of Lysimachia clethroides is characterized by having a vasorelaxant effect.
- the extract of Lysimachia clethroides is characterized by an effect of enhancing the activity of endothelial-type nitric oxide synthase.
- the extract of Lysimachia clethroides is characterized by having effects of decreasing the blood pressure and reducing the vascular oxidative stress.
- the cardiovascular disease may be selected from the group consisting of congestive heart diseases, coronary artery diseases (heart attack), ischemic heart diseases (myocardial ischemia), hyperlipidemia, arteriosclerosis, hypertension, hypotension, arrhythmia, cardiac failure, vascular restenosis, cerebrovascular diseases (stroke, dementia), peripheral vascular diseases and metabolic diseases.
- the health functional food product for prevention of a cardiovascular disease of the present invention is characterized by containing an extract of Lysimachia clethroides as an active ingredient.
- the extract of Lysimachia clethroides of the present invention strongly inhibits the activity of NAD(P)H oxidases and exhibits a vasorelaxant effect at the same time, and thus can be usefully utilized as a pharmaceutical composition or health functional food product for prevention and treatment of a cardiovascular disease.
- Hg. 1 is a diagram showing the measurement of the vasorelaxant activity of an extract of Lysimachia clethroides on swine coronary arteries.
- Hg. 2 is a diagram showing the measurement of the vasorelaxant activity of an extract of Lysimachia clethroides on the aorta of a white rat.
- Hg. 3 is a diagram showing the measurement of the degree of activity of endothelial- type nitric oxide synthase (eNOS) and Akt protein under the action of an extract of Lysimachia clethroides.
- eNOS endothelial- type nitric oxide synthase
- Akt protein under the action of an extract of Lysimachia clethroides.
- Hg. 4 is a diagram showing the measurement of the degree of influence of an extract of Lysimachia clethroides on the heart rate.
- Hg. 5 is a diagram showing the measurement of the degree of decrease in vascular oxidative stress under the action of an extract of Lysimachia clethroides.
- Hg. 6 is a diagram showing the measurement of the degree of cytotoxicity of an extract of Lysimachia clethroides. Best Mode for Carrying out the Invention
- the extract of Lysimachia clethroides of the present invention can be obtained as follows.
- the whole plant, including roots and the aerial part, of Lysimachia clethroides can be used without limitation, in the form of plants collected from nature, cultivated plants, commercially available plants, or the like.
- the solvent for extraction is selected from the group consisting of water, a C -C lower alcohol, and a mixture thereof.
- the inventors of the present invention washed the twigs and leaves of Lysimachia clethroides to remove impurities and salts, and dried them.
- a polar solvent such as water or a C -C lower alcohol such as methanol, ethanol or butanol, or a mixed solvent of these at a mixing ratio of about 1:0.1 to 1:10, preferably with a 30 to 95 wt% aqueous solution of ethanol, in a volume reaching about 5- to 50-fold, and preferably 10- to 30-fold, the weight of the Lys imachia clethroides sample, at 50 to 95 0 C for 1 hour to 7 days.
- the above-described extraction process is repeated two or five times, and then the resultant is subjected to concentration under reduced pressure and/or freeze-drying, to obtain a crude extract of Lysimachia clethroides.
- a non-polar solvent- soluble extract can be obtained by suspending the aforementioned crude extract in distilled water, subsequently adding a non-polar solvent sirh as hexane, ethyl acetate or chloroform in a volume of about 0.1 to 100 times, and preferably about 1 to 5 times, the volume of the suspension, and performing extraction and isolation once to 10 times, and preferably two to five times.
- a non-polar solvent sirh as hexane, ethyl acetate or chloroform
- conventional fractionation processes can also be additionally carried out (Harborne, J.B., Phytochemical methods: A guide to modern techniques of plant analysis, 3 r Ed., pp. 6-7, 1998).
- the crude extract of Lysimachia clethroides obtained by the above- described processes preferably an extract of Lysimachia clethroides in an aqueous solution of ethanol
- organic solvents such as n-butanol, hexane and ethyl acetate, in order from less polar solvent to more polar solvent, preferably in order of hexane, ethyl acetate and n-butanol, and to concentration under reduced pressure, and thus hexane, ethyl acetate and n-butanol fractions of Lysimachia clethroides can be obtained.
- organic solvents such as n-butanol, hexane and ethyl acetate
- the present invention provides a composition for prevention and treatment of a cardiovascular disease, which comprises the crude extract or non-polar solvent-soluble extract of Lysimachia clethroides obtained by the above-described production method, as an active ingredient.
- composition for prevention and treatment of a cardiovascular disease according to the present invention contains 0.1 to 99% by weight of the aforementioned extract based on the total weight of the composition.
- composition containing the extract of Lysimachia clethroides of the present invention may further contain appropriate carriers, excipients and diluents that are conventionally used in the production of compositions.
- the pharmaceutical dosage form of the extract of the present invention can be used in the form of pharmaceutically acceptable salts thereof, and also can be used alone, or in the form of conjugate as well as appropriate assembly with other pharmaceutically active compounds.
- the pharmaceutical composition containing the extract according to the present invention can be used after being formulated into oral formulations svch as powders, granules, tablets, capsules, suspensions, emulsions, syrups and aerosols, and into topical formulations, suppositories and sterile injectable solutions, respectively according to conventional methods.
- excipients and diluents that can be contained in the composition containing the extract, there may be mentioned lactose, dextrose, svcrose, sorbitol, mannitol, xylytol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, non-crystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, tal ⁇ magnesium stearate, and mineral oil.
- preparations are prepared using conventionally used diluents or excipients, such as fillers, bulking agents, binding agents, wetting agents, disintegrants and surfactants.
- diluents or excipients such as fillers, bulking agents, binding agents, wetting agents, disintegrants and surfactants.
- solid preparations for oral administration include tablets, pills, powders, granules, capsules and the like, and these solid preparations are prepared by mixing at least one exdpient, for example, starch, calcium carbonate, sucrose or lactose, gelatin and the like to the aforementioned extract. Furthermore, in addition to simple excipients, lubricants such as magnesium stearate and talc are also used.
- liquid preparations for oral administration include suspensions, liquids for internal use, emulsions, syrups and the like. These liquid preparations may include various exdpients, for example, wetting agents, sweeteners, fragrances, preservatives and the like, in addition to water and liquid paraffins, which are frequently used simple diluents.
- preparations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories.
- non-aqueous solvents or suspending agents propylene glycol, polyethylene glycol, plant oils such as olive oil, injectable esters such as ethyl oleate, and the like can be used.
- base of the suppositories witepsol, Macrogol, Tween, cacao butter, laurin fat, glycerogelatin and the like can be used.
- a preferable amount of administration of the extract of the present invention may vary with the condition and weight of the patient, severity of the disease, form of drug, the route and period of administration, but can be appropriately selected by a person having ordinary skill in the art. However, for preferable effects, it is desirable to administer the extract of the present invention in an amount of 0.0001 to 100 mg/kg, and preferably 0.001 to 100 mg/kg, per day. Administration may be carried out once a day, or may be carried out several times a day. The amount of administration is not intended to limit the scope of the invention by any means.
- the present invention provides a health functional food product containing the aforementioned extract showing an effect of preventing a cardiovascular disease, and sito- logically acceptable food additives.
- Lysimachia clethroides for example, there may be mentioned various general food products, beverages, chewing gums, tea, vitamin complexes, and the like.
- the extract of Lysimachia clethroides can also be added to foods or beverages for the purpose of obtaining an effect of preventing a cardiovascular disease.
- the amount of the extract in a food product or beverage may be 0.01 to 15% by weight based on the total weight of the food.
- the amount of the extract in a health beverage composition may be 0.02 to 5 g, and preferably 0.3 to 1 g, relative to 100 g of the total weight of the beverage.
- the health functional beverage composition of the present invention is not particularly limited in containing other components, in addition to containing the extract as an essential component at the indicated proportions, and can contain additional components such as various flavoring agents or natural carbohydrates, as conventional beverages do.
- natural carbohydrates include conventional saccharides, such as monosaccharides, for example, glucose, fructose and the like; disaccharides, for example, maltose, sirrose and the like; and polysaccharides, for example, dextrin, cyclodextrin and the like, and sugar alcohols such as xylytol, sorbitol and erythritol.
- flavoring agents in addition to the aforementioned agents, thaumatin, stevia extracts, for example, levaudioside A, glycyrrhizin and the like; and synthetic flavoring agents, for example, saccharin, aspartame and the like can be advantageously used.
- the proportion of the natural carbohydrates is generally about 1 to 20 g, and preferably about 5 to 12 g, per 100 g of the composition of the present invention.
- the extract of the present invention may contain various nutrients, vitamins, minerals (electrolytes), synthetic and natural flavoring agents, colorants and weighting agents (cheese, chooolate and the like), pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH adjusting agents, stabilizers, antiseptics, glycerin, alcohols, carbonating agents used in carbonated drinks, and the like.
- the extracts of the present invention may contain natural fruit juices, and fruit fleshes for the production of fruit juice beverages and vegetable beverages. These components can be used individually or in combinations. In this case, the proportion of the additives is not critical, but is generally selected from the range of 0.01 to about 20 parts by weight per 100 parts by weight of the extract of the present invention.
- Lysimachia clethroides collected in Kangwon-do province was washed with water to remove impurities, and then were dried and crushed.
- an extraction vessel 25 g of Lysimachia clethroides, and 500 ml in total of a 70 wt% aqueous solution of ethanol were added, and thermal extraction was repeatedly performed three times at 7O 0 C, each time taking 3 hours, under reflux cooling.
- the resultant was filtered through a filter paper, and the filtrate was concentrated under reduced pressure in a water bath at 4O 0 C, and was freeze-dried. As a result, 53 g of a crude extract of Lysimachia clethroides was obtained.
- Test Example 1 Measurement of inhibitory effect of extracts of Lysimachia clethroides on NAD(P)H oxidase activity
- Example 2 as described above were subjected to the measurement of an effect of inhibiting the activity of NAD(P)H oxidases, which are index enzymes for the development of cardiovascular diseases.
- NAD(P)H oxidases which are index enzymes for the development of cardiovascular diseases.
- the arterial smooth muscle cells of white rat Raat aortic smooth muscle cells; RASMC
- the vascular endothelial cells of calf Bovine aortic endothelial cells; BAECs
- the arterial smooth muscle cells and the vascular endothelial cells were respectively mixed with MEM (minimum essential medium), DMEM (Dubleco's minimum essential medium) and a 10% FBS (fetal bovine serum) solution, and the cells were respectively incubated on a 96-well plate for 24 hours under the conditions of 5% CO /37 0 C. Then, the cells were incubated again for 24 hours in the culture
- the IC50 value is the concentration, expressed in ⁇ g/ml, of a test material, at which 50% of the NADPH oxidase activity is inhibited.
- Test Example 2 Measurement of vasorelaxant effect of extracts of Lysimachia clethroides (coronary arteries and aorta)
- the aorta was extracted from a male SD (Sparague-Dawley) white rat, was immersed in the Krebs solution (pH 7.4) containing 18 mM NaCl, 47 mM KCl, LI mM MgSO , 1.2 mM KH PO , 1.5 mM CaCl , 25 mM
- the ED50 value refers to the concentration ( ⁇ g/ml) of the sample at which the contracted blood vessels show 50% vasorelaxation as a result of the treatment with the sample.
- the extracts of Lysimachia clethroides of the present invention started significant relaxation from the concentration of 1 to 10 ⁇ g/ml, and reached 96+2% relaxation at the concentration of 30 ⁇ g/ml.
- Table 2 and Table 3 it can be seen that the extracts of Lysimachia clethroides are excellent in the extent of relaxing the blood vessels of the coronary arteries and the aorta.
- the n-butanol extract shows excellent effects.
- Test Example 3 Test with extracts of Lysimachia clethroides on endothelial-type nitric oxide synthase activity
- vascular endothelial cells were mixed with DMEM (Dubleco's minimum essential medium) and a 10% EBS (Fetal bovine serum) solution and incubated, and then the cells were incubated again for 24 hours in the culture solution with FBS excluded. After the cells were stabilized, the cells were treated with the samples at the respective concentrations, and then were allowed to react for 30 minutes. Then, the proteins were extracted and centrifuged, and the supernatant was collected to remove debris of the cells. The extracted proteins were subjected to electrophoresis on SDS- polyacrylamide gel, and then the proteins in the gel were blotted with a nitrocellulose membrane.
- DMEM Dubleco's minimum essential medium
- EBS Fetal bovine serum
- Test Example 4 Test of effects of extracts of Lysimachia clethroides in animal model of cardiovascular disease
- the rats were acclimatized for one week while freely supplying solid feedstuff and water in a small animal breeding chamber which was regulated to have a light- dark period of 12 hours. Then, the rats were arbitrarily grouped into a control group and an angiotensin 2-treated group, with each group including 6 animals. From three days before the treatment with angiotensin 2, the extracts of Lysimachia clethroides obtained in Example 2 were respectively suspended in 0.5% CMC (carboxymethylcellulose) at a concentration of 100 mg/kg, and the suspensions were orally administered twice a day. The control group was administered with 0.5% CMC only.
- CMC carboxymethylcellulose
- Angiotensin 2 was dissolved in physiological saline at a concentration of 65 ng/ min/kg, and the solution was placed in a mini-osmotic pump (Alzet Model 2002). The white rats were anesthetized, and the angiotensin 2 treatment was carried out by cutting the skin open, and inserting the mini-pump in the interscapular region. The blood pressure measurement was conducted simultaneously with the initiation of oral administration, and further measurements were made once in two days for 2 weeks, one hour after the oral administration in the morning.
- the specimen was heated in advance for about 10 minutes at 45 to 5O 0 C, and then the maximum blood pressure (systolic pressure) of the tail artery was measured in a non-invasive manner by the tail- cuff plethysmography method using an automated blood pressure recording system.
- the heart rate was also measured at the same time.
- the aorta was extracted in the same manner as in Test Example 2, and the degree of staining by DHE (dihydroetidium) and the degree of relaxation by acetylcholine were characterized to measure the extents of vascular oxidative stress and vascular endothelial dysfunction. The results were compared with the results of the control group.
- Hg. 5 is a product of black-and-white modification of a photograph which indicates the object in red and the background in black, and at the time of modification, the background was rendered white for clear distinction of the object).
- Test Example 5 Test on cytotoxicity of extracts of Lysimachia clethroides
- MEM minimum essential medium
- FBS fetal bovine serum
- Example 2 were treated with the extracts of Lysimachia clethroides obtained in the Example 2, shaken, and allowed to react for 24 hours. Thereafter, the cells were incubated for one hour in the presence of an MTS solution (CellTiter 96 Aqueous One Solution,
- Preparation Example 2 Production of tablet preparation [102] Powdered extract of Lysimachia clethroides 10 mg [103] Corn starch 100 mg [IW] Lactose 100 mg [105] Magnesium stearate 2 mg [105] The components were mixed and then tableted a ⁇ cording to a conventional tablet production method, and thereby a tablet preparation was produced. [107] Preparation Example 3: Production of capsule preparation [108] Powdered extract of Lysimachia clethroides 10 mg [109] Crystalline cellulose 3 mg [110] Lactose 148 mg [111] Magnesium stearate 2 mg
- an injectable preparation was produced at the aforementioned component contents per ampoule (2 ml).
- Vitamin E (powdered) 100 g
Abstract
Description
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PCT/KR2008/007485 WO2009091121A2 (en) | 2008-01-18 | 2008-12-17 | Composition comprising the extracts of lysimachia clethroides for prevention and treatment of cardiovascular diseases |
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KR101168566B1 (en) | 2010-05-20 | 2012-07-27 | 재단법인 제주테크노파크 | Compostion and Method for Controling Plant Disease Occurred by Magnaporthe grisea |
KR102014824B1 (en) | 2018-05-09 | 2019-08-28 | 주식회사 진생바이팜 | Health food composition for vascular relaxation and anti-thrombotic effects comprising Black Ginseng Radix, Salviae Miltiorrhizae Radix, Leonuri Herba and Cnidii Rhizoma |
CN110403199A (en) * | 2018-08-07 | 2019-11-05 | 湖南炎帝生物工程有限公司 | Nostoc composition and its application in adjusting blood glucose, treatment diabetes |
WO2023128540A1 (en) * | 2021-12-31 | 2023-07-06 | 한국 한의학 연구원 | Composition for preventing, ameliorating, or treating metabolic diseases, containing extract of lysimachia mauritiana as active ingredient |
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CN1278737C (en) * | 2003-12-17 | 2006-10-11 | 昆明紫健生物技术有限公司 | Compound medicinal formulation with bioactivity |
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Title |
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DATABASE TCM [Online] SIPO; 11 October 2000 (2000-10-11), SONG DONGLIANG: XP002617545, Database accession no. CN1269402 & CN 1 269 402 A (SONG DONGLIANG [CN]) 11 October 2000 (2000-10-11) * |
DATABASE TCM [Online] SIPO; 22 June 2005 (2005-06-22), Kunming Zijian Biotechnology Co. Ltd: XP002617544, Database accession no. CN1628845 & CN 1 628 845 A (KUNMING ZIJIAN BIOTECHNOLOGY C [CN]) 22 June 2005 (2005-06-22) * |
DATABASE WPI Week 200559 Thomson Scientific, London, GB; AN 2005-579271 XP002617551, & KR 2005 023 191 A (UNIV HALLYM) 9 March 2005 (2005-03-09) * |
DATABASE WPI Week 200868 Thomson Scientific, London, GB; AN 2008-L53980 XP002617543, & CN 101 199 563 A (UNIV SUZHOU) 18 June 2008 (2008-06-18) * |
See also references of WO2009091121A2 * |
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CN101969969A (en) | 2011-02-09 |
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WO2009091121A2 (en) | 2009-07-23 |
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