WO2024090654A1 - Composition for preventing or treating coronavirus infection, containing maple leaf extract - Google Patents

Composition for preventing or treating coronavirus infection, containing maple leaf extract Download PDF

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Publication number
WO2024090654A1
WO2024090654A1 PCT/KR2022/018704 KR2022018704W WO2024090654A1 WO 2024090654 A1 WO2024090654 A1 WO 2024090654A1 KR 2022018704 W KR2022018704 W KR 2022018704W WO 2024090654 A1 WO2024090654 A1 WO 2024090654A1
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Prior art keywords
coronavirus
composition
extract
extraction
maple leaf
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PCT/KR2022/018704
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French (fr)
Korean (ko)
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마진열
조원경
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한국한의학연구원
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/20—Aceraceae (Maple family)
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K10/00—Animal feeding-stuffs
    • A23K10/30—Animal feeding-stuffs from material of plant origin, e.g. roots, seeds or hay; from material of fungal origin, e.g. mushrooms
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/13—Coniferophyta (gymnosperms)
    • A61K36/14—Cupressaceae (Cypress family), e.g. juniper or cypress
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/29—Berberidaceae (Barberry family), e.g. barberry, cohosh or mayapple
    • A61K36/296—Epimedium
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/538—Schizonepeta
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/72—Rhamnaceae (Buckthorn family), e.g. buckthorn, chewstick or umbrella-tree
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/324—Foods, ingredients or supplements having a functional effect on health having an effect on the immune system

Definitions

  • the present invention provides an antiviral composition for coronavirus containing maple leaf extract as an active ingredient;
  • a method for preventing or treating a coronavirus infectious disease comprising administering a composition containing maple leaf extract as an active ingredient to an individual who is showing or is likely to show symptoms of a coronavirus infectious disease; And it relates to the antiviral use of a composition containing maple leaf extract as an active ingredient against coronavirus.
  • Coronavirus was first discovered in chickens in 1937, then passed through animals such as dogs, pigs, and birds, and was discovered in humans in 1965. It was given this name because its appearance is similar to the corona phenomenon, which is a phenomenon in which the sun's photosphere glows white around it when it is obscured by the moon during a total solar eclipse.
  • Coronaviruses are known to mainly cause pneumonia and enteritis in humans and animals, and are also known to occasionally cause nervous system infections and hepatitis. Coronaviruses belong to the Coronaviridae family and are positive sense RNA viruses with a spherical outer membrane and a size of approximately 100-120 nm (Master, 2006).
  • the coronavirus is composed of a total of five structural proteins, including the outermost spike protein (S), hemagglutinin-esterase (HE) protein, transmembrane (M) protein, small membrane (E) protein, and nucleocapsid (N) protein (Lai and Homes, 2001. Fields Virology).
  • the spike protein acts as a ligand that binds to cell receptors, and is a protein that induces fusion between host cells and viruses, and is known to be the most variable protein.
  • coronaviruses have been recognized as pathogens that rarely infect humans and mainly infect animals such as dogs, pigs, and cows. It is one of several viruses that cause respiratory symptoms even when infecting humans, and in some cases, it causes simple colds or intestinal diseases such as diarrhea, which are not very dangerous in children.
  • MERS Middle East Respiratory Syndrome
  • COVID-19 is a disease that was first identified in Wuhan, the capital of Hubei province, China, in late 2019 and has spread worldwide, causing a progressive pandemic. It is an infectious disease caused by SARS-coronavirus-2. As of May 7, 2020, more than 3.75 million cases have been reported in 187 countries, with 263,000 deaths and 1.24 million recoveries. Common symptoms are fever, cough, fatigue, shortness of breath, and loss of smell and taste. In most cases, symptoms are mild, but some progress to viral pneumonia, multi-organ failure, and cytokine storm. The time from onset of symptoms to onset is usually about 5 days, but can be between 2 and 14 days.
  • the virus spreads from person to person mainly during close contact and sometimes through droplets produced when coughing, sneezing and talking. It is most contagious during the first three days after symptoms appear, and can spread even before symptoms appear or in the later stages of the disease.
  • the standard method for diagnosing this is real-time reverse transcription polymerase chain reaction (rRT-PCR) from a nasopharyngeal swab.
  • MERS was first discovered in Saudi Arabia in 2012, and is a disease that causes severe respiratory symptoms such as high fever, cough, and difficulty breathing, and in severe cases can lead to death due to complications. Although the clear source and route of infection have not been confirmed, it has been reported that there is a high possibility of infection through contact with camels in the Middle East and that transmission through close contact between people is possible. Patients were mainly concentrated in the Middle East, but since May 2015, more than 100 people have been infected throughout Korea.
  • MERS-coronavirus As mentioned earlier, both MERS and SARS are known to be caused by variant coronaviruses (MERS-coronavirus, SARS-coronavirus, and SARS-coronavirus-2) belonging to the Beta coronavirus genus. Therefore, MERS-coronavirus, SARS-coronavirus, and SARS-coronavirus-2 share similar characteristics in clinical symptoms, pathogenesis, and infection.
  • MERS-coronavirus, SARS-coronavirus, and SARS-coronavirus-2 are all believed to have originated from bats, which are the primary reservoir hosts for various coronaviruses (Antiviral Res 101:45-56), and their exact route of infection is unknown. This has not yet been fully revealed. Meanwhile, interspecies transmission of the virus to civets and dromedary camels has increased the likelihood of zoonotic infection in humans (Nat Rev Microbiol 14:523-534), and nosocomial infection has increased in humans. It is believed to be the main cause of MERS-coronavirus and SARS-coronavirus infections among humans (BMC Med13:1-12).
  • the present inventors completed the present invention by confirming that a maple leaf extract with guaranteed stability has an excellent effect in inhibiting the proliferation of coronavirus.
  • the purpose of the present invention is to provide an antiviral composition against coronavirus containing maple leaf extract as an active ingredient.
  • Another object of the present invention is to provide a pharmaceutical composition for preventing or treating coronavirus infectious diseases, comprising the composition.
  • Another object of the present invention is to provide a method for preventing or treating a coronavirus infection disease, including the step of administering the composition to an individual who is exhibiting or is likely to exhibit symptoms of a coronavirus infection disease.
  • Another object of the present invention is to provide a health functional food composition for preventing or improving coronavirus infectious diseases, including the composition.
  • Another object of the present invention is to provide a feed composition for preventing or improving coronavirus infectious diseases comprising the composition.
  • Another object of the present invention is to provide an antiviral use against coronavirus of a pharmaceutical composition containing maple leaf extract as an active ingredient.
  • Another object of the present invention is to provide an antiviral use against coronavirus of a health functional food composition containing maple leaf extract as an active ingredient.
  • Another object of the present invention is to provide an antiviral use against coronavirus of a feed composition containing maple leaf extract as an active ingredient.
  • maple leaf extract of the present invention Since the maple leaf extract of the present invention has an effect of suppressing coronavirus infection, it can be used to develop an antiviral agent for preventing or treating the viral disease.
  • Figure 1 is a graph showing the coronavirus inhibition efficacy of maple leaf hot water extract.
  • Figure 2 is a graph showing the coronavirus inhibitory efficacy of a hot water mixed extract (tea) composed of maple leaf, sycamore leaf, lotus leaf, and arborvitae leaf.
  • tea hot water mixed extract
  • Figure 3 is a graph showing the coronavirus inhibitory efficacy of a hot water mixed extract (Yaktanggi) composed of maple leaf, hyeonggae, lotus leaf, and arborvitae leaf.
  • Yaktanggi hot water mixed extract
  • Figure 4 is a graph showing the coronavirus inhibitory effect of a hot water mixed extract (Yaktanggi) composed of maple leaf, hyeongae, lotus leaf, and milky white bark.
  • Yaktanggi hot water mixed extract
  • Figure 5 is a graph showing the coronavirus inhibitory efficacy of the hot water mixed extract (Yaktanggi) consisting of maple leaf, Hyeonggae, lotus leaf, milky white bark, and Yinyanggwak.
  • Yaktanggi hot water mixed extract
  • Figure 6 is a graph showing the coronavirus inhibitory efficacy of the hot water mixed extract (Yaktanggi) consisting of maple leaf, Hyeonggae, lotus leaf, milky white bark, Arborvitae leaf, Yin-Yang Gwak and Jijizi.
  • Yaktanggi hot water mixed extract
  • Figure 7 is a graph showing the coronavirus inhibition efficacy of the positive control group remdesivir, chloroquine, and lopinavir.
  • One aspect of the present invention provides an antiviral composition against coronavirus containing maple leaf extract as an active ingredient.
  • the composition may further include, but is not limited to, one or more extracts selected from the group consisting of Hyeonggae, lotus leaf, arborvitae, and milky white bark.
  • the composition may further include, but is not limited to, one or more extracts selected from the group consisting of Yinyanggwak and Jijizi.
  • the term “maple leaf” refers to the leaf of a maple tree, Acer palmatum Thunb.
  • the maple tree is a deciduous tree with a height of about 10 to 20 m and a circular tree shape.
  • the maple leaves can be purchased commercially, or those collected or cultivated in nature can be used.
  • the term "hyeonggae” refers to the dried whole plant of Hyeonggae, a plant of the Lamiaceae family, and has the herbal name Schizonepetae Spica and the scientific name Schizonepeta tenuifolia Briquet. It is characterized by a bitter taste and a warm nature, and is known to be effective in menopause, liver cirrhosis, etc., and to have digestive and antibacterial effects.
  • the term "lotus leaf” refers to the leaf of the lotus flower, Nelumbo nucifera (Nelumbo nucifera Gaertn.) leaf, and has been called bouyong, hayeop, etc. in folk and oriental medicine since ancient times, and is used to treat hemorrhagic properties. It has been used for stomach ulcers, gastritis, hemorrhoids, and bleeding.
  • the term "Arborvitae” refers to an evergreen coniferous tree of the Arborvitae family, and has the scientific name Thuja orientalis L.. The height is about 25 meters, and the leaves are densely packed in the shape of small scales.
  • the arborvitae tree may mean a specific part of the arborvitae tree, such as the roots, leaves, flowers, stems, etc., or may mean the entire plant.
  • the composition may include Thuja orientalis L. leaves and Thuja orientalis L.
  • milky bark also called radicle bark
  • radicle bark refers to the bark of Ulmus macrocarpa Hance, a large elm tree of the elm family, from which the cork layer has been peeled off. In appearance, it is tubular or plate-shaped, and the outer surface is dark brown with spots and a cork layer. The broken surface is rough and light brown, has a clear fibrous pattern, is hard, and has black-yellow powder.
  • the term "yin-yang-gwak” refers to the above-ground parts (stem and leaves) of Epimedium koreanum Nakai, a perennial herb of the dicotyledonous plant Ranunculaceae barberry family, or other closely related plants, It has no odor, tastes spicy and sweet, and is warm in nature.
  • the term "Hoveniae Semen Seu Fructus” refers to the fruit or seed of Hovenia dulcis Thunberg, a buckthorn tree of the buckthorn family. It is said to have a sweet taste, so it is used to refer to the honey produced from the tree. It is also called mokmil. In China, it is called Hyeonpori, which means pear tree that grows in the garden of immortals, and it is also called Baekseokmok because it is white and hard like a stone.
  • extract refers to the extract obtained by extracting and processing the maple leaves, a diluted or concentrated liquid of the extract, a dried product obtained by drying the extract, a crude product or purified product of the extract, or a mixture thereof, or the extract itself. and extracts of all formulations that can be formed using the extract.
  • the method for extracting the maple leaves is not particularly limited, and may be extracted according to methods commonly used in the art.
  • Non-limiting examples of the extraction method include hot water extraction, ultrasonic extraction, room temperature extraction, cold needle extraction, filtration, reflux extraction, steam extraction, etc., which can be performed alone or by combining two or more methods. there is.
  • the type of extraction solvent used to extract the maple leaves in the present invention is not particularly limited, and any solvent known in the art can be used.
  • Non-limiting examples of the extraction solvent include water, alcohols having 1 to 4 carbon atoms, or mixed solvents thereof, and these may be used alone or in combination of one or more types.
  • the solvent that exhibits an antiviral effect is not limited.
  • the maple leaf extract in the present invention may be a maple leaf hot water extract, but is not limited thereto.
  • maple leaf extract in order to prepare maple leaf extract and various mixed extracts selected from the group consisting of maple leaf, lotus leaf, milky white bark, arborvitae leaf, yin-yang gwak, and earthenberry, the mixture was heated at 70 to 100 ° C., 3 to 100 degrees Celsius. It was extracted by boiling it for 10 minutes or boiling it in a water boiler at 80 ⁇ 130°C for 130 ⁇ 180 minutes.
  • antiviral refers to the property of suppressing viral infection
  • virus refers to a microorganism that parasitizes living cells such as animals, plants, and bacteria and can proliferate only within the cells.
  • the virus may be a coronavirus, but is not limited thereto.
  • coronavirus is one of the three major viruses that cause colds in humans, along with adenovirus and rhinovirus, and is an RNA virus with a gene size of 27 to 32 kb that can infect humans and various animals.
  • Coronavirus infectious disease refers to a disease caused by an infection that invades the body of a coronavirus host organism.
  • the coronavirus is SARS-Coronavirus-2 (Covid-19) and SARS-Coronavirus. It may be one or more selected from the group consisting of viruses and MERS-coronavirus, and more specifically, it may be SARS-coronavirus-2.
  • maple leaf extract alone had excellent ability to inhibit coronavirus infection (Figure 1).
  • Figure 1 As a result of extracting the lily, lotus leaf, arborvitae leaf, and maple leaf by making tea or boiling it using a boiler, it was confirmed that all of them had excellent anti-coronavirus infection inhibitory properties.
  • the mixed extract of eucalyptus, lotus leaf, arborvitae leaf, and maple leaf was used to prevent coronavirus. It was found that there was an inhibitory ability ( Figures 2 and 3).
  • Another aspect of the present invention provides a pharmaceutical composition for preventing or treating coronavirus infectious diseases, comprising the composition.
  • the maple leaf, antiviral, coronavirus and extract are as described above.
  • composition may include 0.000001 to 80% by weight of the maple leaf extract relative to the weight of the total composition, and may specifically include 0.00001 to 40% by weight, but is not limited thereto. .
  • the pharmaceutical composition may further include a pharmaceutically acceptable carrier, excipient, or diluent commonly used in the preparation of the pharmaceutical composition, and the carrier may include a non-naturally occurring carrier.
  • the pharmaceutical composition can be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, and sterile injection solutions according to conventional methods.
  • composition exhibits non-toxic properties to cells or humans exposed to the composition.
  • the type of the carrier is not particularly limited, and any carrier commonly used in the art and pharmaceutically acceptable can be used.
  • Non-limiting examples of the carrier include saline solution, sterile water, Ringer's solution, buffered saline solution, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol, etc. These may be used alone or in combination of two or more types.
  • other common additives such as antioxidants, buffers, and/or bacteriostatic agents can be added and used, and diluents, dispersants, surfactants, binders, lubricants, etc. can be additionally added to form solutions such as aqueous solutions, suspensions, emulsions, etc. It can be formulated and used in dosage form, pills, capsules, granules, or tablets.
  • the administration method of the antiviral pharmaceutical composition according to the present invention is not particularly limited and may follow a method commonly used in the art.
  • the composition may be administered by oral administration or parenteral administration.
  • the composition for preventing, improving, or treating coronavirus infectious diseases of the present invention can be prepared in various formulations depending on the desired administration method.
  • infectious disease refers to a disease caused by infection.
  • infection refers to a state in which pathogenic microorganisms invade the body of a host organism and grow and proliferate.
  • prevention of the present invention refers to all actions that suppress or delay viral infectious diseases by administering the pharmaceutical composition of the present invention containing maple leaf extract.
  • treatment refers to any action in which a viral infectious disease is improved or beneficially altered by administration of the pharmaceutical composition.
  • Another aspect of the present invention provides a method for preventing or treating a coronavirus infectious disease, comprising administering a composition containing maple leaf extract as an active ingredient to an individual who is showing or is likely to show symptoms of a coronavirus infectious disease. do.
  • maple leaf antiviral, coronavirus, extract.
  • Pharmaceutical compositions, infectious diseases, prevention and treatment are as described above.
  • the composition may further include, but is not limited to, one or more extracts selected from the group consisting of Hyeonggae, lotus leaf, arborvitae, and milky white bark.
  • the composition may further include, but is not limited to, one or more extracts selected from the group consisting of Yinyanggwak and Jijiji.
  • administration means introducing a given substance into a subject by an appropriate method.
  • the term “individual” refers to all animals, including rats, mice, and livestock, including humans, that have or may develop a coronavirus infectious disease. As a specific example, it may be a mammal, including humans.
  • the method for preventing or treating a coronavirus infectious disease of the present invention may include administering a composition containing maple leaf extract to an individual in a pharmaceutically effective amount.
  • the term "pharmaceutically effective amount” refers to an amount that is sufficient to treat a disease with a reasonable benefit/risk ratio applicable to medical treatment and does not cause side effects, and the effective dose level is determined by the patient's gender, Factors including age, weight, health status, type and severity of the disease, activity of the drug, sensitivity to the drug, method of administration, time of administration, route of administration, and excretion rate, duration of treatment, drugs combined or used simultaneously, and other medical factors. It can be easily determined by a person skilled in the art according to factors well known in the art.
  • the pharmaceutical composition of the present invention can be administered at 0.000001 to 100 mg/kg of body weight per day, more specifically 0.0001 to 100 mg/kg of body weight, based on solid content.
  • the recommended dosage may be administered once a day, or it may be administered several times.
  • the pharmaceutical 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. Additionally, it can be administered single or multiple times. Considering all of the above factors, it is important to administer an amount that can achieve maximum effect with the minimum amount without causing side effects, and this can be easily determined by a person skilled in the art.
  • the administration route and administration method for administering the composition are not particularly limited, and any administration may be performed as long as the composition containing the composition can reach the target site. It may depend on the route and method of administration.
  • the composition may be administered through various oral or parenteral routes, and non-limiting examples of the administration route include oral, rectal, topical, intravenous, intraperitoneal, intramuscular, intraarterial, transdermal, and nasal. It may be administered intralaterally or through inhalation. Because the maple leaf extract of the present invention is effective in preventing or treating coronavirus infectious diseases, the composition may be administered orally.
  • Another aspect of the present invention provides a health functional food composition for preventing or improving coronavirus infectious diseases, including the composition.
  • maple leaf antiviral, coronavirus, extract.
  • Pharmaceutical compositions, infectious diseases, prevention and treatment are as described above.
  • the term "functional food” of the present invention is the same as food for special health use (FoSHU), and is a medicine processed to efficiently exhibit bioregulatory functions in addition to nutritional supply, and medical effects. refers to foods with high .
  • the health functional food is compatible with health food or health supplement food.
  • the health functional food composition of the present invention can be consumed on a daily basis, it can be expected to have a high effect on improving coronavirus infectious diseases, so it can be very useful for health promotion purposes.
  • the content of the extract included in the health functional food composition is not particularly limited, but may be included in 0.01 to 100% by weight, more preferably 1 to 80% by weight, based on the total weight of the health functional food composition.
  • the health functional food may be manufactured in a form selected from the group consisting of pills, powders, granules, precipitates, tablets, capsules and beverages in order to obtain useful effects in preventing or improving coronavirus infectious diseases.
  • a form selected from the group consisting of pills, powders, granules, precipitates, tablets, capsules and beverages in order to obtain useful effects in preventing or improving coronavirus infectious diseases.
  • the type of food to which the composition containing the maple leaf extract of the present invention can be added for example, various beverages, gum, tea, vitamin complexes, health supplements, etc.
  • ingredients that do not interfere with the preventive or improving effect of the health functional food may be added to the health functional food composition, and their types are not particularly limited.
  • the health functional food composition may contain various herbal extracts, foodologically acceptable food additives, or natural carbohydrates as additional ingredients.
  • the health functional food composition may further include a foodologically acceptable carrier, which can be appropriately selected and used by a person skilled in the art.
  • a foodologically acceptable carrier for example, various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic and natural flavors, colorants and fillers, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters. , stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated drinks, etc., but the types are not limited to the above examples.
  • the health functional food composition may include additional ingredients that are commonly used in food compositions to improve smell, taste, vision, etc.
  • it may include vitamins A, C, D, E, B1, B2, B6, B12, niacin, biotin, folate, pantothenic acid, etc.
  • minerals such as zinc (Zn), iron (Fe), calcium (Ca), chromium (Cr), magnesium (Mg), manganese (Mn), and copper (Cu).
  • it may contain amino acids such as lysine, tryptophan, cysteine, and valine.
  • preservatives can be added.
  • disinfectants bleaching powder, high bleaching powder, sodium hypochlorite, etc.
  • antioxidants butylhydroxyanisole (BHA), butylhydroxytoluene ( BHT), etc.
  • colorants tar color, etc.
  • coloring agents sodium nitrite, sodium nitrite, etc.
  • bleaching agents sodium sulfite
  • seasonings MSG monosodium glutamate, etc.
  • sweeteners dulcine, cyclemate, saccharin, sodium, etc.
  • food additives such as flavorings (vanillin, lactones, etc.), leavening agents (alum, D-potassium hydrogen tartrate, etc.), strengthening agents, emulsifiers, thickeners (grease), coating agents, gum base agents, anti-foam agents, solvents, improvers, etc.
  • emulsifiers emulsifiers
  • thickeners emulsifiers
  • thickeners emuls
  • Another aspect of the present invention provides a feed composition for preventing or improving coronavirus infectious diseases, including the composition.
  • maple leaf antiviral, coronavirus, extract.
  • Pharmaceutical compositions, infectious diseases, prevention and treatment are as described above.
  • feed means any natural or artificial diet, meal, etc., or a component of the meal, for or suitable for eating, ingestion, and digestion by animals.
  • the type of feed is not particularly limited, and feed commonly used in the art can be used.
  • Non-limiting examples of the feed include plant feeds such as grains, roots and fruits, food processing by-products, algae, fiber, pharmaceutical by-products, oils and fats, starches, cucurbits or grain by-products;
  • Examples include animal feeds such as proteins, inorganic substances, fats and oils, minerals, fats and oils, single-cell proteins, zooplanktons or foods. These may be used singly or in combination of two or more types.
  • Another aspect of the present invention provides an antiviral use against coronavirus of a pharmaceutical composition containing maple leaf extract as an active ingredient.
  • Another aspect of the present invention provides an antiviral use against coronavirus of a health functional food composition containing maple leaf extract as an active ingredient.
  • Another aspect of the present invention provides an antiviral use against coronavirus of a feed composition containing maple leaf extract as an active ingredient.
  • maple leaf antiviral, coronavirus, extract.
  • Pharmaceutical compositions, infectious diseases, prevention and treatment are as described above.
  • maple leaf extract and various mixed extracts selected from the group consisting of maple leaf, lotus leaf, milky white bark, arborvitae leaf, yin-yang gwak, and earthenberry maple leaf (Acer palmatum Thunb.), Hyeonggae (Schizonepeta tenuifolia Briquet), Lotus (Nelumbo nucifera Gaertn.) leaf, Ulmus macrocarpa Hance, Thuja orientalis L., Epimedium koreanum Nakai (aerial part of Thuja orientalis L.), and Earth berry (Hovenia chinensis) Hovenia dulcis) fruits or seeds (Hoveniae Semen Seu Fructus) were purchased and used as samples. It was extracted by brewing it as tea or decocting it using a water boiler.
  • SARS-CoV-2 (NCCP no, 43326, Human corona virus, ⁇ CoV/Korea/KCDC03/2020) was provided by the Korea Centers for Disease Control and Prevention (KCDC), and Vero cells were obtained from ATCC (ATCC-CCL81).
  • Vero cells 1.2x10 4 Vero cells per well were inoculated into a 384-tissue culture plate. The next day, the cells were treated with compounds prepared at 10 points by serially diluting 2-fold in DMSO to a maximum concentration of 200 ⁇ g/ml. Approximately 1 hour after compound treatment, cells were infected with SARS-CoV-2 (0.025 MOI) in a BSL3 facility and cultured at 37°C for 24 hours. Afterwards, cells were fixed with 4% paraformaldehyde (PFA) and permeabilized.
  • SARS-CoV-2 0.025 MOI
  • PFA paraformaldehyde
  • the acquired images were analyzed using Columbus software.
  • the total number of cells per well was calculated as the number of nuclei stained with Hoechst, and the number of infected cells was calculated as the number of cells expressing the viral N protein.
  • the infection ratio was calculated as 'number of cells expressing N protein/total number of cells' in each well.
  • the % inhibition of infection of each well is calculated as the average infection rate of wells containing non-infected cells (mock) and the average infection rate of wells containing infected cells treated with 0.5% DMSO (v/v) in the same plate, respectively. It was calculated by normalizing to % and 0%.
  • the cell viability of the compound was normalized by normalizing the number of cells in each well to the average number of cells in the mock group wells and expressed as '% Cell viability' in the graph. Each value was obtained through two repeated experiments (technical duplicate).
  • Selectivity index (SI) value was calculated as CC 50 /IC 50 .
  • Blue ⁇ indicates the SARS-CoV-2 infection inhibition rate (% Inhibition of infection) of the compound, and red ⁇ indicates the cell viability (% Cell viability) for the compound.
  • Remdesivir, Chloroquine, and Lopinavir known as coronavirus treatments, were set as positive controls, and cytotoxicity and effective drug concentration were confirmed (Figure 7).
  • Example 1-1 Inhibitory effect of maple leaf extract KIOM1 on coronavirus infection
  • the cytotoxicity (CC 50 ) of the maple leaf extract was higher than the highest tested concentration of 200 ⁇ g/ml, the effective drug concentration (IC 50 ) was confirmed to be 43.81 ⁇ g/ml, and the SI (selectivity index, CC 50 /IC 50 ) was 4.57. It was measured as ( Figure 1).
  • maple leaf extract of the present invention inhibits coronavirus with a significant effect.
  • Example 1-2 Corona virus infection inhibition effect of maple leaf mixed extract KIOM2
  • the cytotoxicity (CC 50 ) of the mixed extract was higher than the highest tested concentration of 200 ⁇ g/ml, the effective drug concentration (IC 50 ) was confirmed to be 85.78 ⁇ g/ml, and the SI (selectivity index, CC 50 /IC 50 ) was 2.33. It was measured as ( Figure 2).
  • Example 1-3 Corona virus infection inhibition effect of maple leaf mixed extract KIOM3
  • the cytotoxicity (CC 50 ) of the mixed extract was higher than the highest tested concentration of 200 ⁇ g/ml, the effective drug concentration (IC 50 ) was confirmed to be 96.21 ⁇ g/ml, and the SI (selectivity index, CC 50 /IC 50 ) was 2.08. It was measured as ( Figure 3).
  • Example 1-4 Corona virus infection inhibition effect of maple leaf mixed extract KIOM4
  • the cytotoxicity (CC 50 ) of the mixed extract was higher than the highest tested concentration of 200 ⁇ g/ml, the effective drug concentration (IC 50 ) was confirmed to be 119.4 ⁇ g/ml, and the SI (selectivity index, CC 50 /IC 50 ) was 1.68. It was measured as ( Figure 4).
  • the mixed extract of maple leaf, gyeonggae, lotus leaf, and milky bark (KIOM4) of the present invention effectively inhibits coronavirus.
  • the cytotoxicity (CC 50 ) of the mixed extract was higher than the highest tested concentration of 200 ⁇ g/ml, the effective drug concentration (IC 50 ) was confirmed to be 121.1 ⁇ g/ml, and the SI (selectivity index, CC 50 /IC 50 ) was 1.65. It was measured as ( Figure 5).
  • the cytotoxicity (CC 50 ) of the mixed extract was higher than the highest tested concentration of 200 ⁇ g/ml, the effective drug concentration (IC 50 ) was confirmed to be 120.4 ⁇ g/ml, and the SI (selectivity index, CC 50 /IC 50 ) was 1.66. It was measured as ( Figure 6).
  • the mixed extract (KIOM6) of maple leaf, Hyeonggae, lotus leaf, milky white bark, Arborvitae leaf, Earthworm and Yin-Yang Gwak of the present invention effectively inhibits coronavirus.

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Abstract

The present invention pertains to: an antiviral composition against coronavirus, containing a maple leaf extract as an active ingredient; a method for preventing or treating coronavirus infection diseases, the method comprising the step of administering a composition containing a maple leaf extract as an active ingredient to an individual who shows symptoms of coronavirus infection or is at risk of developing such symptoms; and a use of a composition containing a maple leaf extract as an active ingredient for antiviral activity against coronavirus. The present invention can be utilized in the development of antiviral agents for preventing or treating coronavirus diseases.

Description

단풍잎 추출물을 포함하는 코로나바이러스 감염 예방 또는 치료용 조성물Composition for preventing or treating coronavirus infection comprising maple leaf extract
본 발명은 단풍잎 추출물을 유효성분으로 포함하는 코로나바이러스에 대한 항바이러스용 조성물; 단풍잎 추출물을 유효성분으로 포함하는 조성물을 코로나바이러스 감염질환 증상이 나타나거나 또는 나타날 우려가 있는 개체에 투여하는 단계를 포함하는 코로나바이러스 감염질환의 예방 또는 치료 방법; 및 단풍잎 추출물을 유효성분으로 포함하는 조성물의 코로나바이러스에 대한 항바이러스 용도에 관한 것이다.The present invention provides an antiviral composition for coronavirus containing maple leaf extract as an active ingredient; A method for preventing or treating a coronavirus infectious disease comprising administering a composition containing maple leaf extract as an active ingredient to an individual who is showing or is likely to show symptoms of a coronavirus infectious disease; And it relates to the antiviral use of a composition containing maple leaf extract as an active ingredient against coronavirus.
코로나바이러스 (coronavirus)는 1937년 닭에서 처음 발견된 뒤 개, 돼지, 조류 등의 동물을 거쳐 1965년에는 사람에게서도 발견되었다. 개기일식 때 태양의 광구가 달에 가려졌을 때 그 둘레에서 하얗게 빛나는 현상인 코로나 현상과 생김새가 비슷하여 이러한 이름이 붙여졌다.Coronavirus was first discovered in chickens in 1937, then passed through animals such as dogs, pigs, and birds, and was discovered in humans in 1965. It was given this name because its appearance is similar to the corona phenomenon, which is a phenomenon in which the sun's photosphere glows white around it when it is obscured by the moon during a total solar eclipse.
코로나바이러스는 사람과 동물에서 주로 폐렴과 장염을 유발하는 것으로 알려져 있으며, 간혹 신경계 감염과 간염을 유발하는 것으로도 알려져 있다. 코로나바이러스는 코로나바이러스과(Coronaviridae)에 속하며 구형의 외막을 가지는, 약 100-120 nm 크기의 positive sense RNA 바이러스이다(Master, 2006). 코로나바이러스는 가장 외각에 있는 spike 단백질 (S), hemagglutinin-esterase (HE) 단백질, transmembrane (M) 단백질, small membrane (E) 단백질 및 nucleocapsid (N) 단백질 등 총 5개의 구조 단백질로 이루어져 있다(Lai and Homes, 2001. Fields Virology). 이 중 spike 단백질은 세포 수용체와 결합하는 리간드 역할을 하며, 숙주세포와 바이러스간의 융합을 유도하는 단백질로 가장 변이가 심한 단백질로 알려져 있다.Coronaviruses are known to mainly cause pneumonia and enteritis in humans and animals, and are also known to occasionally cause nervous system infections and hepatitis. Coronaviruses belong to the Coronaviridae family and are positive sense RNA viruses with a spherical outer membrane and a size of approximately 100-120 nm (Master, 2006). The coronavirus is composed of a total of five structural proteins, including the outermost spike protein (S), hemagglutinin-esterase (HE) protein, transmembrane (M) protein, small membrane (E) protein, and nucleocapsid (N) protein (Lai and Homes, 2001. Fields Virology). Among these, the spike protein acts as a ligand that binds to cell receptors, and is a protein that induces fusion between host cells and viruses, and is known to be the most variable protein.
지금까지 코로나바이러스는 사람에게는 거의 감염되지 않고 주로 개, 돼지, 소 등의 동물에 감염되는 병원균으로 인식되어 왔다. 사람에게 감염될 때에도 호흡기 증상을 유발하는 여러 바이러스 가운데 하나로서 단순한 감기를 유발하거나 어린이에게 위험성이 그리 높지 않은 설사 등의 장 질환을 일으키는 경우가 있을 뿐이었다. 그러나 세계적으로 수백명이 넘는 사망자와 수천여 명의 환자를 발생시킨 중동 호흡기 증후군(메르스;MERS)의 원인균이 신종(변종) 코로나바이러스인 것으로 알려지면서 점차적으로 주목받았다.Until now, coronaviruses have been recognized as pathogens that rarely infect humans and mainly infect animals such as dogs, pigs, and cows. It is one of several viruses that cause respiratory symptoms even when infecting humans, and in some cases, it causes simple colds or intestinal diseases such as diarrhea, which are not very dangerous in children. However, it gradually attracted attention as it was revealed that the causative agent of Middle East Respiratory Syndrome (MERS), which has caused more than hundreds of deaths and thousands of patients worldwide, is a new (mutant) coronavirus.
COVID-19는 2019년 말 중국 후베이 지방의 수도인 우한에서 처음 확인되어 전세계로 확산되어 진행성 팬데믹을 초래한 질환으로, 사스-코로나바이러스-2에 의해 유발되는 감염성 질환이다. 2020년 5월 7일을 기준으로 3.75백만 케이스 이상이 187개국에서 보고되었고, 사망자는 263천명에 이르며, 1.24백만명이 회복되었다. 보편적인 증상은 발열(fever), 기침(cough), 피로(fatigue), 호흡곤란(shortness of breath) 및 후각 및 미각의 상실이다. 대부분의 경우 증상이 경미하나 몇몇은 바이러스성 폐렴(viral pneumonia), 다중기관부전(multi-organ failure) 및 사이토카인 폭풍(cyrokine storm)으로 진행한다. 증상의 발현으로부터 발병까지의 시간은 일반적으로 약 5일이지만 2 내지 14일 사이일 수 있다. 바이러스는 주로 밀접접촉 하는 동안, 때로는 기침, 재채기 및 대화시 발생하는 비말을 통해 사람 간에 전파된다. 증상 발현 후 처음 3일 동안 가장 전염성이 높으며, 증상이 나타나기 전이나 질환의 말기에라도 전파될 수 있다. 이를 진단하는 표준 방법은 비인두 면봉검사(nasopharyngeal swab)로부터의 실시간 역전사 PCR(real-time reverse transcription polymerase chain reaction; rRT-PCR)을 이용한다.COVID-19 is a disease that was first identified in Wuhan, the capital of Hubei Province, China, in late 2019 and has spread worldwide, causing a progressive pandemic. It is an infectious disease caused by SARS-coronavirus-2. As of May 7, 2020, more than 3.75 million cases have been reported in 187 countries, with 263,000 deaths and 1.24 million recoveries. Common symptoms are fever, cough, fatigue, shortness of breath, and loss of smell and taste. In most cases, symptoms are mild, but some progress to viral pneumonia, multi-organ failure, and cytokine storm. The time from onset of symptoms to onset is usually about 5 days, but can be between 2 and 14 days. The virus spreads from person to person mainly during close contact and sometimes through droplets produced when coughing, sneezing and talking. It is most contagious during the first three days after symptoms appear, and can spread even before symptoms appear or in the later stages of the disease. The standard method for diagnosing this is real-time reverse transcription polymerase chain reaction (rRT-PCR) from a nasopharyngeal swab.
메르스는 2012년 사우디아라비아에서 처음 발견되었고, 고열, 기침 및 호흡곤란 등 심한 호흡기 증상을 나타내며, 심한 경우 합병증이 동반되면서 사망에 이르기도 하는 질환이다. 명확한 감염원과 감염경로는 확인되지 않았으나, 중동 지역의 낙타와의 접촉을 통해 감염될 가능성이 크고 사람 간 밀접접촉에 의한 전파가 가능하다고 보고되었다. 주로 중동 지역에서 환자가 집중적으로 발생하였다가 2015년 5월부터 우리나라 전역에서 100명이 넘는 감염자가 발생한 바 있다.MERS was first discovered in Saudi Arabia in 2012, and is a disease that causes severe respiratory symptoms such as high fever, cough, and difficulty breathing, and in severe cases can lead to death due to complications. Although the clear source and route of infection have not been confirmed, it has been reported that there is a high possibility of infection through contact with camels in the Middle East and that transmission through close contact between people is possible. Patients were mainly concentrated in the Middle East, but since May 2015, more than 100 people have been infected throughout Korea.
앞서 언급한대로, 메르스 및 사스는 모두 베타 코로나바이러스(Beta coronavirus) 속에 속하는 변종 코로나바이러스(메르스-코로나바이러스, 사스-코로나바이러스 및 사스-코로나바이러스-2)가 원인이 되는 것으로 알려져 있다. 따라서 메르스-코로나바이러스, 사스-코로나바이러스 및 사스-코로나바이러스-2는 임상 증상, 병인 및 감염 등에 있어서 유사한 특성을 공유한다. 계통수(phylogenetic tree)에서, 사스-코로나바이러스 및 사스-코로나바이러스-2는 박쥐 사스-유사 코로나바이러스와 다른 박쥐 유래의 코로나바이러스를 포함하는 계통 B에 속하며, 메르스-코로나바이러스는 박쥐 유래의 코로나바이러스를 포함하는 계통 C에 속한다(Trends Microbiol 24:490-502; https://nextstrain.org/groups/blab/sars-like-cov?f_virus_type=SARS-CoV-2).As mentioned earlier, both MERS and SARS are known to be caused by variant coronaviruses (MERS-coronavirus, SARS-coronavirus, and SARS-coronavirus-2) belonging to the Beta coronavirus genus. Therefore, MERS-coronavirus, SARS-coronavirus, and SARS-coronavirus-2 share similar characteristics in clinical symptoms, pathogenesis, and infection. In the phylogenetic tree, SARS-coronavirus and SARS-coronavirus-2 belong to lineage B, which includes bat SARS-like coronaviruses and other bat-borne coronaviruses, while MERS-coronavirus is a bat-borne coronavirus. It belongs to lineage C, which contains viruses (Trends Microbiol 24:490-502; https://nextstrain.org/groups/blab/sars-like-cov?f_virus_type=SARS-CoV-2).
메르스-코로나바이러스, 사스-코로나바이러스 및 사스-코로나바이러스-2는 모두 다양한 코로나바이러스의 1차적인 보유 숙주인 박쥐로부터 유래한 것으로 여겨지며(Antiviral Res 101:45-56), 그 정확한 감염 경로에 대해서는 아직 완전히 밝혀지지 않았다. 한편, 사향 고양이(palm civet) 및 단봉낙타(dromedary camel)에 대한 상기 바이러스의 종간 전염은 인간에 대해 인수 공통 감염의 가능성을 증가시켰고(Nat Rev Microbiol 14:523-534), 병원 내 감염은 인간과 인간 사이의 메르스-코로나바이러스 및 사스-코로나바이러스 감염의 주된 원인으로 여겨진다(BMC Med13:1-12).MERS-coronavirus, SARS-coronavirus, and SARS-coronavirus-2 are all believed to have originated from bats, which are the primary reservoir hosts for various coronaviruses (Antiviral Res 101:45-56), and their exact route of infection is unknown. This has not yet been fully revealed. Meanwhile, interspecies transmission of the virus to civets and dromedary camels has increased the likelihood of zoonotic infection in humans (Nat Rev Microbiol 14:523-534), and nosocomial infection has increased in humans. It is believed to be the main cause of MERS-coronavirus and SARS-coronavirus infections among humans (BMC Med13:1-12).
한편, 현재 사스 코로나바이러스-2에 대한 여러 치료제가 개발되고 있기는 하나, 주로 화합물이나 기존 약재를 중심으로 개발이 되고 있으며, 천연물 치료제는 아직 개발된 바가 없다. Meanwhile, although several treatments for SARS coronavirus-2 are currently being developed, they are mainly developed based on compounds or existing medicines, and no natural product treatment has yet been developed.
특히, 현재까지 개발된 항바이러스들은 심한 부작용을 나타내고 있으므로, 그 응용에 있어서 많은 주의가 필요하다. 이러한 치료제는 효과적이지 못하며 부작용 또한 나타나고 있는 실정이다. 그러므로 코로나바이러스의 발생을 예방하고 치료하기 위한 감염 억제 효과가 뛰어나고 독성이 적은 우수한 새로운 코로나바이러스제의 개발의 필요성이 증가하고 있다.In particular, antivirals developed to date have severe side effects, so great caution is required in their application. These treatments are not effective and have side effects. Therefore, there is an increasing need to develop excellent new coronavirus agents with excellent infection control effects and low toxicity to prevent and treat coronavirus outbreaks.
본 발명자들은, 신규한 코로나바이러스 치료제를 개발하기 위한 노력을 계속한 결과, 안정성이 보장된 단풍잎 추출물이 코로나바이러스의 증식을 억제하는 우수한 효과가 있음을 확인함으로써, 본 발명을 완성하였다.As a result of continuing efforts to develop a new coronavirus treatment, the present inventors completed the present invention by confirming that a maple leaf extract with guaranteed stability has an excellent effect in inhibiting the proliferation of coronavirus.
본 발명의 목적은 단풍잎 추출물을 유효성분으로 포함하는 코로나바이러스에 대한 항바이러스용 조성물을 제공하는 것이다.The purpose of the present invention is to provide an antiviral composition against coronavirus containing maple leaf extract as an active ingredient.
본 발명의 다른 목적은 상기 조성물을 포함하는 코로나바이러스 감염질환의 예방 또는 치료용 약학 조성물을 제공하는 것이다.Another object of the present invention is to provide a pharmaceutical composition for preventing or treating coronavirus infectious diseases, comprising the composition.
본 발명의 또 다른 목적은 상기 조성물을 코로나바이러스 감염질환 증상이 나타나거나 또는 나타날 우려가 있는 개체에 투여하는 단계를 포함하는 코로나바이러스 감염질환의 예방 또는 치료 방법을 제공하는 것이다.Another object of the present invention is to provide a method for preventing or treating a coronavirus infection disease, including the step of administering the composition to an individual who is exhibiting or is likely to exhibit symptoms of a coronavirus infection disease.
본 발명의 또 다른 목적은 상기 조성물을 포함하는 코로나바이러스 감염질환의 예방 또는 개선용 건강기능식품 조성물을 제공하는 것이다.Another object of the present invention is to provide a health functional food composition for preventing or improving coronavirus infectious diseases, including the composition.
본 발명의 또 다른 하나의 목적은 상기 조성물을 포함하는 코로나바이러스 감염질환의 예방 또는 개선용 사료 조성물을 제공하는 것이다. Another object of the present invention is to provide a feed composition for preventing or improving coronavirus infectious diseases comprising the composition.
본 발명의 또 다른 하나의 목적은 단풍잎 추출물을 유효성분으로 포함하는 약학 조성물의 코로나바이러스에 대한 항바이러스 용도를 제공하는 것이다.Another object of the present invention is to provide an antiviral use against coronavirus of a pharmaceutical composition containing maple leaf extract as an active ingredient.
본 발명의 또 다른 하나의 목적은 단풍잎 추출물을 유효성분으로 포함하는 건강기능식품 조성물의 코로나바이러스에 대한 항바이러스 용도를 제공하는 것이다.Another object of the present invention is to provide an antiviral use against coronavirus of a health functional food composition containing maple leaf extract as an active ingredient.
본 발명의 또 다른 하나의 목적은 단풍잎 추출물을 유효성분으로 포함하는 사료 조성물의 코로나바이러스에 대한 항바이러스 용도를 제공하는 것이다.Another object of the present invention is to provide an antiviral use against coronavirus of a feed composition containing maple leaf extract as an active ingredient.
본 발명의 단풍잎 추출물은 코로나 바이러스의 감염을 억제하는 효과를 나타내므로, 상기 바이러스 질환을 예방 또는 치료를 위한 항바이러스제 개발에 이용될 수 있다.Since the maple leaf extract of the present invention has an effect of suppressing coronavirus infection, it can be used to develop an antiviral agent for preventing or treating the viral disease.
도 1은 단풍잎 열수 추출물의 코로나바이러스 억제 효능을 나타내는 그래프이다. Figure 1 is a graph showing the coronavirus inhibition efficacy of maple leaf hot water extract.
도 2는 단풍잎, 형개, 연잎 및 측백엽으로 구성된 열수 혼합 추출물 (차)의 코로나바이러스 억제 효능을 나타내는 그래프이다. Figure 2 is a graph showing the coronavirus inhibitory efficacy of a hot water mixed extract (tea) composed of maple leaf, sycamore leaf, lotus leaf, and arborvitae leaf.
도 3은 단풍잎, 형개, 연잎 및 측백엽으로 구성된 열수 혼합 추출물 (약탕기)의 코로나바이러스 억제 효능을 나타내는 그래프이다. Figure 3 is a graph showing the coronavirus inhibitory efficacy of a hot water mixed extract (Yaktanggi) composed of maple leaf, hyeonggae, lotus leaf, and arborvitae leaf.
도 4는 단풍잎, 형개, 연잎 및 유백피으로 구성된 열수 혼합 추출물 (약탕기)의 코로나바이러스 억제 효능을 나타내는 그래프이다. Figure 4 is a graph showing the coronavirus inhibitory effect of a hot water mixed extract (Yaktanggi) composed of maple leaf, hyeongae, lotus leaf, and milky white bark.
도 5은 단풍잎, 형개, 연잎, 유백피 및 음양곽으로 구성된 열수 혼합 추출물 (약탕기)의 코로나바이러스 억제 효능을 나타내는 그래프이다. Figure 5 is a graph showing the coronavirus inhibitory efficacy of the hot water mixed extract (Yaktanggi) consisting of maple leaf, Hyeonggae, lotus leaf, milky white bark, and Yinyanggwak.
도 6은 단풍잎, 형개, 연잎, 유백피, 측백엽, 음양곽 및 지구자로 구성된 열수 혼합 추출물 (약탕기)의 코로나바이러스 억제 효능을 나타내는 그래프이다.Figure 6 is a graph showing the coronavirus inhibitory efficacy of the hot water mixed extract (Yaktanggi) consisting of maple leaf, Hyeonggae, lotus leaf, milky white bark, Arborvitae leaf, Yin-Yang Gwak and Jijizi.
도 7은 양성대조군 렘데시비르, 클로로퀸, 로피나비어의 코로나바이러스 억제 효능을 나타내는 그래프이다.Figure 7 is a graph showing the coronavirus inhibition efficacy of the positive control group remdesivir, chloroquine, and lopinavir.
이를 구체적으로 설명하면 다음과 같다. 한편, 본 발명에서 개시된 각각의 설명 및 실시형태는 각각의 다른 설명 및 실시 형태에도 적용될 수 있다. 즉, 본 발명에서 개시된 다양한 요소들의 모든 조합이 본 발명의 범주에 속한다. 또한, 하기 기술된 구체적인 서술에 의하여 본 발명의 범주가 제한된다고 볼 수 없다.This is explained in detail as follows. Meanwhile, each description and embodiment disclosed in the present invention may also be applied to each other description and embodiment. That is, all combinations of the various elements disclosed in the present invention fall within the scope of the present invention. Additionally, the scope of the present invention cannot be considered limited by the specific description described below.
또한, 당해 기술분야의 통상의 지식을 가진 자는 통상의 실험만을 사용하여 본 발명에 기재된 본 발명의 특정 양태에 대한 다수의 등가물을 인지하거나 확인할 수 있다. 또한, 이러한 등가물은 본 발명에 포함되는 것으로 의도된다.Additionally, those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Additionally, such equivalents are intended to be encompassed by this invention.
본 발명의 하나의 양태는 단풍잎 추출물을 유효성분으로 포함하는 코로나바이러스에 대한 항바이러스용 조성물을 제공한다.One aspect of the present invention provides an antiviral composition against coronavirus containing maple leaf extract as an active ingredient.
본 발명에서 상기 조성물은 형개, 연잎, 측백나무 및 유백피로 이루어진 군에서 선택된 하나 이상의 추출물을 추가로 포함할 수 있으나, 이에 제한되지 않는다. In the present invention, the composition may further include, but is not limited to, one or more extracts selected from the group consisting of Hyeonggae, lotus leaf, arborvitae, and milky white bark.
본 발명에서 상기 조성물은 음양곽 및 지구자로 이루어진 군에서 선택된 하나 이상의 추출물을 추가로 포함할 수 있으나, 이에 제한되지 않는다.In the present invention, the composition may further include, but is not limited to, one or more extracts selected from the group consisting of Yinyanggwak and Jijizi.
본 발명에서 용어, "단풍잎"은 단풍나무, 아처 팔마툼 (Acer palmatum Thunb.)의 잎을 의미한다. 상기 단풍나무는 낙엽 활목 교목으로 높이는 10 내지 20m 내외이며 수형이 원형 형태인 식물을 의미한다. 상기 단풍나무 잎은 상업적으로 판매되는 것을 구입하거나, 자연에서 채취 또는 재배된 것을 사용할 수 있다.In the present invention, the term “maple leaf” refers to the leaf of a maple tree, Acer palmatum Thunb. The maple tree is a deciduous tree with a height of about 10 to 20 m and a circular tree shape. The maple leaves can be purchased commercially, or those collected or cultivated in nature can be used.
본 발명에서 용어, "형개"는 꿀풀과 식물인 형개의 전초를 말린 것으로, 생약명 스키조네페태 스피카 (Schizonepetae Spica), 학명 스키토네페타 테니폴리아 브리케(Schizonepeta tenuifolia Briquet)을 갖는다. 맛은 쓰고 성질은 따뜻한 것이 특징이며, 폐경, 간경 등에 작용하고 소화작용, 향균작용 등을 나타낸다고 알려져 있다.In the present invention, the term "hyeonggae" refers to the dried whole plant of Hyeonggae, a plant of the Lamiaceae family, and has the herbal name Schizonepetae Spica and the scientific name Schizonepeta tenuifolia Briquet. It is characterized by a bitter taste and a warm nature, and is known to be effective in menopause, liver cirrhosis, etc., and to have digestive and antibacterial effects.
본 발명에서 용어, "연잎"은 연꽃, 넬룸보 누시페라(Nelumbo nucifera)의 잎 (Lotus (Nelumbo nucifera Gaertn.) leaf)을 의미하는 것으로, 예로부터 민간 및 한방에서는 부용, 하엽 등으로 불리며, 출혈성 위궤양이나 위염, 치질, 출혈 등에 사용되어 왔다. In the present invention, the term "lotus leaf" refers to the leaf of the lotus flower, Nelumbo nucifera (Nelumbo nucifera Gaertn.) leaf, and has been called bouyong, hayeop, etc. in folk and oriental medicine since ancient times, and is used to treat hemorrhagic properties. It has been used for stomach ulcers, gastritis, hemorrhoids, and bleeding.
본 발명에서 용어, "측백나무"는 측백나뭇과의 상록 침엽 교목으로, 학명 투자 오리엔탈릴스 (Thuja orientalis L.)를 갖는다. 높이는 25미터 정도이며, 잎은 작은 비늘 모양으로 밀집하여 있다. 본 발명에서 상기 측백나무는 측백나무의 뿌리, 잎, 꽃, 줄기 등과 같은 특정 부위를 의미할 수 있고, 식물 전체를 의미할 수 있다. 구체적으로, 본 발명에서 조성물은 측백나무 잎, 측백엽 (Thuja orientalis L.)을 포함할 수 있다. In the present invention, the term "Arborvitae" refers to an evergreen coniferous tree of the Arborvitae family, and has the scientific name Thuja orientalis L.. The height is about 25 meters, and the leaves are densely packed in the shape of small scales. In the present invention, the arborvitae tree may mean a specific part of the arborvitae tree, such as the roots, leaves, flowers, stems, etc., or may mean the entire plant. Specifically, in the present invention, the composition may include Thuja orientalis L. leaves and Thuja orientalis L.
본 발명에서 용어, "유백피"는 유근피로도 불리며, 느릅나무과의 왕느릅나무, 울므스 마크로카르파 한스(Ulmus macrocarpa Hance)의 코르크층을 벗긴 수피를 의미한다. 생김새로는 관상 또는 판상으로 바깥면은 흑갈색으로 반점이 있고 코르크층이 있다. 꺾은면은 거칠고 엷은 갈색이며, 섬유상의 가는 무늬가 뚜렷하고 질은 단단하며 흑황색의 가루가 있다.In the present invention, the term "milky bark", also called radicle bark, refers to the bark of Ulmus macrocarpa Hance, a large elm tree of the elm family, from which the cork layer has been peeled off. In appearance, it is tubular or plate-shaped, and the outer surface is dark brown with spots and a cork layer. The broken surface is rough and light brown, has a clear fibrous pattern, is hard, and has black-yellow powder.
본 발명에서 용어, "음양곽"은 쌍떡잎식물 미나리아재비목 매자나무과의 여러해살이풀인 삼지구엽초, 에피메디움 코리아눔 나카이 (Epimedium koreanum Nakai) 또는 기타 동속근연식물의 지상부(줄기와 잎)를 의미하며, 냄새가 없으며 맛은 맵고 달며 성질은 따뜻하다.In the present invention, the term "yin-yang-gwak" refers to the above-ground parts (stem and leaves) of Epimedium koreanum Nakai, a perennial herb of the dicotyledonous plant Ranunculaceae barberry family, or other closely related plants, It has no odor, tastes spicy and sweet, and is warm in nature.
본 발명에서 용어, "지구자 (Hoveniae Semen Seu Fructus)"는 갈매나무과의 헛개나무, 호베니아 둘시스 (Hovenia dulcis Thunberg)의 과병을 가진 열매 또는 씨를 말하는 것으로, 맛이 달다고 해서 나무에서 나는 꿀이라는 뜻으로 목밀이라고도 한다. 중국에서는 신선의 정원에서는 나는 배나무라는 뜻으로 현포리라고 하기도 하고, 돌과 같이 희고 단단해서 백석목이라고도 한다.In the present invention, the term "Hoveniae Semen Seu Fructus" refers to the fruit or seed of Hovenia dulcis Thunberg, a buckthorn tree of the buckthorn family. It is said to have a sweet taste, so it is used to refer to the honey produced from the tree. It is also called mokmil. In China, it is called Hyeonpori, which means pear tree that grows in the garden of immortals, and it is also called Baekseokmok because it is white and hard like a stone.
본 발명의 용어, "추출물"은 상기 단풍잎을 추출 처리하여 얻어지는 추출액, 상기 추출액의 희석액이나 농축액, 상기 추출액을 건조하여 얻어지는 건조물, 상기 추출액의 조정제물이나 정제물, 또는 이들의 혼합물 등, 추출액 자체 및 추출액을 이용하여 형성 가능한 모든 제형의 추출물을 포함한다.As used herein, the term "extract" refers to the extract obtained by extracting and processing the maple leaves, a diluted or concentrated liquid of the extract, a dried product obtained by drying the extract, a crude product or purified product of the extract, or a mixture thereof, or the extract itself. and extracts of all formulations that can be formed using the extract.
상기 단풍잎을 추출하는 방법은 특별히 제한되지 않으며, 당해 기술 분야에서 통상적으로 사용하는 방법에 따라 추출할 수 있다. 상기 추출 방법의 비제한적인 예로는, 열수 추출법, 초음파 추출법, 상온 추출법, 냉침 추출법, 여과법, 환류 추출법, 증기 추출법 등을 들 수 있으며, 이들은 단독으로 수행되거나 2종 이상의 방법을 병용하여 수행될 수 있다.The method for extracting the maple leaves is not particularly limited, and may be extracted according to methods commonly used in the art. Non-limiting examples of the extraction method include hot water extraction, ultrasonic extraction, room temperature extraction, cold needle extraction, filtration, reflux extraction, steam extraction, etc., which can be performed alone or by combining two or more methods. there is.
본 발명에서 상기 단풍잎을 추출하는데 사용되는 추출 용매의 종류는 특별히 제한되지 않으며, 당해 기술 분야에서 공지된 임의의 용매를 사용할 수 있다. 상기 추출 용매의 비제한적인 예로는 물, 탄소수 1 내지 4의 알코올 또는 이들의 혼합 용매 등을 들 수 있으며, 이들은 단독으로 사용되거나 1종 이상 혼합하여 사용될 수 있다. The type of extraction solvent used to extract the maple leaves in the present invention is not particularly limited, and any solvent known in the art can be used. Non-limiting examples of the extraction solvent include water, alcohols having 1 to 4 carbon atoms, or mixed solvents thereof, and these may be used alone or in combination of one or more types.
본 발명에서, 항바이러스 효과를 나타내는 한 용매는 제한되지 않고, 구체적으로 본 발명에서 단풍잎 추출물은 단풍잎 열수 추출물인 것일 수 있으나, 이에 제한되지 않는다.In the present invention, the solvent that exhibits an antiviral effect is not limited. Specifically, the maple leaf extract in the present invention may be a maple leaf hot water extract, but is not limited thereto.
본 발명의 일 실시예서는, 단풍잎 추출물과, 단풍잎에 형개, 연잎, 유백피, 측백엽, 음양곽, 및 지구자로 이루어진 군에서 선택하여 추가한 다양한 혼합 추출물을 제조하기 위하여, 70~100℃, 3~10분 차로 우리거나 80~130℃, 130분~180분 동안 약탕기를 이용하여 달여 추출하였다. In one embodiment of the present invention, in order to prepare maple leaf extract and various mixed extracts selected from the group consisting of maple leaf, lotus leaf, milky white bark, arborvitae leaf, yin-yang gwak, and earthenberry, the mixture was heated at 70 to 100 ° C., 3 to 100 degrees Celsius. It was extracted by boiling it for 10 minutes or boiling it in a water boiler at 80~130℃ for 130~180 minutes.
본 발명의 용어, "항바이러스"는 바이러스 감염을 억제하는 성질을 말하며, 상기 "바이러스"란 동물, 식물, 세균 등 살아 있는 세포에 기생하고, 세포 안에서만 증식이 가능한 미생물을 의미한다. 본 발명에서 바이러스는 코로나바이러스일 수 있으나, 이에 제한되지 않는다.As used herein, the term "antiviral" refers to the property of suppressing viral infection, and the "virus" refers to a microorganism that parasitizes living cells such as animals, plants, and bacteria and can proliferate only within the cells. In the present invention, the virus may be a coronavirus, but is not limited thereto.
본 발명에서 "코로나바이러스"는 아데노바이러스·리노바이러스와 함께 사람에게 감기를 일으키는 3대 바이러스 중 하나로, 사람과 다양한 동물에 감염될 수 있는 유전자 크기 27~32kb의 RNA 바이러스이다. In the present invention, "coronavirus" is one of the three major viruses that cause colds in humans, along with adenovirus and rhinovirus, and is an RNA virus with a gene size of 27 to 32 kb that can infect humans and various animals.
코로나바이러스 감염질환은 코로나바이러스가 숙주가 되는 생물체의 체내에 침입하는 감염에 의해 발병되는 질환을 의미하는 것으로서, 구체적으로는 상기 코로나바이러스는 사스-코로나바이러스-2(Covid-19), 사스-코로나바이러스 및 메르스-코로나바이러스로 이루어진 군에서 선택된 하나 이상일 수 있고, 보다 구체적으로는 사스- 코로나바이러스-2일 수 있다.Coronavirus infectious disease refers to a disease caused by an infection that invades the body of a coronavirus host organism. Specifically, the coronavirus is SARS-Coronavirus-2 (Covid-19) and SARS-Coronavirus. It may be one or more selected from the group consisting of viruses and MERS-coronavirus, and more specifically, it may be SARS-coronavirus-2.
본 발명의 일 실시예에서는 단풍잎 추출물은 단독으로 코로나바이러스 감염 억제능이 우수함을 확인하였다 (도 1). 형개, 연잎, 측백엽 및 단풍잎을 차로 우리거나, 약탕기를 이용하여 달여 추출한 결과, 모두 코로나바이러스 감염 억제능이 우수함을 확인하였고, 이를 통해 추출방법과 상관 없이 형개, 연잎, 측백엽 및 단풍잎 혼합 추출물은 코로나바이러스 억제능이 있음을 알 수 있었다 (도 2, 도 3). In one example of the present invention, it was confirmed that maple leaf extract alone had excellent ability to inhibit coronavirus infection (Figure 1). As a result of extracting the lily, lotus leaf, arborvitae leaf, and maple leaf by making tea or boiling it using a boiler, it was confirmed that all of them had excellent anti-coronavirus infection inhibitory properties. Regardless of the extraction method, the mixed extract of eucalyptus, lotus leaf, arborvitae leaf, and maple leaf was used to prevent coronavirus. It was found that there was an inhibitory ability (Figures 2 and 3).
또한, 형개, 연잎, 측백엽, 유백피 및 단풍잎; 형개, 연잎, 유백피, 단풍잎 및 음양곽; 형개, 연잎, 유백피, 측백엽, 지구자, 음양곽 및 단풍잎 혼합 추출물은 코로나바이러스 억제능이 우수함을 확인하였다. 이를 통해, 단풍잎 단독 추출물뿐만 아니라, 혼합 추출물의 경우에도 항바이러스 효과가 우수함을 알 수 있었다 (도 4 내지 도 6).In addition, Hyeonggae, lotus leaf, Arborvitae leaf, milky white bark and maple leaf; Hyeonggae, lotus leaf, milky white bark, maple leaf and yin-yang gwak; It was confirmed that the mixed extracts of Hyeonggae, lotus leaf, milky white bark, Arborvitae leaf, Earth berry, Yin Yang Gwak, and maple leaf have excellent anti-coronavirus ability. Through this, it was found that the antiviral effect was excellent not only for the maple leaf extract alone, but also for the mixed extract (Figures 4 to 6).
본 발명의 다른 하나의 양태는 상기 조성물을 포함하는 코로나바이러스 감염질환의 예방 또는 치료용 약학 조성물을 제공한다. Another aspect of the present invention provides a pharmaceutical composition for preventing or treating coronavirus infectious diseases, comprising the composition.
상기 단풍잎, 항바이러스, 코로나바이러스 및 추출물은 전술 한 바와 같다. The maple leaf, antiviral, coronavirus and extract are as described above.
본 발명의 용어, "약학 조성물"은 총 조성물의 중량 대비 상기 단풍잎 추출물을 0.000001 내지 80 중량%로 포함할 수 있으며, 구체적으로 0.00001 중량% 내지 40 중량%로 포함할 수 있으나, 이에 제한되는 것은 아니다.The term "pharmaceutical composition" of the present invention may include 0.000001 to 80% by weight of the maple leaf extract relative to the weight of the total composition, and may specifically include 0.00001 to 40% by weight, but is not limited thereto. .
상기 약학 조성물은 약학 조성물의 제조에 통상적으로 사용하는 약학적으로 허용가능한 담체, 부형제 또는 희석제를 추가로 포함할 수 있고, 상기 담체는 비자연적 담체(non-naturally occuring carrier)를 포함할 수 있다. The pharmaceutical composition may further include a pharmaceutically acceptable carrier, excipient, or diluent commonly used in the preparation of the pharmaceutical composition, and the carrier may include a non-naturally occurring carrier.
상기 약학 조성물은, 각각 통상의 방법에 따라 산제, 과립제, 정제, 캡슐제, 현탁액, 에멀젼, 시럽, 에어로졸 등의 경구형 제형, 외용제, 좌제 및 멸균 주사용액의 형태로 제형화하여 사용될 수 있다.The pharmaceutical composition can be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, and sterile injection solutions according to conventional methods.
상기 "약학적으로 허용가능한"은 상기 조성물에 노출되는 세포나 인간에게 독성이 없는 특성을 나타내는 것을 의미한다.The term “pharmaceutically acceptable” means that the composition exhibits non-toxic properties to cells or humans exposed to the composition.
구체적으로, 상기 담체의 종류는 특별히 제한되지 않으며, 당해 기술 분야에서 통상적으로 사용되고 약학적으로 허용되는 담체라면 어느 것이든 사용할 수 있다. 상기 담체의 비제한적인 예로, 식염수, 멸균수, 링거액, 완충 식염수, 알부민 주사 용액, 덱스트로즈 용액, 말토 덱스트린 용액, 글리세롤, 에탄올 등을 들 수 있다. 이들은 단독으로 사용되거나 2종 이상을 혼합하여 사용될 수 있다. 또한, 필요한 경우 항산화제, 완충액 및/또는 정균제 등 다른 통상의 첨가제를 첨가하여 사용할 수 있으며, 희석제, 분산제, 계면 활성제, 결합제, 윤활제 등을 부가적으로 첨가하여 수용액, 현탁액, 유탁액 등과 같은 주사용 제형, 환약, 캡슐, 과립 또는 정제 등으로 제제화하여 사용할 수 있다.Specifically, the type of the carrier is not particularly limited, and any carrier commonly used in the art and pharmaceutically acceptable can be used. Non-limiting examples of the carrier include saline solution, sterile water, Ringer's solution, buffered saline solution, albumin injection solution, dextrose solution, maltodextrin solution, glycerol, ethanol, etc. These may be used alone or in combination of two or more types. In addition, if necessary, other common additives such as antioxidants, buffers, and/or bacteriostatic agents can be added and used, and diluents, dispersants, surfactants, binders, lubricants, etc. can be additionally added to form solutions such as aqueous solutions, suspensions, emulsions, etc. It can be formulated and used in dosage form, pills, capsules, granules, or tablets.
본 발명에 따른 항바이러스용 약학 조성물의 투여 방식은 특별히 제한되지 않으며, 당해 기술 분야에서 통상적으로 사용하는 방식에 따를 수 있다. 상기 투여 방식의 비제한적인 예로, 조성물을 경구 투여 또는 비경구 투여 방식으로 투여할 수 있다. 또한, 본 발명의 코로나바이러스 감염질환의 예방, 개선 또는 치료용 조성물은 목적하는 투여 방식에 따라 다양한 제형으로 제조될 수 있다.The administration method of the antiviral pharmaceutical composition according to the present invention is not particularly limited and may follow a method commonly used in the art. As a non-limiting example of the administration method, the composition may be administered by oral administration or parenteral administration. In addition, the composition for preventing, improving, or treating coronavirus infectious diseases of the present invention can be prepared in various formulations depending on the desired administration method.
본 발명의 용어, "감염질환"은 감염에 의해 발병되는 질환을 의미한다.As used herein, the term “infectious disease” refers to a disease caused by infection.
본 발명에서 "감염"은 병원성 미생물이 숙주가 되는 생물체의 체내에 침입하여, 발육ㆍ증식한 상태를 의미한다.In the present invention, “infection” refers to a state in which pathogenic microorganisms invade the body of a host organism and grow and proliferate.
본 발명의 용어, "예방"은 단풍잎 추출물을 포함하는 본 발명의 약학 조성물의 투여에 의해 바이러스 감염질환을 억제시키거나 또는 지연시키는 모든 행위를 의미한다.The term "prevention" of the present invention refers to all actions that suppress or delay viral infectious diseases by administering the pharmaceutical composition of the present invention containing maple leaf extract.
본 발명의 용어, "치료"는 상기 약학 조성물의 투여에 의해 바이러스 감염질환이 호전되거나 이롭게 변경되는 모든 행위를 의미한다.As used herein, the term “treatment” refers to any action in which a viral infectious disease is improved or beneficially altered by administration of the pharmaceutical composition.
본 발명의 다른 하나의 양태는 단풍잎 추출물을 유효성분으로 포함하는 조성물을 코로나바이러스 감염질환 증상이 나타나거나 또는 나타날 우려가 있는 개체에 투여하는 단계를 포함하는 코로나바이러스 감염질환의 예방 또는 치료 방법을 제공한다. Another aspect of the present invention provides a method for preventing or treating a coronavirus infectious disease, comprising administering a composition containing maple leaf extract as an active ingredient to an individual who is showing or is likely to show symptoms of a coronavirus infectious disease. do.
상기 단풍잎, 항바이러스, 코로나바이러스, 추출물. 약학 조성물, 감염질환, 예방 및 치료는 전술 한 바와 같다.The above maple leaf, antiviral, coronavirus, extract. Pharmaceutical compositions, infectious diseases, prevention and treatment are as described above.
본 발명에서 상기 조성물은 형개, 연잎, 측백나무 및 유백피로 이루어진 군에서 선택된 하나 이상의 추출물을 추가로 포함할 수 있으나, 이에 제한되지 않는다. In the present invention, the composition may further include, but is not limited to, one or more extracts selected from the group consisting of Hyeonggae, lotus leaf, arborvitae, and milky white bark.
본 발명에서 상기 조성물은 음양곽 및 지구자로 이루어진 군에서 선택된 하나 이상의 추출물을 추가로 포함할 수 있으나, 이에 제한되지 않는다.In the present invention, the composition may further include, but is not limited to, one or more extracts selected from the group consisting of Yinyanggwak and Jijiji.
본 발명의 용어, "투여"는 적절한 방법으로 개체에게 소정의 물질을 도입하는 것을 의미한다. As used herein, the term “administration” means introducing a given substance into a subject by an appropriate method.
본 발명의 용어, "개체"는 코로나바이러스 감염질환이 발병하였거나, 발병할 수 있는 인간을 포함한 쥐, 생쥐, 가축 등의 모든 동물을 의미한다. 구체적인 예로, 인간을 포함한 포유동물일 수 있다.As used herein, the term “individual” refers to all animals, including rats, mice, and livestock, including humans, that have or may develop a coronavirus infectious disease. As a specific example, it may be a mammal, including humans.
구체적으로, 본 발명의 코로나바이러스 감염질환의 예방 또는 치료 방법은 개체에 단풍잎 추출물을 포함하는 조성물을 약학적으로 유효한 양으로 투여하는 단계를 포함할 수 있다.Specifically, the method for preventing or treating a coronavirus infectious disease of the present invention may include administering a composition containing maple leaf extract to an individual in a pharmaceutically effective amount.
본 발명의 용어, "약학적으로 유효한 양"은 의학적 치료에 적용 가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분하며 부작용을 일으키지 않을 정도의 양을 의미하며, 유효 용량 수준은 환자의 성별, 연령, 체중, 건강상태, 질병의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 방법, 투여 시간, 투여 경로, 및 배출 비율, 치료 기간, 배합 또는 동시에 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 당업자에 의해 용이하게 결정될 수 있다.As used herein, the term "pharmaceutically effective amount" refers to an amount that is sufficient to treat a disease with a reasonable benefit/risk ratio applicable to medical treatment and does not cause side effects, and the effective dose level is determined by the patient's gender, Factors including age, weight, health status, type and severity of the disease, activity of the drug, sensitivity to the drug, method of administration, time of administration, route of administration, and excretion rate, duration of treatment, drugs combined or used simultaneously, and other medical factors. It can be easily determined by a person skilled in the art according to factors well known in the art.
본 발명의 약학 조성물은 고형분을 기준으로 1일 0.000001 내지 100 mg/체중 kg으로, 더욱 구체적으로 0.0001 내지 100 mg/체중 kg으로 투여할 수 있다. 투여는 상기 권장 투여량을 하루에 한 번 투여할 수도 있고, 수회 나누어 투여할 수도 있다.The pharmaceutical composition of the present invention can be administered at 0.000001 to 100 mg/kg of body weight per day, more specifically 0.0001 to 100 mg/kg of body weight, based on solid content. The recommended dosage may be administered once a day, or it may be administered several times.
본 발명의 약학 조성물은 개별 치료제로 투여되거나 다른 치료제와 병용하여 투여될 수 있고, 종래의 치료제와는 순차적 또는 동시에 투여될 수 있다. 또한, 단일 또는 다중 투여될 수 있다. 상기 요소를 모두 고려하여 부작용을 유발하지 않으면서 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 이는 당업자에 의해 용이하게 결정될 수 있다.The pharmaceutical 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. Additionally, it can be administered single or multiple times. Considering all of the above factors, it is important to administer an amount that can achieve maximum effect with the minimum amount without causing side effects, and this can be easily determined by a person skilled in the art.
본 발명의 코로나바이러스 감염질환의 예방 또는 치료 방법에서, 상기 조성물을 투여하는 투여 경로 및 투여 방식은 특별히 제한되지 않으며, 목적하는 해당 부위에 상기 조성물을 포함하는 조성물이 도달할 수 있는 한 임의의 투여 경로 및 투여 방식에 따를 수 있다. 구체적으로, 상기 조성물은 경구 또는 비경구의 다양한 경로를 통하여 투여될 수 있으며, 그 투여 경로의 비제한적인 예로는, 구강, 직장, 국소, 정맥내, 복강내, 근육내, 동맥내, 경피, 비측내 또는 흡입 등을 통하여 투여되는 것을 들 수 있다. 본 발명의 단풍잎 추출물이 코로나바이러스 감염질환의 예방 또는 치료에 효과가 있는 특성상, 조성물의 투여 경로는 경구를 통하여 투여될 수 있다.In the method for preventing or treating coronavirus infectious diseases of the present invention, the administration route and administration method for administering the composition are not particularly limited, and any administration may be performed as long as the composition containing the composition can reach the target site. It may depend on the route and method of administration. Specifically, the composition may be administered through various oral or parenteral routes, and non-limiting examples of the administration route include oral, rectal, topical, intravenous, intraperitoneal, intramuscular, intraarterial, transdermal, and nasal. It may be administered intralaterally or through inhalation. Because the maple leaf extract of the present invention is effective in preventing or treating coronavirus infectious diseases, the composition may be administered orally.
본 발명의 다른 하나의 양태는 상기 조성물을 포함하는 코로나바이러스 감염질환의 예방 또는 개선용 건강기능식품 조성물을 제공한다. Another aspect of the present invention provides a health functional food composition for preventing or improving coronavirus infectious diseases, including the composition.
상기 단풍잎, 항바이러스, 코로나바이러스, 추출물. 약학 조성물, 감염질환, 예방 및 치료는 전술 한 바와 같다.The above maple leaf, antiviral, coronavirus, extract. Pharmaceutical compositions, infectious diseases, prevention and treatment are as described above.
본 발명의 용어, "건강기능식품"(functional food)은 특정보건용 식품(food for special health use, FoSHU)과 동일한 용어로, 영양 공급 외에도 생체조절기능이 효율적으로 나타나도록 가공된 의학, 의료효과가 높은 식품을 의미한다. 본 발명에서, 상기 건강기능식품은 건강식품 또는 건강보조식품과 호용된다.The term "functional food" of the present invention is the same as food for special health use (FoSHU), and is a medicine processed to efficiently exhibit bioregulatory functions in addition to nutritional supply, and medical effects. refers to foods with high . In the present invention, the health functional food is compatible with health food or health supplement food.
본 발명의 건강기능식품 조성물은 일상적으로 섭취하는 것이 가능하기 때문에 높은 코로나바이러스 감염질환 개선 효과를 기대할 수 있으므로, 건강 증진 목적으로 매우 유용하게 사용될 수 있다.Since the health functional food composition of the present invention can be consumed on a daily basis, it can be expected to have a high effect on improving coronavirus infectious diseases, so it can be very useful for health promotion purposes.
이때, 상기 건강기능식품 조성물에 포함되는 추출물의 함량은 특별히 이에 제한되지 않으나, 건강기능식품 조성물의 총 중량에 대하여 0.01 내지 100 중량%, 보다 바람직하게는 1 내지 80 중량%로 포함될 수 있다.At this time, the content of the extract included in the health functional food composition is not particularly limited, but may be included in 0.01 to 100% by weight, more preferably 1 to 80% by weight, based on the total weight of the health functional food composition.
상기 건강기능식품은 코로나바이러스 감염질환의 예방 또는 개선에 유용한 효과를 얻기 위하여 환제, 분말, 과립, 침제, 정제, 캡슐 및 음료 형태로 이루어지는 군에서 선택되는 것으로 제형화된 것으로 제조될 수 있다. 본 발명의 단풍잎 추출물을 포함하는 조성물을 첨가할 수 있는 식품의 종류에는 별다른 제한이 없으며, 예를 들어 각종 음료, 껌, 차, 비타민 복합제, 건강보조 식품류 등이 있다. The health functional food may be manufactured in a form selected from the group consisting of pills, powders, granules, precipitates, tablets, capsules and beverages in order to obtain useful effects in preventing or improving coronavirus infectious diseases. There is no particular limitation on the type of food to which the composition containing the maple leaf extract of the present invention can be added, for example, various beverages, gum, tea, vitamin complexes, health supplements, etc.
상기 건강기능식품 조성물에는 건강기능식품의 예방 또는 개선 효과에 방해가 되지 않는 다른 성분을 추가할 수 있으며, 그 종류는 특별히 제한되지 않는다. 예를 들어, 통상의 식품과 같이 여러 가지 생약 추출물, 식품학적으로 허용 가능한 식품보조첨가제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다.Other ingredients that do not interfere with the preventive or improving effect of the health functional food may be added to the health functional food composition, and their types are not particularly limited. For example, like regular foods, it may contain various herbal extracts, foodologically acceptable food additives, or natural carbohydrates as additional ingredients.
또한, 상기 건강기능식품 조성물은 식품학적으로 허용가능한 담체를 추가로 포함할 수 있으며, 이는 당업자가 적절히 선택하여 사용할 수 있다. 예를 들어 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 충진제, 펙트산 및 그의 염, 알긴산 및 그의 염, 유기산, 보호성 콜로이드 증점제, pH 조절제, 안정화제, 방부제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등이 포함되지만, 상기 예들에 의해 그 종류가 제한되는 것은 아니다.In addition, the health functional food composition may further include a foodologically acceptable carrier, which can be appropriately selected and used by a person skilled in the art. For example, various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic and natural flavors, colorants and fillers, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters. , stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated drinks, etc., but the types are not limited to the above examples.
또한, 상기 건강기능식품 조성물은 식품 조성물에 통상 사용되어 냄새, 맛, 시각 등을 향상시킬 수 있는 추가 성분을 포함할 수 있다. 예를 들어, 비타민 A, C, D, E, B1, B2, B6, B12, 니아신(niacin), 비오틴(biotin), 폴레이트(folate), 판토텐산(panthotenic acid) 등을 포함할 수 있다. 또한, 아연(Zn), 철(Fe), 칼슘(Ca), 크롬(Cr), 마그네슘(Mg), 망간(Mn), 구리(Cu) 등의 미네랄을 포함할 수 있다. 또한, 라이신, 트립토판, 시스테인, 발린 등의 아미노산을 포함할 수 있다. In addition, the health functional food composition may include additional ingredients that are commonly used in food compositions to improve smell, taste, vision, etc. For example, it may include vitamins A, C, D, E, B1, B2, B6, B12, niacin, biotin, folate, pantothenic acid, etc. Additionally, it may contain minerals such as zinc (Zn), iron (Fe), calcium (Ca), chromium (Cr), magnesium (Mg), manganese (Mn), and copper (Cu). Additionally, it may contain amino acids such as lysine, tryptophan, cysteine, and valine.
또한, 방부제(소르빈산 칼륨, 벤조산나트륨, 살리실산, 데히드로초산나트륨 등), 살균제(표백분과 고도 표백분, 차아염소산나트륨 등), 산화방지제(부틸히드록시아니졸(BHA), 부틸히드록시톨류엔(BHT) 등), 착색제(타르색소 등), 발색제(아질산 나트륨, 아초산 나트륨 등), 표백제(아황산나트륨), 조미료(MSG 글루타민산나트륨 등), 감미료(둘신, 사이클레메이트, 사카린, 나트륨 등), 향료(바닐린, 락톤류 등), 팽창제(명반, D-주석산수소칼륨 등), 강화제, 유화제, 증점제(호료), 피막제, 검기초제, 거품억제제, 용제, 개량제 등의 식품 첨가물(food additives)을 첨가할 수 있다.In addition, preservatives (potassium sorbate, sodium benzoate, salicylic acid, sodium dehydroacetate, etc.), disinfectants (bleaching powder, high bleaching powder, sodium hypochlorite, etc.), antioxidants (butylhydroxyanisole (BHA), butylhydroxytoluene ( BHT), etc.), colorants (tar color, etc.), coloring agents (sodium nitrite, sodium nitrite, etc.), bleaching agents (sodium sulfite), seasonings (MSG monosodium glutamate, etc.), sweeteners (dulcine, cyclemate, saccharin, sodium, etc.) , food additives such as flavorings (vanillin, lactones, etc.), leavening agents (alum, D-potassium hydrogen tartrate, etc.), strengthening agents, emulsifiers, thickeners (grease), coating agents, gum base agents, anti-foam agents, solvents, improvers, etc. ) can be added.
본 발명의 다른 하나의 양태는 상기 조성물을 포함하는 코로나바이러스 감염질환의 예방 또는 개선용 사료 조성물을 제공한다. Another aspect of the present invention provides a feed composition for preventing or improving coronavirus infectious diseases, including the composition.
상기 단풍잎, 항바이러스, 코로나바이러스, 추출물. 약학 조성물, 감염질환, 예방 및 치료는 전술 한 바와 같다.The above maple leaf, antiviral, coronavirus, extract. Pharmaceutical compositions, infectious diseases, prevention and treatment are as described above.
본 발명의 용어, "사료"는 동물이 먹고, 섭취하며, 소화시키기 위한 또는 이에 적당한 임의의 천연 또는 인공 규정식, 한끼식 등 또는 상기 한끼식의 성분을 의미한다.As used herein, the term "feed" means any natural or artificial diet, meal, etc., or a component of the meal, for or suitable for eating, ingestion, and digestion by animals.
상기 사료의 종류는 특별히 제한되지 아니하며, 당해 기술 분야에서 통상적으로 사용되는 사료를 사용할 수 있다. 상기 사료의 비제한적인 예로는, 곡물류, 근과류, 식품 가공 부산물류, 조류, 섬유질류, 제약 부산물류, 유지류, 전분류, 박류 또는 곡물 부산물류 등과 같은 식물성 사료; 단백질류, 무기물류, 유지류, 광물성류, 유지류, 단세포 단백질류, 동물성 플랑크톤류 또는 음식물 등과 같은 동물성 사료를 들 수 있다. 이들은 단독으로 사용되거나 2종 이상을 복합하여 사용될 수 있다.The type of feed is not particularly limited, and feed commonly used in the art can be used. Non-limiting examples of the feed include plant feeds such as grains, roots and fruits, food processing by-products, algae, fiber, pharmaceutical by-products, oils and fats, starches, cucurbits or grain by-products; Examples include animal feeds such as proteins, inorganic substances, fats and oils, minerals, fats and oils, single-cell proteins, zooplanktons or foods. These may be used singly or in combination of two or more types.
본 발명의 다른 하나의 양태는 단풍잎 추출물을 유효성분으로 포함하는 약학 조성물의 코로나바이러스에 대한 항바이러스 용도를 제공한다.Another aspect of the present invention provides an antiviral use against coronavirus of a pharmaceutical composition containing maple leaf extract as an active ingredient.
본 발명의 다른 하나의 양태는 단풍잎 추출물을 유효성분으로 포함하는 건강기능식품 조성물의 코로나바이러스에 대한 항바이러스 용도를 제공한다.Another aspect of the present invention provides an antiviral use against coronavirus of a health functional food composition containing maple leaf extract as an active ingredient.
본 발명의 다른 하나의 양태는 단풍잎 추출물을 유효성분으로 포함하는 사료 조성물의 코로나바이러스에 대한 항바이러스 용도를 제공한다.Another aspect of the present invention provides an antiviral use against coronavirus of a feed composition containing maple leaf extract as an active ingredient.
상기 단풍잎, 항바이러스, 코로나바이러스, 추출물. 약학 조성물, 감염질환, 예방 및 치료는 전술 한 바와 같다.The above maple leaf, antiviral, coronavirus, extract. Pharmaceutical compositions, infectious diseases, prevention and treatment are as described above.
이하 본 발명을 실시예 또는 실험예를 통하여 보다 상세하게 설명한다. 그러나 이들 실시예 또는 실험예는 본 발명을 예시적으로 설명하기 위한 것으로 본 발명의 범위가 이들 실시예 또는 실험예에 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail through examples or experimental examples. However, these examples or experimental examples are for illustrative purposes only and the scope of the present invention is not limited to these examples or experimental examples.
실험예 1. 추출물 제조방법Experimental Example 1. Extract manufacturing method
단풍잎 추출물과, 단풍잎에 형개, 연잎, 유백피, 측백엽, 음양곽, 및 지구자로 이루어진 군에서 선택하여 추가한 다양한 혼합 추출물을 제조하기 위하여, 단풍잎 (Acer palmatum Thunb.), 형개 (Schizonepeta tenuifolia Briquet), 연잎 (Lotus (Nelumbo nucifera Gaertn.) leaf), 유백피 (왕느릅나무 수피, Ulmus macrocarpa Hance), 측백엽 (Thuja orientalis L.), 음양곽 (삼지구엽초 지상부, Epimedium koreanum Nakai) 및 지구자 (헛개나무 (Hovenia dulcis) 열매 또는 씨, Hoveniae Semen Seu Fructus)를 구입하여 시료로 사용하였다. 차로 우리거나 약탕기를 이용하여 달여 추출하였다. In order to prepare maple leaf extract and various mixed extracts selected from the group consisting of maple leaf, lotus leaf, milky white bark, arborvitae leaf, yin-yang gwak, and earthenberry, maple leaf (Acer palmatum Thunb.), Hyeonggae (Schizonepeta tenuifolia Briquet), Lotus (Nelumbo nucifera Gaertn.) leaf, Ulmus macrocarpa Hance, Thuja orientalis L., Epimedium koreanum Nakai (aerial part of Thuja orientalis L.), and Earth berry (Hovenia chinensis) Hovenia dulcis) fruits or seeds (Hoveniae Semen Seu Fructus) were purchased and used as samples. It was extracted by brewing it as tea or decocting it using a water boiler.
먼저, 단풍잎 추출물의 경우, 단풍잎 약 1g에 100℃ 의 물 100ml을 가하여 5분 침출 후 매시 200번으로 필터하고, 동결건조하여 분말화하였다. First, in the case of maple leaf extract, 100 ml of water at 100°C was added to about 1 g of maple leaf, leached for 5 minutes, filtered at 200 times per hour, freeze-dried, and powdered.
다음으로, 단풍잎, 형개, 연잎 및 측백엽 혼합 추출물의 경우, 약 1g에 100°C의 물 100ml을 가한 후 5분 동안 열수 추출하였다. 그 후, 매시 200번으로 필터하고, 동결건조하여 분말화하였다. 또한, 다른 방법으로, 단풍잎, 형개, 연잎, 측백엽 10g에 생수 1L를 넣고, 대웅약탕기 150분 가열하여 매시 200번으로 여과한 후 100ml 농축하고 동결건조하여 분말화하였다. Next, in the case of mixed extracts of maple leaf, Hyeonggae, lotus leaf, and Arborvitae leaf, 100 ml of water at 100°C was added to about 1 g, followed by hot water extraction for 5 minutes. Afterwards, it was filtered at mash number 200, freeze-dried, and powdered. In addition, in another method, 1L of mineral water was added to 10g of maple leaves, Hyeonggae, lotus leaves, and arborvitae leaves, heated in a Daewoong Yaktanggi for 150 minutes, filtered at 200 mash, concentrated to 100ml, freeze-dried, and powdered.
그 외, 약탕기를 이용하여 단풍잎, 형개, 연잎 및 유백피 혼합 추출물, 단풍잎, 형개, 연잎, 유백피 및 음양곽 혼합 추출물, 형개, 연잎, 유백피, 측백엽, 지구자 및 음양곽 혼합 추출물을 동일한 조건으로 제조하였다 (표 1).In addition, using a medicinal boiler, mixed extracts of maple leaf, hyunggae, lotus leaf and milky bark, mixed extracts of maple leaf, hyunggae, lotus leaf, milky bark and yin-yang extract, mixed extract of hyunggae, lotus leaf, milky bark, arborvitae leaf, earth berry and yin-yang extract were mixed under the same conditions. prepared (Table 1).
추출물extract 추출방법 (열수)Extraction method (thermal water) 건조함량dry content 조제량dosage 투여량dosage 소재Material
KIOM1KIOM1 차 (1g) 3gTea (1g) 3g 0.690.69 200mg200 mg 100mg/ml100mg/ml 단풍잎 (차)Maple Leaf (Tea)
KIOM2KIOM2 차 (1g) 3gTea (1g) 3g 0.560.56 200mg200 mg 100mg/ml100mg/ml 형개25
연잎25
측백엽25
단풍잎25Hyeonggae 25
lotus leaf25
Arborvitae 25
Maple Leaf25
KIOM3KIOM3 약탕기 (10g)Medicine boiler (10g) 2.042.04 200mg200mg 100mg/ml100mg/ml 형개25연잎25
측백엽25
단풍잎25Hyeonggae 25 Lotus Leaf 25
Arborvitae 25
Maple Leaf25
KIOM4KIOM4 약탕기 (10g)Medicine boiler (10g) 1.671.67 200mg200 mg 100mg/ml100mg/ml 형개20연잎20
유백피30
단풍잎30Hyeonggae 20 Lotus Leaf 20
Milky white blood 30
Maple Leaf30
KIOM5KIOM5 약탕기 (10g)Medicine boiler (10g) 1.771.77 200mg200mg 100mg/ml100mg/ml 형개10
연잎15
유백피25
단풍잎25
음양곽25Hyeonggae 10
lotus leaf15
Yubaekpi25
Maple Leaf25
Yin Yang Kwak 25
KIOM6KIOM6 약탕기 (10g)Medicine boiler (10g) 2.232.23 200mg200mg 100mg/ml100mg/ml 형개10
연잎15
유백피15
측백엽10
지구자15
음양곽15
단풍잎20Hyeonggae 10
lotus leaf15
Yubaekpi15
Arborvitae 10
Earth 15
Yin Yang Kwak 15
Maple Leaf20
실험예 2. 바이러스, 세포주 및 시약 준비Experimental Example 2. Preparation of viruses, cell lines, and reagents
SARS-CoV-2 (NCCP no, 43326, Human corona virus, βCoV/Korea/KCDC03/2020) 한국질병관리본부(KCDC)에서 제공받았으며, Vero 세포는 ATCC (ATCC-CCL81) 로부터 획득하였다. SARS-CoV-2 (NCCP no, 43326, Human corona virus, βCoV/Korea/KCDC03/2020) was provided by the Korea Centers for Disease Control and Prevention (KCDC), and Vero cells were obtained from ATCC (ATCC-CCL81).
기준 화합물로 사용한 클로로퀸 (chloroquine)과 로피나비어 (Llopinavir), 렘데시비르 (remdesivir)는 각각 Sigma-Aldrich, SelleckChem, MedChemExpress에서 구입하였다. Anti-SARS-CoV-2 N 단백질에 특이적인 1차 항체는 Sino Biological에서 구입하였으며 2차 항체인 Alexa Fluor 488 goat anti-rabbit IgG와 Hoechst 33342는 Molecular Probes에서 구입하였다. Chloroquine, Llopinavir, and remdesivir, used as reference compounds, were purchased from Sigma-Aldrich, SelleckChem, and MedChemExpress, respectively. The primary antibody specific for anti-SARS-CoV-2 N protein was purchased from Sino Biological, and the secondary antibodies, Alexa Fluor 488 goat anti-rabbit IgG and Hoechst 33342, were purchased from Molecular Probes.
실험예 3. 면역 형광법에 의한 용량반응곡선 분석Experimental Example 3. Dose response curve analysis by immunofluorescence
384-조직배양 플레이트에 웰당 1.2x104개의 Vero 세포를 접종하였다. 다음날, DMSO에 2배 연속 희석하여 10포인트로 준비된 화합물을 최고농도가 200 μg/ml이 되도록 하여 세포에 처리하였다. 화합물 처리 약 1시간 후, BSL3 시설에서 세포에 SARS-CoV-2 (0.025 MOI)를 감염시키고 37℃에서 24시간 동안 배양하였다. 이후 4% paraformaldehyde (PFA)로 세포를 고정한 뒤, permeabilization 하였다. 그 후 anti-SARS-CoV-2 뉴클레오캡시드 (nucleocapsid, N) 1차 항체를 처리하고, Alexa Fluor 488-conjugated goat anti-rabbit IgG 2차 항체와 Hoechst 33342를 처리하여 세포를 염색하였다. 감염된 세포의 형광 이미지는 대용량 이미지 분석 기기인 Operetta (Perkin Elmer)를 이용하여 획득했다. 1.2x10 4 Vero cells per well were inoculated into a 384-tissue culture plate. The next day, the cells were treated with compounds prepared at 10 points by serially diluting 2-fold in DMSO to a maximum concentration of 200 μg/ml. Approximately 1 hour after compound treatment, cells were infected with SARS-CoV-2 (0.025 MOI) in a BSL3 facility and cultured at 37°C for 24 hours. Afterwards, cells were fixed with 4% paraformaldehyde (PFA) and permeabilized. Afterwards, cells were stained with anti-SARS-CoV-2 nucleocapsid (N) primary antibody, Alexa Fluor 488-conjugated goat anti-rabbit IgG secondary antibody and Hoechst 33342. Fluorescent images of infected cells were acquired using Operetta (Perkin Elmer), a high-capacity image analysis device.
실험예 4. 이미지분석Experimental Example 4. Image analysis
획득된 이미지는 Columbus 소프트웨어를 이용하여 분석하였다. 웰당 총 세포수는 Hoechst로 염색된 핵 수로 산출하였고, 감염된 세포 수는 바이러스N 단백질을 발현하는 세포수로 산출하였다. 감염률(infection ratio)는 각 웰에서 'N 단백질을 발현하는 세포수/총 세포수'로 계산하였다. 각 웰의 감염저해율(% Inhibition of infection)은 동일한 플레이트 내에서 비감염세포(mock)를 포함한 웰들의 평균 감염률과 0.5% DMSO (v/v)가 처리된 감염세포를 포함한 웰들의 평균 감염률을 각각 100%와 0%으로 노말라이제이션하여 산출하였다. 화합물의 세포생존율은 각 웰의 세포수를 mock 그룹 웰들의 평균 세포수로 노말라이제이션하여 그래프에 '% Cell viability'으로 표기하였다. 각 수치들은 두 번의 반복 실험 (Technical duplicate)을 통해 획득하였다. 화합물 농도에 따른 반응 곡선과 IC50, CC50 값은 XLFit 4 (IDBS) 소프트웨어의 Y = Bottom + (Top-Bottom)/(1 + (IC50/X)Hillslope) 수식을 활용해 도출하였다. 선택지수 (Selectivity index; SI) 값은 CC50/IC50으로 계산하였다. The acquired images were analyzed using Columbus software. The total number of cells per well was calculated as the number of nuclei stained with Hoechst, and the number of infected cells was calculated as the number of cells expressing the viral N protein. The infection ratio was calculated as 'number of cells expressing N protein/total number of cells' in each well. The % inhibition of infection of each well is calculated as the average infection rate of wells containing non-infected cells (mock) and the average infection rate of wells containing infected cells treated with 0.5% DMSO (v/v) in the same plate, respectively. It was calculated by normalizing to % and 0%. The cell viability of the compound was normalized by normalizing the number of cells in each well to the average number of cells in the mock group wells and expressed as '% Cell viability' in the graph. Each value was obtained through two repeated experiments (technical duplicate). The reaction curve and IC 50 and CC 50 values according to compound concentration were derived using the formula Y = Bottom + (Top-Bottom)/(1 + (IC 50 /X)Hillslope) in XLFit 4 (IDBS) software. Selectivity index (SI) value was calculated as CC 50 /IC 50 .
파란색 ●는 해당 화합물의 SARS-CoV-2 감염저해율(% Inhibition of infection)을 나타내며, 붉은색 ■는 해당 화합물에 대한 세포생존율(% Cell viability)을 의미한다. Blue ● indicates the SARS-CoV-2 infection inhibition rate (% Inhibition of infection) of the compound, and red ■ indicates the cell viability (% Cell viability) for the compound.
실시예 1. 추출물의 코로나바이러스 감염 억제 효과 확인 Example 1. Confirmation of the effect of the extract on inhibiting coronavirus infection
상기 실시예 1-3에 따라, 추출물 KIOM1 내지 KIOM6의 세포독성 및 코로나바이러스 감염 억제 효과를 확인하였다.According to Examples 1-3, the cytotoxicity and inhibitory effects of coronavirus infection of extracts KIOM1 to KIOM6 were confirmed.
코로나바이러스 치료제로 알려진 렘데시비르 (Remdesivit), 클로로퀸 (Chloroquine), 로피나비어 (Lopinavir)를 양성대조군으로 설정하여, 세포독성 및 유효약효농도를 확인하였다 (도 7).Remdesivir, Chloroquine, and Lopinavir, known as coronavirus treatments, were set as positive controls, and cytotoxicity and effective drug concentration were confirmed (Figure 7).
실시예 1-1. 단풍잎 추출물 KIOM1의 코로나바이러스 감염 억제 효과 Example 1-1. Inhibitory effect of maple leaf extract KIOM1 on coronavirus infection
단풍잎 추출물의 세포독성(CC50)은 최고실험농도인 200μg/ml 이상이며, 유효약효농도 (IC50)는 43.81 μg/ml로 확인되어, S.I.(selectivity index, CC50/IC50)는 4.57인 것으로 측정하였다 (도 1). The cytotoxicity (CC 50 ) of the maple leaf extract was higher than the highest tested concentration of 200 μg/ml, the effective drug concentration (IC 50 ) was confirmed to be 43.81 μg/ml, and the SI (selectivity index, CC 50 /IC 50 ) was 4.57. It was measured as (Figure 1).
이를 통해 본 발명의 단풍잎 추출물이 현저한 효과로 코로나바이러스를 억제하는 것을 확인할 수 있었다.Through this, it was confirmed that the maple leaf extract of the present invention inhibits coronavirus with a significant effect.
실시예 1-2. 단풍잎 혼합 추출물 KIOM2의 코로나바이러스 감염 억제 효과 Example 1-2. Corona virus infection inhibition effect of maple leaf mixed extract KIOM2
혼합 추출물의 세포독성(CC50)은 최고실험농도인 200μg/ml 이상이며, 유효약효농도 (IC50)는 85.78 μg/ml로 확인되어, S.I.(selectivity index, CC50/IC50)는 2.33 인 것으로 측정하였다 (도 2).The cytotoxicity (CC 50 ) of the mixed extract was higher than the highest tested concentration of 200 μg/ml, the effective drug concentration (IC 50 ) was confirmed to be 85.78 μg/ml, and the SI (selectivity index, CC 50 /IC 50 ) was 2.33. It was measured as (Figure 2).
이를 통해 본 발명의 단풍잎, 형개, 연잎, 및 측백엽 혼합 추출물 (KIOM2)이 효과적으로 코로나바이러스를 억제하는 것을 확인할 수 있었다.Through this, it was confirmed that the mixed extract of maple leaf, gyeonggae, lotus leaf, and cucumber leaf (KIOM2) of the present invention effectively inhibits coronavirus.
실시예 1-3. 단풍잎 혼합 추출물 KIOM3의 코로나바이러스 감염 억제 효과 Example 1-3. Corona virus infection inhibition effect of maple leaf mixed extract KIOM3
혼합 추출물의 세포독성(CC50)은 최고실험농도인 200μg/ml 이상이며, 유효약효농도 (IC50)는 96.21 μg/ml로 확인되어, S.I.(selectivity index, CC50/IC50)는 2.08 인 것으로 측정하였다 (도 3). The cytotoxicity (CC 50 ) of the mixed extract was higher than the highest tested concentration of 200 μg/ml, the effective drug concentration (IC 50 ) was confirmed to be 96.21 μg/ml, and the SI (selectivity index, CC 50 /IC 50 ) was 2.08. It was measured as (Figure 3).
이를 통해 본 발명의 단풍잎, 형개, 연잎 및 측백엽 혼합 추출물 (KIOM3)이 효과적으로 코로나바이러스를 억제하는 것을 확인할 수 있었다.Through this, it was confirmed that the mixed extract of maple leaf, gyeonggae, lotus leaf, and cucumber leaf (KIOM3) of the present invention effectively inhibits coronavirus.
실시예 1-4. 단풍잎 혼합 추출물 KIOM4의 코로나바이러스 감염 억제 효과 Example 1-4. Corona virus infection inhibition effect of maple leaf mixed extract KIOM4
혼합 추출물의 세포독성(CC50)은 최고실험농도인 200μg/ml 이상이며, 유효약효농도 (IC50)는 119.4 μg/ml로 확인되어, S.I.(selectivity index, CC50/IC50)는 1.68 인 것으로 측정하였다 (도 4). The cytotoxicity (CC 50 ) of the mixed extract was higher than the highest tested concentration of 200 μg/ml, the effective drug concentration (IC 50 ) was confirmed to be 119.4 μg/ml, and the SI (selectivity index, CC 50 /IC 50 ) was 1.68. It was measured as (Figure 4).
이를 통해 본 발명의 단풍잎, 형개, 연잎 및 유백피 혼합 추출물 (KIOM4)이 효과적으로 코로나바이러스를 억제하는 것을 확인할 수 있었다.Through this, it was confirmed that the mixed extract of maple leaf, gyeonggae, lotus leaf, and milky bark (KIOM4) of the present invention effectively inhibits coronavirus.
실시예 1-5. 단풍잎 혼합 추출물 KIOM5의 코로나바이러스 감염 억제 효과 Examples 1-5. Corona virus infection inhibition effect of maple leaf mixed extract KIOM5
혼합 추출물의 세포독성(CC50)은 최고실험농도인 200μg/ml 이상이며, 유효약효농도 (IC50)는 121.1 μg/ml로 확인되어, S.I.(selectivity index, CC50/IC50)는 1.65 인 것으로 측정하였다 (도 5). The cytotoxicity (CC 50 ) of the mixed extract was higher than the highest tested concentration of 200 μg/ml, the effective drug concentration (IC 50 ) was confirmed to be 121.1 μg/ml, and the SI (selectivity index, CC 50 /IC 50 ) was 1.65. It was measured as (Figure 5).
이를 통해 본 발명의 단풍잎, 형개, 연잎, 유백피 및 음양곽 혼합 추출물 (KIOM5)이 효과적으로 코로나바이러스를 억제하는 것을 확인할 수 있었다.Through this, it was confirmed that the mixed extract of maple leaf, Hyeonggae, lotus leaf, milky white bark, and Yin-Yang Gwak (KIOM5) of the present invention effectively inhibits coronavirus.
실시예 1-6. 단풍잎 혼합 추출물 KIOM6의 코로나바이러스 감염 억제 효과 Examples 1-6. Corona virus infection inhibition effect of maple leaf mixed extract KIOM6
혼합 추출물의 세포독성(CC50)은 최고실험농도인 200μg/ml 이상이며, 유효약효농도 (IC50)는 120.4 μg/ml로 확인되어, S.I.(selectivity index, CC50/IC50)는 1.66 인 것으로 측정하였다 (도 6). The cytotoxicity (CC 50 ) of the mixed extract was higher than the highest tested concentration of 200 μg/ml, the effective drug concentration (IC 50 ) was confirmed to be 120.4 μg/ml, and the SI (selectivity index, CC 50 /IC 50 ) was 1.66. It was measured as (Figure 6).
이를 통해 본 발명의 단풍잎, 형개, 연잎, 유백피, 측백엽, 지구자 및 음양곽 혼합 추출물 (KIOM6)이 효과적으로 코로나바이러스를 억제하는 것을 확인할 수 있었다.Through this, it was confirmed that the mixed extract (KIOM6) of maple leaf, Hyeonggae, lotus leaf, milky white bark, Arborvitae leaf, Earthworm and Yin-Yang Gwak of the present invention effectively inhibits coronavirus.
이상의 설명으로부터, 본 발명이 속하는 기술분야의 당업자는 본 발명이 그 기술적 사상이나 필수적 특징을 변경하지 않고서 다른 구체적인 형태로 실시될 수 있다는 것을 이해할 수 있을 것이다. 이와 관련하여, 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적인 것이 아닌 것으로 이해해야만 한다. 본 발명의 범위는 상기 상세한 설명보다는 후술하는 특허 청구범위의 의미 및 범위 그리고 그 등가 개념으로부터 도출되는 모든 변경 또는 변형된 형태가 본 발명의 범위에 포함되는 것으로 해석되어야 한다.From the above description, those skilled in the art to which the present invention pertains will understand that the present invention can be implemented in other specific forms without changing its technical idea or essential features. In this regard, the embodiments described above should be understood in all respects as illustrative and not restrictive. The scope of the present invention should be construed as including the meaning and scope of the patent claims described below rather than the detailed description above, and all changes or modified forms derived from the equivalent concept thereof are included in the scope of the present invention.

Claims (10)

  1. 단풍잎 추출물을 유효성분으로 포함하는 코로나바이러스에 대한 항바이러스용 조성물.An antiviral composition against coronavirus containing maple leaf extract as an active ingredient.
  2. 제1항에 있어서, 상기 조성물은 형개, 연잎, 측백나무 및 유백피로 이루어진 군에서 선택된 하나 이상의 추출물을 추가로 포함하는 것인, 조성물. According to claim 1, The composition further comprises one or more extracts selected from the group consisting of Hyeonggae, lotus leaf, Cupressaria arborvitae, and milky bark.
  3. 제2항에 있어서, 상기 조성물은 음양곽 및 지구자로 이루어진 군에서 선택된 하나 이상의 추출물을 추가로 포함하는 것인, 조성물. The composition according to claim 2, wherein the composition further comprises one or more extracts selected from the group consisting of Yin Yang Gwak and Earth Ja.
  4. 제1항 내지 제3항 중 어느 한 항에 있어서, 상기 코로나바이러스는 사스-코로나바이러스-2(Covid-19), 사스-코로나바이러스 및 메르스-코로나바이러스로 이루어진 군에서 선택된 하나 이상인 것인, 조성물.The method of any one of claims 1 to 3, wherein the coronavirus is at least one selected from the group consisting of SARS-coronavirus-2 (Covid-19), SARS-coronavirus, and MERS-coronavirus. Composition.
  5. 제1항 내지 제3항 중 어느 한 항에 있어서, 상기 추출물은 물, 탄소수 1 내지 4의 알코올 또는 이들의 혼합 용매로 추출하여 수득한 것인, 조성물.The composition according to any one of claims 1 to 3, wherein the extract is obtained by extraction with water, an alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof.
  6. 제5항에 있어서, 상기 추출은 열수 추출, 초음파 추출, 상온추출, 냉침추출, 환류 냉각 추출 또는 증기 추출인 것인, 조성물.The composition according to claim 5, wherein the extraction is hot water extraction, ultrasonic extraction, room temperature extraction, cold needle extraction, reflux cooling extraction, or steam extraction.
  7. 제1항 내지 제3항 중 어느 한 항의 조성물을 포함하는 코로나바이러스 감염질환의 예방 또는 치료용 약학 조성물.A pharmaceutical composition for preventing or treating coronavirus infectious diseases, comprising the composition of any one of claims 1 to 3.
  8. 단풍잎 추출물을 유효성분으로 포함하는 조성물을 코로나바이러스 감염질환 증상이 나타나거나 또는 나타날 우려가 있는 개체에 투여하는 단계를 포함하는 코로나바이러스 감염질환의 예방 또는 치료 방법.A method for preventing or treating a coronavirus infectious disease, comprising administering a composition containing maple leaf extract as an active ingredient to an individual who is showing or is likely to show symptoms of a coronavirus infectious disease.
  9. 제1항 내지 제3항 중 어느 한 항의 조성물을 포함하는 코로나바이러스 감염질환의 예방 또는 개선용 건강기능식품 조성물.A health functional food composition for preventing or improving coronavirus infectious diseases, comprising the composition of any one of claims 1 to 3.
  10. 제1항 내지 제3항 중 어느 한 항의 조성물을 포함하는 코로나바이러스 감염질환의 예방 또는 개선용 사료 조성물.A feed composition for preventing or improving coronavirus infectious diseases comprising the composition of any one of claims 1 to 3.
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