KR101705760B1 - Composition for composition for prevention or treatment of rotavirus infection comprising ecklonia cava - Google Patents

Abstract

The present invention relates to a composition for prevention or treatment of rotavirus infection comprising a gangsia extract or a fraction thereof, wherein the gangsiae extract or a fraction thereof has an effect of a rotavirus, And thus can be effectively used for prevention or treatment of rotavirus infection.

Description

TECHNICAL FIELD The present invention relates to a composition for prevention or treatment of rotavirus infection,

The present invention relates to a composition for prevention and treatment of rotavirus infection comprising a gangrene extract or a fraction thereof.

Rotavirus is one of the most important causes of severe diarrhea in young animals (cattle, pigs, and goats) and infants worldwide, and is associated with severe diarrhea as well as encephalitis, otitis media, necrotizing colitis, liver abscess, (Ester, MK Rotaviruses and Their Replication in Fields Virology, pp. 1747-1785, 2001). Rotavirus belongs to the genus Reoviridae, which surrounds a 70-mm-diameter, 11-segmented double-stranded RNA genome with a three-layer capsid layer. The outermost layer of these three-layered capsid layers is composed of VP4 and VP7 proteins. Because the VP4 protein is divided into VP5 and VP8 by the protease of the host, its serotype is called P type and the VP7 protein is glycosylated, so its serotype is called G type (Ciarlet, M. and Ester, MK Rotaviruses: basic biology, epidemiology and methodologies in encyclopedia of envirionmental microbiology. Pp. 2753-2773, 2002). VP4 and VP7 proteins are important for host defense by inducing neutralizing antibodies.

The serotypes are divided into a total of seven species, from serotype to VP6, the middle-layer capsid protein, to A-G. Of these, serotyping A rotaviruses occur most commonly in humans and animals, causing annually 130 million worldwide to enteritis, of which 873,000 are known to be very important infectious agents leading to death.

Serotype A rotaviruses have been reported to be G and P type specific for each host. In humans, the combination of G1-G3, G9 and P [4] and P [8] is most prevalent (Kapikian et al., 2001). In pigs, the combination of G3-G5, G11 and P [6] and P [7] is known to be the most prevalent (Gouvea and Timenetsky, 1994). The cattle are advantageously a combination of G6, G8, G10 and P [1], P [5], and P [11] (Alfieri et al., 2004). However, similar to the influenza virus, cases where recombinant viruses are generated and infected to humans have been reported in people in countries where physical contact with animals is frequent, as different serotypes A and B viruses of humans and animals are infected (Jain et al., 2001). In Brazil and the United States, G9 rotaviruses, which predominantly occur in humans, also occur in pigs (Paul et al., 1988). Thus, an animal-derived rotavirus is detected in humans, which means that it is a "causal agent of common infectious disease," and propagation between species is also occurring among other animals.

In general, for the purpose of treating such viral diseases, methods such as inhibition of adsorption to epithelial cells, inhibition of invasion into cells, inhibition of gene transcription and replication, inhibition of protein synthesis and release from cells can be considered. Although the target of antivirals is reported, no clear target for rotavirus has been known to date.

Many vaccines have been developed to inhibit rotavirus infection, and in particular, animal-human recombinant virus vaccines made by recombining human and animal rotaviruses have been produced and sold. For example, RotaTeq (Merk), a vaccine containing VP4 with the specificity of human rotavirus main serotype based on bovine rotavirus host WC3, was approved by the US FDA in 2006 Are being sold. However, these recombinant virus vaccines are not only reported as side effects such as intrussusception, but also have a serious disadvantage that they can not prevent various serotypes of rotavirus.

To overcome the drawbacks of these vaccines, research is being conducted on natural materials that can inhibit rotavirus. Takahashi et al. Reported that the hydrothermal extract of Stevia has an antiviral effect (Takahashi, K et al., Antiviral Res. 49, 15, 2001).

Accordingly, the present inventors have confirmed that the phytotoxin extract, its fractions, or the compounds isolated therefrom have an activity to inhibit rotavirus infection and have a virucidal and cytoprotective effect against rotavirus, thereby completing the present invention .

It is an object of the present invention to provide a pharmaceutical composition for preventing or treating rotavirus infection and a therapeutic method using the same.

It is another object of the present invention to provide a food composition for preventing or treating rotavirus infection.

It is another object of the present invention to provide a quasi-drug composition for preventing or treating rotavirus infection.

In one aspect of the present invention for achieving the above object, there is provided a composition for preventing or treating rotavirus infection comprising a gangsia extract or a fraction thereof as an active ingredient.

According to another aspect of the present invention, there is provided a method of inhibiting the activity of rotavirus comprising contacting said composition with rotavirus.

Hereinafter, the present invention will be described in detail.

The present invention provides a composition for preventing or treating rotavirus infection, comprising a gangrene extract or a fraction thereof as an active ingredient.

The composition of the present invention can be used for the prevention or treatment of rotavirus infection because it simultaneously exhibits virulence virus and cytopathic effect against rotavirus.

As used herein, the term "prevention" means any action that inhibits or delays the onset of rotavirus infection by administration of the composition.

In the present invention, the term "treatment" means any action that improves or alleviates symptoms caused by rotavirus infection by the administration of the composition.

The rotavirus may be Human, Pocine, Bovine, or Goat rotavirus. In addition, the rotavirus may cause enteritis, diarrhea, cold, sore throat, bronchitis, and pneumonia.

Typically Ecklonia cava (Ecklonia cava ) is a perennial seaweed of Alariaceae and grows deep in the lunch band. The length is usually 1 ~ 2m, the stem is cylindrical, and the base is roots.

In the present invention, phytotoxin can be purchased commercially or used directly from Jeju Island.

As the method for producing the extracts of the menthol, the conventional extraction methods such as an ultrasonic extraction method, a filtration method and a reflux extraction method can be used. Preferably, the dry matter obtained by pulverizing the impurities from which the impurities are removed by washing and drying can be extracted with water, a C ₁ to C ₄ alcohol or a mixed solvent thereof, more preferably C ₁ to C ₄ It may be an alcohol-extracted extract, and most preferably an extract extracted with methanol or ethanol. At this time, the extraction solvent is preferably 2 to 20 times the dry weight of the gut. For example, the dried gangue is cut into small pieces and placed in an extraction container, and a lower alcohol of C ₁ to C ₄ or a mixed solvent thereof, preferably methanol or ethanol, is added, and the mixture is allowed to stand at room temperature for a certain period of time and then filtered to obtain an alcoholic extract . At this time, the extraction is preferably allowed to stand at room temperature for 1 week, and thereafter, a method such as concentration or freeze-drying may further be carried out.

In addition, hot water of 80 to 90 ° C is connected to a reflux apparatus and allowed to stand for 6 hours, and then filtered to obtain a hot-water extract. Thereafter, a method such as concentration or freeze-drying may further be carried out.

On the other hand, the gut fractions in the present invention can be obtained by fractionation from the gut extract obtained above. More specifically, the menthol fraction can be obtained by suspending the menthol extract in water and then fractionating the concentrate with hexane and ethyl acetate, respectively, to obtain hexane fraction, ethyl acetate fraction and water fraction.

Meanwhile, the composition for preventing or treating rotavirus infection of the present invention may be a pharmaceutical composition.

When the composition of the present invention is a pharmaceutical composition, the composition may include a pharmaceutically acceptable carrier. The composition comprising a pharmaceutically acceptable carrier can be of various oral or parenteral formulations. 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 one or more excipients such as starch, calcium carbonate, sucrose or lactose lactose, gelatin and the like. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like are also used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the non-aqueous solvent and the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate. Examples of the suppository base include witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like.

The pharmaceutical composition may be in the form of tablets, pills, powders, granules, capsules, suspensions, solutions, emulsions, syrups, sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations and suppositories It can have one formulation.

The composition of the present invention is administered in a pharmaceutically effective amount.

The term "pharmaceutically effective amount " as used herein means an amount sufficient to treat a disease at a reasonable benefit / risk ratio applicable to medical treatment, and the effective dose level will vary depending on the species and severity, age, sex, , The activity of the drug, the sensitivity to the drug, the time of administration, the route of administration and rate of release, the duration of the treatment, factors including co-administered drugs, and other factors well known in the medical arts. The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. And can be administered singly or multiply. It is important to take into account all of the above factors and to administer the amount in which the maximum effect can be obtained in a minimal amount without adverse effect, and can be easily determined by those skilled in the art.

The composition of the present invention can be used alone or in combination with methods for the prevention or treatment of rotavirus infection or using surgery, hormone therapy, drug therapy and biological response modifiers.

Meanwhile, the present invention provides a method for treating a rotavirus infection disease comprising the step of administering a composition for preventing or treating the rotavirus infection to a subject having an invention or incidence of rotavirus infection in a pharmaceutically effective amount . The rotavirus may be Human, Pocine, Bovine, or Goat rotavirus. In addition, the rotavirus infection diseases may be enteritis, diarrhea, cold, sore throat, bronchitis, and pneumonia.

The term "individual" as used herein refers to all animals, including humans, that are already infected or infected with rotavirus, and by administering to the individual a composition comprising the extract or fraction of the present invention, the disease is effectively prevented and treated . For example, humans infected with various rotavirus subtypes or variant human rotaviruses can be treated with the composition of the present invention. In addition, the composition of the present invention can treat humans infected with various rotavirus subtypes or variant rotaviruses. In addition, pigs, cows, or chlorine infected with various rotavirus subtypes or variant rotaviruses can be treated. The composition of the present invention can be administered in combination with a conventional therapeutic agent for rotavirus infection.

The route of administration of the composition may be administered via any conventional route so long as it can reach the target tissue. The composition of the present invention may be administered intraperitoneally, intravenously, intramuscularly, subcutaneously, intradermally, orally, intranasally, intrapulmonarily, or rectally, though it is not intended to be limited thereto. The composition may also be administered by any device capable of transferring the active agent to the target cell.

In addition, the present invention provides a food composition for prevention or treatment of rotavirus infection, which comprises a Ganoderma lucidum extract or a fraction thereof as an active ingredient.

That is, the gut extract or fraction thereof of the present invention may be added to a food composition for preventing or treating rotavirus infection. When the extract or fraction thereof of the present invention is used as a food additive, the extract or fraction may be directly added or used together with other food or food ingredients, and may be appropriately used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (prevention, health or therapeutic treatment). Generally, in the production of food or beverage, the composition of the present invention is added in an amount of 0.01 to 10% by weight, preferably 0.05 to 1% by weight based on the raw material. However, in the case of long-term ingestion intended for health and hygiene purposes or for the purpose of controlling health, the amount can also be used in the above-mentioned range.

There is no particular limitation on the kind of the food. Examples of the food to which the above substances can be added include dairy products including meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, other noodles, gums, ice cream, various soups, drinks, tea, Alcoholic beverages, and vitamin complexes, all of which include healthy foods in a conventional sense.

The health beverage composition of the present invention may contain various flavors or natural carbohydrates as an additional ingredient such as ordinary beverages. Such natural carbohydrates are monosaccharides such as glucose and fructose, disaccharides such as maltose and sucrose, and polysaccharides such as dextrin and cyclodextrin, and sugar alcohols such as xylitol, sorbitol and erythritol. Examples of sweeteners include natural sweeteners such as tau martin and stevia extract, synthetic sweeteners such as saccharin and aspartame, and the like. The ratio of the natural carbohydrate is generally about 0.01 to 0.04 g, preferably about 0.02 to 0.03 g per 100 ml of the composition of the present invention.

In addition to the above, the composition of the present invention may further contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acids and salts thereof, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusting agents, stabilizers, preservatives, A carbonating agent used in a carbonated beverage, and the like. In addition, the composition of the present invention may contain flesh for the production of natural fruit juice, fruit juice beverage and vegetable beverage. These components may be used independently or in combination. The proportion of such additives is not critical, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention. These components can be used independently or in combination.

In addition, the present invention provides a quasi-drug composition for prevention or treatment of rotavirus infection, comprising a gangsia extract or a fraction thereof as an active ingredient.

That is, the composition of the present invention may be added to a quasi-drug composition for the purpose of preventing or treating rotavirus infection. When the gut extract or its fractions of the present invention are used as a quasi-drug additive, the extract or fraction may be used as it is or may be used together with other quasi-drug components, and may be suitably used according to a conventional method. The amount of the active ingredient to be mixed can be suitably determined according to the intended use (prevention, health or therapeutic treatment).

Preferably, the quasi-drug composition may be a disinfectant solution, a shower foam, a gagrin, a wet tissue, a detergent soap, a hand wash, a humidifier filler, a mask, an ointment or a filter filler.

The present invention also provides a method for inhibiting the activity of rotavirus comprising contacting said composition with rotavirus. At this time, the contact is made by a conventional method, and the rotavirus includes living organisms, tissues or cell cultures, biological material samples (blood, serum, urine, cerebrospinal fluid, tears, sputum, saliva, It can usually contain pathogenic organisms such as viruses. These samples can be contained in any medium containing water and an organic solvent / water mixture.

It can also be observed by any method, including direct or indirect, methods of diagnosing antiviral activity after administration of the composition of the present invention. Any of the quantitative, qualitative or semi-quantitative methods for diagnosing rotavirus infection-inhibiting activity may be used, and any other method may be applied, such as observing the physiological characteristics of living organisms.

The compositions containing the gangsia extract or fractions thereof according to the present invention exhibit an effect of inhibiting the activity of rotavirus and simultaneously exhibit a live virus and a cytopathic inhibitory effect against various rotaviruses and thus are useful for the prevention or treatment of rotavirus infection Lt; / RTI >

FIG. 1 is a graph showing the effect of virucidal virus according to the administration dose of Ganoderma lucidum extract.

Hereinafter, the present invention will be described in more detail with reference to Examples and Experimental Examples. However, the following examples are illustrative of the present invention and are not intended to limit the scope of the present invention.

Example  One : Moth  Preparation of extract

In general, the spirits used in the present invention can be easily collected from nature, and the extracts of the present invention are pulverized in powder form in order to efficiently obtain the extract of the present invention.

20 kg of 95% ethanol (EtOH) was added to 2 kg of salted and left at room temperature for 7 days. The mixture was filtered through a filter paper, and then concentrated to obtain 182 g of an ethanol extract of Rhodophyta.

Example  2 : Moth  From the extract Fraction  And separation and purification of the compound

182 g of the ethanol extract of menthol obtained in Example 1 was suspended in 2 L of water. This was put in a separating funnel, and hexane soluble extract (48 g), ethyl acetate soluble extract (90 g) and water soluble extract (20 g) were obtained.

90 g of the ethyl acetate-soluble extract obtained above was subjected to silica gel column chromatography [silica gel 700 g, 70-230 mesh] using chloroform, methanol and a mixed solvent thereof (30: 1 to 1: And separated into 12 fractions (Fr.1 to 12). Of these, the second fraction (Fr.2, 1.2 g) The residue was subjected to silica gel column chromatography (100 g, 230-400 mesh) again using TLC eluting solvent hexane: ethyl acetate (1: 2) as a mobile phase solvent mixture of hexane: ethyl acetate to obtain three fractions -1 to 2-3). The first fraction (Fr. 2-1, 230 mg) was subjected to Sephadex (LH-20) column chromatography packed with methanol to obtain pure compound 1 (21 mg). Pure compound 2 (21 mg) was purified by reverse phase chromatography (RP-18) using a second solvent (Fr. 2-2, 330 mg) using a mixed solvent of methanol: water (30/70, v / v) ≪ / RTI > The third fraction (Fr. 2-3, 560 mg) was further purified by silica gel column chromatography (50 g, 230-250 cm) using a mixed solvent of hexane: ethyl acetate as mobile phase under TLC developing solvent hexane: ethyl acetate (1: 400 mesh) and pure compound 3 (30 mg) was obtained by reverse phase chromatography (RP-18) using a mixed solvent of methanol: water (30/70, v / v).

Example  3: Compound 1 To 3 of  Structure analysis

Molecular weights and molecular weights of the compounds obtained in Example 2 were analyzed by ¹ H NMR, ¹³ C NMR and 2D NMR spectroscopic data, melting point and infrared spectroscopy (Bruker AM 300, 500) through nuclear magnetic resonance IR) data were used to determine the molecular structure.

Experimental Example  One: Moth  extract, Fraction  And Polyphenolic  Measuring the inhibitory effect of compounds on rotavirus

First, in order to measure the virucidal effect and the CPE reduction effect on the porcine rotavirus KJ205 (G5P [7]) of the Ganoderma lucidum extract, Tf-104 (Fetal rhesus monkey The following in vitro experiments were carried out using kidney.

First, TF-104 cells were plated in 96-well microplates at 4 × 10 ⁴ / well and cultured in medium alpha-MEM (penicillin 100 units, streptomycin 100 mg, 5% FBS). When TF-104 cells became monolayers, they were washed twice with alpha-MEM medium containing only antibiotics. KJ205 were each diluted to 0.01 MOI and placed in an EP tube. The extracts were then diluted with DMSO (dimethylsulfoxide) and added to each tube at a concentration of 1: 1. After one hour, the cells were inoculated into 3 wells of TF-104 cells previously washed (hereinafter, referred to as a sample-treated group). On the other hand, uninfected + untreated control group (control, cells not treated with compound and untreated with KJ205) and infection control (virus control, group treated with no compound after infection with KJ205) After 1 hour of reaction, TF-104 cells were inoculated and incubated at 37 ° C for 1 hour. After 1 hour, the plate medium was removed, and the plate was washed once with PBS. 100 mL of each of the antibiotics and alpha-MEM medium supplemented with 1 μg / mL trypsin was added to each well and incubated at 37 ° C. for 5 to 6 days Respectively. The cells were cultured for 5 to 6 days until the cytopathic effect (CPE) was completely exerted in the infected + non-administered control group. The condition of the cells was observed daily with an inverted microscope. After 5 to 6 days of culture, 1 mL of a neutral red solution (Sigma, UK) was added to each well and incubated at 37 ° C for 2 hours. Subsequently, 100 mL of destaining soultion (1% glacial acetic acid, 49% DDW, 50% EtOH) was added to each well and the absorbance was measured at 540 nm after 15 minutes. At this time, the virulence effect (% inhibition) exhibited by the non-infected + non-administered control group and the infected + non-administered control group and the phlegm extract of the present invention was compared by the following formula 1, .

In this equation, the OD value means the absorbance value measured at 540 nm.

On the other hand, in order to examine the cytotoxic effect of porcine rotavirus KJ205 (G5P [7]) on the extracts of T. matsutake, viruses were inoculated into TF-104 cells washed twice with alpha-MEM medium containing only antibiotics for 1 hour Gt; 37 C < / RTI > After 1 hour, all of the inoculated viral solutions were removed, and the gangrene extract was treated with virus-infected TF-104 cells at different concentrations. Thereafter, the cytotoxic inhibitory effect (inhibition rate (%)) of the phlegm extract of the present invention was compared by the above-mentioned formula (1), and the results are shown in Table 1 below.

sample The pig rotavirus KJ205 (G5P [7]) Live virus effect
(Virucidal effect) Cytopathic effect
(CPE inhibition effect) CC ₅₀ ^{1 )} (μM) EC ₅₀ ^{2 )} ([mu] M) SI ³⁾ CC ₅₀ ([mu] M) EC ₅₀ ([mu] M) S.I. Ethanol extract > 100 > 100 - > 100 53.5 > 1.9 3) selection index, CC ₅₀ / EC ₅₀ , 50% concentration value from the inhibitory effect concentration,

As shown in the above Table 1, the extracts of Ganoderma lucidum exhibited a superior viral effect with a seletive index (SI) of 1.9 or more showing a virucidal effect. As shown in FIG. 1, this viral viral effect appears to be concentration-dependent. In particular, the CC ₅₀ of Ganoderma lucidum extract did not show toxicity at concentrations as high as 100 μg / mL. This suggests that the phytotoxic extracts have low toxicity and excellent antiviral activity.

Experimental Example  2: Acute Toxicity Test of Compounds 1 to 3

In order to examine the acute toxicity of the compounds obtained in Example 2, the following experiment was conducted.

C57BL / 6J mice were divided into 4 groups (male / female, each 3 male / female) of 12 male and 6 female mice at 6 weeks of age. 12D animal room. Mice were purified for approximately one week prior to use in the experiment. Feeds for laboratory animals (mouse and rats, Cheil Jedang Co., Seoul, Korea) and drinking water were sterilized and fed freely.

Compound 2 prepared in Example 2 was adjusted to a concentration of 50 mg / mL in 0.5% Tween 80, and then 0 mL, 0.04 mL (100 mg / kg), and 0.2 mL (500 mg / kg) and 0.4 mL (1,000 mg / kg), respectively. Samples were administered orally once, and adverse events or deaths were observed for 7 days after administration. That is, on the day of administration, the general symptom changes and the presence of dead animals were observed at 1 hour, 4 hours, 8 hours, 12 hours after the administration and at least once every morning and at the afternoon from the next day to 7 days after administration.

As a result, no clinical symptoms were observed in all of the mice to which the sample was administered, no mortal mice were observed, and no toxic change was observed in weight changes, blood tests, blood biochemical tests, and autopsy findings.

Therefore, the compound of the present invention did not show any toxic change up to 1,000 mg / kg in mouse, and it was confirmed that it is a safe substance with a minimum oral dose (LD ₅₀ ) of 1,000 mg / kg or more.

Hereinafter, an example of a pharmaceutical preparation or a health food containing a Ganoderma lucidum extract and fractions thereof will be described.

Manufacturing example  1: Preparation of pharmaceutical preparations

1-1. Sanje  Produce

Fentanyl extract, fractions, or compounds isolated therefrom 2 g

Lactose 1 g

After mixing the above components, the mixture was packed in an airtight container to prepare a powder.

1-2. Manufacture of tablets

Gentian extract, fractions, or compounds isolated therefrom 100 mg

Corn starch 100 mg

Lactose 100 mg

2 mg of magnesium stearate

After mixing the above components, tablets were prepared by tableting according to a conventional method for producing tablets.

1-3. Preparation of capsules

Gentian extract, fractions, or compounds isolated therefrom 100 mg

Corn starch 100 mg

Lactose 100 mg

2 mg of magnesium stearate

After mixing the above components, the capsules were filled in gelatin capsules according to the conventional preparation method of capsules.

1-4. Injection preparation

Fentanyl extract, fractions, or compounds isolated therefrom 10 [mu] g / ml

Until dilute hydrochloric acid BP pH 3.5

Sodium chloride BP injected up to 1 ml

The pH of the resulting solution was adjusted to pH 3.5 with dilute hydrochloric acid BP, and sodium chloride BP was added to the solution. The pH of the resulting solution was adjusted to pH 3.5 using a suitable amount of sodium chloride BP. The volume was adjusted and mixed thoroughly. The solution was filled in a 5 ml type I ampoule made of transparent glass, sealed in an upper lattice of air by dissolving the glass, sterilized by autoclaving at 120 DEG C for 15 minutes or longer, and an injection solution was prepared.

Manufacturing example  2: Manufacture of health food

2-1. Manufacture of cooking seasonings

0.2% to 10% by weight of the extracts, fractions, or compounds isolated therefrom.

2-2. Manufacture of tomato ketchup and sauce

0.2-1. 0% by weight of the extracts, fractions, or compounds isolated therefrom were added to tomato ketchup or sauce to prepare healthy tomato ketchup or sauce.

2-3. Manufacture of flour food products

0.1 to 5.0% by weight of the extracts, fractions or the compounds isolated therefrom were added to wheat flour, and breads, cakes, cookies, crackers and noodles were prepared using the mixture to prepare foods for health promotion.

2-4. soup  And juicy ( gravies )

0.1-1.0 wt% of the extracts, fractions, or compounds isolated therefrom were added to soups and juices to prepare health-promoting meat products, noodles and juices.

2-5. ground Beef  ( ground beef )

10% by weight of the extracts, fractions or compounds isolated therefrom were added to the ground beef to prepare ground beef for health promotion.

2-6. dairy product ( dairy products )

0.1 to 1.0% by weight of a chewing gum extract, fractions, or a compound isolated therefrom was added to milk, and milk was used to make various dairy products such as butter and ice cream.

2-7. Solar  Produce

The brown rice, barley, glutinous rice, and yulmu were dried by a known method and dried, and the powder was prepared into a powder having a particle size of 60 mesh by a pulverizer.

Black beans, black sesame seeds, and perilla seeds were steamed and dried by a known method, and then they were prepared into powders having a particle size of 60 mesh by a pulverizer.

The extracts, fractions or compounds separated therefrom were concentrated under reduced pressure in a vacuum concentrator, sprayed, and dried with a hot air drier, and the resulting dried product was pulverized to a size of 60 mesh with a pulverizer to obtain a dry powder.

The dried grains, seeds and phytase extracts, fractions, compounds isolated therefrom, or salts thereof prepared above were blended in the following proportions.

Cereals (30% by weight of brown rice, 15% by weight of yulmu, 20% by weight of barley)

Seeds (7% by weight of perilla, 8% by weight of black beans, 7% by weight of black sesame seeds)

(1% by weight) of the extracts, fractions or compounds isolated therefrom,

(0.5% by weight),

(0.5% by weight)

2-8. Manufacture of carbonated drinks

Syrup was prepared by mixing additives of 5 to 10% of sugar, 0.05 to 0.3% of citric acid, 0.005 to 0.02% of caramel and 0.1 to 1% of vitamin C and 79 to 94% of purified water. The syrup prepared above is sterilized at 85 to 98 ° C for 20 to 180 seconds and mixed with cooling water at a ratio of 1: 4. Then, 0.5 to 0.82% of carbon dioxide gas is injected into the extract, fraction or a compound Was prepared.

2-9. Health drink  Produce

The components such as liquid fructose (0.5%), oligosaccharide (2%), sugar (2%), salt (0.5%) and water (75%) and phytotoxic extracts, fractions or compounds isolated therefrom are homogeneously mixed After sterilization, they were packaged in small containers such as glass bottles and plastic bottles to produce health drinks.

2-10. Vegetable juice  Produce

The health promotion vegetable juice was prepared by adding 0.5 g of the extracts, fractions, or compounds isolated therefrom to 1,000 ml of tomato or carrot juice.

2-11. Of fruit juice  Produce

The fruit juice for health promotion was prepared by adding 0.1 g of the ginger extract, fraction or the compound separated therefrom to 1,000 ml of apple or grape juice.

Claims (9)

A pharmacological composition for preventing or treating rotavirus infection, comprising a gangueaceous extract or a fraction thereof as an active ingredient.
The pharmaceutical composition for preventing or treating rotavirus infection according to claim 1, wherein the extract is extracted from water, a C ₁ -C ₄ alcohol or a mixed solvent thereof.
The pharmaceutical composition for preventing or treating rotavirus infection according to claim 1, wherein the fraction is a hexane fraction, an ethyl acetate fraction or a water fraction.
The pharmaceutical composition for preventing or treating rotavirus infection according to claim 1, wherein the rotavirus is human, pig, povine, or goat rotavirus.
The pharmaceutical composition for preventing or treating rotavirus infection according to claim 1, wherein the rotavirus causes enteritis, diarrhea, cold, sore throat, bronchitis, and pneumonia.
delete The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition is in the form of tablets, pills, powders, granules, capsules, suspensions, solutions, emulsions, syrups, sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, Wherein the pharmaceutical composition is a pharmaceutical composition for preventing or treating rotavirus infection.
A food composition for preventing or ameliorating rotavirus infection, comprising a gentian extract or a fraction thereof as an active ingredient.
A quasi-drug composition for preventing or ameliorating rotavirus infection comprising an extract of Ganoderma lucidum or a fraction thereof as an active ingredient.

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