WO2022220339A1 - Composition pour la prévention ou le traitement d'une infection par le coronavirus (sras-cov-2), comprenant un extrait de galla rhois en tant que principe actif - Google Patents

Composition pour la prévention ou le traitement d'une infection par le coronavirus (sras-cov-2), comprenant un extrait de galla rhois en tant que principe actif Download PDF

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WO2022220339A1
WO2022220339A1 PCT/KR2021/009659 KR2021009659W WO2022220339A1 WO 2022220339 A1 WO2022220339 A1 WO 2022220339A1 KR 2021009659 W KR2021009659 W KR 2021009659W WO 2022220339 A1 WO2022220339 A1 WO 2022220339A1
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sars
cov
infection
extract
corona virus
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PCT/KR2021/009659
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English (en)
Korean (ko)
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강세찬
박대원
이영근
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에이피알지 주식회사
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    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • 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)
    • A61K36/22—Anacardiaceae (Sumac family), e.g. smoketree, sumac or poison oak
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/31—Foods, ingredients or supplements having a functional effect on health having an effect on comfort perception and well-being
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/324—Foods, ingredients or supplements having a functional effect on health having an effect on the immune system

Definitions

  • the present invention relates to a composition for preventing, improving or treating coronavirus (SARS-CoV-2) infection comprising an extract of Galla rhois as an active ingredient.
  • SARS-CoV-2 coronavirus
  • coronavirus infection SARS-CoV-2, COVID-19, hereafter referred to as Corona 19
  • Corona 19 the cause of cluster pneumonia in China in December 2019, the possibility of a prolonged and re-infestation of the COVID-19 situation is increasing.
  • the World Health Organization declared an international public health emergency on January 30, 2020, and is making all-out efforts to develop therapeutic agents and vaccines. have.
  • the coronavirus which is currently a worldwide problem, is defined as a respiratory syndrome caused by SARS-CoV-2 infection.
  • a virus isolated from pneumonia patients in Wuhan, China in December 2019 was identified as a novel coronavirus belonging to beta coronavirus and distinct from SARS-CoV as a result of whole genome sequencing.
  • the nucleotide sequence of this virus was 79.0% and 51.8% identical to the nucleotide sequence of SARS-CoV and MERS-CoV, respectively, and approximately 87.6 to 89% identical to the SARS-like coronavirus (bat-SL-CoVC45) of bats. (Park Soo-eun.
  • SARS-CoV-2 Characteristics, transmission, and clinical manifestations of the virus (SARS-CoV-2) of Coronavirus Infectious Disease-19. Pediatr Infect Vaccine. 2020).
  • SARS-CoV-2 has a very advantageous feature in that the spike protein is activated and the virus and cell membrane bind together.
  • This pathogen was named SARS-CoV-2, which is an RNA virus belonging to the Coronaviridae family. Therefore, it is known that spread through droplets (saliva drops) generated when coughing or sneezing, or by touching an object contaminated with the Corona 19 virus and then touching your eyes, nose, and mouth.
  • the global fatality rate is about 3.57% (based on WHO, August 16), however, the level of fatality rate varies greatly by country and by age. The elderly, immunocompromised patients, and patients with underlying diseases mainly cause severe and death.
  • coronavirus The incubation period of coronavirus is 1 to 14 days (average 4 to 7 days), and as a diagnostic standard, it is diagnosed by isolating the virus from a sample of a person who has been infected with an infectious disease pathogen according to the diagnostic test standards or by detecting a specific gene in the sample.
  • Corona virus symptoms include a variety of respiratory infections ranging from mild to severe, such as fever, malaise, cough, shortness of breath, and pneumonia.
  • there is no specific antiviral drug other than conservative treatment such as fluid supplementation and antipyretic drugs.
  • Corona virus infection is initiated through the binding of the spike protein on the surface of the virus to the cell membrane. Therefore, by inhibiting the binding of the spike protein to the cell membrane, it is possible to fundamentally block the viral infection of the cell.
  • Galla rhois refers to an insect nest formed by Aphis chinensis J. Bell giving a punctured wound to the leaves of Rhus javanica L. belonging to the Anacardiaceae family. do. Looking at the shape of the pentagram, the outer surface is grayish-brown with soft hairs, the length is 3 ⁇ 7cm, the width is 2 ⁇ 5cm, and the thickness is about 2mm, and it is hard and easily broken. The inside is usually empty or has grayish-white dead bugs and secretions, sometimes with a foul odor. The collected five pears are dried in the sun, boiled, or steamed for use. The main component contains 50 to 70% of pyrrogallol tannin, and gallic acid and gallic acid.
  • the present invention when infected with the corona virus (SARS-CoV-2) in the host cell, 30 to 70% ethanol extract, more preferably 50% ethanol extract, corona virus infection (Corona 19) in the host cell effectively inhibition was confirmed. That is, it was confirmed that the corona virus was prevented from infecting host cells.
  • the mechanism of inhibiting infection by blocking the cell membrane binding of the spike protein is similar to that of a neutralizing antibody that binds to a virus and blocks cell infection, so it can be used as a very useful therapeutic agent. Under the same conditions, remdesivir (inhibits viral RNA replication) and chloroquine (inhibits intracellular migration after viral infection) did not inhibit coronavirus infection at all.
  • the extract can strongly inhibit the proliferation of the corona virus (SARS-CoV-2) even after intracellular penetration as well as the effect of inhibiting the infection of the corona virus (SARS-CoV-2).
  • an object of the present invention is to provide a composition for preventing, improving or treating coronavirus (SARS-CoV-2) infection comprising an extract of baekjaeja as an active ingredient.
  • SARS-CoV-2 coronavirus
  • SARS-CoV-2 corona virus
  • Another object of the present invention is to provide a pharmaceutical composition for preventing or treating corona virus (SARS-CoV-2) infection, which includes an extract of Galla rhois as an active ingredient.
  • SARS-CoV-2 corona virus
  • Another object of the present invention is a pharmaceutical composition for the prevention or treatment of corona virus (SARS-CoV-2) infection comprising penta-O-galloyl- ⁇ -D-glucose (PGG) isolated from pentagram as an active ingredient is to provide
  • Another object of the present invention is for the prevention or treatment of corona virus (SARS-CoV-2) infection containing penta-O-galloyl- ⁇ -D-glucose (PGG) isolated from penta-O-galloyl- ⁇ -D-glucose (PGG) as an active ingredient
  • SARS-CoV-2 corona virus
  • PSG penta-O-galloyl- ⁇ -D-glucose isolated from penta-O-galloyl- ⁇ -D-glucose
  • the present invention confirms the prevention, improvement, or therapeutic effect on corona virus (SARS-CoV-2) infection by using the extract or penta-O-galloyl- ⁇ -D-glucose (PGG) isolated therefrom, and , Through this, a composition that can be used as a health functional food or pharmaceutical that can prevent, improve or treat coronavirus (SARS-CoV-2) using penta-O-galloyl- ⁇ -D-glucose (PGG) or penta-O-galloyl- ⁇ -D-glucose (PGG) is manufactured aim to do
  • the present invention provides a health functional food composition for the prevention or improvement of corona virus (SARS-CoV-2) infection, comprising the extract of baekjae baeja as an active ingredient.
  • SARS-CoV-2 corona virus
  • the 'Five baeja extract' of the present invention is water, C 1 to It may be extracted with at least one solvent selected from C 4 alcohol, ethyl acetate, chloroform, and hexane, preferably extracted using 30 to 70% ethanol, more preferably 50% ethanol It may be extracted using, but is not limited thereto.
  • the 'coronavirus' of the present invention may be a beta-coronavirus, but is not limited thereto.
  • the 'Pucea extract' of the present invention may have a plaque reducing effect on the corona virus (SARS-CoV-2), but is not limited thereto.
  • SARS-CoV-2 corona virus
  • the 'Pubic baeja extract' of the present invention may be to inhibit corona virus (SARS-CoV-2) replication, but is not limited thereto.
  • the 'Pagoda extract' of the present invention may include a penta-O-galloyl- ⁇ -D-glucose (PGG) component, but is not limited thereto.
  • PSG penta-O-galloyl- ⁇ -D-glucose
  • the 'extract of baekjae baeja' of the present invention may have an effect of suppressing fever due to corona virus, but is not limited thereto.
  • the 'composition' of the present invention may block the cell membrane binding of the corona virus spike protein to inhibit infection, but is not limited thereto.
  • the present invention provides a pharmaceutical composition for the prevention or treatment of corona virus (SARS-CoV-2) infection comprising an extract of baekjaeja as an active ingredient.
  • SARS-CoV-2 corona virus
  • the present invention provides a pharmaceutical composition for the prevention or treatment of corona virus (SARS-CoV-2) infection comprising penta-O-galloyl- ⁇ -D-glucose (PGG) isolated from pentagram as an active ingredient .
  • SARS-CoV-2 corona virus
  • PSG penta-O-galloyl- ⁇ -D-glucose
  • the present invention is a pharmaceutical composition for preventing or treating a corona virus (SARS-CoV-2) infection comprising penta-O-galloyl- ⁇ -D-glucose (PGG) isolated from penta-O-galloyl- ⁇ -D-glucose (PGG) as an active ingredient
  • SARS-CoV-2 corona virus
  • PSG penta-O-galloyl- ⁇ -D-glucose isolated from penta-O-galloyl- ⁇ -D-glucose
  • corona virus SARS-CoV-2
  • the extract of baekjae 30 to 70% ethanol extract of baekjae, more preferably 50% ethanol extract, is corona virus in the host cell. It was confirmed that it effectively inhibits virus (SARS-CoV-2) infection.
  • the corona virus was prevented from infecting host cells.
  • the mechanism of inhibiting infection by blocking the cell membrane binding of the spike protein is similar to that of a neutralizing antibody that binds to a virus and blocks cell infection, so it can be used as a very useful therapeutic agent. Under the same conditions, remdesivir (inhibits viral RNA replication) and chloroquine (inhibits intracellular migration after viral infection) did not inhibit coronavirus infection at all.
  • FIG. 1 is a diagram showing antiviral efficacy by inhibiting the cell infection of the corona virus (SARS-CoV-2) of the extract of the present invention.
  • FIG. 2 is a diagram showing the results of an experiment for plaque reduction analysis using the extract of the present invention.
  • FIG. 3 is a diagram showing the results of an experiment for suppressing vrial RNA using an extract of the present invention.
  • FIG. 4 is a diagram showing the results of an experiment for plaque reduction analysis using the pentagram component of the present invention.
  • FIG. 5 is a diagram showing the analysis of molecular docking of PGG and SARS-CoV-2 spike RBD, which are five baeja components of the present invention.
  • FIG. 6 is a diagram showing the antipyretic effect of the extract and positive control (indomethacin) on the fever caused by the body temperature increase inducer (LPS).
  • an object of the present invention is to provide a health functional food composition for preventing or improving corona virus (SARS-CoV-2) infection comprising an extract of baekjae baeja as an active ingredient.
  • SARS-CoV-2 corona virus
  • the extract according to the present invention may be obtained by extraction and separation from natural baekjae using extraction and separation methods known in the art, and “extract” as defined in the present invention is extracted from baeja using an appropriate solvent.
  • extract for example, include all crude extracts, polar solvent-soluble extracts, or non-polar solvent-soluble extracts.
  • any pharmaceutically acceptable organic solvent may be used, and water or an organic solvent may be used, but is not limited thereto, for example, purified water, methanol ( methanol), ethanol, propanol, isopropanol, alcohol having 1 to 4 carbon atoms, including butanol, acetone, ether, benzene, chloroform ( Various solvents such as chloroform), ethyl acetate, methylene chloride, hexane and cyclohexane may be used alone or in combination, preferably 30 to 70% of ethanol It was used as a solvent, more preferably 50% ethanol was used as a solvent.
  • any one of methods such as hot water extraction, cold extraction, reflux cooling extraction, solvent extraction, steam distillation, ultrasonic extraction, elution, and compression may be selected and used.
  • the desired extract may be further subjected to a conventional fractionation process, and may be purified using a conventional purification method.
  • the extract included in the composition of the present invention may be prepared in a powder state by an additional process such as distillation under reduced pressure and freeze-drying or spray-drying the primary extract extracted by the hot water extraction or solvent extraction method described above.
  • the first extract was further purified using various chromatography methods such as silica gel column chromatography, thin layer chromatography, high performance liquid chromatography, and the like. can also get Therefore, in the present invention, the extract is a concept including all extracts, isolated compounds, fractions and purified substances obtained in each step of extraction, fractionation or purification, and dilutions, concentrates or dried products thereof.
  • the extract of the present invention can be added as it is or used with other foods or food ingredients, and can be used appropriately according to a conventional method.
  • the composition may contain a food additive that is pharmaceutically acceptable, and the mixing amount of the active ingredient may be suitably determined according to the purpose of use (prevention, health or therapeutic treatment).
  • the term "food supplement additive” refers to a component that can be supplementally added to food, and is added to manufacture health functional food of each formulation, and those skilled in the art can appropriately select and use it.
  • food supplement additives include various nutrients, vitamins, minerals (electrolytes), synthetic flavoring agents and flavoring agents such as natural flavoring agents, coloring agents and fillers, pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners , pH adjuster, stabilizer, preservative, glycerin, alcohol, carbonation agent used in carbonated beverages, etc., but the above examples are not limited to the type of food supplement additive of the present invention.
  • the food composition of the present invention may include a health functional food.
  • health functional food used in the present invention refers to food manufactured and processed in the form of tablets, capsules, powders, granules, liquids, pills, etc. using raw materials or ingredients useful for the human body.
  • the term 'functionality' refers to obtaining useful effects for health purposes such as regulating nutrients or physiological effects on the structure and function of the human body.
  • the health functional food of the present invention can be manufactured by a method commonly used in the conventional technical field, and at the time of the production, it can be prepared by adding raw materials and components commonly added in the conventional technical field.
  • the dosage form of the health functional food may also be manufactured without limitation as long as it is a dosage form recognized as a health functional food.
  • composition for food of the present invention can be prepared in various forms, and unlike general drugs, it has the advantage that there are no side effects that may occur during long-term administration of the drug using food as a raw material, and has excellent portability, and the present invention health functional food can be consumed as a supplement to enhance the anti-inflammatory effect.
  • compositions comprising the extract of the present invention as an active ingredient can be prepared by mixing known additives with other suitable auxiliary ingredients that may be contained in health functional foods according to the selection of those skilled in the art.
  • suitable auxiliary ingredients include meat, sausage, bread, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages and
  • vitamins complexes and the like can be prepared by adding the extract according to the present invention as a main component to juice, tea, jelly, juice, and the like.
  • Vitamin B 1 0.13 mg
  • Vitamin B 2 0.15 mg
  • Vitamin B 6 0.5mg
  • the present invention provides a pharmaceutical composition for the prevention or treatment of corona virus (SARS-CoV-2) infection comprising an extract of pentagram as an active ingredient, or penta-O-galloyl- ⁇ -D-glucose (SARS-CoV-2) infection comprising PGG) as an active ingredient.
  • SARS-CoV-2 corona virus
  • PGG penta-O-galloyl- ⁇ -D-glucose
  • prevention refers to any action that inhibits or delays the occurrence, spread and recurrence of a coronavirus infection, preferably a coronavirus (SARS-CoV-2) infection, by administration of the pharmaceutical composition according to the present invention.
  • a coronavirus infection preferably a coronavirus (SARS-CoV-2) infection
  • treatment refers to any action that improves or advantageously changes the symptoms of a coronavirus infection, preferably a coronavirus (SARS-CoV-2) infection, by administration of the composition of the present invention.
  • SARS-CoV-2 coronavirus
  • Those of ordinary skill in the art to which the present invention pertains with reference to the data presented by the Korean Medical Association, etc., know the exact standard of the disease for which the composition of the present invention is effective, and can determine the degree of improvement, improvement and treatment There will be.
  • the pharmaceutical composition may be one or more formulations selected from the group including oral formulations, topical formulations, suppositories, sterile injection solutions and sprays, and injection formulations are more preferred.
  • the pharmaceutical composition of the present invention may further include a pharmaceutically acceptable additive, wherein the pharmaceutically acceptable additive includes starch, gelatinized starch, microcrystalline cellulose, lactose, povidone, colloidal silicon dioxide, calcium hydrogen phosphate, Lactose, mannitol, syrup, gum arabic, pregelatinized starch, corn starch, powdered cellulose, hydroxypropyl cellulose, Opadry, sodium starch glycolate, lead carnauba, synthetic aluminum silicate, stearic acid, magnesium stearate, aluminum stearate, stearic acid Calcium, sucrose, dextrose, sorbitol and talc and the like can be used.
  • the pharmaceutically acceptable additive according to the present invention is preferably included in an amount of 0.1 to 90 parts by weight based on the composition, but is not limited thereto.
  • compositions of the present invention may also include carriers, diluents, excipients or combinations of two or more commonly used in biological agents.
  • a pharmaceutically acceptable carrier is not particularly limited as long as it is suitable for in vivo delivery of the composition, see, for example, Merck Index, 13th ed., Merck & Co. Inc.
  • the compound described in , saline, sterile water, Ringer's solution, buffered saline, dextrose solution, maltodextrin solution, glycerol, ethanol, and one or more of these components can be mixed and used, and if necessary, other antioxidants, buffers, bacteriostats, etc. Conventional additives may be added.
  • diluents such as aqueous solutions, suspensions, emulsions, pills, capsules, granules or tablets.
  • injectable formulations such as aqueous solutions, suspensions, emulsions, pills, capsules, granules or tablets.
  • injectable formulations such as aqueous solutions, suspensions, emulsions, pills, capsules, granules or tablets.
  • it can be preferably formulated according to each disease or component using an appropriate method in the art or a method disclosed in Remington's Pharmaceutical Science (Mack Publishing Company, Easton PA, 18th, 1990).
  • composition of the present invention may be administered parenterally (for example, intravenously, subcutaneously, intraperitoneally or locally as an injection formulation) or orally, depending on the desired method, and the dosage may vary depending on the patient's weight, age, sex, The range varies according to health status, diet, administration time, administration method, excretion rate, and severity of disease.
  • the daily dose of the composition according to the present invention is 0.0001 to 10 mg/ml, preferably 0.0001 to 5 mg/ml, and it is more preferable to divide and administer once to several times a day.
  • Liquid formulations for oral administration of the composition of the present invention include suspensions, internal solutions, emulsions, syrups, etc., and various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. etc. may be included.
  • Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried preparations, suppositories, and the like.
  • the pharmaceutical composition of the present invention together with the existing composition for treating coronavirus infection, it is possible to increase the therapeutic effect of coronavirus infection.
  • the combined administration may be performed simultaneously or sequentially with the existing composition for treating coronavirus infection.
  • the present invention is for the prevention or treatment of corona virus (SARS-CoV-2) infection comprising penta-O-galloyl- ⁇ -D-glucose (PGG) isolated from the extract or penta-O-galloyl- ⁇ -D-glucose (PGG) as an active ingredient
  • SARS-CoV-2 corona virus
  • PSG penta-O-galloyl- ⁇ -D-glucose isolated from the extract or penta-O-galloyl- ⁇ -D-glucose
  • An object of the present invention is to provide a method for preventing or treating coronavirus (SARS-CoV-2) infection comprising administering a pharmaceutical composition to an individual.
  • the method of the present invention includes the above-described extract of baeja baeja, the content overlapping with the extract of baekjae of the present invention is omitted in order to avoid excessive complexity of the present specification due to the description of the overlapped content.
  • the term "individual” refers to a subject in need of a method for preventing, controlling or treating a disease, and may be used without limitation, such as humans, dogs, monkeys, cats, rodents, such as mice, genetically engineered mice, and the like. More specifically, it refers to mammals such as human or non-human primates, mice, rats, dogs, cats, horses, and cattle.
  • the pharmaceutical composition of the present invention may be administered in a therapeutically effective amount or a pharmaceutically effective amount.
  • the term "therapeutically effective amount” refers to an amount of a pharmaceutically acceptable salt of a composition effective for preventing or treating a target disease
  • the therapeutically effective amount of the composition of the present invention depends on several factors, for example, It may vary depending on the method of administration, the target site, and the condition of the patient. Therefore, when used in the human body, the dosage should be determined as an appropriate amount in consideration of both safety and efficiency. It is also possible to estimate the amount used in humans from the effective amount determined through animal experiments. These considerations in determining effective amounts are found, for example, in Hardman and Limbird, eds., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 10th ed. (2001), Pergamon Press; and E.W. Martin ed., Remington's Pharmaceutical Sciences, 18th ed. (1990), Mack Publishing Co.
  • the term “pharmaceutically effective amount” refers to an amount sufficient to treat a disease at a reasonable benefit/risk ratio applicable to medical treatment and not to cause side effects, and the effective dose level is determined by the patient's health condition. , disease type, severity, drug activity, sensitivity to drug, administration method, administration time, administration route and excretion rate, treatment period, factors including drugs used in combination or concurrently, and other factors well known in the medical field can be decided.
  • the composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered singly or multiple times. In consideration of all of the above factors, it is important to administer an amount that can obtain the maximum effect with a minimum amount without side effects, which can be easily determined by those skilled in the art.
  • baeja extract of the present invention is a drug widely used since ancient times in oriental medicine and is used as astringent, antidiarrheal, hemostatic agent for diarrhea, sputum, diabetes, hemorrhage, anemia, and the like. That is, when used as a health functional food, food or pharmaceutical composition, side effects may be less than that of a general synthetic compound, so it can be safely included in a health functional food, food or pharmaceutical composition to be usefully used.
  • DMEM -/-
  • overlay media (0.6% agarose in DMEM)
  • 12 well plate Vero E6, 1x PBS (cell culture grade) was used and the experiment was carried out according to the following experimental method.
  • baeja Galla rhois
  • the leaves of baeja were obtained from BioKorea Co., Ltd. in Seoul. It was purchased from LTd (Seoul), and the voucher sample (BMRI-RG-1602) was deposited at the Biomedical Research Center of Kyunghee University, Yongin, Korea.
  • the dried sample (20 kg) was extracted with 50% ethanol at 80 ⁇ 2° C. for 6 hours and then filtered. Then, it was concentrated using a rotary evaporator and lyophilized. The final product yield was 11.59 kg of quince.
  • the five baeja extracts were stored at 4 °C until use.
  • the ethanol 50% baeja extract is water, methanol 10%, methanol 30%, methanol 50%, methanol 70%, methanol 90%, ethanol 10%, ethanol 30%, ethanol 50%, ethanol 70%, ethanol 90%
  • the experiment was carried out using an ethanol 50% baeja extract in an optimized concentration in the preliminary experiment using the extract.
  • Vero E6 cells were seeded in a 12 well plate at 3.0 x 10 5 cells/well, and 2 cultured at 37°C, 5% CO 2 in an incubator. 3 The supernatant was removed, and the wash step was performed twice with 1x PBS. 4 Gobaeja extract (37 °C, 5% CO 2 incubator, 1 hour) and virus adsorption (50 pfu/well, shake/10 min) proceed simultaneously, 5 Remove the supernatant, add 1.5 mL overlay media , 6 The results were confirmed after 3 days (72 hours).
  • Vero E6 cells were seeded in a 12 well plate at 3 x 10 5 cells/well, and 2 cultured at 37°C, 5% CO 2 in an incubator. 3 The supernatant was removed and washed twice with PBS. 4 Virus adsorption (50 pfu/well, shake/10 min), 5 Remove the supernatant, treatment (P. extract, 37°C, 5% CO 2 incubator, 2 hours) 6 Remove the supernatant, add 1.5 mL Overlay media, 7 The results were confirmed after 3 days (72 hours).
  • the virus replication inhibitory efficacy was measured by treatment with the extract of baekjae.
  • the extract of baeja extract had an excellent effect on reducing plaque in a concentration-dependent manner, and at a high concentration of 25 ⁇ g/mL, similar to remdesivir used as a control group, it showed an inhibitory effect close to 100%.
  • the SARS-CoV-2 gene was quantitatively analyzed by real-time PCR to verify the antiviral effect of the extract. As a result, as shown in FIG. 3, a concentration-dependent decrease in viral RNA was observed in the extract of baekjaeja, and the antiviral efficacy was close to 100% at a high concentration of 25 ⁇ g/mL.
  • the virus replication inhibitory efficacy was measured by treating the pentagram component after infecting Vero E6 cells with SARS-CoV-2.
  • methyl gallate exhibited 16.3%, 18.0%, and 21.4% of virus replication inhibitory effects, respectively, and in the case of penta-O-galloyl- ⁇ -D-glucose (PGG), virus replication inhibition from low to 100% showed effect.
  • PSG penta-O-galloyl- ⁇ -D-glucose
  • Binding energies calculated in molecular docking analysis are shown in Table 1 below. In PGG, both SARS-CoV-2 spike RBD and B.1.1.7 spike RBD showed similar values. These results indicate that the extract of baekjaeja has potential as an antiviral treatment for both SARS-CoV-2 spike RBD and B.1.1.7 spike RBD.
  • a body temperature increase inducer (lipopolysaccharides, LPS; sigma, USA) was dissolved in saline at 2.5 mg/kg and administered intraperitoneally to the experimental animals to induce fever.
  • the experimental group consisted of 6 groups of 5 animals, and an extract of baeja baeja (25, 50, 100 mg/kg) and a positive control group (indomethacin, INN, 100 mg/kg) were orally administered 30 minutes before the induction of fever.
  • the rectal body temperature was measured before induction of fever (0 h) and 6 hours after induction (6 h) and shown in FIG. 6 .
  • the extract of baekjaeja inhibits the corona virus by inhibiting both the infection of SARS-CoV-2 into the host cells and the virus replication in the host cells.
  • a composition for the prevention or treatment of corona virus infection that is non-toxic at high concentration and has excellent therapeutic effect, and through this, it is developed as a health functional food or drug through additional research as a composition for prevention, improvement or treatment of corona virus It will be possible.

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Abstract

Le but de la présente invention est de préparer une composition permettant de prévenir, de soulager ou de traiter une maladie du coronavirus 2019 (COVID-19), laquelle est un problème mondial, à l'aide d'un extrait de Galla rhois, sur la base de la confirmation d'un effet de prévention, de soulagement ou de traitement de l'extrait de Galla rhois sur une infection par le coronavirus (SRAS-CoV-2).
PCT/KR2021/009659 2021-04-15 2021-07-26 Composition pour la prévention ou le traitement d'une infection par le coronavirus (sras-cov-2), comprenant un extrait de galla rhois en tant que principe actif WO2022220339A1 (fr)

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