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WO2023249393A1 - Composition pour la prévention, l'atténuation ou le traitement d'une infection à coronavirus, contenant un extrait d'herbe médicinale utilisé en tant que principe actif - Google Patents

Composition pour la prévention, l'atténuation ou le traitement d'une infection à coronavirus, contenant un extrait d'herbe médicinale utilisé en tant que principe actif Download PDF

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Publication number
WO2023249393A1
WO2023249393A1 PCT/KR2023/008574 KR2023008574W WO2023249393A1 WO 2023249393 A1 WO2023249393 A1 WO 2023249393A1 KR 2023008574 W KR2023008574 W KR 2023008574W WO 2023249393 A1 WO2023249393 A1 WO 2023249393A1
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WO
WIPO (PCT)
Prior art keywords
composition
extract
coronavirus
active ingredient
preventing
Prior art date
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Ceased
Application number
PCT/KR2023/008574
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English (en)
Korean (ko)
Inventor
권선오
진영희
김상현
윤지원
이상명
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Korea Institute of Oriental Medicine KIOM
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Korea Institute of Oriental Medicine KIOM
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Publication of WO2023249393A1 publication Critical patent/WO2023249393A1/fr
Anticipated expiration legal-status Critical
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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 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
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • 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
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin

Definitions

  • the present invention relates to a composition for preventing, improving, or treating coronavirus infection containing herbal extracts, especially rare extracts, as active ingredients.
  • the new type 2 severe acute respiratory syndrome coronavirus (SARS-CoV2) is a virus that has a single-stranded positive RNA genome consisting of approximately 30,000 base pairs, and the viral surface is surrounded by an envelope. Since it was first reported in Wuhan, China at the end of December 2019, the number of infected people has rapidly increased worldwide. The virus spreads so efficiently between people that the World Health Organization has declared it a pandemic with the potential to spread around the world and is seeking responses.
  • Typical Covid-19 patients show relatively mild symptoms such as increased body temperature, cough, and chest pain, but some patients develop serious diseases such as difficulty breathing and pneumonia, leading to death.
  • coronavirus infections include ribavirin, famciclovir, nitazoxanide, nafamostat, and chloroquine.
  • Remdesi Remdesivir (GS-5734) and favipiravir are being used to treat coronavirus infections, but their effectiveness is low and the incidence of variant viruses is high due to the nature of nucleic acid analog antivirals, so two or more types of antivirals are applied together. .
  • Most antiviral drugs used for coronavirus infections have the ability to inhibit RNA polymerase, but mouse hepatitis virus, a type of coronavirus that is resistant to remdesivir, has been discovered, and existing antiviral drugs have been discovered. Viral drugs are ineffective.
  • antiviral drugs developed to date have severe side effects, so great caution is required in their application.
  • Korean Patent Publication No. 2022-0013625 discloses an anti-coronavirus composition characterized by containing an extract of Ulgoebul tree as an active ingredient
  • Korean Patent Publication No. 2022-0018953 discloses an anti-coronavirus composition containing fern extract or a fraction thereof.
  • the present invention was developed in response to the above-mentioned needs, by providing an antiviral composition for coronavirus containing a rare extract as an active ingredient, and confirming that the rare extract inhibits coronavirus infection and proliferation.
  • the invention was completed.
  • the present invention provides an antiviral composition for coronavirus containing Siegesbeckia glabrescens extract as an active ingredient.
  • the present invention provides a pharmaceutical composition for preventing or treating coronavirus infection, comprising Siegesbeckia glabrescens extract as an active ingredient.
  • the present invention provides a health functional food composition for preventing or improving coronavirus infection containing Siegesbeckia glabrescens extract as an active ingredient.
  • the present invention provides a quasi-drug composition for preventing or improving coronavirus infection containing Siegesbeckia glabrescens extract as an active ingredient.
  • the present invention provides a cosmetic composition for preventing or improving coronavirus infection containing Siegesbeckia glabrescens extract as an active ingredient.
  • the present invention provides a feed additive for preventing or improving coronavirus infection containing Siegesbeckia glabrescens extract as an active ingredient.
  • the present invention relates to a composition for preventing, ameliorating or treating coronavirus infection containing an extract of Heereum as an active ingredient.
  • the extract of Heereum has the effect of protecting cells from coronavirus infection and inhibits the replication of the virus within cells and the inhibition of the virus in cells. It has the effect of suppressing my infection.
  • Figure 1 shows the results of confirming the antiviral effect of Heereum extract against SARS-CoV2 through CPE (Cytopathic effect) inhibition analysis.
  • A is a photo of a plate stained with crystal violet showing the antiviral effect against SARS-CoV2 according to treatment with Heeryeom extract at different concentrations, and
  • B is the result of quantifying this.
  • NC is the normal group
  • VC is the control group treated with SARS-CoV2.
  • Figure 2 shows the results confirming the viral replication inhibitory effect of Heereum extract on SARS-CoV2.
  • NC is the normal group
  • VC is the control group treated with SARS-CoV2.
  • **** means that there was a statistically significant decrease in the number of viral copies in the group treated with SARS-CoV2 and rare extract compared to the control group (VC) treated with SARS-CoV2, p ⁇ 0.0001.
  • Figure 3 is a fluorescent photograph (A) confirming the viral infection inhibition effect of Heereum extract on SARS-CoV2 and the quantification result (B).
  • NC is the normal group
  • VC is the control group treated with SARS-CoV2. **** means that there was a statistically significant decrease in viral infection in the group treated with SARS-CoV2 and rare extract compared to the control group (VC) treated with SARS-CoV2, p ⁇ 0.0001.
  • the present invention provides an antiviral composition against coronavirus containing Siegesbeckia glabrescens extract as an active ingredient.
  • the coronavirus may be one or more types selected from the group consisting of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV2), severe acute respiratory syndrome coronavirus (SARS CoV), and Middle East respiratory syndrome (MERS) coronavirus, Preferably, it is type 2 severe acute respiratory syndrome coronavirus (SARS-CoV2), but is not limited thereto.
  • SARS-CoV2 severe acute respiratory syndrome coronavirus
  • SARS CoV severe acute respiratory syndrome coronavirus
  • SARS CoV severe acute respiratory syndrome coronavirus
  • MERS Middle East respiratory syndrome
  • the extraction solvent for the rare extract is preferably water, a lower alcohol of C 1 to C 4 , or a mixture thereof, and more preferably water, but is not limited thereto.
  • any part of the above-mentioned heiryeom can be used, and preferably the aerial part is used, but it is not limited to this.
  • the Heereum extract of the present invention has the effect of inhibiting the proliferation of type 2 severe acute respiratory syndrome coronavirus.
  • the present invention provides a pharmaceutical composition for preventing or treating coronavirus infection, comprising Siegesbeckia glabrescens extract as an active ingredient.
  • the pharmaceutical composition according to the present invention can be formulated and used in the form of oral dosage forms such as capsules, powders, granules, tablets, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, and sterile injection solutions according to conventional methods. You can.
  • the pharmaceutical composition according to the present invention may further include a pharmaceutically acceptable carrier, excipient, or diluent.
  • Carriers, excipients and diluents that may be included in the pharmaceutical composition of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate. , cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oil.
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc. These solid preparations contain at least one excipient such as starch, calcium carbonate, sucrose or lactose, gelatin, etc. in the pharmaceutical composition. It is prepared by mixing. Additionally, in addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral use include suspensions, oral solutions, emulsions, syrups, etc.
  • Preparations for parenteral administration include sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories.
  • Non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate.
  • injectable ester such as ethyl oleate.
  • Withepsol, Macrogol, Tween 61, cacao, laurin, glycerogelatin, etc. can be used as a base for suppositories.
  • the appropriate dosage of the pharmaceutical composition of the present invention may be prescribed in various ways depending on factors such as formulation method, administration method, patient's age, weight, sex, pathological condition, food, administration time, administration route, excretion rate, and reaction sensitivity. You can.
  • the pharmaceutical composition of the present invention can be administered orally or parenterally, and in the case of parenteral administration, it can be administered topically on the skin, intravenous injection, subcutaneous injection, intramuscular injection, intraperitoneal injection, transdermal administration, etc.
  • the present invention provides a health functional food composition for preventing or improving coronavirus infection containing Siegesbeckia glabrescens extract as an active ingredient.
  • composition may be manufactured in any one formulation selected from powder, granule, pill, tablet, capsule, candy, syrup, and beverage, but is not limited thereto.
  • the health functional food composition of the present invention When using the health functional food composition of the present invention as a food additive, the health functional food composition may be added as is or used together with other foods or food ingredients, and may be used appropriately according to conventional methods.
  • the amount of active ingredient can be appropriately used depending on the purpose of use (prevention or improvement).
  • the health functional food composition of the present invention is added in an amount of 15 parts by weight or less, preferably 10 parts by weight or less, based on the total raw materials.
  • the amount may be 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.
  • Health functional foods There are no particular restrictions on the types of health functional foods. Examples of foods to which the health functional food composition can be added include meat, sausages, bread, chocolate, candies, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, and tea. There are drinks, alcoholic beverages, and vitamin complexes, and it includes all health foods in the conventional sense.
  • the health functional food composition of the present invention can be manufactured into food, especially functional food.
  • the functional food of the present invention includes ingredients commonly added during food production, and includes, for example, proteins, carbohydrates, fats, nutrients and seasonings.
  • ingredients commonly added during food production includes, for example, proteins, carbohydrates, fats, nutrients and seasonings.
  • natural carbohydrates or flavoring agents may be included as additional ingredients in addition to the active ingredient.
  • the natural carbohydrates include monosaccharides (e.g., glucose, fructose, etc.), disaccharides (e.g., maltose, sucrose, etc.), oligosaccharides, polysaccharides (e.g., dextrins, cyclodextrins, etc.), or sugar alcohols (e.g., For example, xylitol, sorbitol, erythritol, etc.) is preferable.
  • the flavoring agent may be a natural flavoring agent (e.g., thaumatin, stevia extract, etc.) or a synthetic flavoring agent (e.g., saccharin, aspartame, etc.).
  • the ratio of the ingredients added is not very important, but is generally selected in the range of 0.01 to 0.1 parts by weight based on 100 parts by weight of the health functional food composition of the present invention.
  • the present invention provides a quasi-drug composition for preventing or improving coronavirus infection containing Siegesbeckia glabrescens extract as an active ingredient.
  • the quasi-drugs may include external skin preparations and personal hygiene products.
  • it may be a disinfectant cleaner, shower foam, garnish, wet tissue, detergent soap, hand wash, or ointment, but is not limited thereto.
  • the composition can be added as is or used with other quasi-drugs or quasi-drug components, and can be used appropriately according to conventional methods.
  • the mixing amount of the active ingredient can be appropriately determined depending on the purpose of use.
  • the quasi-drug composition of the present invention may be manufactured in the form of a general emulsified formulation or solubilized formulation.
  • it may have a formulation such as lotion, cream, ointment, spray, oil gel, gel, oil, or aerosol, but can be used without limitation as long as it shows the effect of preventing or improving the coronavirus infection of the present invention. there is.
  • the quasi-drug composition contains oil, water, surfactants, moisturizers, lower alcohols with 1 to 4 carbon atoms, thickeners, chelating agents, colorants, preservatives or fragrances, etc., which are generally mixed in quasi-drug compositions, as appropriate for each dosage form. Can be used in combination.
  • the present invention provides a cosmetic composition for preventing or improving coronavirus infection containing Siegesbeckia glabrescens extract as an active ingredient.
  • the cosmetic composition of the present invention includes ingredients commonly used in cosmetic compositions, such as antioxidants, stabilizers, solubilizers, vitamins, conventional auxiliaries such as pigments and fragrances, and carriers.
  • the cosmetic composition of the present invention can be prepared in any formulation commonly prepared in the art, for example, solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, soaps, surfactant-containing cleansing products. , oil, powder foundation, emulsion foundation, wax foundation, spray, etc., but is not limited thereto. More specifically, it can be manufactured in the form of flexible lotion (skin), nourishing lotion (milk lotion), nourishing cream, massage cream, essence, eye cream, cleansing cream, cleansing foam, cleansing water, shampoo, pack, spray or powder. You can.
  • the formulation of the present invention is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tragacantha, cellulose derivatives, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide are used as carrier ingredients. It can be.
  • the formulation of the present invention is a powder or spray
  • lactose, talc, silica, aluminum hydroxide, calcium silicate, or polyamide powder can be used as the carrier ingredient.
  • chlorofluorohydrocarbon and propane may be used as carrier ingredients.
  • May contain propellants such as butane or dimethyl ether.
  • a solvent, solubilizing agent, or emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1 , 3-butyl glycol oil, glycerol aliphatic esters, polyethylene glycol or fatty acid esters of sorbitan.
  • the carrier ingredients include water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester, and microcrystals.
  • a liquid diluent such as ethanol or propylene glycol
  • a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester
  • microcrystals ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester
  • Cellulose, aluminum metahydroxide, bentonite, agar or tragacantha can be used.
  • the carrier ingredients include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosinate, and fatty acid amide.
  • Ether sulfate, alkylamidobetaine, fatty alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanolin derivative, or ethoxylated glycerol fatty acid ester can be used.
  • the present invention provides a feed additive for preventing or improving coronavirus infection containing Siegesbeckia glabrescens extract as an active ingredient.
  • the feed additive of the present invention corresponds to supplementary feed under the Feed Management Act.
  • the term 'feed' may mean 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;
  • animal feeds such as proteins, inorganic substances, fats and oils, minerals, oils and fats, single-cell proteins, zooplanktons or food. These may be used alone or in combination of two or more types.
  • Heeryum purchased a standard product from Gwangmyeongdang Pharmaceutical. Specifically, 10 parts by weight of water (100°C) was added to 1 part by weight of Heeryum dried raw material, extracted under reflux for 3 hours, and then filtered through a strainer (extraction cloth). The material passed through a 53 ⁇ m filter was concentrated under reduced pressure and then freeze-dried to prepare a rare extract.
  • SARS-CoV2 was inoculated at an m.o.i of 0.01.
  • the rare extract of Preparation Example 1 was diluted with DMEM containing 2% (v/v) FBS and 1% (v/v) penicillin-streptomycin and cultured for 3 days.
  • the cell culture medium was removed, and then treated with a 1:1 volume ratio of methanol:acetone and fixed for 10 minutes at room temperature.
  • the solution was removed, 0.4% (w/v) crystal violet was added to each well, and the cells were stained at room temperature for 10 minutes, then all of the solution was removed and dried.
  • methanol:acetic acid was mixed at a 1:1 volume ratio, and 100 ⁇ l of a solution diluted 5 times with distilled water was added to each well. Crystal violet was extracted for 2 hours, and the absorbance was measured at 550 nm.
  • the Heereum extract of the present invention inhibited the proliferation of SARS-CoV2, and the IC 50 value was confirmed to be 90.36 ⁇ g/mL, indicating that the Heereum extract is an antibody that protects cells from the SARS-CoV2 virus. The virus effect was excellent.
  • the viral replication inhibitory effect of Heereum extract was confirmed by qPCR. Specifically, after culturing Vero E6 cells in a 96-well plate, SARS-CoV2 was inoculated at an m.o.i of 0.01, samples of Preparation Example 1 were treated at different concentrations, and cultured for 24 hours. After incubation, viral RNA released out of the cells was extracted using Bioneer's AccuPrep Viral RNA Extraction kit. Then, cDNA was synthesized using Toyobo's ReverTra Ace qPCR RT kit, then PCR was performed with specific primers for the RBD of the spike protein, and the viral RNA copy number was measured using the spike protein gene plasmid standard sample. Calculated.
  • the extract of Heereum was excellent in inhibiting the replication of the SARS-CoV2 virus.
  • the inhibitory effect of SARS-CoV2 virus infection using Heereum extract was confirmed using immunofluorescence analysis. Specifically, Vero E6 cells were distributed on a plate at 1 ⁇ 10 4 cells/well, and samples of Preparation Example 1 were processed at each concentration, followed by 2% (v/v) FBS and 1% (v/v) antibiotics. SARS-CoV2 diluted 1000 times was treated with DMEM and cultured for 24 hours. After incubation, the cells were fixed with a 4% (v/v) formaldehyde solution, reacted with a primary antibody (Nucleocapsid protein) diluted 2000 times, and then reacted with a secondary antibody diluted 200 times. After the reaction, the cells were observed under a fluorescence microscope, and the fluorescence intensity was analyzed.

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Abstract

La présente invention concerne une composition pour la prévention, l'atténuation ou le traitement d'une infection à coronavirus, la composition comprenant un extrait de Siegesbeckia pubescens en tant que principe actif. L'extrait de Siegesbeckia pubescens a pour effet de protéger des cellules contre une infection à coronavirus, et a un excellent effet de suppression de la réplication virale dans les cellules et de l'infection virale dans les cellules, et ainsi, la composition comprenant l'extrait de Siegesbeckia pubescens en tant que principe actif selon la présente invention peut être efficacement utilisée en tant qu'agent thérapeutique pour une infection à coronavirus ou en tant qu'aliment fonctionnel de santé anti-coronavirus, pseudo-médicament, cosmétique ou additif pour nourriture animale.
PCT/KR2023/008574 2022-06-22 2023-06-21 Composition pour la prévention, l'atténuation ou le traitement d'une infection à coronavirus, contenant un extrait d'herbe médicinale utilisé en tant que principe actif Ceased WO2023249393A1 (fr)

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KR1020220076179A KR102524071B1 (ko) 2022-06-22 2022-06-22 한약재 추출물을 유효성분으로 포함하는 코로나바이러스 감염증의 예방, 개선 또는 치료용 조성물
KR10-2022-0076179 2022-06-22

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WO2023249393A1 true WO2023249393A1 (fr) 2023-12-28

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KR102524071B1 (ko) * 2022-06-22 2023-04-21 한국 한의학 연구원 한약재 추출물을 유효성분으로 포함하는 코로나바이러스 감염증의 예방, 개선 또는 치료용 조성물

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KR102524071B1 (ko) * 2022-06-22 2023-04-21 한국 한의학 연구원 한약재 추출물을 유효성분으로 포함하는 코로나바이러스 감염증의 예방, 개선 또는 치료용 조성물

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