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WO2022065972A2 - Composition pour la prévention ou le traitement d'une infection à coronavirus comprenant un extrait d'epimedium koreanum - Google Patents

Composition pour la prévention ou le traitement d'une infection à coronavirus comprenant un extrait d'epimedium koreanum Download PDF

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Publication number
WO2022065972A2
WO2022065972A2 PCT/KR2021/013197 KR2021013197W WO2022065972A2 WO 2022065972 A2 WO2022065972 A2 WO 2022065972A2 KR 2021013197 W KR2021013197 W KR 2021013197W WO 2022065972 A2 WO2022065972 A2 WO 2022065972A2
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Prior art keywords
coronavirus
extract
prevention
pharmaceutical composition
present
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PCT/KR2021/013197
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English (en)
Korean (ko)
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WO2022065972A3 (fr
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마진열
조원경
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한국한의학연구원
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Priority claimed from KR1020210067201A external-priority patent/KR102570595B1/ko
Application filed by 한국한의학연구원 filed Critical 한국한의학연구원
Publication of WO2022065972A2 publication Critical patent/WO2022065972A2/fr
Publication of WO2022065972A3 publication Critical patent/WO2022065972A3/fr

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K10/00—Animal feeding-stuffs
    • A23K10/30—Animal feeding-stuffs from material of plant origin, e.g. roots, seeds or hay; from material of fungal origin, e.g. mushrooms
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—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
    • 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

Definitions

  • the present invention relates to an antiviral use against a coronavirus comprising an yin and yanggwak 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 first identified the antiviral effect on coronavirus containing the eumyanggak extract or a fraction thereof, and an antiviral pharmaceutical composition for coronavirus containing the eumyanggak extract or a fraction thereof, for the prevention or treatment of a coronavirus infectious disease
  • a pharmaceutical composition, 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 comprising an eumyangguk extract or a fraction thereof, and an eumyanggak extract or a fraction thereof The present application was completed by developing a feed composition for the prevention or improvement of coronavirus infectious diseases.
  • One object of the present invention is to provide a pharmaceutical composition for antiviral against coronavirus comprising a eumyanggwak extract or a fraction thereof.
  • Another object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of a coronavirus infection disease comprising an eumyanggwak 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 to provide a health functional food composition for the prevention or improvement of a coronavirus infection disease comprising a eumyanggwak extract or a fraction thereof.
  • Another object of the present invention is to provide a feed composition for the prevention or improvement of a coronavirus infection disease comprising a eumyanggwak extract or a fraction thereof.
  • Another object of the present invention provides the use of a composition comprising a eumyanggwak extract or a fraction thereof for preparing an antiviral pharmaceutical composition for coronavirus.
  • Another object of the present invention provides the use of a composition comprising a eumyanggwak extract or a fraction thereof for preparing a pharmaceutical composition for the prevention or treatment of coronavirus infectious disease.
  • Another object of the present invention provides the use of a composition comprising a eumyanggwak extract or a fraction thereof for preparing a health functional food composition for the prevention or improvement of coronavirus infection disease.
  • Another object of the present invention provides the use of a composition comprising a eumyanggwak extract or a fraction thereof for preparing a feed composition for the prevention or improvement of coronavirus infectious disease.
  • the eumyanggwak extract of the present invention exhibits the effect of inhibiting infection of coronaviruses such as SARS-coronavirus-2, SARS-coronavirus and MERS-coronavirus, it is used in the development of antiviral agents for preventing or treating the viral diseases.
  • coronaviruses such as SARS-coronavirus-2, SARS-coronavirus and MERS-coronavirus
  • 1 is a graph showing the SARS-coronavirus-2 inhibitory efficacy according to the concentration of the extract of the present invention and the control remdesivir.
  • One embodiment of the present invention for achieving the above object provides a pharmaceutical composition for antiviral against coronavirus comprising an eumyanggak extract or a fraction thereof.
  • Another embodiment of the present invention for achieving the above object provides a pharmaceutical composition for the prevention or treatment of coronavirus infection disease comprising the eumyanggwak extract 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.
  • 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
  • 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 eumyanggwak extract of the present invention includes not only the one obtained by 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 of extracting the eumyanggwak 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 eumyanggwak extract may be extracted by adding 2-10 times the amount of water of eumyanggwak and then extracting it at a temperature of 70°C to 125°C for 3 hours to 4 hours, but is not limited thereto.
  • 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 pharmaceutical composition for preventing or treating a coronavirus infectious disease comprising the yin and yanggwak extract or a fraction thereof is a coronavirus infectious disease, such as SARS-coronavirus-2, SARS-coronavirus and MERS-coronavirus. It is characterized in that it inhibits one or more viruses selected from the group consisting of. Specifically, in one embodiment of the present invention, it was confirmed that the Yinyanggwak extract or a fraction thereof has the ability to inhibit the infection of SARS-coronavirus-2, and it was compared with the positive control remdesivir (FIG. 1).
  • 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 amount of Yin-Yang Kwak extract contained in the pharmaceutical composition of the present invention is not particularly limited, and may include a pharmaceutically effective amount of Yin-Yang Kwak extract.
  • 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 provides a health functional food composition for the prevention or improvement of a coronavirus infection disease comprising a eumyanggwak extract or a fraction thereof.
  • the eumyanggwak extract according to the present invention exhibits an excellent coronavirus inhibitory effect, it may be included in a food composition for the purpose of preventing or improving infectious diseases caused by coronavirus, and since the food composition can be consumed routinely, the coronavirus A high effect can be expected for the prevention or improvement of infection caused by
  • 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 eumyanggwak extract of the present invention may be added as it is or used 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 eumyanggwak extract of the present invention may be included in various weight % in the food composition if it can exhibit the effect of preventing or improving infectious diseases caused by coronavirus. 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. In the case of long-term ingestion 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 provides a feed composition for the prevention or improvement of a coronavirus infection disease comprising an eumyanggak extract or a fraction thereof as an active ingredient.
  • the eumyanggwak extract according to the present invention exhibits an excellent coronavirus inhibitory effect, it can be included in a feed composition for the purpose of preventing or improving infectious diseases caused by coronavirus, and the feed composition can be consumed by animals on a daily basis. A high effect can be expected for the prevention or improvement of infectious diseases caused by coronavirus.
  • 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 provides the use of a composition comprising a eumyanggwak extract or a fraction thereof for preparing an antiviral pharmaceutical composition for coronavirus.
  • Another object of the present invention provides the use of a composition comprising a eumyanggwak extract or a fraction thereof for preparing a pharmaceutical composition for the prevention or treatment of coronavirus infectious disease.
  • Another object of the present invention provides the use of a composition comprising a eumyanggwak extract or a fraction thereof for preparing a health functional food composition for the prevention or improvement of coronavirus infection disease.
  • Another object of the present invention provides the use of a composition comprising a eumyanggwak extract or a fraction thereof for preparing a feed composition for the prevention or improvement of coronavirus infectious disease.
  • 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 yin and yanggwak extract
  • the Vero cell line (ATCC, CCL-81) was placed in a 96-well plate at 2 x 104 cells/well and cultured for one day. SARS-coronavirus-2 was infected 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 using 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 cytotoxicity (CC50) of the extract of the present invention was not measured up to the highest experimental concentration of 100 ⁇ g/ml, and the effective concentration (EC50) was 10.9 ⁇ g/ml, SI (selectivity index, CC50/EC50) was measured to be >9.2.
  • 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 eumyanggwak extract of the present invention had the effect of inhibiting the infection of SARS-coronavirus-2 similarly to the positive control.

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  • General Chemical & Material Sciences (AREA)
  • Microbiology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
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  • Alternative & Traditional Medicine (AREA)
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  • Medicines Containing Plant Substances (AREA)
  • Fodder In General (AREA)
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Abstract

La présente invention concerne une utilisation antivirale contre le coronavirus, comprenant un extrait d'Epimedium koreanum ou un fragment associé et, plus particulièrement : une composition pharmaceutique antivirale contre le coronavirus, comprenant un extrait d'Epimedium koreanum ou une fraction associée ; une composition pharmaceutique pour la prévention ou le traitement d'une maladie infctieuse à coronavirus ; une méthode pour la prévention ou le traitement d'une maladie infectieuse à coronavirus au moyen de la composition pharmaceutique ; une composition alimentaire fonctionnelle de santé pour la prévention ou le traitement d'une maladie infectieuse à coronavirus, comprenant un extrait d'Epimedium koreanum ou un fragment associé ; et une composition alimentaire pour la prévention ou le traitement d'une maladie infectieuse à coronavirus, comprenant un extrait d'Epimedium koreanum ou une fraction associée. L'extrait d'Epimedium koreanum de la présente invention présente un effet inhibiteur sur l'infection par des coronavirus tels que MERS-CoV, SARS-CoV, et SARS-CoV-2, et par conséquent, peut être utilisé dans la mise au point de médicaments antiviraux pour la prévention ou le traitement des maladies virales.
PCT/KR2021/013197 2020-09-28 2021-09-28 Composition pour la prévention ou le traitement d'une infection à coronavirus comprenant un extrait d'epimedium koreanum WO2022065972A2 (fr)

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KR20200126187 2020-09-28
KR10-2020-0126187 2020-09-28
KR10-2021-0067201 2021-05-25
KR1020210067201A KR102570595B1 (ko) 2020-09-28 2021-05-25 음양곽 추출물을 포함하는 코로나바이러스 감염 예방 또는 치료용 조성물

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KR101140582B1 (ko) * 2009-10-09 2012-05-09 주식회사 옵티팜솔루션 음양곽 추출물을 포함하는 돼지유행성설사병 예방 또는 치료용 조성물
KR101271601B1 (ko) * 2009-11-04 2013-06-11 한국 한의학 연구원 인플루엔자 바이러스 유래 질병의 예방 또는 치료용 조성물
KR101731607B1 (ko) * 2014-08-12 2017-05-02 한국 한의학 연구원 음양곽 추출물을 유효성분으로 함유하는 항 바이러스용 조성물

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