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WO2024090654A1 - Composition pour la prévention ou le traitement d'une infection à coronavirus, contenant un extrait de feuille d'érable - Google Patents

Composition pour la prévention ou le traitement d'une infection à coronavirus, contenant un extrait de feuille d'érable 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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Ceased
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Korean (ko)
Inventor
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
    • 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
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
    • 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D11/00—Solvent extraction
    • B01D11/02—Solvent extraction of solids
    • B01D11/0261—Solvent extraction of solids comprising vibrating mechanisms, e.g. mechanical, acoustical
    • B01D11/0265—Applying ultrasound
    • 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
    • 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
    • A23V2250/00—Food ingredients
    • A23V2250/20—Natural extracts
    • A23V2250/21—Plant extracts
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH

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

La présente invention concerne : une composition antivirale contre le coronavirus, contenant un extrait de feuille d'érable en tant que principe actif ; une méthode de prévention ou de traitement de maladies d'infection à coronavirus, la méthode comprenant l'étape d'administration d'une composition contenant un extrait de feuille d'érable en tant que principe actif à un individu qui présente des symptômes d'infection à coronavirus ou présente un risque de développer de tels symptômes ; et une utilisation d'une composition contenant un extrait de feuille d'érable en tant que principe actif pour une activité antivirale contre le coronavirus. La présente invention peut être utilisée dans le développement d'agents antiviraux pour prévenir ou traiter des maladies à coronavirus.
PCT/KR2022/018704 2022-10-28 2022-11-24 Composition pour la prévention ou le traitement d'une infection à coronavirus, contenant un extrait de feuille d'érable Ceased WO2024090654A1 (fr)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6187316B1 (en) * 1994-02-17 2001-02-13 Merck Patent Gmbh Antiviral or antifungal composition and method
WO2011030158A2 (fr) * 2009-09-10 2011-03-17 University Of Surrey Composition antimicrobienne
CN109122849A (zh) * 2018-10-22 2019-01-04 温碧君 一种大米保鲜剂及其制备方法和应用

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6187316B1 (en) * 1994-02-17 2001-02-13 Merck Patent Gmbh Antiviral or antifungal composition and method
WO2011030158A2 (fr) * 2009-09-10 2011-03-17 University Of Surrey Composition antimicrobienne
CN109122849A (zh) * 2018-10-22 2019-01-04 温碧君 一种大米保鲜剂及其制备方法和应用

Non-Patent Citations (2)

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Title
BI WU; GAO YING; SHEN JIE; HE CHUNNIAN; LIU HAIBO; PENG YONG; ZHANG CHUNHONG; XIAO PEIGEN: "Traditional uses, phytochemistry, and pharmacology of the genusAcer(maple): A review", JOURNAL OF ETHNOPHARMACOLOGY, ELSEVIER IRELAND LTD, IE, vol. 189, 29 April 2016 (2016-04-29), IE , pages 31 - 60, XP029683653, ISSN: 0378-8741, DOI: 10.1016/j.jep.2016.04.021 *
WEI QIANG: "Study on chemical components of the essential oils of leaf,stem and fruit from Acer palmatum cv.atropurpureum and their antiviral activities", JOURNAL OF YUNNAN UNIVERSITY(NATURAL SCIENCES EDITION), vol. 38, no. 2, 10 March 2016 (2016-03-10), pages 282 - 290, XP093162220 *

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