WO1996040181A1 - Processed ginseng having enhanced pharmacological effect - Google Patents

Processed ginseng having enhanced pharmacological effect Download PDF

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Publication number
WO1996040181A1
WO1996040181A1 PCT/KR1996/000087 KR9600087W WO9640181A1 WO 1996040181 A1 WO1996040181 A1 WO 1996040181A1 KR 9600087 W KR9600087 W KR 9600087W WO 9640181 A1 WO9640181 A1 WO 9640181A1
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WO
WIPO (PCT)
Prior art keywords
ginseng
processed
present
extract
heating
Prior art date
Application number
PCT/KR1996/000087
Other languages
French (fr)
Inventor
Man Ki Park
Nak Doo Kim
Seung Ki Lee
Jeong Hill Park
Jong Moon Kim
Original Assignee
Cheil Je Dang Co.
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Filing date
Publication date
Application filed by Cheil Je Dang Co. filed Critical Cheil Je Dang Co.
Priority to AT96917725T priority Critical patent/ATE205395T1/en
Priority to DE69615181T priority patent/DE69615181T2/en
Priority to EP96917725A priority patent/EP0831864B1/en
Priority to AU60176/96A priority patent/AU6017696A/en
Priority to JP50032197A priority patent/JP3663213B2/en
Priority to TW085107669A priority patent/TW587940B/en
Publication of WO1996040181A1 publication Critical patent/WO1996040181A1/en

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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)
    • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A61K36/258—Panax (ginseng)
    • 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)
    • A61K36/69—Polygalaceae (Milkwort family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A61P39/06—Free radical scavengers or antioxidants
    • 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
    • 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
    • A61P9/08—Vasodilators for multiple indications
    • 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
    • A61P9/12—Antihypertensives

Definitions

  • the present invention relates to a processed ginseng having an enhanced pharmacological effect and a beverage composition comprising the same. More specifically, the present invention relates to a processed ginseng produced by heating ginseng at a high temperature, of which the ratio of ginsenoside (Rg 3 +Rg 5 )/(Rc+Rd+Rb ⁇ Rb j ) is above 1.0 and thus exhibits an enhanced pharmacological activi ⁇ ty, and to a beverage composition comprising said proc- essed ginseng.
  • ginseng Since ancient times, ginseng has been widely known 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. Hitherto, various pharmaco ⁇ logical effects of ginseng such as suppression of aging, anti-arteriosclerosis, improvement of hyperlipidemia, improvement of liver function, defense against radiation hazard, immunological enhancement, anti-thrombotic effect, improvement of cerebral function, anti-stress, decrease of blood sugar, decrease of blood pressure, anti-tumor ef ⁇ fect, etc. have been known.
  • 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.
  • the red ginseng is recognized as a very valuable herbal drug because its. pharmacological effect is more potent than that of white ginseng.
  • red ginseng has been actively conducted, and as a result, an interest in novel pharmacological effects of those minor components has greatly increased.
  • the minor components are produced during the process for preparing red ginseng by heating the fresh ginseng, they are appre ⁇ ciated as the specific components which can explain the excellent effect of red ginseng.
  • the specific components identified as contained in the red ginseng only until now are saponins such as ginsenoside Rh2, Rsl, Rs2, Rg3, Rg5, Rhl, etc., polyacetylene compounds such as panaxytriol, etc. and the like. Such components are produced during the procedures for preparing the red ginseng and are present in a very minor amounts -in the red ginseng.
  • the red ginseng is generally prepared by steaming the fresh ginseng for about 2 hours at a temperature of 98 to 100°C.
  • the quality of red ginseng is mainly estimated on the basis of the apparent shape. Specifically, the red ginseng which has a good shape with no inside pores, cracks, inside whites, white peels, etc. is classified as a high-grade one. Accordingly, in order to produce a red ginseng having a better apparent shape there has been developed the method for preparing red ginseng by carrying out the heating procedure at the temperature of less than 98°C as low as possible. Said method is the subject of the pending patent application(Korean Patent Publication No. 92-5995) . Since the apparent shape of a ginseng is regarded as the main standard for judgement of the commer ⁇ cial value thereof, as aforementioned, it was not attempt ⁇ ed to heat the ginseng at a high temperature of 100°C or more.
  • Japa- nese Laid-Open Patent Publication No. (Sho) 62-158,490 discloses a method for preparing tissue cultures having an increased content of ginsenoside Rh by heating the tissue cultures of ginseng at 110 to 160°C.
  • this method processes the tissue cultures of ginseng, not the ginseng itself, the processed product does not have the shape of ginseng, and further the tissue cultures of ginseng has different components and composition thereof as compared with the original ginseng cultivated in na ⁇ ture(see: Korean Journal of Pharmacognosy, 16, 171-171, 1985) and thus, natually has the phamacological effect different from that of original ginseng.
  • this method is complicated and uneconomical since it must be carried out through tissue culture step.
  • some other methods for heating ginseng at a high tempera- ture were attempted. However, they are merely the step utilized in the procedure for preparing cosmetics or teas, and the pharmacological effect of ginseng resulted from such high temperature-treatment has not even been studied.
  • the present inventors have scientifically stud- ied about the components and pharmacological effects, particularly processing methods and physiological activi ⁇ ties of the ginseng.
  • ginseng such as fresh ginseng, white ginseng, fine root of ginseng or an extract thereof treated at a much higher temperature than the temperature generally used for preparation of red ginseng
  • the compo ⁇ nents which are contained merely in minor amounts in red ginseng greatly increase and new components which are not contained in red ginseng are formed, and therefore, the pharmacological activities of ginseng are highly enhanced.
  • the present invention relates to a processed ginseng prepared by heating a ginseng for 0.5 to 20 hours at a high temperature of 120 to 180°C wherein the sum of ginsenosides Rg 3 and Rg 5 is always greater than the sum of ginsenosides Re, Rd, Rb 1 and Rb 2 , that is the ratio of ginsenoside (Rg 3 +Rg 5 )/(Rc+Rd+Rb 1 +Rb 2 ) is above 1.0.
  • It is a further object of the present invention to provide a beverage composition comprising the processed ginseng as mentioned above.
  • Figure 1 represents the change in an amount of the essential oil fraction in accordance with the change of heating conditions(temperature and time) for fresh gin ⁇ seng;
  • Figure 2 represents gas chromatograms of the essential oil fractions of the processed ginsengs obtained by heat- ing ginseng for 2 hours at 120°C ( Figure 2-b) ; and for 2 hours at 150 ⁇ C ( Figure 2-c) according to the present invention in comparison with gas chromatogram of the essential oil fraction of fresh ginseng which is not heat- treated ( Figure 2-a) ;
  • Figure 3 represents an anti-oxidant activity of the processed ginsengs prepared by heating ginseng for 2 hours(-#-), 3 hours(->-) at 120 ⁇ C and for 2 hours at 110 ⁇ C(-A-) in comparison with that of white ginseng not heated(- ⁇ -) and red ginseng commercially available( ); and
  • Figure 4 represents a vasodilation activity of the processed ginseng of the present invention prepared by heating ginseng for 2 hours at 120°C(-A-) in comparison with that of ginseng treated at 110°C for 2 hours(-#-), red ginseng(-0-) and white ginseng(- ⁇ -) .
  • a processed gin- seng having an enhanced pharmacological effect is obtained by heating a ginseng at a high temperature to increase the content of the pharmacologically active components.
  • the kind of ginseng which can be heated according to the present invention is not specially restricted and any of fresh ginseng, white ginseng, fine root of ginseng or leaves of ginseng plants or extracts thereof can be used in an intact form or a finely divided or a powder.
  • the ginseng to be treated according to the present inven ⁇ tion is generally Panax ginseng, Panax quinque folium or Panax notoginseng can also be used in the present inven ⁇ tion.
  • the heat-treatment of gin ⁇ seng is carried out for 0.5 to 20 hours at 120 to 180°C, preferably for 2 to 5 hours at 120 to 140°C.
  • the time required for heating depends on the heat temperature. Specifically, the heat-treatment should be conducted for a long time at a low temperature but can be conducted for a relatively short time at a high temperature.
  • the heating is carried out utilizing hot air, steam, nitrogen, helium, carbon dioxide or mixed gas thereof. It is preferable to carry out the heating in a sealed container such as an autoclave to increase the heating efficiency. If de ⁇ sired, it may be preferable to introduce some water into the container or to heat the ginseng immersed in water in the sealed container.
  • the processed ginseng thus prepared can be dried according to a known method at a lower tempera ⁇ ture than the temperature at the preceding heating step, for example at the normal temperature to 80°C, to obtain the dried processed ginseng or a powder thereof.
  • the processed ginseng can be extracted according to a known method to prepare the processed ginseng extract.
  • the processed ginseng can be extracted with water, lower alcohol (for example, methanol, ethanol, etc.), lower ketone (for example, acetone, methylethylketone, etc.), super critical fluid or a mixed solvent thereof, and then the solvent is removed from the extract by concentration or lyophiliza- tion to prepare the processed ginseng extract in the form of a dried powder.
  • the ginseng extract or the extract fraction can be subjected to heat-treatment according to the same manner as applied for fresh ginseng, white ginseng or fine root of ginseng to obtain the processed ginseng extract.
  • the use of the ginseng extract can provide the merits that since the sample volume is reduced and therefore the device for processing ginseng can have a smaller size, the energy required for heating can be saved and the heating conditions including time and temperature can be con ⁇ trolled more precisely.
  • the processed ginseng of the present invention pre ⁇ pared according to the method as mentioned above shows a greatly enhanced pharmacological effect because it con ⁇ tains several components, for example nonpolar saponins, phenolic compounds, polyacetylene compounds, etc. in large quantities, which are contained merely in infinitesimal quantities or not contained in fresh ginseng, white gin ⁇ seng or red ginseng. That is, in the processed ginseng the various new volatile components produced during the heating step are present and they have been identified as having anti-oxidant activity, anti-tumor activity, and the like.
  • the processed ginseng of the present invention contains various saponins, for example, ginsenosides Rg 3 , Rg 5 , Rh lf Rh 2 , Rh 3 , Rh , F 4 , etc. which are not contained or contained merely in infinitesimal quantities in the white ginseng or red ginseng.
  • saponins ginse ⁇ nosides F 4 , Rg 3 , Rg 5 ( 20-ginsenoside Rg 3 ) are contained particularly in large quantities.
  • the processed ginseng according to the present invention exhibits valuable physiological activities since the ratio of (Rg 3 +Rg 5 )/(Rc+Rd+Rb ⁇ Rb j ) is above 1.0 in contrast to the fresh ginseng or red ginseng in which ginsenoside components such as Rg 3 and Rg 5 are substantially not present.
  • the processed ginseng having an enhanced pharmacologi- cal effect prepared by heating ginseng according to the present invention for example, processed ginseng powder, processed ginseng extract, etc.
  • the processed ginseng of the present invention can be prepared in the form of a beverage composition.
  • the present invention also provides a beverage composition which comprises the processed ginseng in the form of a powder or an extract. It is appropriate for the beverage composition according to the present invention to contain the dried processed ginseng in an amount of 200 to 2000mg, preferably 400 to lOOOmg, for a single dosage.
  • the beverage composition of the present invention can additionally contain the extracts of medicinal- nal herbs such as Zingiberis rhizoma, Ziziphi fructus, Cinnamomi cortex, Lycii fructus, Polygalae radix, Astraga ⁇ li radix, etc.
  • the additives such as sweeteners, fla ⁇ vors, preservatives and the like which are conventionally used in a beverage composition can also be contained in the beverage composition of the present invention.
  • 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.
  • the heat-treated ginseng was removed from the autoclave and dried at temperature of 50 to 60°C to obtain the desired processed ginseng.
  • the heat-treated ginseng was removed from the autoclave and dried at temperature of 50 to 60°C to obtain the desired processed ginseng.
  • lkg of dried fine root of ginseng was extracted by refluxing with 2L of methanol for 4 hours under water bath and then filtered.
  • the ginseng extract thus obtained was dried under reduced pressure.
  • the resulting ginseng extract in the form of syrup was introduced into an auto- clave and then heated for 4 hours at 120°C. Then, the heat-treated ginseng extract was dried at 60°C to prepare the processed ginseng extract in the form of a concentrat ⁇ ed syrup.
  • the processed ginseng prepared in Example 1 was ex- tracted by refluxing with methanol for 4 hours under water bath and then filtered.
  • the ginseng extract thus ob ⁇ tained was dried under reduced pressure to obtain the processed ginseng extract in the form of a powder.
  • each of the proc ⁇ essed ginseng according to the present invention fresh ginseng, white ginseng and red ginseng was analyzed by the method described in the following.
  • the processed ginseng obtained by heating gin ⁇ seng according to the present invention can show an excel- lent pharmacological effect due to a remarkable increase in content of ginseng saponins Rg 3 and Rg 5 which are not or substantially not present in fresh ginseng, white ginseng and red ginseng.
  • Non-treated ginseng(fresh ginseng) 2) The content of each component represents the content% with respect to the used amount of fresh ginseng.
  • the con ⁇ tents of ginsenosides such as Rg 3 and Rg 5 in the processed ginseng heated at 120 to 180°C according to the present invention have greatly increased in contrast to the non- treated fresh ginseng or red ginseng(heated at 100°C) .
  • the heating is carried out at a high temperature of 180°C or more, although the contents of ginsenosides Rg 3 and Rg 5 in the processed ginseng are somewhat higher than in the fresh ginseng or red ginseng, such a high tempera ⁇ ture-heating is not desirable because special equipments or excessive costs are needed for heating at such a high temperature.
  • Amount of essential oil fraction according to the heatin ⁇ conditions 10 containers were divided into 2 groups with 5 per each group. The first group will be heated for 2 hours and the second group will be heated for 4 hours, at 100 ⁇ C, 110 ⁇ C, 120°C, 130°C and 150°C, respectively. lOg of fresh ginseng was introduced into each containers and heated for
  • the essential oil fraction of ginseng contains phenolic components, polyacetylene compounds, etc. which have anti-oxidant effect, anti-tumor effect and the like. From the result illustrated in Figure 1, it can be seen that the amount of essential oil fraction contained in the processed ginseng of the present invention greatly increases in contrast to fresh ginseng which is not heated or red ginseng heated at 100°C. This means that the processed ginseng of the present invention can show much more potent anti-oxidant and anti-tumor effects than the fresh ginseng or red ginseng.
  • the essential oil fraction of ginseng contains nonpo ⁇ lar compounds such as phenolic compounds, polyacetylene compounds, etc., which have been known as having the anti- oxidant effect, anti-tumor effect, and the like.
  • Figure 2-a is the gas chromatogram for ginseng not processed
  • Figure 2-b is the gas chromatogram for ginseng heated for 2 hours at 120 ⁇ C
  • Figure 2-c is the gas chromatogram for ginseng heated for 2 hours at 150°C. From these gas chromatograms, it can be identified that the content of nonpolar components such as volatile essential oil compo ⁇ nents, polyacetylene compounds, and the like increases and new components are produced according to the increase of heating temperature. This result means that the anti- oxidant effect of ginseng increases according as the heating temperature is raised.
  • the extract of ginseng processed at a high temperature(120°C) according to the present invention exhibits a remarkably improved anti-oxidant activity compared with the unprocessed ginseng.
  • Such an anti- oxidant activity increases dependently on the dose. Therefore, in view of 50% inhibition concentration, the anti-oxidant effect of the ginseng processed for 2 hours at 120 ⁇ C is about 4 times greater than that of the ginseng processed for 2 hours at 110°C as well as red ginseng.
  • Sprague-Dawley rats 300-400g were sacrificed and their thoracic aortae were removed and placed in a modi ⁇ fied Krebs-Ringer-bicarbonate solution containing(in mM):NaCl, 118.3; KC1, 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, 11.1 (control solution) .
  • the aortae were cleaned of loose connective tissue and then cut into eight rings (2-3mm wide) . In some rings, the endothelium was removed me ⁇ chanically.
  • the aortic rings were suspended horizontally between two stainless steel stirrups in organ chambers filled with 25ml of control solution (37°C, pH 7.4) and bubbled with 95% 0 2 and 5% C0 2 .
  • One of the stirrups was anchored to the organ chamber and one was connected to a transducer coupler(Narco bio-system) for the recording of isometric tension.
  • the aortic rings were stretched progressively to the optimal tension(2g) before the addi ⁇ tion of phenylephrine(10 ⁇ 6 M) . Once the plateau of the contraction to phenylephrine was obtained, the aortic rings were rinsed three times with warm (37°C) control solution.
  • a cumulative concentration-response curve to ginseno ⁇ side (10 ⁇ 6 -3xl ⁇ "4 g/ml) was performed following the concen- tration of aortic rings with phenylephrine(10 "6 M) .
  • Ginseng extracts significantly relaxed rat aortic rings contracted with phenylephrine in the presence of the endothelium in a concentration-dependent manner (see, Fig 4) .
  • the processed ginseng obtained by heat treatment for 2 hours at 120°C according to the present invention shows a vasodilation at much lower concentra- tion.
  • the vasodilation activity of the processed ginseng extract having the ratio of (Rg 3 +Rg 5 )/(Rc+Rd+Rb 1 +Rb 2 ) of above 1, which is produced by heat treatment at 120°C, at 50% contraction level is about 50 times as high as that of fresh ginseng.
  • Such vasodi- lation activity of the processed ginseng does not show in the blood vessel from which endothelial cells are removed. This means that the vasodilation activity of the processed ginseng is dependent on the endothelial cell.
  • the processed ginseng of the present invention can be used as an agent for prevention or treatment of disorders resulted from circulatory disturbance such as hypertension, arterioscle ⁇ rosis, diabetes mellitus, sexual disorder, etc.
  • fructose, glucose and white sugar were first dissolved in purified water with heating to 95°C, and then cooled slowly to 70°C.
  • Citric acid, sodium citrate and sodium benzoate were dissolved therein while stirring, and subsequently zingib- eris rhizoma extract, ziziphi fructus extract, cinnamomi cortex extract, lycii fructus extract and taurine were added thereto while stirring to dissolve.
  • To the result ⁇ ing solution was added the processed ginseng extract prepared in Example 4 and then the mixture was thoroughly stirred. Sutable amount of purified water was added thereto so that the total volume may be 100ml to prepare 100ml of the beverage composition containing 360mg of the processed ginseng extract.
  • Purified water add by 100 ml 100ml of the beverage composition containing 600mg of the processed ginseng extract was prepared according to the substantially same method as Composition Example l above.

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Abstract

The present invention relates to a processed ginseng having an enhanced pharmacological effect by heating ginseng at a high temperature. More specifically, the present invention relates to a processed ginseng produced by heating ginseng for 0.5 to 20 hours at 120 to 180 °C, of which the ratio of ginsenoside (Rg3+Rg5)/(Rc+Rd+Rb1+Rb2) is above 1.0 and thus exhibits an enhanced pharmacological activity, and to a beverage composition comprising said processed ginseng. The processed ginseng heat-treated according to the present invention provides an enhanced pharmacological effect since it contains greatly increased amount of the existing pharmacologically active components as well as newly formed pharmacologically active components in comparison with white ginseng, fresh ginseng and the like which are utilized until now.

Description

PROCESSED GINSENG HAVING ENHANCED PHARMACOLOGICAL EFFECT
TECHNICAL FIELD
The present invention relates to a processed ginseng having an enhanced pharmacological effect and a beverage composition comprising the same. More specifically, the present invention relates to a processed ginseng produced by heating ginseng at a high temperature, of which the ratio of ginsenoside (Rg3+Rg5)/(Rc+Rd+Rb^Rbj) is above 1.0 and thus exhibits an enhanced pharmacological activi¬ ty, and to a beverage composition comprising said proc- essed ginseng.
BACKGROUND ART
Since ancient times, ginseng has been widely known 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. Hitherto, various pharmaco¬ logical effects of ginseng such as suppression of aging, anti-arteriosclerosis, improvement of hyperlipidemia, improvement of liver function, defense against radiation hazard, immunological enhancement, anti-thrombotic effect, improvement of cerebral function, anti-stress, decrease of blood sugar, decrease of blood pressure, anti-tumor ef¬ fect, etc. have been known.
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.
Particularly, the red ginseng is recognized as a very valuable herbal drug because its. pharmacological effect is more potent than that of white ginseng. Recently, many researches on the minor components in red ginseng have been actively conducted, and as a result, an interest in novel pharmacological effects of those minor components has greatly increased. Particularly, since the minor components are produced during the process for preparing red ginseng by heating the fresh ginseng, they are appre¬ ciated as the specific components which can explain the excellent effect of red ginseng. The specific components identified as contained in the red ginseng only until now are saponins such as ginsenoside Rh2, Rsl, Rs2, Rg3, Rg5, Rhl, etc., polyacetylene compounds such as panaxytriol, etc. and the like. Such components are produced during the procedures for preparing the red ginseng and are present in a very minor amounts -in the red ginseng.
The red ginseng is generally prepared by steaming the fresh ginseng for about 2 hours at a temperature of 98 to 100°C. The quality of red ginseng is mainly estimated on the basis of the apparent shape. Specifically, the red ginseng which has a good shape with no inside pores, cracks, inside whites, white peels, etc. is classified as a high-grade one. Accordingly, in order to produce a red ginseng having a better apparent shape there has been developed the method for preparing red ginseng by carrying out the heating procedure at the temperature of less than 98°C as low as possible. Said method is the subject of the pending patent application(Korean Patent Publication No. 92-5995) . Since the apparent shape of a ginseng is regarded as the main standard for judgement of the commer¬ cial value thereof, as aforementioned, it was not attempt¬ ed to heat the ginseng at a high temperature of 100°C or more.
However, recently some attempts to treat the ginseng at a high temperature have been made. For example, Japa- nese Laid-Open Patent Publication No. (Sho) 62-158,490 discloses a method for preparing tissue cultures having an increased content of ginsenoside Rh by heating the tissue cultures of ginseng at 110 to 160°C. However, since this method processes the tissue cultures of ginseng, not the ginseng itself, the processed product does not have the shape of ginseng, and further the tissue cultures of ginseng has different components and composition thereof as compared with the original ginseng cultivated in na¬ ture(see: Korean Journal of Pharmacognosy, 16, 171-171, 1985) and thus, natually has the phamacological effect different from that of original ginseng. Moreover, this method is complicated and uneconomical since it must be carried out through tissue culture step. In addition, some other methods for heating ginseng at a high tempera- ture were attempted. However, they are merely the step utilized in the procedure for preparing cosmetics or teas, and the pharmacological effect of ginseng resulted from such high temperature-treatment has not even been studied.
DISCLOSURE OF INVENTION
Thus, the present inventors have scientifically stud- ied about the components and pharmacological effects, particularly processing methods and physiological activi¬ ties of the ginseng. As a result of such studies, we have identified that when ginseng such as fresh ginseng, white ginseng, fine root of ginseng or an extract thereof treated at a much higher temperature than the temperature generally used for preparation of red ginseng the compo¬ nents which are contained merely in minor amounts in red ginseng greatly increase and new components which are not contained in red ginseng are formed, and therefore, the pharmacological activities of ginseng are highly enhanced. Thus, we have completed the present invention.
Therefore, it is an object of the present invention to provide a processed ginseng having enhanced pharmacologi¬ cal effect which is prepared by heating a ginseng at a high temperature.
More specifically, the present invention relates to a processed ginseng prepared by heating a ginseng for 0.5 to 20 hours at a high temperature of 120 to 180°C wherein the sum of ginsenosides Rg3 and Rg5 is always greater than the sum of ginsenosides Re, Rd, Rb1 and Rb2, that is the ratio of ginsenoside (Rg3+Rg5)/(Rc+Rd+Rb1+Rb2) is above 1.0.
It is a further object of the present invention to provide a beverage composition comprising the processed ginseng as mentioned above.
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 the change in an amount of the essential oil fraction in accordance with the change of heating conditions(temperature and time) for fresh gin¬ seng;
Figure 2 represents gas chromatograms of the essential oil fractions of the processed ginsengs obtained by heat- ing ginseng for 2 hours at 120°C (Figure 2-b) ; and for 2 hours at 150βC (Figure 2-c) according to the present invention in comparison with gas chromatogram of the essential oil fraction of fresh ginseng which is not heat- treated (Figure 2-a) ;
Figure 3 represents an anti-oxidant activity of the processed ginsengs prepared by heating ginseng for 2 hours(-#-), 3 hours(->-) at 120βC and for 2 hours at 110βC(-A-) in comparison with that of white ginseng not heated(-♦-) and red ginseng commercially available( ); and
Figure 4 represents a vasodilation activity of the processed ginseng of the present invention prepared by heating ginseng for 2 hours at 120°C(-A-) in comparison with that of ginseng treated at 110°C for 2 hours(-#-), red ginseng(-0-) and white ginseng(-Δ-) .
BEST MODE FOR CARRYING OUT THE INVENTION
According to the present invention, a processed gin- seng having an enhanced pharmacological effect is obtained by heating a ginseng at a high temperature to increase the content of the pharmacologically active components. The kind of ginseng which can be heated according to the present invention is not specially restricted and any of fresh ginseng, white ginseng, fine root of ginseng or leaves of ginseng plants or extracts thereof can be used in an intact form or a finely divided or a powder. Although the ginseng to be treated according to the present inven¬ tion is generally Panax ginseng, Panax quinque folium or Panax notoginseng can also be used in the present inven¬ tion. In the present invention, the heat-treatment of gin¬ seng is carried out for 0.5 to 20 hours at 120 to 180°C, preferably for 2 to 5 hours at 120 to 140°C. The time required for heating depends on the heat temperature. Specifically, the heat-treatment should be conducted for a long time at a low temperature but can be conducted for a relatively short time at a high temperature. The heating is carried out utilizing hot air, steam, nitrogen, helium, carbon dioxide or mixed gas thereof. It is preferable to carry out the heating in a sealed container such as an autoclave to increase the heating efficiency. If de¬ sired, it may be preferable to introduce some water into the container or to heat the ginseng immersed in water in the sealed container.
If necessary, the processed ginseng thus prepared can be dried according to a known method at a lower tempera¬ ture than the temperature at the preceding heating step, for example at the normal temperature to 80°C, to obtain the dried processed ginseng or a powder thereof.
In addition, if desired, the processed ginseng can be extracted according to a known method to prepare the processed ginseng extract. Specifically, the processed ginseng can be extracted with water, lower alcohol (for example, methanol, ethanol, etc.), lower ketone (for example, acetone, methylethylketone, etc.), super critical fluid or a mixed solvent thereof, and then the solvent is removed from the extract by concentration or lyophiliza- tion to prepare the processed ginseng extract in the form of a dried powder.
According to the present invention, similar results can be obtained by treating leaves of ginseng plants, instead of the ginseng itself, according to the same manner. Until now, the leaves of ginseng plants are not used for medicinal purposes but has generally been wasted or used merely as feedstuffs. Only some of them have been used as a source of cosmetics or food. But, when the leaves of ginseng plants are heated according to the process of the present invention, the pharmacological effect thereof much more increases, and therefore they can be used even for medicinal purposes as well as for their original use known heretofore.
Furthermore, according to the present invention the ginseng extract or the extract fraction can be subjected to heat-treatment according to the same manner as applied for fresh ginseng, white ginseng or fine root of ginseng to obtain the processed ginseng extract. In this case, the use of the ginseng extract can provide the merits that since the sample volume is reduced and therefore the device for processing ginseng can have a smaller size, the energy required for heating can be saved and the heating conditions including time and temperature can be con¬ trolled more precisely.
The processed ginseng of the present invention pre¬ pared according to the method as mentioned above shows a greatly enhanced pharmacological effect because it con¬ tains several components, for example nonpolar saponins, phenolic compounds, polyacetylene compounds, etc. in large quantities, which are contained merely in infinitesimal quantities or not contained in fresh ginseng, white gin¬ seng or red ginseng. That is, in the processed ginseng the various new volatile components produced during the heating step are present and they have been identified as having anti-oxidant activity, anti-tumor activity, and the like. The processed ginseng of the present invention contains various saponins, for example, ginsenosides Rg3, Rg5, Rhlf Rh2, Rh3, Rh , F4, etc. which are not contained or contained merely in infinitesimal quantities in the white ginseng or red ginseng. Among the saponins, ginse¬ nosides F4, Rg3, Rg5( 20-ginsenoside Rg3) are contained particularly in large quantities. Particularly, the processed ginseng according to the present invention exhibits valuable physiological activities since the ratio of (Rg3+Rg5)/(Rc+Rd+Rb^Rbj) is above 1.0 in contrast to the fresh ginseng or red ginseng in which ginsenoside components such as Rg3 and Rg5 are substantially not present.
The processed ginseng having an enhanced pharmacologi- cal effect prepared by heating ginseng according to the present invention, for example, processed ginseng powder, processed ginseng extract, etc., can be used as a source having a more potent efficacy in the field of all kinds of pharmaceuticals, herb medicines, health food, food, teas, cosmetics and the like, in which the ginsengs have been conventionally used. More particularly, the processed ginseng of the present invention can be prepared in the form of a beverage composition.
Accordingly, the present invention also provides a beverage composition which comprises the processed ginseng in the form of a powder or an extract. It is appropriate for the beverage composition according to the present invention to contain the dried processed ginseng in an amount of 200 to 2000mg, preferably 400 to lOOOmg, for a single dosage.
If necessary, the beverage composition of the present invention can additionally contain the extracts of medici- nal herbs such as Zingiberis rhizoma, Ziziphi fructus, Cinnamomi cortex, Lycii fructus, Polygalae radix, Astraga¬ li radix, etc. The additives such as sweeteners, fla¬ vors, preservatives and the like which are conventionally used in a beverage composition can also be contained in the beverage composition of the present invention. 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
lkg of fine root of ginseng was introduced into an autoclave and then heated with steam for 3 hours at 120°C.
The heat-treated ginseng was removed from the autoclave and dried at temperature of 50 to 60°C to obtain the desired processed ginseng.
EXAMPLE 2
lkg of fresh ginseng(main root) was introduced into an autoclave and then heated with steam for 2 hours at 130°C.
The heat-treated ginseng was removed from the autoclave and dried at temperature of 50 to 60°C to obtain the desired processed ginseng.
EXAMPLE 3
lkg of dried fine root of ginseng was extracted by refluxing with 2L of methanol for 4 hours under water bath and then filtered. The ginseng extract thus obtained was dried under reduced pressure. The resulting ginseng extract in the form of syrup was introduced into an auto- clave and then heated for 4 hours at 120°C. Then, the heat-treated ginseng extract was dried at 60°C to prepare the processed ginseng extract in the form of a concentrat¬ ed syrup.
EXAMPLE 4
The processed ginseng prepared in Example 1 was ex- tracted by refluxing with methanol for 4 hours under water bath and then filtered. The ginseng extract thus ob¬ tained was dried under reduced pressure to obtain the processed ginseng extract in the form of a powder.
TEST EXAMPLE 1
Analysis of saponins contained in the processed σinsenσ of the present invention
The saponin components contained in each of the proc¬ essed ginseng according to the present invention, fresh ginseng, white ginseng and red ginseng were analyzed by the method described in the following.
5g of white ginseng and 5ml of water were introduced into each of four 40ml stainless steel containers which were then sealed. The mixtures were heated for 2 hours at 110°C, for 2 hours at 120°C, for 3 hours at 120°C and for 2 hours at 130°C, respectively. 5g each of the heat- treated processed ginseng obtained above, commercially available white ginseng and red ginseng was extracted 3 times with 100ml of methanol and then the extract was concentrated. The residue was suspended in water and extracted 3 times with 100ml of ether. The remaining aqueous layer was extracted 3 times with 100ml of butanol and then the butanol fraction was concentrated. The concentrate was dissolved in methanol and analyzed by HPLC(column: LiChrosorb NH2, mobile phase: CH3CN/H20/i- PrOH=80/5/15→80/20/15, detector: ELSD(Evaporative light scattering detector)). The measured results are described in the following Table 1. Table 1. Relative peak area of saponins in ginseng
Figure imgf000013_0001
Note A : (Rg3+Rg5)/(Rc+Rd+Rb1+Rb2)
From the results described in Table 1 above, it can be seen that the processed ginseng obtained by heating gin¬ seng according to the present invention can show an excel- lent pharmacological effect due to a remarkable increase in content of ginseng saponins Rg3 and Rg5 which are not or substantially not present in fresh ginseng, white ginseng and red ginseng.
On the basis of the results as mentioned above, in order to identify more specifically the content change of saponins, particularly ginsenosides Rg3 and Rg5 in accord¬ ance with the heating temperature change, the contents of Rg3 and Rg5 in the ginsengs heated for 2 hours at 100°C, 110°C, 120°C, 130°C, 150°C, 160°C, 180°C and 200°C, re¬ spectively, were determined and compared with the ginseng which is not heated(fresh ginseng) . The results are de- scribed in the following Table 2.
Table 2. Content change of ginsenosides Rg3 and Rg5 in accordance with the change of heating temperature change
Figure imgf000014_0001
Note : 1) A : Heating temperature(hrs)
B : Non-treated ginseng(fresh ginseng) 2) The content of each component represents the content% with respect to the used amount of fresh ginseng.
It can be seen from the above results that the con¬ tents of ginsenosides such as Rg3 and Rg5 in the processed ginseng heated at 120 to 180°C according to the present invention have greatly increased in contrast to the non- treated fresh ginseng or red ginseng(heated at 100°C) . In case the heating is carried out at a high temperature of 180°C or more, although the contents of ginsenosides Rg3 and Rg5 in the processed ginseng are somewhat higher than in the fresh ginseng or red ginseng, such a high tempera¬ ture-heating is not desirable because special equipments or excessive costs are needed for heating at such a high temperature.
TEST EXAMPLE 2
Amount of essential oil fraction according to the heatinσ conditions 10 containers were divided into 2 groups with 5 per each group. The first group will be heated for 2 hours and the second group will be heated for 4 hours, at 100βC, 110βC, 120°C, 130°C and 150°C, respectively. lOg of fresh ginseng was introduced into each containers and heated for
2 or 4 hours at 100°C, 110βC, 120°C, 130°C and 150°C, respectively, and then extracted with 200ml of methanol under refluxing. Methanol was removed from the extract by evaporation to obtain the methanol extract. This extract was suspended in 100ml of water and then extracted
3 times with 100ml of ether. The extracted ether frac¬ tions were combined and the solvent was removed by evapo¬ ration. The weight of the remaining essential oil frac- tion was measured to observe the change in amount of essential oil fraction according to the change of heating temperature and time. The measured results are depicted in Figure 1.
It has been reported that the essential oil fraction of ginseng contains phenolic components, polyacetylene compounds, etc. which have anti-oxidant effect, anti-tumor effect and the like. From the result illustrated in Figure 1, it can be seen that the amount of essential oil fraction contained in the processed ginseng of the present invention greatly increases in contrast to fresh ginseng which is not heated or red ginseng heated at 100°C. This means that the processed ginseng of the present invention can show much more potent anti-oxidant and anti-tumor effects than the fresh ginseng or red ginseng.
TEST EXAMPLE 3
Gas chromatoσram of essential oil fraction of the proc¬ essed ginseng
lOg of fresh ginseng was introduced into each of two sealed containers and heated for 2 hours at 120°C and 150°C, respectively. After heating, the fresh ginseng was extracted with 200ml of methanol under refluxing and then the methanol was removed by evaporation. The residue was suspended in 100ml of water and then extracted with 100ml of ether. The ether fraction was concentrated to obtain the essential oil fraction which was dissolved in 2ml of chloroform and then subjected to gas chromatography (conditions: column OV-1 25m, capillary column, increasing the oven temperature from 170βC to 280°C, detector FID) to examine the components of the essential oil fraction. In addition, the essential oil fraction extracted from the fresh ginseng which is not heat-treated was examined according to the same method as mentioned above. The obtained results are depicted in Figure 2.
The essential oil fraction of ginseng contains nonpo¬ lar compounds such as phenolic compounds, polyacetylene compounds, etc., which have been known as having the anti- oxidant effect, anti-tumor effect, and the like. Figure 2-a is the gas chromatogram for ginseng not processed, Figure 2-b is the gas chromatogram for ginseng heated for 2 hours at 120βC and Figure 2-c is the gas chromatogram for ginseng heated for 2 hours at 150°C. From these gas chromatograms, it can be identified that the content of nonpolar components such as volatile essential oil compo¬ nents, polyacetylene compounds, and the like increases and new components are produced according to the increase of heating temperature. This result means that the anti- oxidant effect of ginseng increases according as the heating temperature is raised.
TEST EXAMPLE 4
Anti-oxidant effect of the processed ginseng
5g of white ginseng and 5ml of water were introduced into each of three 40ml stainless steel containers which were then sealed and heated for 2 hours at 110°C, for 2 hours at 120°C and for 3 hours at 120°C, respectively. The heat-treated processed ginseng was extracted with 200ml of methanol under refluxing and then filtered. Methanol was removed from the filtrate by evaporation under reduced pressure and the residue was suspended in 100ml of water and then extracted 3 times with 100ml of butanol saturated with water. The butanol fraction was concentrated under reduced pressure to remove butanol and the residue was dissolved in 20ml of ethanol. This solution was diluted gradually with ethanol to prepare 1/2, 1/4, 1/8, 1/16 and 1/32 dilution samples. In addi¬ tion, white ginseng and red ginseng were extracted and diluted to prepare sample solutions according to the same procedure as mentioned above except the heating step is excluded. 0.1ml of each of the sample solutions was introduced into a test tube and 1.9ml of 0.004% DPPH(diphenylpicrylhydrazyl)-ethanol solution was added thereto. The resulting solution was heated for 30 minutes at 37°C and then the absorbance at 515nm was measured. The measured results are depicted in Figure 3.
From the results illustrated in Figure 3, it can be seen that the extract of ginseng processed at a high temperature(120°C) according to the present invention exhibits a remarkably improved anti-oxidant activity compared with the unprocessed ginseng. Such an anti- oxidant activity increases dependently on the dose. Therefore, in view of 50% inhibition concentration, the anti-oxidant effect of the ginseng processed for 2 hours at 120βC is about 4 times greater than that of the ginseng processed for 2 hours at 110°C as well as red ginseng. From the results above, it can be seen that the processed ginseng prepared according to the present invention in which the ratio of (Rg3+Rg5)/(Rc+Rd+Rb1+Rb2) is above 1.0 has more potent nutritive and tonic effect in comparison with fresh ginseng or red ginseng. TEST EXAMPLE 5
Endothelium-dependent vasodilation activity of the proc¬ essed ginseng extract of the present invention
Male Sprague-Dawley rats (300-400g) were sacrificed and their thoracic aortae were removed and placed in a modi¬ fied Krebs-Ringer-bicarbonate solution containing(in mM):NaCl, 118.3; KC1, 4.7; MgS04, 1.2; KH2P04, 1.2; CaCl2, 2.5; NaHC03 , 25.0; CaEDTA, 0.016; and glucose, 11.1 (control solution) . The aortae were cleaned of loose connective tissue and then cut into eight rings (2-3mm wide) . In some rings, the endothelium was removed me¬ chanically. The aortic rings were suspended horizontally between two stainless steel stirrups in organ chambers filled with 25ml of control solution (37°C, pH 7.4) and bubbled with 95% 02 and 5% C02. One of the stirrups was anchored to the organ chamber and one was connected to a transducer coupler(Narco bio-system) for the recording of isometric tension. The aortic rings were stretched progressively to the optimal tension(2g) before the addi¬ tion of phenylephrine(10~6M) . Once the plateau of the contraction to phenylephrine was obtained, the aortic rings were rinsed three times with warm (37°C) control solution. After a resting period (30min) , the aortic rings were exposed again to phenylephrine (10~6M) . When the contraction had stabilized, acetylcholine (10"6M) was added to test the presence or the absence of the endothe¬ lium. The organ chambers were rinsed three times with warm (37βC) control solution before the addition of in- domethacin (10~5M) to prevent the production of endogenous vasoactive prostanoids.
A cumulative concentration-response curve to ginseno¬ side (10~6-3xlθ"4g/ml) was performed following the concen- tration of aortic rings with phenylephrine(10"6M) . Ginseng extracts significantly relaxed rat aortic rings contracted with phenylephrine in the presence of the endothelium in a concentration-dependent manner (see, Fig 4) . Particularly, the processed ginseng obtained by heat treatment for 2 hours at 120°C according to the present invention shows a vasodilation at much lower concentra- tion. Specifically, the vasodilation activity of the processed ginseng extract having the ratio of (Rg3+Rg5)/(Rc+Rd+Rb1+Rb2) of above 1, which is produced by heat treatment at 120°C, at 50% contraction level is about 50 times as high as that of fresh ginseng. Such vasodi- lation activity of the processed ginseng does not show in the blood vessel from which endothelial cells are removed. This means that the vasodilation activity of the processed ginseng is dependent on the endothelial cell.
The result as mentioned above suggests that the processed ginseng of the present invention can be used as an agent for prevention or treatment of disorders resulted from circulatory disturbance such as hypertension, arterioscle¬ rosis, diabetes mellitus, sexual disorder, etc.
COMPOSITION EXAMPLES
COMPOSITION EXAMPLE 1 : Beverage composition
Component Content(in 100ml)
Processed ginseng extract 360 mg
Zingiberis rhizoma extract 180 mg
Ziziphi fructus extract 1900 mg
Cinnamomi cortex extract 180 mg
Lycii fructus extract 200 mg
Taurine • 500 mg
Fructose 10 g
Glucose 0. 5g
White sugar 1 g
Citric acid 200 mg
Sodium citrate 100 mg Sodium benzoate 60 mg Purified water add by 100 ml
According to the composition above, fructose, glucose and white sugar were first dissolved in purified water with heating to 95°C, and then cooled slowly to 70°C. Citric acid, sodium citrate and sodium benzoate were dissolved therein while stirring, and subsequently zingib- eris rhizoma extract, ziziphi fructus extract, cinnamomi cortex extract, lycii fructus extract and taurine were added thereto while stirring to dissolve. To the result¬ ing solution was added the processed ginseng extract prepared in Example 4 and then the mixture was thoroughly stirred. Sutable amount of purified water was added thereto so that the total volume may be 100ml to prepare 100ml of the beverage composition containing 360mg of the processed ginseng extract.
COMPOSITION EXAMPLE 2 : Beverage composition
Component Content(in 100ml)
Processed ginseng extract 600 mg
Ziziphi fructus extract 600 mg
Polygalae radix extract 300 mg
Cinnamomi cortex extract 200 mg
Taurine 500 mg
Fructose 10 g
Glucose 0. 5g
White sugar 1 g
Citric acid 200 mg
Sodium citrate 100 mg
Sodium benzoate 60 mg
Purified water add by 100 ml 100ml of the beverage composition containing 600mg of the processed ginseng extract was prepared according to the substantially same method as Composition Example l above.

Claims

WHAT IS CLAIMED IS :
1. A processed ginseng or processed ginseng extract characterized in that the ratio of ginsenoside
(Rg3+Rg5)/(Rc+Rd+Rb1+Rb2) is above 1.0.
2. The processed ginseng or processed ginseng extract according to claim 1, characterized in that it is prepared from ginseng, leaves of ginseng plant or ginseng extract.
3. The processed ginseng or processed ginseng extract according to claim 2, wherein the ginseng is selected from a group consisting of fresh ginseng, white gin¬ seng and fine root of ginseng.
4. A beverage composition comprising the processed gin¬ seng or processed ginseng extract according to any one of claims 1 to 3.
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EP0873131B1 (en) * 1995-11-22 2004-09-08 Cheil Je Dang Co. Processes for preparation of rg3 and rg5 ginsenosides
EP1032403A1 (en) * 1997-10-24 2000-09-06 Cornell Research Foundation, Inc. Nutritional supplement for cerebral metabolic insufficiencies
EP1032403A4 (en) * 1997-10-24 2004-03-31 John P Blass Nutritional supplement for cerebral metabolic insufficiencies
KR20020029138A (en) * 2000-10-11 2002-04-18 복성해 Recombinant enzyme from Thermus caldophilus GK24 strain and process for preparation of ginsenoside Rd using the same
KR100497665B1 (en) * 2002-03-28 2005-07-01 주식회사 진생사이언스 A composition containing the extract of processed ginseng for treatment of skin disease
WO2003086438A1 (en) * 2002-04-08 2003-10-23 Ginseng Science Inc. Extract of processed panax genus plant, the preparation method thereof, and compositions containing the same
US7645465B2 (en) 2002-04-08 2010-01-12 Kuan Industrial Co., Ltd. Method of preparing a pharmaceutical composition comprising fermented ginseng
US8604010B2 (en) 2008-09-09 2013-12-10 Lion Corporation Method for producing high sapogenin content composition

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AU6017696A (en) 1996-12-30
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DE69615181D1 (en) 2001-10-18

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