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WO2022065970A2 - Composition, comprenant un extrait mixte de produit naturel, pour la prévention ou le traitement d'une infection à coronavirus - Google Patents

Composition, comprenant un extrait mixte de produit naturel, pour la prévention ou le traitement d'une infection à coronavirus Download PDF

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Publication number
WO2022065970A2
WO2022065970A2 PCT/KR2021/013194 KR2021013194W WO2022065970A2 WO 2022065970 A2 WO2022065970 A2 WO 2022065970A2 KR 2021013194 W KR2021013194 W KR 2021013194W WO 2022065970 A2 WO2022065970 A2 WO 2022065970A2
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coronavirus
gold
pharmaceutical composition
mixed extract
rhubarb
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Korean (ko)
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WO2022065970A3 (fr
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마진열
조원경
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Korea Institute of Oriental Medicine KIOM
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Korea Institute of Oriental Medicine KIOM
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • 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
    • A61K36/17—Gnetophyta, e.g. Ephedraceae (Mormon-tea family)
    • 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)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • 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)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/232—Angelica
    • 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)
    • A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
    • A61K36/234—Cnidium (snowparsley)
    • 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)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • 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
    • A61K36/534—Mentha (mint)
    • 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)
    • A61K36/63—Oleaceae (Olive family), e.g. jasmine, lilac or ash tree
    • 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)
    • A61K36/65—Paeoniaceae (Peony family), e.g. Chinese peony
    • 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)
    • A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock

Definitions

  • the present invention relates to an antiviral use for coronavirus comprising a natural product mixture extract or a fraction thereof.
  • Coronavirus was first discovered in chickens in 1937, followed by animals such as dogs, pigs, and birds, and then in humans in 1965.
  • animals such as dogs, pigs, and birds, and then in humans in 1965.
  • corona phenomenon which is a phenomenon that glows white around the moon.
  • 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.
  • Coronavirus belongs to the coronaviridae and is a positive sense RNA virus with a spherical outer membrane and a size of about 100-120 nm (Master, 2006).
  • Coronavirus consists 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 the cell receptor and induces fusion between the host cell and the virus, and is known as the most mutable protein.
  • coronavirus has been recognized as a pathogen that rarely infects humans and mainly infects animals such as dogs, pigs, and cattle. It is one of several viruses that cause respiratory symptoms even when infecting humans, and only causes a simple cold or intestinal disease such as diarrhea, which is not very dangerous for children.
  • MERS Middle East Respiratory Syndrome
  • COVID-19 is an infectious disease caused by SARS-coronavirus-2, a disease that was first identified in Wuhan, the capital of Hubei province, China at the end of 2019, and has spread worldwide, resulting in a progressive pandemic. As of May 7, 2020, more than 3.75 million cases were 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 a 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 is spread from person to person mainly during close contact, and sometimes through droplets that occur when coughing, sneezing and talking. It is most contagious during the first 3 days after onset of symptoms and can be spread before symptoms appear or even late in the disease.
  • a standard method for diagnosing it is using real-time reverse transcription polymerase chain reaction (rRT-PCR) from a nasopharyngeal swab.
  • MERS was first discovered in Saudi Arabia in 2012, and it presents severe respiratory symptoms such as high fever, cough and shortness of breath. In severe cases, it is accompanied by complications and even death. Although the clear source and route of infection have not been confirmed, it has been reported that infection is highly likely to be transmitted through contact with camels in the Middle East and transmission is possible through close person-to-person contact. The cases were mainly concentrated in the Middle East, but since May 2015, more than 100 cases have been reported across 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 genus Beta coronavirus. Therefore, MERS-coronavirus, SARS-coronavirus and SARS-coronavirus-2 share similar characteristics in clinical symptoms, etiology and infection.
  • SARS-coronavirus and SARS-coronavirus-2 belong to lineage B, which includes bat SARS-like coronaviruses and other bat-derived coronaviruses, and MERS-coronaviruses are bat-derived coronaviruses. It belongs to strain C, which includes the virus (Trends Microbiol 24:490-502).
  • MERS-coronavirus, SARS-coronavirus, and SARS-coronavirus-2 are all believed to originate from bats, the primary carrier hosts for various coronaviruses (Antiviral Res 101:45-56), and their exact route of infection is believed to be has not yet been fully elucidated.
  • interspecies transmission of the virus to palm civet and dromedary camel increased the likelihood of zoonotic infections in humans (Nat Rev Microbiol 14:523-534), and nosocomial infections in humans It is believed to be the main cause of MERS-coronavirus and SARS-coronavirus infections between and humans (BMC Med13:1-12).
  • the present inventors as a result of continuing efforts to develop novel coronavirus therapeutics, ensure stability, cheongung, windbreak, angelica, peony, yeonkyo, mint, ephedra, mango, rhubarb, gypsum, gilgyeong, gold , baekchul, Sanchija, Hyeonggae, ginger, talc, licorice, ginseng, yinyanggwak, raw paper and mulberry extract have an excellent effect in inhibiting the proliferation of SARS-coronavirus-2, SARS-coronavirus and MERS-coronavirus By confirming, the present invention was completed.
  • the present inventors first identified the antiviral effect on coronavirus containing a natural product mixture extract or fraction thereof, and a pharmaceutical composition for antiviral against coronavirus containing a natural product mixture extract or fraction thereof, prevention of coronavirus infection disease or A pharmaceutical composition for treatment, a method for preventing or treating a coronavirus infection disease using the pharmaceutical composition, a health functional food composition for preventing or improving a coronavirus infection disease, including a natural product mixture extract or a fraction thereof, and a natural product mixture extract or its
  • the present application was completed by developing a feed composition for the prevention or improvement of coronavirus-infected diseases, including fractions.
  • One object of the present invention is cheongung, windbreak, Angelica, peony, Yeongyo, Park Ha-yeop, ephedra, mangwort, rhubarb, gypsum, gilgyeong, gold, baekchul, sanchija, hyeonggae, ginger, talc, licorice, gold and silver flower, yinyanggwak, raw paper and mokhyang It is to provide a pharmaceutical composition for antiviral against coronavirus comprising a mixed extract or fraction thereof.
  • Another object of the present invention is the use of cheongung, windbreak, angelica, peony, yeonkyo, hayeop, ephedra, mangcho, rhubarb, gypsum, gilgyeong, gold, baekchul, sanchija, hyeonggae, ginger, talc, licorice, gold and silver flower, eumyanggwak, raw paper and mokhyang. It is to provide a pharmaceutical composition for the prevention or treatment of coronavirus infection disease comprising a mixed extract or a fraction thereof.
  • Another object of the present invention is to provide a method for preventing or treating a coronavirus infection disease using the pharmaceutical composition.
  • Another object of the present invention is cheongung, windbreak, Angelica, peony, Yeongyo, Park Ha-yeop, Ephedra, Mangcho, Rhubarb, Gypsum, Gilgyeong, Golden, Baekchul, Sanchija, Hyeonggae, Ginger, Talc, Licorice, Gold and Silver, Yinyanggwak, Wonji and Mokhyang It is to provide a health functional food composition for the prevention or improvement of a coronavirus infection disease comprising a mixed extract or a fraction thereof.
  • Another object of the present invention is cheongung, windbreak, Angelica, peony, Yeongyo, Park Ha-yeop, Ephedra, Mangcho, Rhubarb, Gypsum, Gilgyeong, Golden, Baekchul, Sanchija, Hyeonggae, Ginger, Talc, Licorice, Gold and Silver, Yinyanggwak, Wonji and Mokhyang It is to provide a feed composition for the prevention or improvement of a coronavirus infection disease comprising a mixed extract or a fraction thereof.
  • Another object of the present invention is to prepare a pharmaceutical composition for antiviral against coronavirus, cheongung, windbreak, angelica, peony, yeonkyo, mint Hayeop, ephedra, mangcho, rhubarb, gypsum, gilgyeong, gold, baekchul, sanchija , Hyeonggae, ginger, talc, licorice, gold ginseng, eumyanggwak, and provides the use of a composition comprising a mixed extract or fractions thereof.
  • Another object of the present invention is to prepare a pharmaceutical composition for the prevention or treatment of a coronavirus infection disease, cheongung, windbreak, angelica, peony, yeonkyo, peppermint, ephedra, mangcho, rhubarb, gypsum, gilgyeong, gold, baekchul , Sanchija, Hyeonggae, ginger, talc, licorice, gold and silver ginseng, eumyanggwak, and provides the use of a composition comprising a mixed extract or fractions thereof.
  • a coronavirus infection disease cheongung, windbreak, angelica, peony, yeonkyo, peppermint, ephedra, mangcho, rhubarb, gypsum, gilgyeong, gold, baekchul , Sanchija, Hyeonggae, ginger, talc, licorice, gold and silver ginseng,
  • Another object of the present invention is to prepare a health functional food composition for the prevention or improvement of coronavirus infection disease, cheongung, windbreak, angelica, peony, yeonkyo, mint hyeop, ephedra, mango, rhubarb, gypsum, gilgyeong, gold , baekchul, sanchija, hyeonggae, ginger, talc, licorice, gold and silver ginseng, eumyanggwak, provides the use of a composition comprising a mixed extract or a fraction thereof.
  • Another object of the present invention is to prepare a feed composition for the prevention or improvement of corona virus infection disease, cheongung, windbreak, angelica, peony, yeonkyo, mint hayeop, ephedra, mangcho, rhubarb, gypsum, gilgyeong, gold, baekchul , Sanchija, Hyeonggae, ginger, talc, licorice, gold and silver ginseng, eumyanggwak, and provides the use of a composition comprising a mixed extract or fractions thereof.
  • the mixed extract of cheongung, Bangpung, Angelica, Peony, Yeongyo, Parkhayeop, Ephedra, Mangcho, Rhubarb, Gypsum, Gilgyeong, Golden, Baekchul, Sanchija, Hyeonggae, Ginger, Talc, Licorice, Gold ginseng, Yinyanggwak, Wonji and Mokhyang is Since SARS-coronavirus-2, SARS-coronavirus, and MERS- shows the effect of inhibiting infection of coronaviruses such as coronavirus, it can be used to develop antiviral agents for preventing or treating the viral diseases.
  • 1 is a view of the present invention of cheongung, bangpung, angelica, peony, yeonkyo, hayeop, ephedra, mango, rhubarb, gypsum, gilgyeong, golden, baekchul, sanchija, hyeonggae, ginger, talc, licorice, gold and silver flower, eumyanggwak, raw paper and mokhyang It is a graph showing the SARS-coronavirus-2 inhibitory efficacy according to the concentration of the mixed extract and control remdesivir.
  • One embodiment of the present invention for achieving the above object is cheongung, windbreak, angelica, peony, yeonkyo, mint hyeop, ephedra, mangcho, rhubarb, gypsum, gilgyeong, gold, baekchul, sanchija, hyeonggae, ginger, talc, licorice, gold and silver coins , It provides an antiviral pharmaceutical composition for coronavirus, comprising a mixed extract or fractions thereof of eumyanggwak, raw paper and mokhyang.
  • Another embodiment of the present invention for achieving the above object is cheongung, windbreak, angelica, peony, yeonkyo, mint hyeop, ephedra, mangcho, rhubarb, gypsum, gilgyeong, gold, baekchul, sanchija, hyeonggae, ginger, talc, licorice, gold and silver coins , It provides a pharmaceutical composition for preventing or treating a coronavirus infection disease comprising a mixed extract of eumyanggwak, raw paper and mokhyang or a fraction thereof as an active ingredient.
  • the pharmaceutical composition of the present invention exhibits an effect of inhibiting coronavirus
  • the present invention can be usefully utilized for the prevention or treatment of infectious diseases caused by coronavirus.
  • Cnidii Rhizoma refers to dried rhizomes of Cnidium officinale MAKINO, a perennial herb belonging to the Umbrella family. . It has an analgesic effect that helps blood circulation and relieves pain, so it is often applied to headaches.
  • leaf Ledebouriella seseloides WOLFF.
  • Angelicae Gigantis Radix refers to the root of Angelicae Gigantis Radix, which is a plant of the Umbelifeae family. It is known to have strong effects such as promoting blood circulation that makes blood circulate smoothly, reducing blood pressure, pain relief, suppressing convulsions, improving constipation through promotion of colonic movement, and removing blood stasis.
  • Peony Paeonia lactiflora Pall.
  • peony is a dicotyledonous perennial grass of the genus Peony and peony, distributed in Korea, Mongolia, Siberia, etc., and is also used for horticulture because of its beautiful flowers.
  • the root is known to be effective in the treatment of analgesia, abdominal pain, amenorrhea, dysmenorrhea, hematemesis, anemia, and bruises.
  • the term "yeonkyo” refers to the fruit of Forsythia Viridissima Lindley or Forsythia suspensa Vahi belonging to the family Oleaceae, and has a characteristic odor, bitter taste, and slightly cold properties. Yeongyo is known to have diuretic and anti-inflammatory effects, used for boils, rashes, appendicitis, lung abscesses, lymphadenitis, sore throat, etc. In addition, pharmacological action is known to have antibacterial action, anti-inflammatory action, lowering blood pressure, hemostatic action, liver treatment action, antipyretic action, anti-emetic action, and diuretic action.
  • mint leaf is a leaf of mint (Mentha arvensis var. piperascens), a perennial succulent plant of the dicotyledonous plant Lamiaceae. there is. Therefore, it is widely used as a treatment for indigestion, thoracoabdominal pain, flatulence (cold), headache, toothache, sore throat, purpura, and sore throat.
  • Ephedra sinica is a medicinal material made using Ephedra sinica Stepf of the ephedra family or soft stems (choplantain) of animals and plants, and has the property of mildly paralyzing the tongue and has an astringent taste. Spicy and bitter, and warm in nature. It is used to dissipate wind and sweat, relieve sweating, fever with chills, headache, asthma, seawater, edema, paralysis of the upper body, skin paralysis, hyperemia, and blood clots.
  • Erigeron canadensis is a dicotyledonous perennial plant of the order Asteraceae, cold in nature and slightly bitter in taste. It is known to be effective in stomatitis, flatulence, incontinence of stool, edema, pain, diarrhea, eye irritation, detoxification, fever, relief from fatigue, and customs.
  • rhubarb is a rhubarb made using the rhizomes of long-leaved rhubarb (Rheum palmatum L.), Rheum tanguticum Maximowicz, and medicinal rhubarb (Rheum officinale Baillon), which are perennial herbaceous plants belonging to the family Guridae. It has a peculiar odor, and when you put it in your mouth and chew it, you feel like you are chewing fine sand, and it has an astringent and bitter taste and has a cold property.
  • the term "gilgyeong” is a medicinal material made by removing the root or epidermis of the bellflower (Platycodon grandiflorum A. De Candolle) of the Chogong family of flowers. . It is used for sore throat, cough due to cold, phlegm, nasal congestion, asthma, bronchitis, pleurisy, headache, chills, and tonsillitis. there is.
  • golden is a drug made from the roots of gold (Scutellaria baicalensis GEORGE), a perennial herb belonging to the family Lamiaceae, acute childhood respiratory infection, chronic bronchitis, acute dysentery, infectious hepatitis, nephritis, It has an effective reaction to high blood pressure, etc., and pharmacological actions such as anti-inflammatory, antipyretic, diuretic, blood pressure lowering action, blood sugar and hyperlipidemia lowering, bile secretion promotion, sedative action, etc. are known.
  • the term "baekchul” is a dried medicinal herb by removing the rhizome or bark of Atractylodes japonica Koidzumi or Atractylodes macrocephala Koidzumi of the Asteraceae family. It has been reported to have intestinal inhibitory action and excitatory action regulation, anti-ulcer and liver function protective action, immune function enhancement action, vasodilator action, diuretic action, and blood sugar lowering action.
  • Gardenia jasminoides refers to the fruit of the wild gardenia tree, which is known to be effective in sapling, fermenting, purgative fever, diuresis, yang blood, and detoxification.
  • Hyeonggae (Schizonepeta rhizome) is an annual herbaceous plant belonging to the family Lamiaceae and uses the whole herb as a medicine. It has an antipyretic effect, so it is used for the purpose of sweating and fever in the early stages of a cold, and is used for sore throat, skin disease, and stroke. .
  • the term "ginger (Zingiberis Rhizoma)” refers to the fresh rhizome of ginger (Zingiber officinale Roscoe) in Korea, China, and Japan. Ginger treats chills, fever, headache, vomiting, seawater, and phlegm caused by an external cold, and is also effective for stomach pain and diarrhea caused by food poisoning. As pharmacological action, gastric juice secretion promotion, digestive power enhancement, cardiac excitatory action, blood circulation promotion, and antibacterial action have been reported.
  • the term "licorice (Glycyrrhiza uralensis Fischer or Glycyrrhiza glabra L.)" is a dicotyledonous perennial grass of the Rosaceae legume, which has a characteristic odor and sweet taste. Licorice harmonizes the toxicity of all medicines so that the medicinal effects appear well, controls the fever and morale of the books, improves the communication of all blood vessels, and has the effect of strengthening muscles and bones. As pharmacological action, it is effective in detoxification, hepatitis, urticaria, dermatitis, eczema, etc. It is known to have antitussive, expectorant, muscle relaxation, diuretic, anti-inflammatory action, and suppress peptic ulcer.
  • the term "silver flower” refers to the flower buds of Lonicera japonica Thunberg or its variants of the Lonicera japonica Thunberg family. Gold and silver coins are used to relieve fever, chest tightness, and thirst. It is good for inflammation, so it is used to discharge boils, poisons from loose skin, inflammation of organs, and pus. In addition, it is used for dysentery, skin tissue necrosis due to heat poisoning, mastitis, etc., colitis, gastric ulcer, cystitis, sore throat, tonsillitis, bronchitis, conjunctivitis and swelling, high fever due to mumps, purulent infection, etc. As pharmacological action, antibacterial action, anti-inflammatory action, antipyretic action, increase leukocyte phagocytic action, central nerve excitability action, serum cholesterol lowering effect, and ulcer prevention effect have been reported.
  • the term “eumyanggwak” refers to the above-ground parts (stems and leaves) of Epimedium koreanum Nakai, a perennial herb of the Dicotyledonous plant Parasiticidae, or other closely related plants, has no odor and has a spicy taste. Sweet and warm in nature.
  • Yin-Yang Kwak is used for erectile dysfunction, lactation, cold uterus, cold extremities, skin palsy, bulging eyes, forgetfulness, hemiplegia, weakness of the back and knees, high blood pressure, and polio.
  • Pharmacological actions include: promotion of semen secretion, strengthening of blood pressure, increase of coronary blood flow, lowering of blood sugar, lowering of cholesterol, enhancement of immune function, Jinhae, Geodam, Pyeongcheon, sedative action, antibacterial action, anti-inflammatory action, growth of chicken femur and activation of polysaccharide synthesis, etc. This has been reported
  • Polygala tenuifolia is a perennial grass of the Dicotyledonous plant of the order Apiaceae, and in oriental medicine, the root is called Wonji. It is used as an expectorant, tonic, and stimulant.
  • epicampane refers to the root of Aucklandia lappa Decne. Mokhyang is used for abdominal pain caused by cold, flatulence, vomiting, and diarrhea. As pharmacological action, it relieves bronchial and small intestine spasms, and is known for its blood pressure lowering action and antibacterial action.
  • the term "mixed extract” means cheongung, windbreak, angelica, peony, yeonkyo, peppermint, ephedra, mangcho, rhubarb, gypsum, gilgyeong, gold, baekchul, sanchija, hyeonggae, ginger, talc, licorice. , refers to a mixture of extracts of ginseng, ginseng, yin and yanggwak, raw paper and mulberry extracts.
  • the mixed extracts are each obtained cheongung, bangpung, angelica, peony, yeonkyo, peppermint, ephedra, mango, rhubarb, gypsum, gilgyeong, gold, baekchul, sanchija, hyunggae, ginger, talc, licorice, gold and silver flower, It can also be obtained by mixing extracts of yin and yanggwak, walnut paper and mokhyang, cheongung, bangpung, angelica, peony, yeonkyo, hayeop bak, ephedra, mangcho, rhubarb, gypsum, gilgyeong, gold, baekchul, sanchija, hyeonggae, ginger, talc, licorice , can also be obtained by extracting a mixture of gold and silver coins, yin and yang
  • the mixing ratio of the natural product is not particularly limited thereto, but as an example, with respect to 1 part by weight of yin and yanggwa, 1 part by weight to 3 parts by weight of cheongung, 1 part by weight to 3 parts by weight of windbreak, 1 part by weight to 3 parts by weight of angelicae, 1 peony 3 parts by weight to 3 parts by weight, 1 part by weight to 3 parts by weight of annual bridge, 1 part by weight to 3 parts by weight of mint leaf, 1 part by weight to 3 parts by weight of ephedra, 1 part by weight to 3 parts by weight of rhubarb, 1 part by weight to 3 parts by weight of rhubarb Parts, gypsum 0.5 parts by weight to 3 parts by weight, length 0.5 parts by weight to 3 parts by weight, gold 0.5 parts by weight to 3 parts by weight, baekcheol 0.5 parts by weight to 2 parts by weight, sanchija 0.5 parts by weight to 2 parts by weight, hyeonggae 0.5 parts
  • extract of the present invention has the meaning commonly used as a crude extract in the art, but in a broad sense it is also meant to include a fraction obtained by additionally fractionating the crude extract. That is, the natural product mixture extract of the present invention includes not only the one obtained using the above-described extraction solvent, but also the fraction obtained by additionally applying a purification process thereto.
  • Fractions obtained through various additional purification methods, such as secondary or tertiary additional extraction fractions by are also included in the extract of the present invention.
  • the method for extracting the natural product mixture is not particularly limited, and may be extracted according to a method commonly used in the art.
  • Non-limiting examples of the extraction method include hot water extraction, ultrasonic extraction, filtration, and reflux extraction, and these may be performed alone or in combination of two or more methods.
  • the type of solvent used for the extraction is not particularly limited, and any solvent known in the art may be used.
  • Non-limiting examples of the extraction solvent include water, alcohol, or a mixed solvent thereof, and these may be used alone or in combination of one or more, and specifically water may be used.
  • alcohol is used as the solvent, alcohol having 1 to 4 carbon atoms may be specifically used.
  • the natural product mixture extract is cheongung, windbreak, angelica, peony, yeonkyo, peppermint, ephedra, mangcho, rhubarb, gypsum, gilgyeong, gold, baekchul, sanchija, hyeonggae, ginger, active, licorice, It may be extracted by adding 2-10 times the amount of water to the natural mixture consisting of gold and silver coins, raw paper, and wood incense, and then extracting it at a temperature of 70° C. to 125° C. for 3 hours to 4 hours, but is not limited thereto.
  • the natural product mixture extract shall include any one of an extract obtained by extraction treatment, a diluted or concentrated solution of the extract, a dried product obtained by drying the extract, and a crude product or a purified product.
  • coronavirus infectious disease refers to a disease caused by an infection in which the coronavirus enters the body of a host organism, and specifically, the coronavirus is SARS-coronavirus-2 (Covid -19), SARS-coronavirus and MERS-coronavirus may be at least one selected from the group consisting of, and more specifically, SARS-coronavirus-2.
  • SARS-CoV-2 is a virus strain that causes coronavirus disease 2019 (COVID-19), a respiratory disease. As known by the National Institutes of Health (NIH), it is the successor of SARS-CoV. SARS-CoV-2 is a positive-sense single-stranded RNA virus. Contagious in humans, the World Health Organization (WHO) has declared the ongoing pandemic of COVID-19 as a Public Health Emergency of International Concern (PHEIC). .
  • WHO World Health Organization
  • SARS-CoV-2 is a taxonomic strain of SARS-CoV, has zoonotic origins, and is considered to have close genetic similarity to bat coronavirus.
  • the SARS-CoV-2 is transmitted mainly through close contact between people and/or through droplets generated during coughing or sneezing, and mainly binds to receptor angiotensin converting enzyme 2 (ACE2) to bind to human cells.
  • ACE2 receptor angiotensin converting enzyme 2
  • SARS-CoV is an ssRNA virus belonging to the genus Beta-coronavirus with an envelope.
  • the entire genome consists of 29,727 nucleotides, and it is a virus with the largest genome among RNA viruses known to date.
  • the SARS-coronavirus genome has 11 open reading frames (ORFs) and is known to encode 23 types of proteins. It has been found that the major structural proteins of SARS-coronavirus are nucleocapsid (N), spike (S), membrane (M), and small envelope (E) proteins.
  • SARS-coronavirus has a very low sequence homology of about 40-50% compared to other coronaviruses. According to the phylogenetic classification according to the antigenicity of the coronavirus, the SARS coronavirus was found to be highly related to group II among groups I, II and III.
  • MERS-coronavirus is an ssRNA virus belonging to the genus beta-coronavirus newly discovered on September 24, 2012, and 5'-replicate-structural protein (spikeenvelope-membrane- It has the structure of nucleocapsid)-poly(A)-3'[5'-ORF1a/bSEMN-poly(A)].
  • the MERS-coronavirus genome is phylogenetically classified into clade A and clade B. Early MERS cases were clade A (EMC/2012 and Jordan-N3/2012), and newly reported cases are genetically distinct. Individual clade B (Emerging Infectious Diseases, Vol. 20, No. 6, June 2014).
  • the cheongung, windbreak, angelica, peony, yeonkyo, mint hyeop, ephedra, mangcho, rhubarb, gypsum, gilgyeong, gold, baekchul, sanchija, hyeonggae, ginger, talc, licorice, ginseng hwalyeok, eumyanggwak, raw paper and mokhyang are mixed
  • a pharmaceutical composition for preventing or treating a coronavirus infection disease comprising an extract or a fraction thereof is a coronavirus infection disease, such as SARS-coronavirus-2, SARS-coronavirus and MERS-Coronavirus at least one selected from the group consisting of It is characterized by inhibiting the virus.
  • a coronavirus infection disease such as SARS-coronavirus-2, SARS-coronavirus and MERS-Coronavirus at least one selected from the group consisting of It
  • 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 develop and multiply.
  • prevention refers to any action that inhibits or delays the onset of an infectious disease caused by a coronavirus by administration of the pharmaceutical composition according to the present invention.
  • treatment refers to any action in which the symptoms of a suspected and infected individual of a coronavirus infection are improved or beneficially changed by administration of the pharmaceutical composition.
  • the pharmaceutical composition of the present invention may further include a pharmaceutically acceptable carrier, excipient or diluent, wherein the carrier may include a non-naturally occurring carrier.
  • carriers, excipients and diluents that may be included in the pharmaceutical composition include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, Calcium silicate, cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, polycaprolactone, polylactic acid ( Poly Lactic Acid), poly-L-lactic acid (poly-L-lactic acid), mineral oil, and the like.
  • the pharmaceutical composition may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, etc., external preparations, suppositories, and sterile injection solutions, respectively, according to conventional methods.
  • the form may include various amorphous carriers, microspheres, nanofibers, and the like.
  • a diluent or excipient such as a filler, extender, binder, wetting agent, disintegrant, surfactant, etc. commonly used.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and these solid preparations include at least one excipient in the extract and its fractions, for example, starch, calcium carbonate, It may be prepared by mixing sucrose or lactose, gelatin, or the like. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used.
  • Liquid formulations for oral administration include suspensions, solutions, emulsions, syrups, etc.
  • various excipients such as wetting agents, sweeteners, fragrances, and preservatives may be included. there is.
  • Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, suppositories, and the like.
  • Non-aqueous solvents and suspending agents include propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate.
  • the content of the mixed extract of Mokhyang is not particularly limited, and may include a pharmaceutically effective amount of the mixed extract of natural products.
  • the term "pharmaceutically effective amount” means an amount sufficient to treat a disease with a reasonable benefit/risk ratio applicable to medical treatment, and is generally in an amount of 0.001 to 1000 mg/kg, preferably 0.05 to 200 mg/kg, more preferably 0.1 to 100 mg/kg, may be administered once a day or divided into several times a day.
  • a specific therapeutically effective amount for a particular patient depends on the type and extent of the response to be achieved, the specific composition, including whether other agents are used, if necessary, the specific composition, the patient's age, weight, general health, It is preferable to apply differently depending on various factors including sex and diet, administration time, administration route and secretion rate of the composition, treatment period, drugs used together or concurrently with a specific composition, and similar factors well known in the pharmaceutical field.
  • the pharmaceutical composition of the present invention may be administered as an individual therapeutic agent or may be administered in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents. and may be administered single or multiple. Taking all of the above factors into consideration, it is important to administer an amount that can obtain the maximum effect with a minimum amount without causing side effects, and can be easily determined by those skilled in the art.
  • the term "administration” means introducing the pharmaceutical composition of the present invention to a patient by any suitable method, and the administration route of the composition of the present invention is oral or parenteral as long as it can reach the target tissue. It can be administered through various routes.
  • the method of administration of the 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 pharmaceutical composition according to the present invention may be prepared in various dosage forms depending on the desired administration method.
  • the dosage of the pharmaceutical composition of the present invention may be, for example, 1 to 20 mg/kg, more preferably 1 to 10 mg/kg of the pharmaceutical composition of the present invention to mammals including humans for one day.
  • the frequency of administration of the composition of the present invention is not particularly limited thereto, but may be administered once a day or administered several times by dividing the dose.
  • Another embodiment of the present invention for achieving the above object is the prevention or treatment of a coronavirus infectious disease, comprising administering the pharmaceutical composition to an individual other than a human exhibiting or likely to appear symptoms of a coronavirus infection disease provide a way
  • the term "individual” may refer to all animals, including humans, that exhibit or are likely to show symptoms of coronavirus infection disease.
  • the animal may be a mammal, such as a cow, a horse, a sheep, a pig, a goat, a camel, an antelope, a dog, or a cat, in need of treatment for symptoms similar to those of a human as well as humans, but is not limited thereto.
  • the prevention or treatment method of the present invention may include the step of administering the composition in a pharmaceutically effective amount to an individual exhibiting or likely to appear symptoms of a coronavirus infection disease.
  • the term "administration” means introducing the pharmaceutical composition of the present invention to an individual who has or is likely to show symptoms of a coronavirus infection disease by any suitable method, and the route of administration of the composition of the present invention can be administered through various routes, either oral or parenteral, as long as it can reach the target tissue.
  • Another embodiment of the present invention for achieving the above object is cheongung, windbreak, angelica, peony, yeonkyo, mint hyop, ephedra, mangcho, rhubarb, gypsum, gilgyeong, gold, baekchul, sanchija, hyeonggae, ginger, talc, licorice, It provides a health functional food composition for the prevention or improvement of coronavirus infectious disease, comprising a mixed extract of gold and silver ginseng, eumyanggwak, raw paper and mulchyang, or a fraction thereof.
  • the term “improvement” refers to any action of at least reducing a parameter related to a condition to be treated, for example, the severity of a symptom by administering the pharmaceutical composition according to the present invention.
  • health functional food refers to food manufactured and processed using raw materials or ingredients useful for the human body in accordance with Act No. 6727 of the Health Functional Food Act, and 'functionality' refers to the structure of the human body. And it means to obtain a useful effect for health use, such as regulating nutrients for function or physiological action.
  • health food means food that has an active health maintenance or promotion effect compared to general food
  • health supplement means food for the purpose of health supplementation.
  • the terms health functional food, health food and health supplement food can be mixed.
  • the mixed extract of cheongung, Bangpung, Angelica, Peony, Yeongyo, Parkhayeop, Ephedra, Mangcho, Rhubarb, Gypsum, Gilgyeong, Golden, Baekchul, Sanchija, Hyeonggae, Ginger, Talc, Licorice, Gold ginseng, Yinyanggwak, Wonji and Mokhyang is It may be added as it is or may be used together with other foods or food ingredients, and may be appropriately used according to a conventional method.
  • the food of the present invention can be prepared by a method commonly used in the art, and at the time of manufacture, it can be prepared by adding raw materials and components commonly added in the art.
  • the food composition may further include a physiologically acceptable carrier, the type of carrier is not particularly limited and any carrier commonly used in the art may be used.
  • the food composition contains food additives such as preservatives, disinfectants, antioxidants, colorants, coloring agents, bleaching agents, seasonings, sweeteners, flavoring agents, expanding agents, strengthening agents, emulsifying agents, thickeners, filming agents, gum base agents, foam inhibitors, solvents, and improving agents. may include The additive may be selected according to the type of food and used in an appropriate amount.
  • the formulation of the food may be prepared without limitation as long as it is a formulation recognized as a food.
  • the composition for food of the present invention can be prepared in various forms, and unlike general drugs, it has the advantage of not having side effects that may occur during long-term administration of drugs using food as a raw material, and is excellent in portability, so the present invention Foods of can be consumed as a supplement to enhance the effect of prevention or improvement of infectious diseases caused by coronavirus.
  • the mixed extract of cheongung, Bangpung, Angelica, Peony, Yeongyo, Parkhayeop, Ephedra, Mangcho, Rhubarb, Gypsum, Gilgyeong, Golden, Baekchul, Sanchija, Hyeonggae, Ginger, Talc, Licorice, Gold ginseng, Yinyanggwak, Wonji and Mokhyang is If it can exhibit the effect of preventing or improving infectious diseases caused by coronavirus, it may be included in various weight % in the food composition. Specifically, it may be included in an amount of 0.00001 to 100% by weight or 0.01 to 80% by weight relative to the total weight of the food composition, but is not limited thereto. When ingested for a long period of time for health and hygiene purposes, it may contain an amount below the above range, and since there is no problem in terms of safety, the active ingredient may be used in an amount above the above range.
  • Another embodiment of the present invention for achieving the above object is cheongung, windbreak, angelica, peony, yeonkyo, mint hyop, ephedra, mangcho, rhubarb, gypsum, gilgyeong, gold, baekchul, sanchija, hyeonggae, ginger, talc, licorice, It provides a feed composition for the prevention or improvement of a coronavirus infection disease comprising a mixed extract or fractions thereof of gold and silver coins, eumyanggwak, raw paper and mokhyang as an active ingredient.
  • a high effect can be expected for the prevention or improvement of
  • feed means any natural or artificial diet, meal, etc., or a component of said meal, intended for or suitable for being eaten, consumed, and digested by an animal.
  • the type of feed is not particularly limited, and feed commonly used in the art may be used.
  • Non-limiting examples of the feed include plant feeds such as grains, root fruits, food processing by-products, algae, fibers, pharmaceutical by-products, oils and fats, starches, gourds or grain by-products; and animal feeds such as proteins, inorganic materials, oils and fats, minerals, oils and fats, single cell proteins, zooplankton, or food. These may be used alone or in mixture of two or more.
  • Another object of the present invention is to prepare a pharmaceutical composition for antiviral against coronavirus, cheongung, windbreak, angelica, peony, yeonkyo, mint Hayeop, ephedra, mangcho, rhubarb, gypsum, gilgyeong, gold, baekchul, sanchija , Hyeonggae, ginger, talc, licorice, gold ginseng, eumyanggwak, and provides the use of a composition comprising a mixed extract or fractions thereof.
  • Another object of the present invention is to prepare a pharmaceutical composition for the prevention or treatment of a coronavirus infection disease, cheongung, windbreak, angelica, peony, yeonkyo, peppermint, ephedra, mangcho, rhubarb, gypsum, gilgyeong, gold, baekchul , Sanchija, Hyeonggae, ginger, talc, licorice, gold and silver ginseng, eumyanggwak, and provides the use of a composition comprising a mixed extract or fractions thereof.
  • a coronavirus infection disease cheongung, windbreak, angelica, peony, yeonkyo, peppermint, ephedra, mangcho, rhubarb, gypsum, gilgyeong, gold, baekchul , Sanchija, Hyeonggae, ginger, talc, licorice, gold and silver ginseng,
  • Another object of the present invention is to prepare a health functional food composition for the prevention or improvement of coronavirus infection disease, cheongung, windbreak, angelica, peony, yeonkyo, mint hyeop, ephedra, mango, rhubarb, gypsum, gilgyeong, gold , baekchul, sanchija, hyeonggae, ginger, talc, licorice, gold and silver ginseng, eumyanggwak, provides the use of a composition comprising a mixed extract or a fraction thereof.
  • Another object of the present invention is to prepare a feed composition for the prevention or improvement of corona virus infection disease, cheongung, windbreak, angelica, peony, yeonkyo, mint hayeop, ephedra, mangcho, rhubarb, gypsum, gilgyeong, gold, baekchul , Sanchija, Hyeonggae, ginger, talc, licorice, gold and silver ginseng, eumyanggwak, and provides the use of a composition comprising a mixed extract or fractions thereof.
  • Example 1 Natural products composed of cheongung, windbreak, angelica, peony, Yeongyo, spearmint, ephedra, mango, rhubarb, gypsum, gilgyeong, gold, baekchul, sanchija, hyeonggae, ginger, talc, licorice, gold and silver flower, yinyanggwak, raw paper and mulberry Preparation of mixed extracts
  • Example 2-1 Cell line and virus preparation
  • Vero cells were used to check whether there is an inhibitory effect on novel SARS-coronavirus-2, and the Vero cells used in the present invention are American Type Culture Collection (ATCC, CCL-81; Manassas, VA) 10 Incubated in Dulbecco's modified Eagle's medium (DMEM; Welgene, Gyeongsan, Korea) containing % heat-inactivated fetal bovine serum and 1x Antibiotic-Antimycotic (Gibco/Thermo Fisher Scientific, Waltham, MA) at 37°C under 5% carbon dioxide. .
  • ATCC American Type Culture Collection
  • CCL-81 Manassas, VA
  • DMEM Dulbecco's modified Eagle's medium
  • % heat-inactivated fetal bovine serum containing % heat-inactivated fetal bovine serum and 1x Antibiotic-Antimycotic (Gibco/Thermo Fisher Scientific, Waltham, MA) at 37°C under 5% carbon dioxide.
  • novel SARS-coronavirus-2 was provided and used by the Korea Centers for Disease Control and Prevention.
  • Virus titer was measured using plaque assay.
  • Example 2-2 Confirmation of SARS-coronavirus-2 infection inhibition of natural product mixture extract
  • the Vero cell line (ATCC, CCL-81) was put in a 96-well plate at 2 x 10 4 cells/well and cultured for one day. Infected with SARS-coronavirus-2 at an MOI of 0.05. 48 hours after infection, cells were fixed with 1:3 acetone:methanol (v/v) for 10 min at room temperature and then reacted with a mouse primary antibody against the S (GeneTex, Irvine, CA) protein of coronavirus. Virus-infected cells were stained with Alex Fluor 488-conjugated goat anti-mouse IgG (Invitrogen, Carlsbd, CA) as a secondary antibody.
  • Alex Fluor 488 used as a secondary antibody fluoresces green, virus-infected cells can be observed in green.
  • Cell nuclei were stained blue through DAPI staining.
  • As a control drug (standard drug) the effect of inhibiting SARS-coronavirus-2 infection was confirmed by using the drug Remdesivir.
  • Cells were imaged using an Operetta (PerkinElmer, Operetta) instrument, and the infection rate was calculated using Harmony software. The case of infection with only the virus was regarded as 100%, and the case of no infection was regarded as 0%, and the infection rate when the drug was treated was calculated.
  • the effective drug concentration (EC50) for inhibiting virus infection by 50% was calculated through Prism software (GraphPad, Prism).
  • cytotoxicity For cytotoxicity, only the drug was treated at the same concentration and for the same time without virus infection, and the cell viability was measured by the MTS method. At this time, the concentration that reduces the viability of the cells by 50% (CC50) was calculated as the cytotoxic concentration. Selectivity Index (SI) was calculated by dividing the EC50 value by the CC50 value as an index indicating how superior the compound was to toxicity.
  • SI Selectivity Index
  • FIG. 1 Specific results are shown in FIG. 1 .
  • the right vertical axis represents the cytotoxicity (%) of the sample, and the left vertical axis (Antiviral activity, red) is the relative amount of Corona-19 (SARS-coronavirus-2) S protein inhibited by the sample ( %) is shown.
  • specific experimental concentrations are 100, 33, 11, 3.7, 1.2 ( ⁇ g/ml).
  • the present invention 's cheongung, windbreak, angelica, peony, yeonkyo, hayeop, ephedra, mangcho, rhubarb, gypsum, gilgyeong, gold, baekchul, sanchija, hyeonggae, ginger, talc, licorice, gold and silver coins
  • the cytotoxicity (CC50) of the natural product mixture extract consisting of CC50/EC50) was determined to be >5.1.
  • the CC50 of remdesivir, a positive control was measured to be >100 ⁇ M
  • the EC50 value was 6.6 ⁇ M
  • the SI was measured to be >15.
  • the present invention 's cheongung, Bangpung, Angelica, peony, Yeongyo, Park Ha-yeop, Ephedra, Mangcho, Rhubarb, Gypsum, Gilgyeong, Geum, Baekchul, Sanchija, Hyeonggae, Ginger, Talc, Licorice, Geumgeumhwa, Yinyanggwak, Wonji and Mokhyang It was confirmed that the composed natural product mixture extract has the effect of effectively inhibiting the infection of SARS-coronavirus-2.

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Abstract

La présente invention concerne une utilisation antivirale d'un extrait mixte de produit naturel ou d'une fraction de celui-ci contre les coronavirus et, plus spécifiquement, une composition pharmaceutique antivirale contre les coronavirus, une composition pharmaceutique pour la prévention ou le traitement de maladies due à une infection à coronavirus, chaque composition pharmaceutique comprenant un extrait mixte de produit naturel ou une fraction de celui-ci, un procédé de prévention ou de traitement de maladies dues à une infection à coronavirus à l'aide de la composition pharmaceutique, une composition alimentaire fonctionnelle de santé comprenant un extrait mixte de produit naturel ou une fraction de celui-ci pour la prévention ou l'atténuation de maladies dues à une infection à coronavirus, et une composition d'aliment pour animaux comprenant un extrait mixte de produit naturel ou une fraction de celui-ci pour la prévention ou l'atténuation de maladies dues à une infection à coronavirus. L'extrait mixte de produit naturel de la présente invention présente l'effet d'inhiber l'infection par des coronavirus tels que le coronavirus du MERS, le coronavirus du SRAS et le coronavirus du SRAS 2 et, en tant que tels, peut être utilisé pour développer un agent antiviral pour la prévention ou le traitement des maladies virales.
PCT/KR2021/013194 2020-09-28 2021-09-28 Composition, comprenant un extrait mixte de produit naturel, pour la prévention ou le traitement d'une infection à coronavirus Ceased WO2022065970A2 (fr)

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WO2024107015A1 (fr) * 2022-11-18 2024-05-23 경희대학교 산학협력단 Composition pour améliorer la circulation sanguine comprenant un extrait complexe de phytothérapie en tant que principe actif

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KR101513247B1 (ko) * 2013-06-17 2015-04-20 구미경 생약혼합물의 추출물을 함유하는 호흡기 질환의 예방 또는 치료용 조성물
KR101731607B1 (ko) * 2014-08-12 2017-05-02 한국 한의학 연구원 음양곽 추출물을 유효성분으로 함유하는 항 바이러스용 조성물
KR101951203B1 (ko) * 2015-09-24 2019-02-25 주식회사 씨엔에이치코퍼레이션 생약 성분을 포함하는 호흡기암 예방 또는 치료용 조성물
KR20190083769A (ko) * 2018-01-05 2019-07-15 알리코제약(주) 금은화 추출물을 포함하는 호흡기질환 예방 또는 치료용 조성물

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WO2024107015A1 (fr) * 2022-11-18 2024-05-23 경희대학교 산학협력단 Composition pour améliorer la circulation sanguine comprenant un extrait complexe de phytothérapie en tant que principe actif

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