VASODILATING COMPOSITION

Abstract: The present invention relates to a vasodilating composition comprising ginsenoside Rg3 and/or Rg5, one of the saponin components of ginseng, as an active ingredient. Since ginsenoside Rg3 and Rg5, the active ingredient of the composition according to the present invention, exhibit an endothelium-dependent vasodilation and do not destroy endothelium cells contrary to the ordinary saponins, they can be used safely without any side effect such as hemolysis or toxicity against fishes. Ginsenoside Rg3 and Rg5 are hardly contained in ginseng plants such as fresh ginseng, white ginseng, etc., and contained in a minor amount in red ginseng. The contents of ginsenoside Rg3 and Rg5 are increased greatly by heating ginseng plant for 0.5 to 20 hours at a high temperature of 110 to 180 DEG C.

Description: VASODILATING COMPOSITION TECHNICAL FIELD The present invention relates to a vasodilating compo¬ sition comprising a specific effective component of gin¬ seng as an active ingredient. More specifically, the present invention relates to a vasodilating composition comprising ginsenoside Rg 3 and/or Rg 5 , one of the saponin components of ginseng, as an active ingredient. BACKGROUND ART Since ancient times, ginseng has been widely used as the most typical nutritive and tonics. Recently, many scientific results on the components and pharmacological effects of ginseng have been reported, thereby the myste¬ rious pharmacological effects of ginseng have been come to light under modern science. Ginseng has been generally used in the form of fresh ginseng as it is harvested after cultivation, white gin¬ seng produced by drying the fresh ginseng at normal tem¬ perature, or red ginseng prepared by heating the fresh ginseng at 98 to 100°C. Among them, particularly, the red ginseng has been recognized as having much more potent pharmacological effect than white ginseng. Accordingly, recently many researches on the specific components in red ginseng have been actively conducted. It has been con¬ sidered that the specific components are produced during the process for preparing red ginseng and can explain the excellent pharmacological effect of red ginseng. DISCLOSURE OF INVENTION Thus, the present inventors have made a study of the means capable of enhancing the pharmacological effect of ginseng by increasing the specific components in red ginseng. As a result of such study, we have identified that a processed ginseng having a much more enhanced pharmacological effect than fresh ginseng, white ginseng or red ginseng can be prepared by heating ginseng for 0.5 to 20 hours at a high temperature of 110 to 180°C. In the course of separating the various components present in such a processed ginseng and determining the pharmacologi¬ cal effects thereof, the present inventors have also identified that ginsenoside Rg.-. and Rg 5 which are not contained or contained in a minor amount in white ginseng or red ginseng and of which the pharmacological effect has been substantially not known, exhibit an excellent vasodi¬ lation effect. Thus, we have completed the present invention. Therefore, the present invention relates to a vasodi¬ lating composition comprising ginsenoside Rg 3 and/or Rg 5 as an active ingredient. BRIEF DESCRIPTION OF DRAWINGS For a thorough understanding of the nature and objects of the invention, reference should be made to the follow¬ ing detailed description taken in connection with the accompanying drawings in which : Figure 1 represents a vasodilation of ginsenoside Rg 3 which is administered alone in the presence of endothelium (-©-) in comparison with vasodilations when ginsenoside Rg 3 is administered after removing endotheliu (- O -) ; and administered with 10 _6 M of methylene blue (MB) (-Δ-) and with 10 ~6 M of nitro-L-arginine (NLA) (- ▲ -) in the presence of endothelium; Figure 2 represents vasodilation effects when the processed panaxadiol-based saponin fraction prepared in Example 7 is administered in the presence of endothelium (- φ -) and after removing endothelium(- O -) ; Figure 3 represents survival ratio of HUVEC cells when the cells are cultured with dimethylsulfoxide (DMSO) (- O -) and with ginsenoside Rg 3 -DMS0 solution (- ▼ -) , as an index of the cytotoxicities to HUVEC cell of ginseno- side Rg 3 and DMSO used as a solvent; Figure 4 represents a vasodilation of ginsenoside Rg^ which is administered alone in the presence of endothelium (- O ") i comparison with vasodilations when ginsenoside Rg ς is administered after removing endothelium(- ■ -) ; and administered with 10 M of methylene blue (MB) (- ▼-) and with 10 ~ °M of nitro-L-arginine (NLA) (- Δ -) in the presence of endothelium; and Figure 5 represents survival ratio of HUVEC cells when the cells are cultured with distilled water (- 0-) and with ginsenoside Rg^-distilled water solution (- 0 -) , as an index of the cytotoxicities to HUVEC cell of ginse¬ noside Rg 5 and distilled water used as a solvent; BEST MODE FOR CARRYING OUT THE INVENTION The ginsenoside Rg 3 and Rg 5 used as active ingredients in the composition according to the present invention are saponin compounds having the following formulas. In the present invention, pure ginsenoside Rg 3 and/or Rg 5 , proc¬ essed ginseng rich in ginsenoside Rg 3 and/or Rg 5 compo¬ nents or an extract therefrom can be used as the source of ginsenoside Rg 3 and Rg 5 . When the processed ginseng extract containing Rg 3 and/or Rg 5 is used as an active ingredient in the composi- tion according to the present invention, it is preferable that the content of Rg 3 and/or Rg^ in the extract is at least 10% (w/w) . The reason is that when the content of Rg 3 and/or Rg 5 in the extract is less than 10%, too much amount of ginseng extract should be used to provide the desired vasodilation effect sufficiently. The pure ginsenoside Rg 3 and/or Rg 5 , or ginseng ex- tract rich in ginsenoside Rg 3 and/or Rgr- to be used in the composition of the present invention can be obtained from the processed ginseng prepared by heating ginseng or its leaves at a high temperature, or from the acid hydrolysate of qinseng extract. Ginseng extract rich in ginsenoside Rg 3 and/or Rg 5 can be obtained by the method wherein plant of Panax genus containing ginseng saponins, for example, Panax ginseng, Panax no toginseng, Panax quinquefolium, Panax japonicus , etc., leaves or tissue cultures thereof, or extract there¬ from with water or lower alcohol are heated for 0.5 to 20 hours at a temperature of 110 to 180°C; the processed ginseng thus obtained is extracted with water or a suit- able organic solvent such as methanol, ethanol, or a solvent mixture thereof, the extract is concentrated under reduced pressure, the residue is suspended in water, and then the suspension is extracted again with a nonpolar organic solvent such as hexane, ether, dichloromethane, chloroform, ethylacetate or a solvent mixture thereof; the remaining aqueous layer is extracted again with a polar organic solvent such as butanol and then the extract is subjected to chromatography to obtain a fraction contain¬ ing Rg 3 or g5» or a fraction containing Rg 3 and Rg 5 simultaneously. By repeatedly carrying out the chromatog¬ raphy procedure, the content of ginsenoside Rg 3 or Rg^ can be more increased. Then, the fraction having a high content can be crystallized from a suitable solvent system such as water, lower alcohol, lower ketone, chloroform or a solvent mixture thereof to obtain pure ginsenoside Rg 3 or Rg r - . In this method, during the procedure of heat- treatment of ginseng, a sugar moiety attached to the 20th carbon of panaxadiol saponins present in ginseng such as ginsenosides Ra, Rb-^, Rb 2 , Rc, Rd, etc. is removed to produce the desired ginsenoside Rg , and a double bond can be subsequently produced at the 20-position of Rg 3 by dehydration reaction to produce the desired ginsenoside Rg 5 . Alternatively, the same results can be obtained in this process by inverting the order of the heat-treatment step and extraction step with organic solvent, or by heating ginseng under mild conditions, for example at 30 to 100°C, preferably at 70°C, simultaneously with carrying out acid-treatment with diluted inorganic acid such as hydrochloric acid, nitric acid, perchloric acid, etc., or lower organic acid such as acetic acid, tartaric acid, oxalic acid, etc., instead of heating at a high tempera- ture, if necessary. In addition, the same result can be obtained by di¬ rectly heating or acid-hydrolyzing the known ginsenoside compounds Ra, Rb-, , Rb 2 , Rc, Rd, etc., or a fraction there- of, instead of ginseng itself, according to the same manner as mentioned above. In preparing ginseng extract containing Rg 3 and/or Rg 5 , a fraction containing panaxadiol saponin component in a high concentration, which is prepared by extracting ginseng with an organic solvent, for example, alcohols such as methanol, ethanol, butanol, etc. , ethers, or a solvent mixture thereof before heat-treatment to remove the undesired panaxatriol saponin components, can be subjected to heat-treatment according to the same manner as mentioned above to obtain a processed panaxadiol sapo¬ nin fraction which contains Rg 3 and/or Rg^ in large quan¬ tities and does not contain the undesired panaxatriol saponin component . The fraction thus obtained can be used as the processed ginseng extract containing Rg 3 and/or Rgr- according to the present invention. Since the composition containing ginsenoside Rg 3 and/or Rgr- as an active ingredient according to the present invention has a potent vasodilation effect, it can be effectively used as an agent for prevention or treat¬ ment of disorders caused by circulatory disturbances such as hypertension , arteriosclerosis , blood circulat ion disturbance , diabetes mellitus, sexual disturbance , memory disturbance , etc . When the composition of the present invention is used for such purposes in the clinical field, it can be combined with pharmaceutically acceptable carri¬ ers to prepare various formulations conventionally used in the pharmaceutical f ield, for example , oral preparations such as tablets , capsules , troches , solut ions , suspen¬ sions , etc . ; inj ectable preparations in the form of in- j ectable solutions or suspensions or ready-to-use inj ect¬ able dried powder which can be re-constituted with inject ¬ able dist i l led water j ust before inj ection , etc . ; or locally applicable preparations such as ointments, creams , solutions , etc . The carriers which can be used in the composition of the present invention are conventional ones in the pharma¬ ceutical field, for example, binders, lubricants, disinte¬ grating agents, excipients, solubilizers, dispersing agents, stabilizers, suspending agents, coloring agents, flavors and the like in the case of oral prepara ions; preservatives, agents for painlessness, solubilizers, stabilizers and the like in the case of injectable prepa¬ rations; bases, excipients, lubricants, preservatives and the like in the case of locally applicable preparations. The pharmaceutical agents thus produced can be adminis¬ tered orally, or parenterally such as for example intrave¬ nously, peritoneally, subcutaneously, or can be topically applied. In addition, the oral preparations may be administered together with an antacid or in the form of an enteric-coated preparation which is formulated by covering the orally administrable solid preparation such as tablet with the enteric coatings, in order to prevent decomposi¬ tion of the preparation by gastric acid when it is admin- istered per orally. Although the administration dosage to a human being of the ginsenoside Rg 3 and/or Rg 5 according to the present invention can be selected depending on the absorption, inactivating rate and excretion rate of the active compo¬ nent in the body, age, sex and condition of the subject patient, severity of the disorders to be treated and the like, it is generally administered to an adult in an amount of 5 to 500mg, preferably 10 to 200mg, daily. Therefore, when the composition of the present invention is formulated into the dosage unit form, each of the dosage unit form can contain ginsenoside Rg 3 and/or Rg 5 in an amount of 5 to 500mg, preferably 10 to 200mg consider¬ ing the effective amount range as mentioned above. If necessary, the dosage unit form thus formulated can be administered using a specialized method according to the judgement of the specialist who arranges or observes the administration and the requirement of the individuals. The total daily dosage can also be divided into several portions and administered over several times, preferably 1 to 6 times. As established by the test results as described below, since ginsenoside Rg 3 and Rg 5 , the active ingredients of the composition according to the present invention, exhib¬ it a vasodilation without any damage to vascular endothe- lium, they show no side effect such as hemolysis or toxic¬ ity against fishes and no acute toxicity against test animals, therefore they can be used safely. The present invention is more specifically explained by the following examples, test examples and composition examples. However, it should be understood that the present invention is not limited to those examples in any manner. EXAMPLE 1 : Preparation of ginseng extract containing ginsenoside Rg 3 lOOg of fresh ginseng was introduced into a sealed container and then heated for 2 hours at 130°C. The obtained processed ginseng was extracted with 200ml of methanol to obtain the methanol extract and then methanol was removed from the extract by evaporation. The residue was suspended in 100ml of water, extracted 3 times with 100ml of ether, and then the remaining aqueous layer was extracted 3 times with 100ml of butanol saturated with water to obtain the butanol extract containing saponins. This butanol extract was dried and then subjected to silica gel column chromatography(eluen ; ethyl acetate/ methanol/water = 20:1:1) to obtain 1.5g of the fraction containing 60% of the desired ginsenoside Rg 3 . EXAMPLE 2 : Preparation of ginseng extract containing ginsenoside Rgr l.Og of a fraction containing 50% of the desired ginsenoside R ^ was obtained according to the same proce¬ dure as Example 1. EXAMPLE 3 : Preparation of ginseng extract containing ginsenoside Rg-, lkg of dried root-hair ginseng was extracted with 2L of methanol for 4 hours under reflux and then filtered. The ginseng extract thus obtained was dried under reduced pressure. The resulting ginseng extract in the form of a syrup was introduced into an autoclave and then heated for 4 hours at 120°C. The heat-treated ginseng extract was subjected to silica gel column chromatography according to the same method as Example 1 to obtain 20g of the fraction containing 65% of the desired ginsenoside Rg . EXAMPLE 4 : Preparation of ginseng extract containing ginsenoside Rgr lOg of a fraction containing 60% of the desired ginse- noside Rg,- was obtained according to the same procedure as Example 3. EXAMPLE 5 : Preparation of ginseng extract containing ginsenoside Rg 3 lkg of white ginseng was extracted with 2L of methanol for 4 hours under reflux and then filtered. The ginseng extract thus obtained was dried under reduced pressure. The resulting ginseng extract in the form of a syrup was treated with an acid according to the known method(see: Yakhak Hoeji, Vol. 35(5) , pp 432-437, 1991) . Specifical¬ ly, the ginseng extract was dissolved in IL of a solvent mixture of water and acetic acid (1:1) and heated for 2 hours at 70°C while stirring. Then, the solvent was removed to obtain the acid-treated ginseng extract, which is subjected to silica gel column chromatography according to the same manner as Example 1 to obtain 20g of the fraction containing 72% of the desired ginsenoside Rg 3 . EXAMPLE 6 : Preparation of ginseng extract containing ginsenoside R r- lOg of a fraction containing 60% of the desired ginse¬ noside Rg^ was obtained according to the same procedure as Example 5. EXAMPLE 7 : Preparation of processed panaxadiol saponin fraction lkg of ginseng was extracted with 200ml of methanol to obtain the methanol extract and then methanol was removed from the extract by evaporation. The residue was sus- pended in 100ml of water and extracted 3 times with 100ml of ether . The remaining aqueous layer was extracted 3 t ime s wi th a s o lvent mixture o f e thy l ac e t a t e and butanol (10 : 1 ) and the remaining aqueous layer was extract - ed again 3 t imes with 100ml of butanol to obta in the panaxadiol saponin f raction . This panaxadiol saponin fraction was heat - treated for 3 hours at 130 °C according to the same manner as Example 1 to obtain about 40g of the processed panaxadiol saponin fraction . Example 8 : Preparation of ginsenoside q 3 lg of the fraction containing ginsenoside Rg 3 prepared in Example 3 above was repeatedly subjected to silica gel column chromatography according to the same manner as Example 1 using the solvent mixture of ethyl acetate/methanol/water (20 : 1 : 1) as an eluent to obtain 500mg of the fraction containing 92% of the desired ginse¬ noside Rg 3 . The fraction containing ginsenoside Rg 3 thus obtained was recrystallized from the solvent mixture of methanol and ethylacetate to obtain about 400mg of the desired ginsenoside Rg 3 . The ginsenoside Rg 3 thus obtained represents 1 J 3C-NMR spectrum and mass εpectrum which coincide with the data known from literature (see : Yakugaku Zasshi, 103(6) , pp 612-622, 1983) . That is, Rg 3 shows a specific peak in CNMR spectrum when about lOmg of ginsenoside Rg 3 thus obtained is dissolved in 600μl of pyridine-d^ (99.5%) and then subjected to CNMR spectroscopy. In addition, a molecular ion peak of 785 ( [M+H] + ) or 807 ( [M+Na] + ) is represented in the mass spectrum(FAB+) of ginsenoside Rg 3 • Example 9 : Preparation of ginsenoside Rg^ 200mg of a fraction containing about 90% of ginseno¬ side Rg 5 was obtained according to the same procedure as Example 8 from lg of the fraction containing Rg 5 prepared in Example 4 above. Then, the fraction thus obtained was recrystallized from a solvent mixture of methanol and ethyl acetate to produce about 150mg of the desired ginse- noside Rg 5 . The ginsenoside Rg 5 thus obtained represents the following characteristics. MS(FAB+, m/z) : 789 ( [M+Na] + ) , 805([M+K] + ) 13 C-NMR (ppm, pyridine-d 5 ) : δ 13.0, 16.0, 16.5, 16.6, 17.0, 17.8, 18.5, 25.8, 26.7, 27.0, 27.4, 28.1, 32.3, 32.6, 35.3, 37.0, 39.2, 39.7, 40.2, 50.5, 50.9, 51.2, 56.4, 62.6, 62.8, 71.4, 72.4, 72.6, 77.2, 77.9, 78.1, 78.3, 78.3, 83.5, 88.9, 105.2, 106.1, 123.5, 124.6, 131.2, 140.2 Test Example 1 : Vasodilation activity of ginsenoside Rg-, and Rgr Vascular endothelium plays a very important role in keeping homeostasis in the body by controlling blood stream and tension of blood vessel and by inhibiting platelet coagulation. Particularly, it is known that the vascular endothelium releases nitric oxide (NO) as an endothelium-derived relaxing factor(EDRF) , which acts on smooth muscle of blood vessel to activate soluble guani- late cyclase and to relax the blood vessel by increasing the cyclic GMP in tissue. When the function of endothe¬ lium is damaged by circulatory disorders such as hyperten¬ sion, hypercholesterolemia, etc., the released amount of nitric oxide is decreased to cause the loss of the normal function of controlling blood vessel. However, since most of the saponin destroy the endothelial cells to cause severe side effects such as hemolysis or toxicity against fishes, etc., they are undesirable. Therefore, it has been required a component which exhibits a vasodilation upon blood vessel without any damage to endothelium. The present inventors have identified that ginsenoside Rg 3 and Rg 5 exhibit a potent endothelium-dependent vasodi¬ lation different from the conventional saponin components, which is established by the following experiment. 1. Experimental Procedure Sprague-Dawley(SD) rats weighing 300-400g were sacri¬ ficed and their thoracic aortae were removed quickly, and then placed in a Krebs-Ringer-sodium bicarbonate solution (control solution, NaCl 118.3; KCI 4.7; MgS0 4 1.2; KH 2 P0 4 1.2; CaCl 2 2.5; NaHC0 3 25.0; CaEDTA 0.016 and glucose 11. ImM) . Blood within the aortae, adipose and connective tissues surrounding the blood vessel were removed and then the clean aortae were cut down to prepare the aortic rings having 2 -3mm length. The aortic rings were suspended vertically in an organ chamber filled with 25ml of control solution (pH 7.4) . In some aortic rings, the endothelium was removed mechanically by rolling the rings 7 to 8 times on a tissue towel with pincette. The bottom of aortic ring was fixed to the organ chamber and the top thereof was connected to a transducer coupler through stirrups for recording of isometric tension. To the aortic rings showing a stable contraction induced by addition of 10 ~ °M phenylephrine to the organ chamber was added ginsenoside Rg 3 or Rg^-dimethylsulfoxide solution alone or together with 10 M methylene blue (MB) or 10 "6 M nitro-L-arginine (NLA) in order to observe the vasodilation thereof. The degree of contraction by 10 M phenylephrine was set to 100% and the degree of relaxation caused by ginsenoside Rg 3 or Rg 5 was represented as per¬ cent (%) with respect thereto. 2. Experimental Result : As depicted in Figures 1 and 4, ginsenoside Rg 3 and Rg 5 show a concentration-dependent relaxation to the blood vessel with endothelium. However, they exhibit no effect to" the blood vessel without endothelium. Also, the vasodilation of ginsenoside Rg 3 or Rg 5 is significantly inhibited by nitro-L-arginine (NLA) , an inhibitor of nitric oxide synthase, or by methylene blue (MB) , an inhibitor of soluble guanylate cyclase. From such results, it can be seen that ginsenoside Rg 3 and Rg 3 exhibit a vasodilation only to the blood vessel with endothelium. Therefore, the results suggest that ginsenoside Rg 3 and Rg 5 are safe medicinal components because they do not exhibit side effects such as hemoly¬ sis, toxicity against fishes, etc., contrary to other saponin components destroying the endothelial cells. Test Example 2 : Vasodilation activity of the processed saponin fraction 1. Experimental Procedure : Vasodilation of the processed panaxadiol saponin fraction obtained in Example 7 as mentioned above was determined according to the same experimental procedure as Test Example 1. 2. Experimental Result : As depicted in Figure 2, the processed panaxadiol saponin fraction shows a concentration-dependent relaxa¬ tion to the blood vessel with endothelium. However, it exhibits no effect to the blood vessel without endotheli¬ um. Also, the vasodilation thereof is significantly inhibited by nitro-L-arginine (NLA) , an inhibitor of nitric oxide synthase, or by methylene blue (MB) , an inhib¬ itor of soluble guanylate cyclase. The results show that the processed panaxadiol saponin fraction exhibits a vasodilation only to the blood vessel with endothelium. Therefore, it suggests that the proc¬ essed panaxadiol fraction is a safe medicinal component because it does not exhibit side effects such as hemoly¬ sis, toxicity against fishes, etc., contrary to other saponin components destroying the endothelial cells. Test Example 3 : Cytotoxicity of ginsenoside Rg 3 1. Experimental Procedure : Human umbilical vein endothelium cells (HUVEC) cultured in M199 medium were suspended in physiological saline to a concentration of 20000 cells/180μl. The cell suspension was introduced into each well of 96-well plate in an amount of 180μl, and then 20μl of dimethylsulfoxide as a solvent or the same volume of Rg 3 dissolved in dimethyl¬ sulfoxide was added thereto. The plate was incubated for 48 hours in a cell-incubator of 37°C while keeping 5% C0 2 . Then, 50μl of MTT (3- (4 , 5-dimethyl-thiazol-2 ' -yl) -2 , 5- diphenyltetrazolium bromide) dissolved in phosphate buff¬ ered solution in a concentration of 2mg/ml was added thereto and incubated again for 4 hours under the same condition as mentioned above. Thereafter, the superna¬ tant was removed and 200μl of dimethylsulfoxide was added to measure the absorbance at 540nm. The absorbance measured was converted into cell number to determine IC^ Q of dimethylsulfoxide solvent and Rg 3 which is the concen¬ tration to inhibit the cell growth by 50% and can be used as an index of cytotoxicity. 2. Experimental Result In the case of dimethylsulfoxide (control group) , it began to exhibit cytotoxicity from 0.6% and suppressed 100% of the cell growth at 6%. Thus, the cytotoxicity of the solvent depends on its amount and IC 50 thereof is 18.4μg/ml. Rg 3 showed the cytotoxity at the concentra¬ tion of 1 to lOOμg/ml in the same manner of results with dimethylsulfoxide. IC 5o of R ^3 ' however, is 26.7μg/ml which is somewhat higher than that of the solvent, and therefore it is recognized that Rg 3 has lower cytotoxicity than the solvent. That is, since survival ratio of the Rg 3 receiving group is higher than that of control group, it is recognized that Rg 3 has a stimulating effect on cell growth (see, Figure 3) . Test Example 4 : Cytotoxicity of ginsenoside Rgr 1. Experimental Procedure : Human umbilical vein endothelium cells (HUVEC) cultured in M199 medium were suspended in physiological saline to a concentration of 20000 cells/l80μl. The cell suspension was introduced into each well of 96-well plate in an amount of 180μl, and then 20μl of distilled water as a solvent or the same volume of Rg 5 dissolved in distilled water was added thereto. The plate was incubated for 48 hours in a cell-incubator of 37°C while keeping 5% C0 2 • Then, 50μl of MTT (3 - (4 , 5-dimethyl-thiazol-2 ' -yl) -2 , 5- diphenyltetrazolium bromide) dissolved in phosphate buff¬ ered solution in a concentration of 2mg/ml was added thereto and incubated again for 4 hours under the same condition as mentioned above. Thereafter, the superna¬ tant was removed and 200μl of dimethylsulfoxide was added to measure the absorbance at 540nm. 2. Experimental Result : As depicted in Figure 5, the cells with ginsenoside Rgr grow more actively than that with distilled water only though there is no statistical significance. Therefore, it can be seen that ginsenoside Rg^ has no cytotoxicity. COMPOSITION EXAMPLES In the following composition examples, Rg 3 or a frac¬ tion containing Rg 3 can be replaced with Rg 5 , Rg 3 and Rg 5 or a fraction containing the same, respectively. COMPOSITION EXAMPLE 1 Component Content Corn starch 44 g Crystalline cellulose 40 g Calcium carboxymethylcellulose 5 g Magnesium stearate 1 g Fraction obtained in Example 1 10 g Total : 100 g According to the composition above, all the components were mixed uniformly and then molded compressively in a tabletting machine to prepare tablets weighing 500mg and containing 50mg of the fraction obtained in Example 1 per each tablet. The daily dosage for an adult, 3 to 10 tablets, can be divided into several portions and adminis- tered over several times. COMPOSITION EXAMPLE 2 Component Content Crystalline cellulose 34.5 g 10% Hydroxypropylcellulose -ethanol solution 50 g Calcium carboxymethylcellulose 5 g Magnesium stearate 0.5 g Fraction obtained in Example 5 10 g Total : 100 g According to the composition above, crystalline cellu- lose, 10% hydroxypropylcellulose-ethanol solution and the fraction obtained in Example 5 were mixed uniformly, dried by using a granulator according to a conventional manner and then grinded. Calcium carboxymethylcellulose and magnesium stearate were mixed therewith and then the mixture was molded compressively in a tabletting machine to prepare tablets weighing 500mg and containing 50mg of the fraction obtained in Example 5 per each tablet. The daily dosage for an adult, 3 to 10 tablets, can be divided into several portions and administered over several times. COMPOSITION EXAMPLE 3 Component Content Injectable distilled water 86.5 g Ethanol 5 g Soybean phospholipid 2.5 g Glycerin 5 g Rg 3 obtained in Example 8 1 9 Total : 100 g According to the composition above , Rg 3 obtained in Example 8 was dissolved in ethanol and soybean phophosl ip- i d . Then , the resul t ing solut i on was emul s i f i ed by adding inj ectable distilled water and glycerin solution to prepare the injectable preparation. COMPOSITION EXAMPLE 4 Component Content Pyridoxine hydrochloride 300 mg Nicotinic acid amide 1 g Calcium pantothenate 1 g Riboflavine 200 mg Citric acid 30 g Fraction obtained in Example 1 20 g Epimedii Herba extract 200 mg Water added by 10 L According to the composition above, components 1) to 7) were dissolved in component 8) to prepare the solution. 100ml of this solution contains 200mg of the fraction obtained in Example 1. COMPOSITION EXAMPLE 5 Component Content Crystalline cellulose 440 mg Magnesium stearate 10 9 Rg 3 obtained in Example 8 50 g Total 500 All the components described in above were mixed uniformly, granulated according to a conventional manner and then filled into capsules. Each capsule preparation thus obtained is 500mg in weight and contains 50mg of Rg 3 . The daily dosage for an adult, 3 to 10 capsules, can be divided into several portions and administered over sever¬ al times.

Claims: WHAT IS CLAIMED IS : 1. A vasodilating composition comprising ginsenoside Rg 3 and/or Rg 5 as an active ingredient. 2. The vasodilating composition of claim 1 characterized in that said ginsenoside Rg 3 and/or Rg 5 as the active ingredient is pure Rg and/or Rg 5 or a ginseng extract containing Rg 3 and/or Rg^ in an amount of 10% (w/w) or more. 3. The vasodilating composition of claim 1 characterized in that it is formulated into a dosage unit form together with a pharmaceutically acceptable carrier. 4. The vasodilating composition of claim 3 characterized in that the dosage unit form is tablets, hard or soft capsules, granules, solutions, suspensions, injectable solutions or injectable suspensions. 5. The vasodilating composition of claim 4 characterized in that the dosage unit form is formulated to contain 10 to 500mg of ginsenoside Rg 3 and/or Rg 5 . 6. A process for preparing ginsenoside Rg 3 and/or Rgr characterized in that the plant of Panax genus is heated for 0.5 to 20 hours at a temperature of 110 to 180°C, the processed ginseng thus obtained is extract- ed with an organic solvent, and then the extract is subjected to chromatography to separate ginsenoside Rg 3 . 7. A process for preparing ginsenoside Rg 3 and/or Rg^ characterized in that the plant of Panax genus is extracted with an organic solvent, and the extract is heated for 0.5 to 20 hours at a temperature of 110 to 180°C and then subjected to chromatography to separate ginsenoside Rg 3 and/or Rg 5 . 8. A process for preparing ginsenoside Rg 3 and/or Rg 5 characterized in that the plant of Panax genus iε extracted with an organic solvent, and the extract is treated with an acid at a temperature of 50 to 100°C and then subjected to chromatography to separate ginsenoside Rg 3 and/or Rg,- . 9. A process for preparing a processed panaxadiol saponin characterized in that the plant of Panax genus is extracted with an organic solvent to obtain a panaxa¬ diol fraction and this fraction is heated for 0.5 to 20 hours at a temperature of 110 to 180°C.

Inventors: KANG SU YEON, KIM JONG MOON, KIM NAK DOO, KIM WANG YOU, PARK JEONG HILL, PARK MAN KI, KANG, SU, YEON, KIM, JONG, MOON, KIM, NAK, DOO, KIM, WANG, YOU, PARK, JEONG, HILL, PARK, MAN, KI
Applicants: CHEIL JE DANG CO, KANG SU YEON, KIM JONG MOON, KIM NAK DOO, KIM WANG YOU, PARK JEONG HILL, PARK MAN KI, CHEIL JE DANG CO., KANG, SU, YEON, KIM, JONG, MOON, KIM, NAK, DOO, KIM, WANG, YOU, PARK, JEONG, HILL, PARK, MAN, KI
Application year: 1996
Main classification: A61K35
IPC codes: A61K31, A61K36, A61P9, C07J17