KR20150095605A - Composition comprising ginsenosides for treating or preventing Cold, Avian influenza, or Swine influenza - Google Patents

Abstract

The present invention relates to a pharmaceutical composition comprising one kind selected from the group consisting of ginsenoside Rd, ginsenoside Rb1, ginsenoside Rb2, ginsenoside F3, ginsenoside F5, ginsenoside Rg1, ginsenoside Re and ginsenoside Rh18 The present invention relates to a composition for preventing or treating cold, avian influenza or swine influenza. The ginsenoside is highly effective in inhibiting intracellular infection of avian influenza or swine influenza virus and can be used as a therapeutic agent for a cold, avian influenza or swine influenza, and is also useful for cosmetics, health food, animal feed, Can be applied.

Description

The present invention relates to a composition for preventing or treating cold, avian influenza or swine influenza comprising ginsenoside,

The present invention relates to a pharmaceutical composition comprising one kind selected from the group consisting of ginsenoside Rd, ginsenoside Rb1, ginsenoside Rb2, ginsenoside F3, ginsenoside F5, ginsenoside Rg1, ginsenoside Re and ginsenoside Rh18 The present invention relates to a composition for preventing or treating cold, avian influenza or swine influenza.

Influenza viruses are classified as A, B, and C as Orthomyxoviruses belonging to Orthomyxia. Type A is a virus that has been confirmed to be infected in pigs, other mammals, and various wild birds compared to B and C types, which are mainly infected to humans. Recently, Avian influenza, Swine influenza and Novel flu, all of which are a problem in the world, all belong to type A virus.

There are two proteins on the surface of influenza virus: hemagglutinin (HA) and neuraminidase (NA). There are 16 species of HA and 9 species of NA. Therefore, 16 × 9 = 144 influenza viruses May occur. Influenza infections in birds are mainly associated with H5, H7 and H9 types, and only three types of hemagglutinin (H1, H2, H3) and two forms of neuraminidase (N1 and N2) In principle, humans should not be infected with avian influenza because they cause infections. However, recent avian influenza viruses have been spreading directly to people without the process of recombination of avian influenza viruses.

In addition to contact with poultry such as chickens, ducks and turkeys, avian influenza is spread rapidly through wild birds and migratory birds in Korea. The avian influenza virus is transmitted periodically from Southeast Asia where avian influenza occurs, and is spread from China through spring dust, especially from China. Bird flu, a disease that is a worldwide problem, has resulted in more than 150 billion won in direct damages, including 5.3 million chickens and ducks slaughtered in Korea since 1996, and 200 million bird flu cases in Asia The livestock products are slaughtered and the economic loss of the poultry industry is enormous.

The new H7N9 avian influenza (AI) virus, which occurred in 2013 and causes panic throughout China, is a virus that can spread from birds to humans. The virus is a deadly virus in humans, and until April 28, 2013, the total number of infected AI patients is as high as 24 deaths among 118 people, with a mortality rate of more than 20%. It is reported that the province where the patients were found in China has increased to 10, which is about one-third of China's 31 provinces and cities. Especially, the worry is that the mutation of virus has already started, There has been a recent argument that it is possible to spread between humans when it goes one step further. A Chinese viral surgeon told The Lancet, "The change in the gene amino acid position of the new AI virus has already occurred three times, and if it goes one more time, the stable gene structure will be destroyed and human transmission will occur." Respectively.

Swine influenza (Swine influenza) was first reported in 1918. Swine influenza (N-acetylneuraminic acid α2, 6 galactose) and influenza receptors (N-acetylneuraminic acid α2,3 galactose) Are known to play the role of virus mixing vessels in which avian influenza virus can be infected to humans through reassortment or adaptation in the pig's body.

It is estimated that H1N1, a swine influenza virus, has been infected with pigs and has been transformed into a disease that can be transmitted to humans. The H1N1 influenza has basically symptoms like high fever and cough like a cold, but it is possible that it becomes a virus that is lethal to humans more than the present condition. The number of people infected by the World Health Organization (WHO) has reached 343,200 by October 2009, more than 4,000 people have died, and in 2010 the World Health Organization (WHO) 6 stage of the pandemic. The general symptoms of H1N1 flu are very difficult to distinguish from common flu. The H1N1 flu is characterized by fever, sore throat, cough, runny nose or nasal congestion similar to common flu. According to recent reports of H1N1 influenza, it is characterized by severe lethal lung injury, Treatment is a very important issue.

In order to prevent the development of influenza virus, it is necessary to secure a vaccine, but it is almost impossible to prepare a vaccine that prevents all RNA viruses that are mutated every time due to preventive national vaccine measures. It is therefore essential to develop therapeutic agents that can prevent and treat avian influenza, swine influenza, swine flu, or the emergence of new pathogenic influenza pandemic influenza A (H1N1) flu. Currently, the only treatment for avian influenza, swine influenza and swine flu is oseltamivir phosphate, an oral therapeutic agent developed as a selective inhibitor of viral originated neurominidase, and the inhaled zanamivir. Nausea, vomiting, nervous system and mental disorders have been reported as adverse effects of Tamiflu, which is widely used as an oral therapeutic agent. In Japan, the number of deaths in pediatric patients confirmed after the approval of Tamiflu is 15 or so. In the meantime, there is a need to prepare for the emergence of resistant virus against Tamiflu, which is used as an oral therapeutic agent. Recently, the emergence of resistant virus against Tamiflu, which is already lethal to the spread of H1N1 virus, Even human transmission is being discovered. Therefore, the development of antiviral drugs against avian influenza, swine influenza and swine flu is essential for human health and safety.

Cold is the most common illness caused by influenza viruses and is a common influenza virus type A, B, C, adenovirus, corona virus, rhinovirus, RS Viruses (respiratory syncytial virus) due to various causes such as treatment, prevention, vaccine production is not easy to belong to the disease. Therefore, it is urgent to develop a therapeutic agent capable of effectively treating various viruses that can cause a cold.

When we look at the general process of virus propagation, we first see that the virus meets the host cell and enters the host cell. This process is called adsorption and penetration. Once a virus enters the host cell, the virus will uncoate all the structures except the genome, process it to replicate the new genome using the exposed genome, and propagate it to produce proteins that surround the genome multiplication, and mass production of new genomes and new proteins of the virus. Then, the new virus is created as a new virus through assembly and maturation, which releases new virus particles using newly created genomes and proteins, and release through which the virus particles leave the cells in the host cells.

Rather than experimentally transforming existing medicines to develop new medicines in general, finding new active ingredients from natural medicines used in traditional medicine has many advantages. Particularly, these active ingredients have been used for a long time and thus they are less toxic to the drugs. This fact can be confirmed from the fact that Tamiflu which is used as a treatment for the H1N1 influenza was developed as a main ingredient of star anise, a native plant of China.

Panax ginseng (P anax ginseng CA Meyer) is mainly used as a medicinal part, and it is used by removing the root roots of the root and drying or using whole plant. Especially in Korea, white ginseng (raw), red ginseng (red ginseng: steamed), and ginseng (蔘 蔘: thin roots) are used according to the medicinal effect. In the private sector, wild ginseng camphor and wild ginseng are distinguished. In China, it refers to the roots and rootstocks of ginseng and distinguishes it from raw ginseng (red ginseng), red ginseng and wild ginseng (wild ginseng). This medicine has a peculiar odor, taste is slightly sweet, and it is known to be slightly warm (甘苦 微 温). It is used for body weakness, boredom, fatigue, anorexia, vomiting and diarrhea. And it is known to increase the anxiety and renal function.

In recent years, ginseng has been hydroponically cultivated, and ginseng including both the ground and the underground part has been cultivated within a certain time, and commercial technology development has been actively conducted. Ginseng cultivated by hydroponics has been reported to be used as a food material by the Food and Drug Administration. It has been reported that crude saponin content is significantly higher in leaves and stems than roots.

Therefore, the inventors of the present invention conducted a cytopathic effect reduction assay (CPE reduction assay) for comparing the survival rate of infected cells after infecting host cells with avian influenza virus and swine influenza virus, The antiviral activity of ginsenoside was measured and the present invention was completed. The cytopathic effect restoration assay is based on the assumption that a specific substance with an antiviral effect directly inhibits 1) the proliferation, replication and release of viruses, 2) increases the amount of interferon- ) It is an experimental method that uses the principle that virus-infected cells will survive if the natural healing power can be increased by strengthening the function of infected cells.

Korean Patent No. 1035463, Korean Patent Publication No. 2009-0037595 and Korean Patent No. 855409 [J. Med. Foods, 2012, 15 (10), 855-862) discloses that black ginseng extract, ginseng or red ginseng extract, and American ginseng fractions, which are one kind of processed ginseng, are effective for avian influenza and cold flu, Of the ginsenosides have an antiviral effect on influenza virus.

Korean Patent No. 1035463 (Composition for prevention and treatment of highly pathogenic avian influenza virus containing root extract of black ginseng as active ingredient, registered on May 11, 2011) Korean Patent Publication No. 2009-0037595 (Anti-avian influenza virus composition, disclosed on Apr. 16, 2009) Korean Patent No. 855409 (Registration of US ginseng fractions, products containing them, and use of US ginseng fractions as an immunomodulator, Aug. 25, 2008)

Yoo, D.G. et al, Protective effect of Korean red ginseng extract on the infections by H1N1 and H3N2 influenza viruses in mice. J. Med. Food., 2012, 15 (10), 855-862.

It is an object of the present invention to provide a pharmaceutical composition which is selected from the group consisting of ginsenoside Rd, ginsenoside Rb1, ginsenoside Rb2, ginsenoside F3, ginsenoside F5, ginsenoside Rg1, ginsenoside Re and ginsenoside Rh18 And a composition for preventing or treating cold, avian influenza or swine influenza comprising at least one compound.

The present invention relates to a pharmaceutical composition comprising ginsenoside Rd (compound 1 ), ginsenoside Rb1 (compound 2 ), ginsenoside Rb2 (ginsenoside Rb2, compound 3 ), ginsenoside F3 , Compound 4 ), ginsenoside F5 (compound 5 ), ginsenoside Rg1 (ginsenoside Rg1, compound 6 ), ginsenoside Re (compound 7 ), and ginsenoside Rh18 , Compound 8 ). The present invention relates to a composition for preventing or treating cold, avian influenza or swine influenza.

[Chemical Formula 1]

The present invention also provides a pharmaceutical composition comprising ginsenoside Rd, ginsenoside Rb1, ginsenoside Rb2, ginsenoside F3, ginsenoside F5, ginsenoside Rg1, ginsenoside Re, and ginsenoside Rh18 of Formula 1 And a health functional food for preventing or ameliorating a cold, avian influenza or swine influenza comprising at least one compound selected from the group consisting of

The present invention also provides a pharmaceutical composition comprising ginsenoside Rd, ginsenoside Rb1, ginsenoside Rb2, ginsenoside F3, ginsenoside F5, ginsenoside Rg1, ginsenoside Re and ginsenoside Rh18 of the above formula An animal medicine or a feed additive for the prevention or treatment of a cold, avian influenza or swine influenza containing at least one compound selected from the group consisting of:

The present invention also provides a pharmaceutical composition comprising ginsenoside Rd, ginsenoside Rb1, ginsenoside Rb2, ginsenoside F3, ginsenoside F5, ginsenoside Rg1, ginsenoside Re and ginsenoside Rh18 of the above formula A natural disinfectant for the prevention or treatment of a cold, avian influenza or swine influenza virus containing at least one compound selected from the group consisting of:

Hereinafter, the present invention will be described in detail.

The ginsenosides of the present invention can be synthesized by a conventional method and can be used in an amount of from 2 to 50 times (w / v) water of ginseng (ginseng roots, leaves or stems) or ginseng (red ginseng or black ginseng) Four lower alcohols, acetone, ethyl acetate, chloroform, or an extract of ginseng or ginseng products extracted with a mixed solvent of these. The lower alcohol may be selected from ethanol, methanol, propanol, isopropanol and butanol.

The ginseng or ginseng extract may be extracted with an organic solvent (alcohol, aqueous alcohol solution, ethyl acetate, acetone, chloroform, etc.), hexane and water, method of using adsorption resin such as Diaion HP-20 resin, The ginsenosides of the present invention can be easily obtained by a known method used for the separation and extraction of plant components, either alone or in a suitable combination.

Preferably, n-hexane, ethyl acetate, n-butanol and the like are sequentially added to the extract of the ginseng or ginseng work product in an amount of 2 to 50 times (w / v) of the weight of the extract, Can be used to isolate compounds with antiviral activity.

Chromatography used in the present invention includes silica gel column chromatography, LH-20 column chromatography, thin layer chromatography (TLC) and high performance liquid chromatography high performance liquid chromatography, etc.) can be used.

The activity of ginsenoside of the present invention can be measured by treating the cells infected with avian influenza virus (H9N2) or swine influenza virus (H1N1) virus to confirm the antiviral effect Assay) can be used to confirm.

The present invention also provides a pharmaceutical composition comprising a compound selected from the group consisting of ginsenoside Rd, ginsenoside Rb1, ginsenoside Rb2, ginsenoside F3, ginsenoside F5, ginsenoside Rg1, ginsenoside Re and ginsenoside Rh18 A pharmaceutical composition comprising at least one compound may be provided. The pharmaceutical compositions may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterilized injection solutions according to a conventional method. Examples of carriers, excipients and diluents that can be included in the composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose or lactose, gelatin, . In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Examples of the liquid preparation for oral administration include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included . Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate, and the like. Examples of the suppository base include witepsol, macrogol, tween 61, cacao butter, laurin, glycerogelatin and the like.

The dosage of the pharmaceutical composition will vary depending on the age, sex, body weight, the specific disease or condition to be treated, the severity of the disease or condition, the route of administration, and the judgment of the prescriber. Dosage determinations based on these factors are within the level of ordinary skill in the art and generally the dosage ranges from 0.01 mg / kg / day to approximately 2000 mg / kg / day. A more preferable dosage is 1 mg / kg / day to 500 mg / kg / day. The administration may be carried out once a day or divided into several times. The dose is not intended to limit the scope of the invention in any way. The pharmaceutical composition of the present invention can be administered to mammals such as rats, livestock, humans, and the like in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine dural or intracerebral injection. Since the pharmaceutical composition of the present invention has little toxicity and side effects, it can be safely used even for long-term administration for the purpose of prevention.

The present invention also provides a pharmaceutical composition comprising a compound selected from the group consisting of ginsenoside Rd, ginsenoside Rb1, ginsenoside Rb2, ginsenoside F3, ginsenoside F5, ginsenoside Rg1, ginsenoside Re and ginsenoside Rh18 Which comprises at least one compound of formula (I) and at least one compound of formula (I) and at least one pharmaceutically acceptable food additive. The health functional food of the present invention includes forms such as tablets, capsules, pills, and liquids. Examples of the foods to which the extract of the present invention can be added include various foods, beverages, gums, tea, vitamins , And health functional foods.

On the other hand, the present invention is characterized in that it is selected from the group consisting of ginsenoside Rd, ginsenoside Rb1, ginsenoside Rb2, ginsenoside F3, ginsenoside F5, ginsenoside Rg1, ginsenoside Re and ginsenoside Rh18 Lt; RTI ID = 0.0 > of at least one < / RTI > The animal drug or feed additive can also be used for influenza diseases commonly occurring in animals and humans.

The present invention relates to a pharmaceutical composition comprising one kind selected from the group consisting of ginsenoside Rd, ginsenoside Rb1, ginsenoside Rb2, ginsenoside F3, ginsenoside F5, ginsenoside Rg1, ginsenoside Re and ginsenoside Rh18 The present invention relates to a composition for preventing or treating cold, avian influenza or swine influenza. The ginsenoside is highly effective in inhibiting avian influenza or swine influenza virus and can be used as a therapeutic agent for a cold, avian influenza or swine influenza, and can be applied to cosmetics, health food, animal feed, and animal medicine industry.

Brief Description of the Drawings Fig. 1 is a graph showing the effect of the compound ginsenoside Rh18 (ginsenoside Rh18, compound 8) ¹³ C NMR results, and shows the HMBC spectrum analysis results.
FIG. 2 shows the results of the cell-lesion recovery assay, After infecting the H1N1 virus, the compound ginsenoside Rb2 (compound 3, Fig. 2A), ginsenoside F3 (compound 4, Fig. 2B), ginsenoside Rg1 (compound 6, Fig. 2C) and ginsenoside Re (Compound 7, Fig. 2D) by concentration and shows the cell viability in MDCK cell line by concentration.
Fig. 3 shows the results of treatment of ginsenoside Rb1 (Fig. 3D), ginsenoside Re (Fig. 3E) and ginsenoside Rh18 (Fig. 3F) at a concentration of 5 / / ml in MDCK cell line as a host cell after infection with H1N1 virus This is a photomicrograph showing the degree of cell recovery.

Hereinafter, preferred embodiments of the present invention will be described in detail. However, the present invention is not limited to the embodiments described herein but may be embodied in other forms. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the concept of the invention to those skilled in the art.

Example 1 Confirmation of Solvent Extraction Conditions of Active Compound from Ginseng Leaf

The ginseng leaf (ginseng leaf part) used in the present invention was purchased in the local market of Gwangju. After drying the ginseng leaves, 10 g of the dried ginseng leaves were extracted using an ultrasonic extractor for 3 hours using distilled water, 200 ml of a solvent such as ethanol, methanol, acetone, ethyl acetate or chloroform for 4 hours. After that, the extract from which the solid content was removed was concentrated under reduced pressure to obtain an extract of 0.35 to 4.40 g per each extract. The antiviral activity of each of the extracts was confirmed using the method of Example 4, and the results are shown in Table 1. As shown in Table 1, the activity of ginseng leaf extract was good in the condition of 50% ethanol aqueous solution, 90% ethanol aqueous solution and 70% aqueous methanol solution, and 70% Respectively.

extract Extraction quantity
(G) extraction amount per 10 g of dry sample) Active measurement concentration
(占 퐂 / ml) For the H1N1 infected group
Cell viability of each extract 30% ethanol aqueous solution extract 4.02 g 20 8.67% 50% ethanol aqueous solution extract 4.40 g 20 25.06% 70% ethanol aqueous solution extract 4.21 g 20 40.23% 90% ethanol aqueous solution extract 4.01 g 20 35.06% 70% aqueous methanol solution extract 3.89 g 20 41.85% Ethanol extract 3.13 g 20 7.85% Methanol extract 3.06 g 20 2.50% Acetone extract 0.86g 20 2.53% Ethyl acetate extract 0.75 g 20 3.45% Chloroform extract 0.35 g 20 4.28% Distilled water extract 4.36 g 20 3.75%

≪ Example 2: Isolation of saponin compound from ginseng leaf extract >

To 5 kg of ginseng leaves, 10 L of 70% aqueous ethanol solution was added and extracted at room temperature. This procedure was performed three times in total. The extract was concentrated under reduced pressure to give a dry product. The dried 70% ethanol extract (550 g) was suspended in 5 L of water, which was then sequentially fractionated with 4 L each of ethyl acetate and n-butanol. Each fractionation step was repeated three times.

Subsequently, the butanol fraction (245 g) was subjected to silica gel column chromatography (20 × 60 cm; 63-200 μm particle size) under the solvent gradient of ethyl acetate-methanol (10: 1 → 0: 1) Seven small fractions were obtained (F1-F7). A portion (110 mg) of the fraction F1 (12.7 g) was subjected to HPLC (YMC J-sphere ODS-H80 column 10 x 250 mm; 10 mu m particle size 2 ml / min; UV detection: a portion of the subject to 205nm was] performed scored compound 8 (16㎎), compound 5 (35㎎) is a small fraction F3 (16.0g) (983㎎) methanol in water (66:34) mobile phase HPLC [YMC J-sphere ODS-H80 column 10 x 250 mm; 10 mu m particle size 2 ml / min; UV detection: 205 nm].

On the other hand, 7 fractions (F5.1-F5.7) were obtained by fractionating F5 (30.5 g) with Sephadex eletch-20 column chromatography (7 x 30 cm) using methanol as a solvent. The small fraction F5.3 (3.2 g) was subjected to reversed phase (RP-18) column chromatography (5.0 × 30 cm; LiChroprep RP-18 40-63 μm (YMC J-sphere ODS-H80 column, 10 × 250 mm) was used as a mobile phase in methanol-water (66:34) as the mobile phase. 10 mu m particle size 2 ml / min; UV detection: 205 nm] to obtain Compound 4 (12.5 mg) and Compound 6 (102.1 mg). Compound 1 (1.2 g) was purified by reverse phase (RP-18) column chromatography (solvent: ethyl acetate: methanol: water = 1: 4 → 11: (1: 2 - > 1: 0) in the same column as the fraction of compound 1, and Compound 7 (111.6 mg) .

The small fraction F6 (70.6 g) was subjected to silica gel column chromatography (10 × 70 cm; 63-200 μm particle size) under a solvent condition of chloroform-methanol (40: 1 → 0: 1) to obtain fraction F6.9 g). The small fraction F6.9 (6.8 g) was subjected to reverse phase (RP-18) column chromatography (5.0 × 60 cm; LiChroprep RP-18 40-63 μm particle size) to obtain F6.9.18. A portion of the small fraction F6.9.18 (293 mg) in which the antiviral activity strongly appeared was purified by HPLC (YMC J-sphere ODS-H80 column 10x250 mm; methanol-water (66:34 → 70:30) as a mobile phase. 10 mu m particle size 2 ml / min; UV detection: 204 nm] was carried out to obtain Compound 2 (25 mg) and Compound 3 (36 mg).

<Example 3> Analysis of physicochemical properties and chemical structure of ginsenoside of the present invention>

The results of mass spectrometry and nuclear magnetic resonance measurement of the compounds isolated from the ginseng leaves are as follows.

Example 3-1. Ginsenoside Rd (compound 1)

ESI-MS m / z : 947 [M + H] &lt; ^{+ &}

¹ H-NMR (400 MHz, d ₅ -pyridine): 0.81 (1H, m, H-1a), 1.55 m, H-2b), 3.27 (1H, dd, J = 7.5, 4.5 Hz, H-3), 0.68 (1H, br d, J = 12.5 Hz, H- (1H, m, H-6), 1.50 (1H, m, H-6b), 1.20 1H, m, H-11a) , 1.50 (1H, m, H-11b), 4.12 (1H, m, H-12), 1.96 (1H, d, J = 10.8 Hz, H-13), 1.62 (1H m, H-15a), 1.04 (1H, m, H-15b), 1.73 (1H, m, H-16a), 1.26 ), 1.16 (3H, s, H-18), 1.01 (3H, s, H-19), 1.58 (3H, s, H-21), 2.37 (1H, td, J = 13.0, 3.2 Hz, H- 22a), 1.79 (1H, td , J = 12.5, 5.0 Hz, H-22b), 2.46 (1H, m, H-23a), 2.21 (1H, m, H-23b), 5.24 (1H, t, J = 7.5 Hz, H-24), 1.58 (3H, s, H-26), 1.58 (3H, s, H- 29), 0.80 (3H, s, H-30); 3-Glc: 4.92 (1H, d, J = 6.5 Hz, H-1 '), 4.25 (1H, dd, J = 6.9, 4.6 Hz, H-2'), 4.30 (1H, t, J = 4.2 Hz , H-3 '), 4.24 (1H, t, J = 4.1 Hz, H-4'), 3.93 (1H, d, J = 4.4 Hz, H-5 '), 4.55 (1H, dd, J = 11.0 , 4.5 Hz, H-6 '), 4.32 (1H, dd, J = 10.8, 4.1 Hz, H-6');2'-Glc: 5.40 (1H, d, J = 7.8 Hz, H-1 "), 4.13 (1H, dd, J = 7.7, 4.3 Hz, H-2"), 4.31 (1H, t, J = 4.8 Hz, H-3 "), 4.15 (1H, t, J = 4.2 Hz, H-4"), 3.90 (1H, d, J = 4.7 Hz, H-5 "), 4.48 (1H, dd, J = 11.1, 4.3 Hz, H-6 "a), 4.36 (1H, dd, J = 11.1, 3.2 Hz, H-6"b); 20-Glc: 5.15 (1H, d, J = 7.5Hz, H-1 "'), 3.98 (1H, t, J = 8.5 Hz, H-2"'), 4.23 (1H, m, H-3 "'), 4.17 (1H, m, H-4"'), 3.91 ( 1H, m, H-5 ''), 4.47 (1H, dd, J = 12.0, 2.5 Hz, H-6 ''), 4.31 (1H, m, H-

^{13 C-NMR (100 Hz,} d 5 -pyridine): 39.1 (C-1), 27.2 (C-2), 89.0 (C-3), 39.7 (C-4), 56.4 (C-5), 18.4 (C-6), 35.2 (C-7), 39.8 (C-8), 50.6 (C-9), 37.0 C-13), 50.7 (C-14), 30.5 (C-15), 26.8 (C-16), 51.7 C-22), 22.0 (C-21), 36.1 (C-22), 23.0 27), 31.9 (C-28), 16.5 (C-29), 17.5 (C-30); (C-1 '), 83.5 (C-2'), 78.2 (C-3 '), 72.0 ); (C-1), 77.1 (C-2), 78.5 (C-3 "), 71.7 "); (C-4 ''), 78.2 (C-5 ''), 62.5 (C- (C-6 "').

Example 3-2. Ginsenoside Rb1 (ginsenoside Rb1, compound 2)

ESI-MS m / z : 1109 [M + H] &lt; ^{+ &}

¹ H-NMR (400 MHz, d ₅ -pyridine): 0.79 (1H, m, H-1a), 1.55 m, H-2b), 3.29 (1H, dd, J = 7.6, 4.5 Hz, H-3), 0.68 (1H, br d, J = 12.0 Hz, H- (1H, m, H-6), 1.50 (1H, m, H-6b), 1.20 1H, m, H-11a) , 1.51 (1H, m, H-11b), 4.12 (1H, m, H-12), 1.96 (1H, d, J = 10.4 Hz, H-13), 1.62 (1H m, H-15a), 1.04 (1H, m, H-15b), 1.75 (1H, m, H-16a), 1.26 ), 1.16 (3H, s, H-18), 1.01 (3H, s, H-19), 1.60 (3H, s, H-21), 2.37 (1H, td, J = 13.0, 3.5 Hz, H- M, H-23b), 5.21 (1H, t, J ), 1.80 (1H, td, J = 12.5, 5.0 Hz, H-22b), 2.46 H-24), 1.58 (3H, s, H-26), 1.59 (3H, s, H-27), 2.05 29), 0.82 (3H, s, H-30); 3-Glc: 4.93 (1H, d, J = 5.8 Hz, H-1 '), 4.23 (1H, dd, J = 7.0, 4.6 Hz, H-2'), 4.30 (1H, t, J = 4.5 Hz , H-3 '), 4.24 (1H, t, J = 4.1 Hz, H-4'), 3.93 (1H, d, J = 4.3 Hz, H-5 '), 4.55 (1H, dd, J = 10.8 , 4.5 Hz, H-6 '), 4.32 (1H, dd, J = 11.1, 4.1 Hz, H-6'b);2'-Glc: 5.42 (1H, d, J = 7.8 Hz, H-1 "), 4.13 (1H, dd, J = 7.7, 4.3 Hz, H-2"), 4.31 (1H, t, J = 4.8 Hz, H-3 "), 4.14 (1H, t, J = 4.2 Hz, H-4"), 3.90 (1H, d, J = 4.7 Hz, H-5 "), 4.48 (1H, dd, J = 11.1, 4.3 Hz, H-6 "a), 4.36 (1H, dd, J = 11.0, 3.2 Hz, H-6"b); 20-Glc: 5.16 (1H, d, J = 7.1 Hz, H-1 (1H, m, H-4 ''), 3.91 (1H, t, J = 8.5 Hz, 1H, m, H-5 ''), 4.65 (1H, dd, J = 12.0, 2.5 Hz, H-6 ''), 4.31 (1H, m, H- (1H, d, J = 6.8 Hz, H-1 '''), 4.01 (1H, t, J = 8.5 Hz, H- 3 ""), 4.17 (1H , m, H-4 ""), 3.91 (1H, m, H-5 ""), 4.35 (1H, dd, J = 12.0, 2.5 Hz, H-6 "" a ), 4.31 (1H, m, H-6 "" b).

^{13 C-NMR (100 Hz,} d 5 -pyridine): 39.0 (C-1), 27.2 (C-2), 89.0 (C-3), 39.7 (C-4), 56.4 (C-5), 18.4 (C-6), 35.1 (C-7), 39.8 (C-8), 50.6 (C-9), 37.0 C-13), 50.8 (C-14), 30.5 (C-15), 26.8 (C-16), 51.7 C-22), 22.1 (C-21), 36.1 (C-22), 23.1 27), 31.9 (C-28), 16.5 (C-29), 17.5 (C-30); 3-Glc: 105.3 (C-1 '), 83.5 (C-2'), 78.5 (C-3 '), 72.0 ); (C-1), 77.1 (C-2), 78.5 (C-3), 71.9 "); (C-2 ''), 78.9 (C-3 ''), 71.7 (C-4 ''), 78.2 (C-6 "'); (C-1) &quot;, 77.1 (C-2) &quot;, 78.5 , 63.0 (C-6 "&quot;),

Example 3-3. Ginsenoside Rb2 (ginsenoside Rb2, compound 3)

ESI-MS m / z : 1101 [M + Na] &lt; ^{+ &}

¹ H-NMR (400 MHz, d ₅ -pyridine): 0.83 (1H, m, H-1a), 1.55 m, H-2b), 3.27 (1H, dd, J = 7.5, 4.7 Hz, H-3), 0.68 (1H, br d, J = 12.5 Hz, (1H, m, H-6), 1.50 (1H, m, H-6b), 1.23 1H, m, H-11a) , 1.52 (1H, m, H-11b), 4.12 (1H, m, H-12), 1.96 (1H, d, J = 10.8 Hz, H-13), 1.62 (1H m, H-15a), 1.06 (1H, m, H-15b), 1.73 (1H, m, H-16a), 1.26 ), 1.16 (3H, s, H-18), 1.00 (3H, s, H-19), 1.58 (3H, s, H-21), 2.37 (1H, td, J = 13.0, 3.2 Hz, H- 22a), 1.79 (1H, td , J = 11.6, 5.0 Hz, H-22b), 2.46 (1H, m, H-23a), 2.21 (1H, m, H-23b), 5.25 (1H, t, J H-24), 1.58 (3H, s, H-26), 1.60 (3H, s, H-27), 2.05 29), 0.80 (3H, s, H-30); 3-Glc: 4.95 (1H, d, J = 6.6 Hz, H-1 '), 4.25 (1H, dd, J = 6.9, 4.6 Hz, H-2'), 4.30 (1H, t, J = 4.2 Hz , H-3 '), 4.24 (1H, t, J = 4.4 Hz, H-4'), 3.93 (1H, d, J = 4.7 Hz, H-5 '), 4.55 (1H, dd, J = 11.0 , 4.5 Hz, H-6 '), 4.32 (1H, dd, J = 10.8, 4.1 Hz, H-6');2'-Glc: 5.42 (1H, d, J = 7.8 Hz, H-1 "), 4.13 (1H, dd, J = 7.7, 4.3 Hz, H-2"), 4.31 (1H, t, J = 4.8 Hz, H-3 "), 4.15 (1H, t, J = 4.2 Hz, H-4"), 3.92 (1H, d, J = 4.7 Hz, H-5 "), 4.48 (1H, dd, J = 11.1, 4.3 Hz, H-6 "a), 4.36 (1H, dd, J = 11.1, 3.2 Hz, H-6"b); 20-Glc: 5.10 (1H, d, J = 7.2 Hz, H-1 (1H, m, H-4 ''), 3.93 (1H, m, H-2 ''), 4.13 (1H, d, J ''), 4.65 (1H, d, J = 10.0 Hz, H-6 ' , J = 5.6 Hz, H- 1 ""), 4.14 (1H, m, H-2 ""), 4.28 (1H, m, H-3 ""), 4.40 (1H, m, H-4 "" ), 3.90 (1H, m, H-5 "&quot;), 4.35 (1H, m, H-5"

^{13 C-NMR (100 Hz,} d 5 -pyridine): 39.1 (C-1), 27.2 (C-2), 89.0 (C-3), 39.8 (C-4), 56.4 (C-5), 18.4 (C-6), 35.2 (C-7), 39.8 (C-8), 50.6 (C-9), 37.0 C-13), 50.7 (C-14), 30.5 (C-15), 26.8 (C-16), 51.6 C-22), 22.0 (C-21), 36.1 (C-22), 23.0 27), 31.9 (C-28), 16.5 (C-29), 17.5 (C-30); C-3 '), 72.0 (C-4'), 78.1 (C-5 '), 63.1 (C-6'); (C-1), 77.1 (C-2), 78.5 (C-3 "), 71.7 "); (C-3 ''), 72.0 (C-4 ''), 77.0 (C-5 ''), 69.0 (C-6 "');6'-Intermediate 104.9 (C-1 '''), 72.3 (C-2'''), 74.2 (C-3 '''), 68.9 (C-4'''), 66.2 (C-5 ''').

Example 3-4. Ginsenoside F3 (Compound 4)

ESI-MS m / z : 771 [M + H] &lt; ^{+ &}

¹ H-NMR (400 MHz, d ₅ -pyridine): 1.71 (1H, m, H-1a), 0.95 , m, H-2b), 3.46 (1H, dd, J = 12.0, 5.1 Hz, H-3), 1.25 (1H, d, J = 11.4 Hz, H-5), 4.47 (1H, t, J = M, H-11a (m, H-11), 2.02 (1H, m, H-7a) ), 1.49 (1H, m, H-11b), 4.15 (1H, m, H-12), 1.93 (1H, t, J = 11.0 Hz, H-13), 1.65 (1H, m, H-15a) M, H-16b), 2.46 (1H, m, H-17), 1.14 (1H, m, H-16b), 1.01 , H-18), 1.00 (3H, s, H-19), 1.61 (3H, s, H-21), 2.33 2.55 (1H, m, H- 23a), 2.30 (1H, m, H-23b), 5.30 (1H, t, J = 7.0 Hz, H-24), 1.60 (3H, s, H-26), 1.62 (3H, s, H-27), 2.01 (3H, s, H-28), 1.60 (3H, s, H-29), 0.80 (3H, s, H-30); 20-Glc: 5.10 (1H, d, J = 7.2 Hz, H-1 '), 3.92 (1H, m, H-2'), 4.13 (1H, m, H-3 '), 4.00 (1H, m , H-4 '), 4.01 (1H, m, H-5'), 4.66 (1H, d, J = 10.0 Hz, H- 6'-Ara: 5.02 (1H, d, J = 5.6 Hz, H-1 "), 4.13 (1H, m, H-2"), 4.28 (1H, m, H-3 "), 4.40 (1H, m, H-4 "), 3.90 (1H, m, H-5"), 4.35 (1H, m, H-5 ").

^{13 C-NMR (100 MHz,} d 5 -pyridine): 39.1 (C-1), 28.1 (C-2), 78.6 (C-3), 40.5 (C-4), 62.3 (C-5), 69.0 (C-6), 48.1 (C-7), 40.1 (C-8), 50.2 (C-9), 39.8 C-13), 50.9 (C-14), 30.7 (C-15), 26.8 (C-16), 51.9 C-23), 126.1 (C-24), 131.0 (C-25), 25.7 (C-26), 18.0 (C- 27), 32.0 (C-28), 16.5 (C-29), 17.2 (C-30); (C-1 '), 75.1 (C-2'), 79.4 (C-3 '), 72.0 ); 6'-Ara: 104.9 (C-1 ''), 72.4 (C-2 ''), 74.2 (C-3 ''), 68.9 (C-4 ''), 66.0 (C-5 '').

Examples 3-5. Ginsenoside F5 (compound 5)

ESI-MS m / z : 771 [M + H] &lt; ^{+ &}

^{1 H-NMR (400 MHz,} d 5 -pyridine): 1.70 (1H, m, H-1a), 0.96 (1H, m, H-1b), 1.90 (1H, m, H-2a), 1.80 (1H J = 11.0 Hz, H-3), 1.25 (1H, d, J = 11.4 Hz, H-5), 4.45 (1H, t, J = (1H, m, H-11a, 10.4 Hz, H-6), 2.03 (1H, m, H-7a), 1.96 ), 1.50 (1H, m, H-11b), 4.15 (1H, m, H-12), 1.93 (1H, t, J = 11.0 Hz, H- M, H-16b), 2.46 (1H, m, H-17), 1.14 (1H, m, H-16b) H-18), 1.00 (3H, s, H-19), 1.60 (3H, s, H-21), 2.33 2.56 (1H, m, H- 23a), 2.30 (1H, m, H-23b), 5.30 (1H, t, J = 7.0 Hz, H-24), 1.60 (3H, s, H-26), 1.63 (3H, s, H-27), 2.03 (3H, s, H-28), 1.60 (3H, s, H-29), 0.79 (3H, s, H-30); 20-Glc: 5.09 (1H, d, J = 8.0 Hz, H-1 '), 3.92 (1H, m, H-2'), 4.15 (1H, m, H-3 '), 4.00 (1H, m H-4 '), 3.99 (1H, m, H-5'), 4.65 (1H, d, J = 10.0 Hz, H- (1H, m, H-2), 4.80 (1H, t, J = 4.8 Hz, H- m, H-4 "), 4.30 (1H, m, H-5"), 4.19 (1H, m, H-5 ").

^{13 C-NMR (100 MHz,} d 5 -pyridine): 39.3 (C-1), 28.1 (C-2), 78.7 (C-3), 40.5 (C-4), 62.2 (C-5), 69.0 (C-6), 48.0 (C-7), 40.1 (C-8), 50.1 (C-9), 39.8 C-13), 50.9 (C-14), 30.5 (C-15), 26.8 (C-16), 51.7 C-22), 22.0 (C-21), 36.1 (C-22), 23.0 27), 31.9 (C-28), 16.5 (C-29), 17.3 (C-30); (C-1 '), 75.1 (C-2'), 79.2 (C-3 '), 72.2 ); (C-1), 83.4 (C-2), 78.9 (C-3), 86.0 (C-4), 62.7 (C-5).

Examples 3-6. Ginsenoside Rg1 (ginsenoside Rg1, compound 6)

ESI-MS m / z : 823 [M + Na] &lt; ^{+ &}

¹ H-NMR (500 MHz, d ₅ -pyridine): 1.70 (1H, m, H-1a), 0.98 , td, J = 12.5, 4.5 Hz, H-2b), 3.49 (1H, dd, J = 11.5, 4.5 Hz, H-3), 1.40 (1H, d, J = 10.5 Hz, H-5), 4.40 (1H, t, J = 10.5, 3.0 Hz, H-6), 2.47 (1H, m, H-7a), 1.91 2.05 (1H, m, H- 11a), 1.50 (1H, m, H-11b), 4.12 (1H, m, H-12), 1.96 (1H, d, J = 10.5 Hz, H-13), 1.62 (1H, m, H-15a), 1.04 (1H, m, H-15b), 1.72 (1H, t, J = 13.0, 3.5 Hz, 1H), 1.14 (3H, s, H-18), 1.01 M, H-23a), 1.79 (1H, td, J = 12.5, 4.5 Hz, H-22b), 2.46 , J = 7.0 Hz, H- 24), 1.58 (3H, s, H-26), 1.58 (3H, s, H-27), 2.05 (3H, s, H-28), 1.59 (3H, s, H-29), 0.79 (3H, s, H-30); 6-Glc: 5.00 (1H, d, J = 7.5 Hz, H-1 '), 4.08 (1H, m, H-2'), 4.25 (1H, m, H-3 '), 4.21 (1H, m (1H, m, H-4 '), 3.92 (1H, m, H-5'), 4.51 (1H, dd, J = 11.5, 2.5 Hz, H- ); 20-Glc: 5.15 (1H, d, J = 7.5 Hz, H-1 "), 3.98 (1H, t, J = 8.5 Hz, H-2"), 4.22 (1H, m, H-3 "), (1H, m, H-5 ''), 4.47 (1H, dd, J = 12.0, 2.5 Hz, H- H-6 "b).

^{13 C-NMR (100 MHz,} d 5 -pyridine): 39.1 (C-1), 28.0 (C-2), 78.8 (C-3), 40.4 (C-4), 61.4 (C-5), 80.1 (C-6), 45.1 (C-7), 41.1 (C-8), 50.0 (C-9), 39.7 C-13), 51.4 (C-14), 30.6 (C-15), 26.6 (C-16), 51.8 C-22), 22.3 (C-21), 36.3 (C-22), 23.2 27), 31.8 (C-28), 16.4 (C-29), 17.5 (C-30); (C-1 '), 75.5 (C-2'), 79.7 (C-3 '), 71.9 ); C-6 &quot;), 76.6 (C-5), 68.9 (C-6) ).

Examples 3-7. Ginsenoside Re (compound 7)

ESI-MS m / z : 947 [M + H] &lt; ^{+ &}

¹ H-NMR (500 MHz, d ₅ -pyridine): 1.62 (1H, m, H-1a), 0.90 m, H-2b), 3.44 (1H, m, H-3), 1.36 (1H, d, J = 11.0 Hz, H- m, H-11b), 1.47 (1H, m, H-11b) (1H, m, H-15), 4.08 (1H, m, H-12), 1.91 H-16a), 1.24 (1H, m, H-16b), 2.45 (1H, m, H-17), 1.14 (1H, m, H-22), 2.45 (1H, d, J = , 2.20 (1H, m, H-23), 5.24 (1H, m, H-24), 1.58 (3H, s, H-26), 1.58 , H-28), 1.33 (3H, s, H-29), 0.92 (3H, s, H-30); 6-Glc: 5.22 (1H, d, J = 7.5 Hz, H-1 '), 4.34 (1H, m, H-2'), 4.31 (1H, m, H-3 '), 4.18 (1H, m M, H-4 '), 3.97 (1H, m, H-5'), 4.48 (1H, br s, H-1 "), 4.76 (1H, m, H-2"), 4.65 H, td, J = 12.5, 6.5 Hz, H-5 "), 1.74 (3H, d, J = 6.0 Hz, H-6"), 20-Glc: 5.13 (1H, d, J = 8.0 Hz, H (1H, m, H-4 ''), 3.96 (1H, m, H-2 ''), 4.96 , H-5 ''), 4.43 (1H, m, H-6 ''), 4.30 (1H, m, H-6 '' b).

^{13 C-NMR (100 MHz,} d 5 -pyridine): 39.4 (C-1), 28.0 (C-2), 78.8 (C-3), 40.4 (C-4), 61.4 (C-5), 80.1 (C-6), 45.1 (C-7), 41.1 (C-8), 50.0 (C-9), 39.7 C-13), 51.4 (C-14), 30.6 (C-15), 26.6 (C-16), 51.8 C-22), 22.3 (C-22), 23.2 (C-23), 126.1 27), 31.8 (C-28), 16.4 (C-29), 17.5 (C-30); (C-2 '), 78.9 (C-3'), 72.7 (C-4 '), 78.3 ); 2'-Rha: 102.2 (C-1 ''), 72.3 (C-2 ''), 72.5 (C-3 ''), 74.2 18.9 (C-6 "'); (C-5), 69.0 (C-6), 72.5 (C-4) ).

Examples 3-8. Ginsenoside Rh18 (ginsenoside Rh18, compound 8)

ESI-MS m / z : 967 [M + Na] &lt; ^{+ &}

¹ H-NMR (400 MHz, d ₅ -pyridine): 1.52 (1H, m, H-1a), 0.87 (1H, brd, J = 12.0 Hz, H- ), 1.72 (1H, m, H-2b), 3.43 (1H, dd, J = 11.2, 5.2 Hz, H-3), 1.36 (1H, overlap, H-5), 4.37 (1H, t, J = (1H, m, H-11a), 1.32 (1H, m, H-7) (1H, m, H-11), 1.34 (1H, m, H-11b), 3.85 m, H-15b), 1.96 (1H, m, H-16a), 1.48 M, H-22b), 4.54 (1H, s), 1.01 (3H, s, H-19), 1.32 , J = 8.7 Hz, H- 23), 5.49 (1H, t, J = 7.8 Hz, H-24), 1.59 (3H, s, H-26), 1.64 (3H, s, H-27), 2.08 (3H, s, H-28), 1.54 (3H, s, H-29), 0.96 (3H, s, H-30); 6-Glc: 5.23 (1H, d, J = 6.8 Hz, H-1 '), 4.34 (1H, t, J = 8.2 Hz, H-2'), 4.29 (1H, t, J = 8.2 Hz, H H-5 '), 4.50 (1H, brd, J = 10.6 Hz, H-6'), 4.24 (1H, t, J = 8.4 Hz, ), 4.62 (1H, m, H-6'b), 20-GIc: 5.16 (1H, d, J = 7.6Hz, H- 1H, m, H-3 " ), 4.32 (1H, m, H-4"), 3.94 (1H, m, H-5 "), 4.45 (1H, brd, J = 10.6 Hz, H-6" a ), 4.34 (1H, br s, H-2 ''), 4.66 (1H, brs, H- , m, H-3 "' ), 4.38 (1H, m, H-4"'), 4.94 (1H, m, H-5 "'), 1.76 (1H, d, J = 6.0 Hz, H-6 "').

^{13 C-NMR (100 MHz,} d 5 -pyridine): 39.7 (C-1), 27.8 (C-2), 78.6 (C-3), 40.1 (C-4), 60.8 (C-5), 74.2 (C-6), 46.6 (C-7), 41.4 (C-8), 50.7 (C-9), 39.5 C-13), 50.9 (C-14), 33.1 (C-15), 25.6 (C-16), 46.2 C-25), 25.8 (C-26), 18.3 (C-23), 129.5 27), 32.1 (C-28), 17.6 (C-29), 18.1 (C-30); (C-3 '), 72.7 (C-4'), 78.3 (C-5 '), 63.2 (C-6'), ); (C-2), 79.0 (C-3), 71.9 (C-4), 78.5 ); 2'-Rha: 102.0 (C-1 ''), 72.3 (C-2 ''), 72.5 (C-3 ''), 74.2 18.8 (C-6 "').

Meanwhile, the results of ¹³ C-NMR and HMBC spectra of Compound 8 are shown in FIG.

< Example 4 > Recovery of cell lesion effect using avian influenza virus ( H9N2 ) and swine influenza virus (H1N1)

The antiviral activity of the compounds of the present invention was confirmed by a cytopathic effect reduction assay (CPE reduction assay) for evaluating the degree of restoration of cell lesion due to virus. CPE represents a morphological change due to viral infection, and degenerative changes in cell shape are associated with infection of the virus (Semin. Neurol., 1999, 19, 113-127; J. Virol. Methods, 2002, 106, 71-79).

(A / chicken / Korea / 01310/2001, H9N2) and swine influenza virus (A / Sw / Kor / CAN1 / 04, H1N1 and KCTC 11165BP) in MDCK (Madin-Darby, canine kidney) Central Vaccine Institute) and each compound was treated.

First, MDCK cells were seeded on a 96-well plate at a density of 1 × 10 4 cells / well and cultured in a 5% FBS (fetal bovine serum), 1% PS (penicillin + streptomycin) and L- glutamine (Dulbeco's Modified Eagle's Medium) supplemented with 2 ml of the culture medium. The culture was washed with PBS (phosphate buffer saline) solution. Then, the infection medium: and handle (infection media DMEM + 0.5% BSA + 1㎍ / ㎖ trypsin) , each of the influenza virus a ₅₀ TCID 50 / 100㎕ / well after compound 1-8 at the concentration of the inoculated 100㎕ . After 5 days of incubation, survival of MDCK cells was confirmed by microscopic observation and MTT. MTT (3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide, Sigma M-2128 1G) reagent is a pale yellow substrate. Living cells use a respiratory enzyme in mitochondria Create a formazan. The formation of formazan in the dead cells does not occur due to the cytotoxicity of the MDCK cells or the material itself, which are killed by virus infection. Therefore, the antiviral efficacy of the compound of the present invention can be evaluated by measuring the concentration of the formazan glass (measured at an absorbance at 550 nm). For this, first, the concentration of compound without MDCK cytotoxicity by compound (2 or 10 μg / ml) was determined through a preliminary experiment and at this concentration, the difference in denaturation of MDCK cells caused by viruses of swine influenza or avian influenza Respectively.

Thus, the CPE recovery activity of each compound concentration at 10 占 퐂 / ml (ginsenoside Rb1 was measured at 2 占 퐂 / ml in consideration of cytotoxicity) was confirmed by MTT assay (see Table 2) 1 to 8 are all found to have excellent antiviral activity.

Treatment concentration virus CPE recovery activity
(cell survial,%) Compound 1 Ginsenoside Rd (10 [mu] g / ml) H1N1 39.8 Compound 2 Ginsenoside Rb1 (2 占 퐂 / ml) * H1N1 41.2 Compound 3 Ginsenoside Rb2 (10 [mu] g / ml) H1N1 58.4 Compound 4 Ginsenoside F3 (10 占 퐂 / ml) H1N1 54.7 Compound 5 Ginsenoside F5 (10 mu g / ml) H1N1 42.3 Compound 6 Ginsenoside Rg1 (10 占 퐂 / ml) H1N1 58.5 Compound 7 Ginsenoside Re (10 占 퐂 / ml) H1N1 76.7 Compound 8 Ginsenoside Rh18 (10 占 퐂 / ml) H1N1 39.8 Compound 1 Ginsenoside Rd (10 [mu] g / ml) H9N2 35.4 Compound 2 Ginsenoside Rb1 (2 占 퐂 / ml) * H9N2 38.5 Compound 3 Ginsenoside Rb2 (10 [mu] g / ml) H9N2 55.4 Compound 4 Ginsenoside F3 (10 占 퐂 / ml) H9N2 50.4 Compound 5 Ginsenoside F5 (10 mu g / ml) H9N2 39.5 Compound 6 Ginsenoside Rg1 (10 占 퐂 / ml) H9N2 55.3 Compound 7 Ginsenoside Re (10 占 퐂 / ml) H9N2 70.7 Compound 8 Ginsenoside Rh18 (10 占 퐂 / ml) H9N2 41.2 Tamiflu (10 μM) H1N1 92.3 Tamiflu (10 μM) H9N2 90.1 * Rb1 measures activity at 2 μg / ml considering cytotoxicity.

Among these compounds, it is also possible to use a compound represented by the following formula (1): ginsenoside Rb2 (compound 3, Fig. 2A), ginsenoside F3 (compound 4, Fig. 2B), ginsenoside Rg1 2D) were examined for each concentration, and it was found that all the antiviral activities against H1N1 and H9N2 were excellent in a concentration-dependent manner.

On the other hand, referring to FIG. 3, in comparison with FIG. 3A (no virus-treated group), the cells treated with swine influenza virus in MDCK cell lines showed mostly abnormal cell morphology or dead cells (FIG. 3B) In the group treated with 5 占 퐂 / ml of Compound 2 of the present invention (ginsenoside Rb1, Fig. 3D), Compound 7 (ginsenoside Re, Fig. 3E) and Compound 8 (ginsenoside Rh18, Fig. 3F) Showed similar cell morphology and viability to the 10 [mu] M treated group (Fig. 3C), demonstrating the superior antiviral effect of the compounds of the present invention.

<Example 5: Toxicity test>

Example 5-1. Acute toxicity

This experiment was conducted to investigate the toxicity of the compound 7 (ginsenoside Re) to the animal body in an acute (within 24 hours) when an excessive amount of the compound 7 (ginsenoside Re) was consumed in a short period and to determine the mortality. Twenty ICR mouse lines were prepared, and 10 mice were assigned to each group. In the control group, only 30% PEG-400 was administered, and in the experimental group, compound 7 (ginsenoside Re) was orally administered at a concentration of 1.0 g / kg. After 24 hours of administration, the respective mortality rates were examined. As a result, the control group and the test group administered with Compound 7 (ginsenoside Re) at a concentration of 1.0 g / kg all survived.

Example 5-2. Organ organs toxicity test in experimental group and control group

To evaluate the effect of the compound 7 (ginsenoside Re) of the present invention at a concentration of 1.0 g / kg on the long-term toxicity test of C57BL / 6J mice, After 8 weeks from the control animals, blood samples were collected from Glutamate-pyruvate transferase (GPT) and Blood Urea Nitrogen (BUN) using Select E (Vital Scientific NV, Netherland). As a result, GPT, which is known to be related to hepatotoxicity, and BUN, which is known to be related to renal toxicity, showed no significant difference compared to the control group. In addition, liver and kidney were cut from each animal and histological observation was carried out with an optical microscope through a conventional tissue section production process. No abnormal abnormalities were observed.

&Lt; Use examples 1. Pharmaceutical formulations >

Use Examples 1-1. Manufacture of tablets

200 g of Compound 7 (ginsenoside Re) of the present invention was mixed with 175.9 g of lactose, 180 g of potato starch and 32 g of colloidal silicic acid. To this mixture was added a 10% gelatin solution, which was pulverized and passed through a 14-mesh sieve. This was dried, and a mixture obtained by adding 160 g of potato starch, 50 g of talc and 5 g of magnesium stearate was made into tablets.

Examples 1-2. Injection preparation

1 g of the present compound 7 (ginsenoside Re), 0.6 g of sodium chloride and 0.1 g of ascorbic acid were dissolved in distilled water to make 100 ml. This solution was placed in a bottle and sterilized by heating at 20 DEG C for 30 minutes.

<Usage example 2. Example of food production>

Use example 2-1. Manufacture of cooking seasonings

Compound 7 (ginsenoside Re) of the present invention was added to the cooking sauce at 0.2 to 10% by weight to prepare health-promoting cooking sauce.

Usage example 2-2. Manufacture of flour food products

Compound 7 (ginsenoside Re) of the present invention was added to wheat flour in an amount of 0.1 to 5.0% by weight, and bread, cake, cookies, crackers and noodles were prepared using this mixture to prepare a health improving food.

Use Example 2-3. Manufacture of soups and gravies

Compound 7 (ginsenoside Re) of the present invention was added to soups and juices in an amount of 0.1 to 1.0 wt% to prepare health-promoting meat products, noodle soups and juices.

Usage example 2-4. Manufacture of dairy products

Compound 7 (ginsenoside Re) of the present invention was added to milk in an amount of 0.1 to 1.0 wt%, and various dairy products such as butter and ice cream were prepared using the milk.

&Lt; Use Example 3 >

Use example 3-1. Vegetable juice manufacturing

0.5 g of the compound 7 of the present invention (ginsenoside Re) was added to 1,000 ml of tomato or carrot juice to prepare vegetable juice for health promotion.

Application example 3-2. Manufacture of fruit juice

0.1 g of the present compound 7 (ginsenoside Re) was added to 1,000 ml of apple or grape juice to prepare fruit juice for health promotion.

&Lt; Use Example 4. Production Example of Feed Additive >

10.0 g of Compound 7 of the present invention (ginsenoside Re) was mixed with 50.0 g of excipient for feed to prepare a feed additive. However, the compounding ratio may be arbitrarily changed, and the above components may be mixed according to a conventional method for producing a feed composition, and the mixture may be used for production.

&Lt; Example of use 5. Example of production of disinfectant >

3.0 g of the compound 7 of the present invention (ginsenoside Re) was added thereto, and 1000 ml of purified water was added thereto to prepare a natural disinfectant for a no-drying agent.

Claims (5)

(Ginsenoside Rb1, compound 2 ), ginsenoside Rb2 (ginsenoside Rb2, compound 3 ), ginsenoside F3, compound 4 , ginsenoside F5, compound 5 ), Ginsenoside Rg1 (ginsenoside Rg1, compound 6 ), and ginsenoside Rh18 (ginsenoside Rh18, compound 8 ). &Lt; / RTI &gt;
[Chemical Formula 1]

(Ginsenoside Rb1, compound 2 ), ginsenoside Rb2 (ginsenoside Rb2, compound 3 ), ginsenoside F3, compound 4 , ginsenoside F5, compound 5 ), Ginsenoside Rg1 (ginsenoside Rg1, compound 6 ), and ginsenoside Rh18 (ginsenoside Rh18, compound 8 ). Health functional foods for prevention or improvement.
[Chemical Formula 1]

(Ginsenoside Rb1, compound 2 ), ginsenoside Rb2 (ginsenoside Rb2, compound 3 ), ginsenoside F3, compound 4 , ginsenoside F5, compound 5 ), Ginsenoside Rg1 (ginsenoside Rg1, compound 6 ), and ginsenoside Rh18 (ginsenoside Rh18, compound 8 ). Animal drugs for prevention or treatment.
[Chemical Formula 1]

(Ginsenoside Rb1, compound 2 ), ginsenoside Rb2 (ginsenoside Rb2, compound 3 ), ginsenoside F3, compound 4 , ginsenoside F5, compound 5 ), Ginsenoside Rg1 (ginsenoside Rg1, compound 6 ), and ginsenoside Rh18 (ginsenoside Rh18, compound 8 ). Animal feed additives for prevention or treatment.
[Chemical Formula 1]

(Ginsenoside Rb1, compound 2 ), ginsenoside Rb2 (ginsenoside Rb2, compound 3 ), ginsenoside F3, compound 4 , ginsenoside F5, compound 5 ), Ginsenoside Rg1 (ginsenoside Rg1, compound 6 ), and ginsenoside Rh18 (ginsenoside Rh18, compound 8 ). Disinfectant for preventive or therapeutic use.
[Chemical Formula 1]

Images