HK1069508B - Method for processing ginseng and the uses of extract of processed ginseng - Google Patents
Method for processing ginseng and the uses of extract of processed ginseng Download PDFInfo
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[ technical field ] A method for producing a semiconductor device
The present invention relates to a method of processing ginseng and the use of an extract of the processed ginseng. More particularly, the present invention relates to an extract of processed ginseng or an extract of saponin fraction of processed ginseng, which improves the ratio of ginseng glucoside (Rg3+ Rg5)/(Rb1+ Rb2+ Rc + Rd) to 10-45 due to synergy effect by mixing human with the following herbs: such as schisandra fruit (Schizandrae Fructus), hawthorn fruit (Crataegi Fructus), dogwood fruit (Corni Fructus), papaya fruit (chaenomelis Fructus), smoked plum (ume Fructus), Citrus sinensis (Citrus junos), bitter orange (Aurantii Fructus), apple, pomegranate and lemon, and a method of processing ginseng by heating a mixture containing ginseng and the aforementioned herbal ingredients at a temperature of 70-120 ℃.
[ background of the invention ]
Ginseng is a well-known globally potent tonic. Thus, a great deal of research has been conducted to identify and characterize the components thereof and the pharmacological effects of the components. These studies revealed that ginseng has various therapeutic effects such as prevention of aging and arteriosclerosis; improving hyperlipidemia, diabetes, hypertension, brain function and liver function; oxidation resistance; resistance to stress (antistress); enhancing the immune response; enhancing the antithrombotic effect; protecting brain neurons; anticancer effect, etc. Recently, red ginseng has been reported to contain a small amount of Rg3, a ginseng glycoside having various effects such as vasodilation [ j.nat. prod.63, 1702(2000) ], inhibition of platelet aggregation [ biol.pharm.bull.21, 79(1998), [ Korean j.ginseng sci.21, 132(1997) ], protection of brain neurons [ j.neuroscience res.53, 426(1998) ], Neuro Report 9, 226(1998) ], while ginseng glycosides Rg3, Rg5, Rh2 and Rh1 have Anticancer activity [ jj.j.J.candr res.87, 357), (1996), j.clin.col.120, 24(1993) ], Anticancer res.17, 1067 (150, 41(2000), dietetic Anticancer antigens, 274) ] (2000).
For the purpose of long-term storage, fresh ginseng is generally processed into white ginseng and red ginseng. It has been reported that red ginseng contains trace amounts of ginseng glycosides such as Rg3, Rg5, Rk1, Rh2 and Rh1 and maltol which is not contained in fresh ginseng or white ginseng, thereby imparting an enhanced therapeutic effect to red ginseng. An apparatus capable of preparing a red ginseng extract from fresh ginseng or white ginseng has also been invented (Korea unaxamined patent publication No. 10-2001-19628). In addition, there have been studies mainly focused on enhancing the pharmaceutical effects by increasing the amount of the aforementioned ginseng glycosides contained in red ginseng.
Recently, "sun ginseng" (sun ginseng), a type of ginseng processed by a new method, has been disclosed, in which ginseng is heat-treated at a temperature of 120-. However, this approach has several disadvantages: require special equipment such as high-pressure heaters and require high heat treatment at temperatures higher than those conventionally used, thus resulting in carbonization of ginseng, particularly in mass production.
[ SUMMARY OF THE INVENTION ]
Accordingly, it is an object of the present invention to provide a novel method for processing ginseng, in which an extract of processed ginseng can significantly increase the content of ginsenoside having more enhanced medicinal effects. In the present invention, the inventors mixed ginseng with other important herbs and heated the resulting mixture at 70-120 ℃ to finally obtain a processed ginseng extract in which the ratio of ginseng glycosides (Rg3+ Rg5)/(Rb1+ Rb2+ Rc + Rd) is increased to 10-45, preferably 20-45, thereby greatly increasing the medicinal effect of the processed ginseng extract. For example, the processed ginseng extract prepared according to the present invention thus obtained shows about 65-97 times higher vasodilation rate compared to other conventional ginseng extracts. Further, in the present invention, ginseng is mixed with at least one herb selected from the group consisting of: schisandra, hawthorn, dogwood, papaya, smoked plum, orange, bitter orange, apple, pomegranate and lemon, and heat-treated at a temperature of 70-120 ℃, resulting in the conversion of protopanaxadiol (protopanaxadiol) -based saponins into ginseng glycosides such as Rg3, Rg5, Rk1, and simultaneously converting protopanaxatriol (protopanaxatriol) -based saponins into ginseng glycosides such as Rg2, F4, Rh1, and the like.
It is another object of the present invention to provide an extract of saponin fraction of processed ginseng and an extract of saponin fraction of processed ginseng in which the ratio of ginsenoside (Rg3+ Rg5)/(Rb1+ Rb2+ Rc + Rd) is increased to 10 to 45, preferably 20 to 45, with more enhanced medicinal effect.
It is still another object of the present invention to provide a supplementary health beverage containing the aforementioned concentrated or diluted extract of processed ginseng.
It is still another object of the present invention to provide supplementary health food or medicine containing the aforementioned processed ginseng extract in the form of tablet, capsule, pill, granule.
[ brief description of the drawings ]
The foregoing aspects and other features of the invention are explained in the following description, taken in connection with the accompanying drawings, wherein:
FIG. 1 shows thin layer chromatography of the saponin fraction of processed ginseng of the present invention and the saponin fraction of conventional ginseng (PG: Comp. Ex.4; GC: Ex.21; GS: Ex.22; RG: Comp. Ex.5; RGS: Ex.28);
FIG. 2 shows thin layer chromatography of the saponin fraction of processed ginseng of the present invention and the saponin fraction of conventional ginseng (1: Comp. Ex.4; 2: Ex.22; 3: Ex.21; 4: Ex.23; 5: Ex.24; 6: Ex.25; 7: Ex.26; 8: Ex.27; 9: Comp. Ex.5; 10: Ex.28);
FIG. 3 shows the HPLC results of the saponin fraction of ginseng processed with white ginseng plus Schisandra chinensis or white ginseng plus Hawthorn (PG-Q: Comp.Ex.4; GC-1: Ex.21; GS-1: Ex.22); and
fig. 4 shows the results of comparing the saponin fraction of ginseng processed according to the present invention, the saponin fraction of conventional ginseng and the ginsenoside Rg3 for vasodilation.
[ disclosure of the invention ]
The present invention relates to processed ginseng extracts or extracts of saponin fractions thereof, wherein the ratio of the ginsenosides (Rg3+ Rg5)/(Rb1+ Rb2+ Rc + Rd) is 10-45.
The present invention also relates to a novel method for processing ginseng, wherein human participants are mixed with at least one herb selected from the group consisting of: fructus Schisandrae, Fructus crataegi, Corni Fructus, Fructus Chaenomelis, mume Fructus, Fructus Citri Junoris, Fructus Aurantii, Fructus Mali Pumilae, Fructus Punicae Granati and Fructus Citri Limoniae (Fructus) by heat treating the obtained mixture at 70-120 deg.C.
The present invention also relates to a pharmaceutical or health food prepared in various forms, which contains the aforementioned extract of processed ginseng or saponin fraction extract thereof as an active ingredient, based on the following results: the processed ginseng or its saponin fraction extract is effective in treating and preventing cardiovascular diseases, erectile dysfunction, cerebral neurons and related diseases, anticancer, etc.
The present invention is described in more detail as set forth below.
In the present invention, the amount of the acidic natural herb is 10-1000 parts with respect to at least one selected from the group consisting of schisandra, hawthorn, cornus officinalis, papaya, smoked plum, orange, bitter orange, apple, pomegranate and lemon with respect to 100 parts of ginseng used. Mixing the selected herbs and ginseng in the presence of 4-10 times by weight of water to the above mixture and heating for 1-6 hours, cooling to room temperature, filtering, concentrating and finally preparing into the form of extract or powder. More specifically, the amount of water used in this step is 7-10 times higher than the above mixture at the initial extraction stage.
The heating is carried out at a temperature of 70-120 c, preferably at the boiling point of the components. In addition, the use of industrially conventional equipment is sufficient for large-scale commercial production without further necessary precision equipment.
The time required for the heating process is 1 to 6 hours, preferably 3 to 5 hours. If the heating process is longer than 6 hours, it is likely that the ginseng glycosides Rg3 and Rg5 will be decomposed without significant change in the overall yield of the extract.
The thus obtained processed ginseng extract can be directly used to satisfy the object of the present invention, however, the extraction may further comprise a step of evaporating water, followed by extraction with heating in the presence of ethanol or methanol for 1 to 3 hours. The introduction of an alcohol extraction process will make it possible to obtain more satisfactory results, especially when it is applied to a process designed to increase the yield of saponin extraction.
The processed ginseng extract thus obtained generally contains impurities derived from herbs and ginseng having no medicinal effect. Thus, the thus obtained extract of processed ginseng may be further purified by using the following steps, including:
extracting by using dichloromethane;
extracting the aqueous phase of the above extract several times with water saturated butanol and combining the butanol extracts;
washing the butanol extract with water;
concentrating the butanol extract; and is
Dissolving the concentrated butanol extract in methanol.
The above steps can increase the purity of the saponin fraction extract of interest, and thus the purified saponin fraction extract can be used to manufacture products requiring higher purity saponins.
Examples of ginseng used in the present invention are fresh ginseng, white ginseng, ginseng radix (hairy rootginseng), red ginseng, ginseng (Panax ginseng) leaf, american ginseng, notoginseng, or Panax japonicus (Panax japonica).
Examples of herbs used in the present invention are those that give acidic properties, such as schisandra, hawthorn, dogwood, papaya, dark plum, orange, bitter orange, apple, pomegranate and lemon. At least one selected from the above herbal medicines may be used together with ginseng as a mixed prescription.
Among the above herbs, schisandra contains various lignans and thus shows effects in the following respects: preventing liver injury, repairing liver injury, normalizing liver function, accelerating secretion of bile acid, and can also be used as antibacterial agent, antioxidant, and digestive agent mainly related to lung, liver and kidney. In addition, it also shows effects in relieving fatigue, relieving stress, relieving asthenopia and promoting cognitive ability.
The hawthorn has the functions of promoting gastric secretion, resisting bacteria and prolonging antihypertensive activity, so that the hawthorn can be used as stomachic and preparations for treating intestinal diseases. In addition, hawthorn has the effects of dilating coronary arteries and lowering cholesterol, and thus is used as a blood circulation-promoting agent.
Cornus officinalis is known to have effects such as diuresis, temporary relief of hypertension, antibacterial activity, antihistamine activity, and thus is used as a nutritional tonic, astringent and hemostatic.
Citrus aurantium is used as a spice while fructus Aurantii is an aromatic stomachic used as a food material or herbal medicine. The fruits of oranges and bitter oranges contain a large amount of plant organic acids and thus can be used as a substitute for vinegar or as a spice for removing fishy smell.
Among the above herbs, ume has antibacterial activity, gastric secretion promotion, energy recovery promotion and thirst quenching effects, and thus is used as an astringent, antitussive, expectorant, antipyretic and anthelmintic.
Among the above herbs, papaya contributes to the metabolism of the body and promotes the secretion of gastric juice.
Among the above herbs, apple is rich in vitamins and minerals, especially cellulose, and is therefore an effective agent and sedative for intestinal disorders.
Among the above herbs, pomegranate is known as a tonic and is effective in preventing hypertension and arteriosclerosis. In addition, pomegranate exhibits therapeutic effects on diarrhea, dysentery, stomachache, and leucorrhea, and is also used as an insect repellent.
Lemon contains a large amount of vitamin C and thus helps to relieve fatigue and maintain healthy skin.
As described above, the present invention is characterized in that the ratio of the ginseng glycoside (Rg3+ Rg5)/(Rb1+ Rb2+ Rc + Rd) is improved to 10-45 due to a synergistic effect caused by heat extraction of a mixture consisting of ginseng and at least one herb selected from the group consisting of schisandra chinensis, hawthorn, cornus officinalis, papaya, smoked plum, orange, bitter orange, apple, pomegranate and lemon. Unlike the conventional extract of ginseng alone, the extract of ginseng processed in the present invention shows excellent pharmaceutical effects in treating and preventing hypertension, arteriosclerosis, thrombosis, erectile dysfunction, cerebral apoplexy, memory disorder, exerting anticancer activity and alleviating side effects of anticancer drugs.
In addition, the present invention relates to a pharmaceutical and health food comprising the processed ginseng extract or saponin fraction extract thereof prepared according to the present invention as an active ingredient, and various pharmaceuticals, health foods and other food additives containing the processed ginseng extract can be manufactured through conventional preparation processes. For example, the above-mentioned drugs can be prepared in the form of tablets, hard capsules, soft capsules, pills, granules, liquids, etc. for oral administration by using conventional additives such as emulsifiers, lubricants, binders, sweeteners, aromatics, and prepared in the form of injections.
The ginseng and the herbal medicine used in the present invention for preparing the processed ginseng extract have been used as medicines and dietary foods, and the heat treatment does not generate harmful substances. Therefore, the processed ginseng extract or the saponin fraction extract thereof can be safely administered.
The adult preferably takes 2-4 times daily, and about 100-1000mg of the ginseng extract or saponin fraction extract thereof per single dose according to the present invention.
When the extracted ginseng extract or its saponin fraction extract is used as a food additive, they can be added to foods in the form of beverages, tablets, granules, pills, chewing gum and candies.
As described above, the processed ginseng extract can be administered in various formulations, and shows effects in promoting erectile dysfunction, blood circulation, relieving fatigue, hypertension, treatment of arteriosclerosis, treatment of thrombosis, treatment of cerebral stroke, enhancing brain function, and also shows anticancer activity and alleviates side effects of anticancer drugs.
The following examples are intended to illustrate the invention, but they should not be construed as limiting the scope of the invention as defined by the appended claims.
[ examples ] A method for producing a compound
Example 1
2.5kg of white ginseng, 1.5kg of schisandra fruit and 40L of water were mixed together in an extraction tank and boiled for 4 hours (internal temperature 120 ℃). After evaporation of 20L of water, the resulting mixture was added to 48L of ethanol, boiled for 2 hours, cooled to room temperature and filtered (first filtrate).
The resulting residue was added to 18L of water and 48L of ethanol, boiled under heating for 3 hours, cooled and filtered (second filtrate). The resulting mixture of the combined first and second filtrates is concentrated to one third of its volume and spray dried to finally obtain a powder of the processed ginseng extract.
Example 2
2.5kg of white ginseng and 1.5kg of hawthorn were processed as in example 1 to finally obtain a powder of the processed ginseng extract.
Example 3
50g of ginseng fibrous root, 30g of schisandra fruit and 700mL of water are mixed and boiled for 4 hours. The resulting mixture was cooled to room temperature and filtered. The obtained filtrate is then concentrated in vacuo to finally obtain a processed ginseng extract.
Example 4
20g of red ginseng, 15g of schisandra fruit and 300mL of water are mixed and boiled for 3 hours. The resulting mixture was cooled to room temperature and filtered. The obtained filtrate is then concentrated in vacuo to finally obtain a processed ginseng extract.
Example 5
25g of chopped fresh ginseng, 20g of hawthorn and 200mL of water were mixed and boiled for 4 hours. The resulting mixture was cooled to room temperature and filtered. The obtained filtrate is then concentrated in vacuo to finally obtain a processed ginseng extract.
Example 6
A processed ginseng extract was obtained by the same method as in example 3 using 20g of white ginseng, 25g of papaya and 400mL of water.
Example 7
A processed ginseng extract was obtained by the same method as in example 3 using 20g of white ginseng, 15g of Prunus mume fruit and 300mL of water.
Example 8
A processed ginseng extract was obtained by the same method as in example 3 using 15g of white ginseng, 15g of orange and 200mL of water.
Example 9
A processed ginseng extract was obtained by the same method as in example 3 using 15g of red ginseng, 20g of bitter orange and 300mL of water.
Example 10
Correspondingly mixing 20g of American ginseng and 20g of dogwood; 20g of Panax japonica and 20g of hawthorn; 15g of pseudo-ginseng, 20g of dried ginseng leaves and 15g of schisandra fruit are mixed with 350mL of water and boiled for 4 hours, after which the water is distilled by evaporation. Then, the mixture was added with 400mL of ethanol, heated for reflux for 2 hours, and cooled to room temperature. The resulting mixture is filtered, and the resulting filtrate is concentrated in vacuo to finally obtain a processed ginseng extract.
Example 11
10g of white ginseng and 10g of hawthorn are mixed with 200mL of water and boiled for 1 hour. After evaporation of 100mL of water, the remaining mixture was boiled for 3 hours and the remaining water was removed by evaporation. Then, the mixture was added with 400mL of methanol and heated for reflux for 1 hour. Cooling the mixture, and filtering to obtain the final processed ginseng extract.
Example 12
10g of white ginseng and 10g of schisandra fruit were processed as in example 11 to finally obtain a powder of the processed ginseng extract.
Example 13
10g of white ginseng and 10g of dogwood were processed in the same manner as in example 11, to finally obtain a powder of a processed ginseng extract.
Example 14
10g of white ginseng and 10g of papaya were processed as in example 11 to finally obtain a powder of the processed ginseng extract.
Example 15
The same procedures as in example 11 were carried out for 10g of white ginseng and 10g of dark plum fruit to finally obtain a powder of the processed ginseng extract.
Example 16
10g of white ginseng and 10g of orange were processed as in example 11 to finally obtain a powder of the processed ginseng extract.
Example 17
10g of white ginseng and 10g of bitter orange were processed as in example 11 to finally obtain a powder of the processed ginseng extract.
Example 18
10g of Ginseng radix Rubri and 10g of Schizandrae fructus were processed as in example 11 to finally obtain a powder of the processed Ginseng radix extract.
Example 19
50g of the processed ginseng extract obtained from example 1 was dissolved in 350mL of water and then extracted 2 times with 350mL of dichloromethane. The aqueous layer was extracted 3 times with 350mL of water saturated butanol and the resulting extracts were combined together. The combined extracts were then washed with 350mL of water. Concentrating the butanol layer under vacuum to obtain the saponin fraction of the processed ginseng extract.
Example 20
50g of the processed ginseng extract obtained from example 2 was dissolved in 350mL of water and then extracted 2 times with 350mL of dichloromethane. The aqueous layer was extracted 3 times with 350mL of water saturated butanol and the resulting extracts were combined together. The combined extracts were then washed with 350mL of water. Concentrating the butanol layer under vacuum to obtain the saponin fraction of the processed ginseng extract.
Example 21
5.1g of the processed ginseng extract obtained from example 11 was dissolved in 50mL of water, and then extracted 2 times with 50mL of dichloromethane. The aqueous layer was extracted 3 times with 50mL of water saturated butanol and the resulting extracts were combined together. The combined extracts were then washed with 50mL of water. Concentrating the butanol layer under vacuum to obtain the saponin fraction of the processed ginseng extract.
Example 22
5.4g of the processed ginseng extract obtained from example 12 was processed in the same manner as in example 21, thereby finally obtaining a saponin fraction of the processed ginseng extract.
Example 23
5g of the processed ginseng extract obtained from example 13 was processed in the same manner as in example 21, thereby finally obtaining a saponin fraction of the processed ginseng extract.
Example 24
5.5g of the processed ginseng extract obtained from example 14 was processed in the same manner as in example 21, thereby finally obtaining a saponin fraction of the processed ginseng extract.
Example 25
4.8g of the processed ginseng extract obtained from example 15 was processed in the same manner as in example 21, thereby finally obtaining a saponin fraction of the processed ginseng extract.
Example 26
4.9g of the processed ginseng extract obtained from example 16 was processed in the same manner as in example 21, thereby finally obtaining a saponin fraction of the processed ginseng extract.
Example 27
5.1g of the processed ginseng extract obtained from example 17 was processed in the same manner as in example 21, thereby finally obtaining a saponin fraction of the processed ginseng extract.
Example 28
5.2g of the processed ginseng extract obtained from example 18 was processed in the same manner as in example 21, thereby finally obtaining a saponin fraction of the processed ginseng extract.
Example 29
15g of white ginseng, 5g of hawthorn and 5g of schisandra chinensis are mixed with 250mL of water and boiled for 5 hours. The mixture was cooled to room temperature and filtered. The filtrate was concentrated in vacuo to finally obtain a processed ginseng extract.
Example 30
15g of white ginseng, 4g of dogwood, 3g of hawthorn and 3g of schisandra fruit were processed in the same manner as in example 29, thereby finally obtaining a processed ginseng extract.
Reference example 1: tablet preparation
500g of the processed ginseng extract powder obtained from example 1, 196g of crystalline cellulose and 4g of magnesium stearate were thoroughly mixed, and 700mg tablets were manufactured according to a conventional tableting method.
Reference example 2: tablet preparation
500g of the processed ginseng extract powder obtained from example 2, 196g of crystalline cellulose and 4g of magnesium stearate were thoroughly mixed, and 700mg tablets were manufactured according to a conventional tableting method.
Reference example 3: hard capsule preparation
100g of the processed ginseng extract powder obtained in example 1, 95g of crystalline cellulose and 5g of silicon dioxide (SiO)2) Thoroughly mixed and made into 400mg hard capsules according to a conventional method.
Reference example 4: preparation of soft capsules
200g of the processed ginseng extract powder obtained from example 1, 280g of soybean oil, 15g of lecithin and 5g of beeswax were thoroughly mixed, and 500mg of soft capsules were manufactured according to a conventional method.
Reference example 5: preparation of granules
500g of the processed ginseng extract powder obtained in example 2, 196g of corn starch, 4g of magnesium stearate were thoroughly mixed, and granules were manufactured according to a conventional method.
Reference example 6: preparation of pills
300g of the processed ginseng extract powder obtained from example 2, 100g of corn starch, 50g of crystalline cellulose and 150g of honey were thoroughly mixed, and 100mg of pills were manufactured according to a conventional method.
Reference example 7: liquid preparation
100g of the processed ginseng extract powder obtained in example 1, 20g of the concentrated red ginseng extract (ginsenoside 140mg/g), 100g of cordyceps sinensis, 50g of jujube concentrate (brix55), 2g of vitamin B1 hydrochloride, 1g of vitamin B2, 2g of vitamin B6 hydrochloride, and 200g of sugar were dissolved in purified water to a final volume of 2L, and finally, a liquid preparation was prepared.
Reference example 8: beverage preparation
10g of the processed ginseng extract powder obtained in example 1, 1g of citric acid, 1g of gum arabic, 5g of sugar were dissolved in purified water to a final volume of 100 mL. The above mixture was sterilized at 95 ℃ for 15 seconds and cooled to finally prepare a beverage.
Comparative example 1
Extract powders were obtained by using 2kg of red ginseng, 5kg of white ginseng, 5kg of schisandra chinensis and 5kg of hawthorn, respectively, in the same manner as in example 3.
Comparative example 2
10g of white water was mixed with 200mL of water and boiled for 1 hour. After evaporation of 100mL of water, the resulting mixture was boiled for 3 hours and the remaining water was removed by distillation. Then, the mixture was added with 400mL of methanol and heated under reflux for 1 hour, cooled, and filtered to finally obtain a processed ginseng extract.
Comparative example 3
10g of red ginseng was processed in the same manner as in comparative example 2, thereby finally obtaining a red ginseng extract.
Comparative example 4
3.4g of the processed ginseng extract obtained from comparative example 2 was dissolved in 50mL of water, and then extracted 2 times with 50mL of dichloromethane. The aqueous layer was extracted 3 times with 50mL of water saturated butanol and the resulting extracts were combined together. The combined extracts were then washed with 50mL of water. Vacuum drying the butanol layer to obtain saponin fraction of the processed ginseng extract.
Comparative example 5
3.4g of the processed red ginseng extract obtained in comparative example 3 was processed in the same manner as in comparative example 4, thereby finally obtaining the saponin fraction of the processed ginseng extract.
Comparative example 6: preparation of sun-dried ginseng (Korean Pat.No.192678)
A40 mL sterile container to which 5g of white ginseng and 5mL of water were added was placed in an autoclave and heated at 120 ℃ for 2 hours. 5g of processed ginseng was collected and then extracted 3 times with 100mL of methanol, respectively. The obtained extract was concentrated, suspended in water, and then extracted 3 times with 100mL of diethyl ether, respectively. The residual aqueous phase was extracted 3 times with 100mL of butanol accordingly. Concentrating the butanol fraction to obtain the saponin fraction of the sun-dried ginseng extract.
Comparative example 7: preparation of sun-dried ginseng (Korean Pat.No.192678)
A40 mL sterile container to which 5g of white ginseng and 5mL of water were added was placed in an autoclave and heated at 130 ℃ for 2 hours. 5g of processed ginseng was collected and then extracted 3 times with 100mL of methanol, respectively. The obtained extract was concentrated, suspended in water, and then extracted 3 times with 100mL of diethyl ether, respectively. The residual aqueous phase was extracted 3 times with 100mL of butanol accordingly. Concentrating the butanol fraction to obtain the saponin fraction of the sun-dried ginseng extract.
Comparative example 8:
5g of red ginseng was extracted 3 times by heating and refluxing with 100mL of methanol for 3 hours. The extract was concentrated, suspended in water and extracted 3 times with 100mL of diethyl ether accordingly. The aqueous phase was extracted 3 times with 100mL of butanol accordingly. Combining the extracts, and concentrating to obtain saponin fraction of Ginseng radix Rubri extract.
Reference is made to comparative example 1
350g of white ginseng extract powder, 210g of the schisandra extract obtained from comparative example 1, 136g of crystalline cellulose and 4g of magnesium stearate were thoroughly mixed, and 700mg tablets were manufactured according to a conventional tableting method.
Reference is made to comparative example 2
350g of white ginseng extract powder, 210g of hawthorn extract obtained from comparative example 1, 136g of crystalline cellulose and 4g of magnesium stearate were thoroughly mixed, and 700mg tablets were manufactured according to a conventional tableting method.
Reference is made to comparative example 3
350g of red ginseng extract powder obtained from comparative example 1, 246g of crystalline cellulose, 100g of corn starch and 4g of magnesium stearate were thoroughly mixed, and 700mg tablets were manufactured according to a conventional tableting method.
Experimental example 1
The saponin fraction extracts obtained from examples 21-28 and comparative examples 4-5 were subjected to thin layer chromatography (developing solvent; chloroform: methanol: water: 15: 10: 2.5/color developer; heated after spraying with 10% sulfuric acid) (FIGS. 1 and 2). High Performance Liquid Chromatography (HPLC) is preferably performed using Capcell pak MG C18 (4.6X 250mm), detected at 203 nm. The separation was performed by elution using a solvent (a) 10% acetonitrile/water and (B) 90% acetonitrile/water gradient, and the results are shown in fig. 3.
As shown in fig. 1 and 2, the ginsenoside was not changed in comparative examples 4 and 5. However, most of the ginseng glycosides became less polar glycosides in examples 21-28.
As shown in FIG. 3, most of the ginseng glycosides in comparative example 4 (as shown in PG-Q) became Rg3, Rg5, Rk1, Rg2, Rh1 and F4 in examples 21 and 22 (GS-1: example 22, GC-1: example 21). Peaks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 represent respectively Rg1, Re, Rb1, Rc, Rb2, Rd, Rg2, Rh1, F4, (20S) -Rg3, (20R) -Rg3, Rk1, Rg 5.
The saponin fraction extracts obtained from examples 19 to 28 and comparative examples 4 to 7 were analyzed by HPLC, and the ratio of ginsenoside (Rg3+ Rg5)/(Rb1+ Rb2+ Rc + Rd) was analyzed according to the peak-related area of each component, and the results are shown in table 1 below.
[ TABLE 1 ]
Comparison of the peak correlation area of the saponin fraction extracts
| Sample (I) | Rg3 | Rg5 | Rb1 | Rb2 | Rc | Rd | (Rg3+Rg5)/(Rb1+Rb2+Rc+Rd) |
| Ex.19 | 27.35 | 29.90 | 0.12 | 1.01 | 0.14 | 0.11 | 41.48 |
| Ex.20 | 28.84 | 31.31 | 0.10 | 1.20 | 0.17 | 0.10 | 38.31 |
| Ex.21 | 24.40 | 26.43 | 0.61 | 0.71 | 2.27 | 0.61 | 12.10 |
| Ex.22 | 25.63 | 28.63 | 0.22 | 1.61 | 0.30 | 0.20 | 23.28 |
| Ex.23 | 26.12 | 28.94 | 0.28 | 1.48 | 0.40 | 0.34 | 22.02 |
| Ex.24 | 27.63 | 29.80 | 1.22 | 1.50 | 1.54 | 1047 | 10.02 |
| Ex.25 | 24.32 | 27.36 | 0.52 | 0.64 | 2.15 | 0.52 | 13.49 |
| Ex.26 | 25.84 | 28.64 | 0.24 | 1.12 | 0.34 | 0.28 | 27.51 |
| Ex.27 | 24.77 | 27.04 | 0.31 | 1.00 | 0.83 | 0.41 | 20.31 |
| Ex.28 | 26.44 | 29.20 | 0.20 | 0.74 | 0.22 | 0.28 | 38.63 |
| Comp.Ex.4 | 3.82 | 4.42 | 19.22 | 11.17 | 17.09 | 10.55 | 0.14 |
| Comp.Ex.6 | 24.12 | 11.35 | 10.46 | 7.74 | 10.66 | 5.58 | 1.03 |
| Comp.Ex.7 | 21.00 | 16.17 | 4.06 | 3.44 | 3.98 | 3.82 | 2.43 |
| Comp.Ex.8 | 1.05 | 1.05 | 30.11 | 9.69 | 12.45 | 1.76 | 0.03 |
As shown in the above table 1, the ratio of the processed ginseng extract ginsenoside (Rg3+ Rg5)/(Rb1+ Rb2+ Rc + Rd) prepared according to the present invention was in the range of 10 to 45, which is much higher than those of the saponins obtained in comparative examples 6 and 7, wherein the ratio was in the range of 1.03 to 2.43. Furthermore, although the processed ginsenosides prepared in examples 19 and 20 were obtained by using the same herbs as examples 21 and 22, the ratio of ginsenoside (Rg3+ Rg5)/(Rb1+ Rb2+ Rc + Rd) of the processed ginsenosides prepared in examples 19 and 20 was greatly increased compared to the ratio obtained in examples 21 and 22, even because the batch process was performed on a larger scale.
Experimental example 2: improving erectile dysfunction
40 men with 45-60 years old erectile dysfunction were divided into 5 groups such that each group consisted of 8 men. They were administered 3 times per day 2 tablets each time for 30 days with the drugs prepared in the above-mentioned reference examples 1 and 2 and reference comparative examples 1, 2 and 3. The effect of the administration is shown in table 2.
[ TABLE 2 ]
Processed ginseng extract for improving erectile dysfunction
| Classification | Reference example 1 | Reference example 2 | Reference is made to comparative example 1 | Reference is made to comparative example 2 | Reference is made to comparative example 3 |
| Is remarkably improved | 4 Male sex | 4 Male sex | 0 Male | 0 Male | 1 Male sex |
| Improvements in or relating to | 2 Male sex | 2 Male sex | 1 Male sex | 1 Male sex | 2 Male sex |
| Minor improvement | 1 Male sex | 1 Male sex | 1 Male sex | 1 Male sex | 1 Male sex |
| Without change | 1 Male sex | 1 Male sex | 6 Male sex | 6 Male sex | 4 Male sex |
| Total number of patients | 8 Male sex | 8 Male sex | 8 Male sex | 8 Male sex | 8 Male sex |
| Effective rate (%) | 87.5 | 87.5 | 25 | 25 | 50 |
As shown in table 2, men administered with the processed ginseng extracts obtained according to the present invention as in reference examples 1 and 2 showed an improvement of erectile dysfunction of 87.5% while the extracts obtained in reference comparative examples 1 and 2 had no significant effect. It is also known that the red ginseng extract (refer to comparative example 3) has a therapeutic effect of improving erectile dysfunction, however, the processed ginseng extract prepared according to the present invention shows a better effect than the conventional ginseng extract in improving erectile dysfunction.
Experimental example 3: improving peripheral blood circulation
40 male diabetic patients, who were 45 to 60 years old and accompanied by mild neurological disorders, were divided into 5 groups, each group consisting of 8 male patients. They were administered 6 tablets of the preparations prepared in the above-mentioned reference examples 1 and 2, reference comparative examples 1 and 2, and blood flow of the right foot of each subject was measured with a Laser Doppler flow meter (Laser Doppler flowmeter) before, 45 and 90 minutes after the administration, respectively. The placebo group was given tablets prepared by using the same amount of corn starch. The effect of the administration is shown in table 3.
[ TABLE 3 ]
Blood circulation improving effect of processed Ginseng radix extract (blood flow mL/min/100g tissue)
| Classification | Before administration | 45 minutes after administration | 90 minutes after administration |
| Reference example 1 | 4.1±1.5 | 5.5±1.8 | 6.2±2.0 |
| Reference example 2 | 4.1±1.4 | 5.8±1.7 | 6.9±1.9 |
| Reference is made to comparative example 1 | 4.0±1.6 | 4.2±1.5 | 4.6±1.6 |
| Reference is made to comparative example 2 | 4.2±1.6 | 4.5±1.6 | 5.0±1.7 |
| Placebo group | 4.2±1.5 | 4.1±1.4 | 4.3±1.6 |
As shown in table 3, the blood circulation was significantly increased by 51.2% and 68.2% in the subjects of examples 1 and 2, respectively, while the blood circulation was increased by only 15% and 19% in the reference comparative examples 1 and 2, respectively, thus illustrating the superior effect of the processed ginseng extract prepared according to the present invention in promoting blood circulation.
Experimental example 4: comparison of vasodilation Effect
The thoracic aorta was isolated from SD rats and cut into 2-3mm wide rings, with extreme care to keep the endothelium intact. The arterial preparations were suspended between hooks in an organic bath containing 20ml Krebs' bicarbonate buffer (mM: NaCl, 118; KCl, 4.7; CaCl)2，2.5；NaHCO3，25；MgSO4，1.2；KH2PO41.2; and glucose, 11.0), with a gas mixture (95% O)2，5％CO2) Bubbled and held at 37 ℃. The arterial preparation was equilibrated for 60 minutes at 2 grams of static pull. The isotonicity response was measured by displacing the transducer with force (Grass FT03, Grass Ins., Quincy, MA, USA) and displayed on a chart recorder (Multicorder MC 6625, Hugo Sachs E1 electronic, March, Germany). Arterial preparations were preshrinked with phenylephrine (PE, 300nM) limits. After contraction stabilization, acetylcholine (1 μ M) was added to confirm endothelial presence. The arterial preparation was then washed 3 times for 45 minutes and re-challenged with PE. After PE, the reaction reached a steady height and all compounds (1. mu.M-1 mM) were added cumulatively to the tissue bath. The samples used were those in examples 21 and 22 and comparative example 4The obtained saponin fraction extract.
As shown in fig. 4, the saponin fraction extract of ginseng processed according to the present invention had a higher vasodilating effect than that of comparative example 4. For example, the saponin fraction extracts of ginseng processed in example 21 (indicated by black circles) and example 22 (indicated by open circles) had 65-fold and 97-fold higher vasodilation effects than the saponin fraction extracts of comparative example 4 (indicated by black triangles), respectively. The processed ginseng prepared according to the present invention shows better pharmaceutical effects than the processed ginseng disclosed in Korean patent No.192678 and j.of Nature Products 63, 1702, 2000.
Experimental example 5: action on hypertension
21 men 45-60 years old with hypertension were divided into 2 groups of 10 and 11. One group was administered with the tablets prepared in reference example 2 for 30 days, 2 tablets each time, 3 times a day; while another group was administered the tablet prepared in reference comparative example 2, and blood pressure was measured. The measurement results of blood pressure are shown in table 4.
[ TABLE 4 ]
Hypotensive effect of processed ginseng
| Patient's health | Reference example 2 (before administration- > after administration) (mmHg) | Variations (mmHg) | Patient's health | Reference is made to comparative example 2 (before administration- > after administration) (mmHg) | Variations (mmHg) |
| 1 | 148-＞120 | -28 | 12 | 160-＞162 | +2 |
| 2 | 150-＞128 | -22 | 13 | 170-＞170 | 0 |
| 3 | 178-＞150 | -28 | 14 | 166-＞164 | -2 |
| 4 | 160-＞146 | -14 | 15 | 158-＞143 | -15 |
| 5 | 162-＞130 | -32 | 16 | 156-＞154 | -2 |
| 6 | 154-＞126 | -28 | 17 | 150-＞148 | -2 |
| 7 | 158-＞130 | -28 | 18 | 160-＞143 | -17 |
| 8 | 166-＞146 | -20 | 19 | 172-＞170 | -2 |
| 9 | 180-＞144 | -36 | 20 | 160-＞164 | +4 |
| 10 | 170-＞168 | -2 | 21 | 154-＞160 | +6 |
| 11 | 158-＞140 | -18 |
As shown in table 4, the processed ginseng extract according to the present invention reduced systolic blood pressure of 90.9% of hypertensive patients when they were administered for one month, and resulted in a reduction in blood pressure of-14 to-36 mmHg, whereas patients administered with a mixture of hawthorn extract and conventional ginseng extract showed only a 20% reduction in blood pressure while the remaining 80% did not significantly change, thus illustrating the superiority of the processed ginseng extract of the present invention in reducing systolic blood pressure.
Experimental example 6: anti-platelet aggregation effect
Blood (15% citric acid-citrate-glucose used as an anticoagulant) collected from gill-like veins of healthy men was centrifuged at 120 × g for 15 minutes to separate plasma. The obtained plasma was centrifuged at 500 Xg for 10 minutes to obtain platelets. Platelets were suspended at 200 million platelets/mL to obtain washed platelets. The effect of the processed Ginseng extract on collagen-induced platelet aggregation was measured in accordance with the method consistent with Journal of Ginseng Research (vol.21, 132, 1997), and the results are shown in Table 5.
[ TABLE 5 ]
Inhibition of collagen-induced platelet aggregation by processed ginseng extract
| Group of | IC(μg/mL) |
| Example 21 | 11.5±1.2 |
| Example 22 | 9.4±1.4 |
| Comparative example 4 | 492.0±14.4 |
As shown in Table 5, the 50% Inhibitory Concentrations (IC) were compared50) The processed ginseng extract of the present invention showed respective 52-fold and 42-fold higher potency than the conventional ginseng extract (comparative example 4) in terms of platelet aggregation inhibition, and thus is expected to be a strong candidate for the treatment of hypertension, arteriosclerosis, cerebral stroke, etc.
Experimental example 7: has effect in relieving side effects of anticancer drugs
The saponin fraction of the processed ginseng extract of the present invention was tested for its effect on reducing the side effects caused by the administration of the anticancer drug cisplatin, in particular, in reducing renal function. 30 SD rats weighing about 200g were divided into 5 groups each consisting of 6 rats, and 5mg/kg/mL cisplatin solution was injected intraperitoneally, except for the control group injected with saline. Separately, 300mg/kg of saponin fraction extracts obtained in example 22 and comparative example 4 were intraperitoneally injected at 72, 48, 24, and 12 hours before cisplatin administration (pre-treatment group), and also at 12, 24, 48, and 72 hours after cisplatin administration (post-treatment group). On day 4, blood was collected from the mice and serum was prepared.
The renal toxicity index blood urea nitrogen was determined using a Blood Urea Nitrogen (BUN) detection kit. 0.02mL of a mixture consisting of 0.1mL of the original urease concentrate and 20mL of a buffer solution, and serum prepared from the above rat blood and 0.02mL of a urea standard solution were incubated at 37 ℃ for 15 minutes, 2mL of a developing reagent was added, incubated at 37 ℃ for 5 minutes, and the optical density was measured at 570 nm.
Creatinine as an index of renal toxicity is determined by a creatinine detection kit.
0.5mL of serum prepared from the above mouse was added with 4mL of tungstate solution, vigorously shaken, and then centrifuged at 1500 Xg for 10 minutes. The supernatant was recovered, mixed with 3mL of creatinine standard solution (control plus 3mL of distilled water), 1mL of picric acid salt solution, and 0.5mL of 1.4M NaOH solution, and thoroughly mixed. After 15 minutes, the optical density was measured at 515 nm.
[ TABLE 6 ]
Use of saponin fraction extract for improving renal toxicity caused by anticancer drugs
| Group of | Urea nitrogen (mg/dL) | Creatinine (mg/dL) |
| Control group | 21.1±2.3 | 0.51±0.14 |
| Cisplatin treatment group | 98.5±2.5 | 3.45±0.40 |
| EXAMPLE 22 pretreatment group | 75.4±2.4 | 1.58±0.20 |
| EXAMPLE 22 post-treatment group | 20.5±2.6 | 0.64±0.18 |
| Comparative example 4 post-treatment group | 78.6±2.4 | 2.48±0.31 |
As shown in table 6, the saponin fraction extract-treated group obtained in example 22 showed that urea nitrogen and creatinine values were restored to near normal states.
Experimental example 8: measurement of cerebral neuron protective Effect
To investigate the effect of the saponin fraction of processed ginseng of the present invention on the treatment and prevention of stroke in brain, the effect of the saponin fraction on the death of neurons in brain caused by excessive glutamate was measured in a manner consistent with that in j.neurosci.res.53, 426(1998), and the results are shown in table 7.
[ TABLE 7 ]
Protective effect of saponin part on death of cerebral neurons caused by excessive glutamate
As shown in table 7, the saponin fraction extract obtained in example 20 showed better preventive effect against neurotoxicity caused by glutamate, compared to the extract in comparative example 4.
Experimental example 9: antitumor activity
Human cancer cells were inoculated in calf serum medium and cultured for 48 hours, followed by subculture in 96-well cultures for 1 day. After 48 hours of treatment with the processed ginseng extract, the culture was added to MTT solution and insoluble formazine was formed. After centrifugation, the pellet was dissolved in formalin in dimethyl sulfoxide and the optical density was determined at 570nm using an automatic plate reader. The concentration at which 50% of the cells survived was calculated and the results are shown in table 8.
[ TABLE 8]
Inhibition of human cancer cell growth by processed saponin fraction extract of ginseng (MTT method)
As shown in Table 8, the processed ginsenoside fraction extracts of the present invention (examples 21 and 22) showed stronger anticancer activity than the conventional extract of white ginseng (comparative example 4).
In addition, the antitumor activity of the saponin fraction extract was measured by the srb (sulfohodamine b) method, and the results are shown in table 8-1.
[ TABLE 8-1 ]
In vitro antitumor Activity (Unit: 50% effective concentration (μ g/mL)
As shown in Table 8-1, the processed ginsenoside fraction extracts of the present invention (examples 21 and 22) showed stronger antitumor activity than the conventional extract of white ginseng (comparative example 4).
Experimental example 10: comparison of improved brain function
20 aged persons (10 persons each of male and female) aged 61-70 years who had a memory loss disorder were divided into 2 groups, and the number of men and women in each group was equal, and tablets prepared in reference example 2 and reference comparative example 2 were administered 2 tablets at a time for 3 months, 2 times a day, respectively. The degree of memory improvement was observed by a questionnaire and the results are shown in table 9.
In table 9, when "improvement" and "significant improvement" are combined as effective, the processed ginseng extract of the present invention showed an effective rate of 80% compared to the 30% effective rate of the conventional ginseng extract in reference example 2, thus illustrating the superiority of the processed ginseng extract of the present invention in improving brain function by improving memory loss disorders.
[ TABLE 9 ]
Level of improvement in brain function
| Group of | Reference example 2 (number of persons) | Reference is made to comparative example 2 (number of persons) |
| Is remarkably improved | 5 | 1 |
| Improvements in or relating to | 3 | 2 |
| Without change | 2 | 7 |
| Total of | 10 | 10 |
Experimental example 11: toxicity test
Toxicity test of the processed ginseng extract was performed as follows. The processed ginseng extracts obtained in examples 1 and 2 were dissolved in a 0.2% Tween 80 solution, and ICR mice weighing about 20g were orally administered with 5g extract per kg body weight (20 mice per group). The mice were observed for 7 days, and no death of the mice was observed.
[ INDUSTRIAL APPLICABILITY ]
As described above, the method used in the present invention, in which human participants are mixed with at least one herb selected from the group consisting of, for example, schisandra, hawthorn, cornus, papaya, smoked plum, orange, bitter orange, apple, pomegranate and lemon and boiled in water, can produce more potent synergistic pharmaceutical effects than the mere ginseng extract or the simple mixing of the ginseng extract and one or more herbs after the ginseng and herbs are processed separately. This is because the processed ginseng extract prepared in the present invention contains a large amount of the ginseng glycosides such as Rg3, Rg5, Rk1, etc., which are not contained in white ginseng and a small amount of the ginseng glycosides (Rg3+ Rg5)/(Rb1+ Rb2+ Rc + Rd) in red ginseng, wherein the ratio of the ginseng glycosides (Rg3+ Rg5)/(Rb1+ Rb2+ Rc + Rd) is 10 to 45. The processed ginseng extract prepared in the present invention shows utility as a preventive and therapeutic agent for improving erectile dysfunction, blood circulation, fatigue, hypertension, arteriosclerosis, thrombosis, brain function, cerebral apoplexy, and as a health supplement food or a pharmaceutical cancer adjuvant therapeutic agent. The processed ginseng extract prepared in the present invention can be conveniently manufactured and administered in the form of, for example, liquid, tablet, granule, pill, hard capsule or soft capsule.
Claims (13)
1. Processed ginseng extract, wherein the ratio of the ginseng glycosides (Rg3+ Rg5)/(Rb1+ Rb2+ Rc + Rd) is 10-45.
2. The processed ginseng extract according to claim 1, wherein the ratio of the ginseng glycosides (Rg3+ Rg5)/(Rb1+ Rb2+ Rc + Rd) is 20-45.
3. A processed ginsenoside fraction extract, wherein the ratio of ginsenoside (Rg3+ Rg5)/(Rb1+ Rb2+ Rc + Rd) is 10-45.
4. A processed ginsenoside fraction extract of claim 3, wherein the ratio of the ginsenosides (Rg3+ Rg5)/(Rb1+ Rb2+ Rc + Rd) is 20-45.
5. A method for processing ginseng by heat extraction, comprising the steps of:
(i) adding 4-10 times by weight of water to the obtained mixture consisting of 100 parts of ginseng and 10-1000 parts of at least one herb selected from the group consisting of schisandra, hawthorn, dogwood, papaya, smoked plum, orange, bitter orange, apple, pomegranate and lemon, and heating at 70-120 ℃ for 1-6 hours;
(ii) cooling the mixture to room temperature and filtering the mixture; and
(iii) concentrating the filtrate to prepare an extract or powder form.
6. The method of processing ginseng according to claim 5, wherein said method further comprises a heat extraction step after step (i), wherein said water is evaporated and the remaining mixture is heated in the presence of ethanol or methanol for 1-3 hours.
7. The method of processing ginseng of any one of claims 5 or 6, wherein said ginseng is selected from the group consisting of white ginseng, fresh ginseng, beard ginseng, red ginseng, ginseng leaf, American ginseng, pseudo-ginseng and panax japonicus.
8. A pharmaceutical composition comprising the processed ginseng extract or the saponin fraction extract of ginseng of claim 1 as an active ingredient.
9. The pharmaceutical composition of claim 8, wherein the pharmaceutical composition is used for improving blood circulation, erectile dysfunction, hypertension, arteriosclerosis, antithrombotic formation, brain function, fatigue alleviation, and treatment and prevention of cerebral stroke.
10. The pharmaceutical composition of claim 8, wherein the pharmaceutical composition is used for preventing and/or treating cancer and alleviating side effects of anticancer drugs.
11. The pharmaceutical composition of any one of claims 8, 9 or 10, wherein the pharmaceutical composition is prepared in a form selected from the group consisting of a liquid preparation, a tablet, a granule, a pill, a hard capsule or a soft capsule.
12. A food additive comprising the processed ginseng extract or the saponin fraction extract of ginseng of claim 1 as an active ingredient.
13. A health supplementary food containing the processed ginseng extract or the saponin fraction extract of ginseng of claim 1 as an active ingredient.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR10-2002-0000572 | 2002-01-05 | ||
| KR10-2002-0000572A KR100425022B1 (en) | 2002-01-05 | 2002-01-05 | Ginseng extract and pharmaceutical composition containing it |
| PCT/KR2003/000003 WO2003056929A1 (en) | 2002-01-05 | 2003-01-02 | Method for processing ginseng and the uses of extract of processed ginseng |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HK1069508A1 HK1069508A1 (en) | 2005-05-27 |
| HK1069508B true HK1069508B (en) | 2009-10-23 |
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