WO2021210852A1 - Composition antivirale comprenant un matériel dérivé du placenta - Google Patents

Composition antivirale comprenant un matériel dérivé du placenta Download PDF

Info

Publication number
WO2021210852A1
WO2021210852A1 PCT/KR2021/004465 KR2021004465W WO2021210852A1 WO 2021210852 A1 WO2021210852 A1 WO 2021210852A1 KR 2021004465 W KR2021004465 W KR 2021004465W WO 2021210852 A1 WO2021210852 A1 WO 2021210852A1
Authority
WO
WIPO (PCT)
Prior art keywords
virus
antiviral composition
coronavirus
placental
composition
Prior art date
Application number
PCT/KR2021/004465
Other languages
English (en)
Korean (ko)
Inventor
유영효
한혜정
임민주
정경수
김은하
김세미
Original Assignee
(주)녹십자웰빙
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by (주)녹십자웰빙 filed Critical (주)녹십자웰빙
Priority to KR1020227037509A priority Critical patent/KR20220167294A/ko
Publication of WO2021210852A1 publication Critical patent/WO2021210852A1/fr

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N63/00—Biocides, pest repellants or attractants, or plant growth regulators containing microorganisms, viruses, microbial fungi, animals or substances produced by, or obtained from, microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermentates
    • A01N63/10—Animals; Substances produced thereby or obtained therefrom
    • 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
    • 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
    • A23L33/17—Amino acids, peptides or proteins
    • 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
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • 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
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/28—Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/48—Reproductive organs
    • A61K35/50—Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells
    • 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
    • A61K8/98—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
    • 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
    • A61K8/98—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
    • A61K8/981—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin of mammals or bird
    • A61K8/982—Reproductive organs; Embryos, Eggs
    • 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
    • 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
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/005—Antimicrobial preparations
    • 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
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/324—Foods, ingredients or supplements having a functional effect on health having an effect on the immune system
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2250/00—Food ingredients
    • A23V2250/20—Natural extracts
    • A23V2250/204—Animal extracts
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the present invention provides an antiviral composition
  • an antiviral composition comprising, as an active ingredient, one or more placental-derived substances selected from the group consisting of placental-derived cells, mesenchymal stem cells, extracellular vesicles, exosomes, microparticles, total RNA and microRNA (miRNA). is about
  • Human placenta extract contains various growth factors, cytokines, and other physiologically active substances, and is widely used for fatigue relief and antioxidant purposes (Lee KK, et al., Evid Based Complement). Alternat. Med., vol. 2012, (2012) p. 130875).
  • human placental extract induces improvement of liver function through liver regeneration in studies using animals and affects wound healing by producing TGF- ⁇ and VEGF.
  • the function of human placental extracts has not yet been fully studied, and in particular, studies on viral infections or diseases caused by viral infections have not been conducted.
  • the placenta of animals including humans is known to contain various types of cells and mesenchymal stem cells, so it is characterized by a very high medical value.
  • extracellular vesicles With many functions in the cell secretions (extracellular vesicle)', so research on its components and functions is being actively conducted.
  • Cells release various membrane types of ERs to the extracellular environment, and these ERs are commonly referred to as extracellular vesicles (EVs).
  • EVs extracellular vesicles
  • the extracellular vesicles are also called cell membrane-derived ERs, ectosomes, shedding vesicles, microparticles, exosomes, and the like, and in some cases, they are used separately from exosomes.
  • Exosomes are generated through the fusion of the plasma membrane with the late endosomes generated through the intracellular endosomal trafficking process. Exosomes not only contain specific proteins and mRNA transcripts expressed in the cell, but also contain various small non-coding RNAs (microRNA, piRNA, etc.) that control gene expression as RNA itself. Therefore, it is known that exosomes reflect the genetic characteristics of the cell of origin.
  • ncRNA small non-coding RNA
  • ncRNA small non-coding RNA
  • ncRNA small non-coding RNA
  • RNA transcript that is not translated into protein, but has been reported to regulate the stability, transcription and translation of various genes.
  • 97% are ncRNAs that are not translated into proteins. Therefore, ncRNA is closely related to various biological processes in vivo, and research on it is evaluated as a hot issue in the field of life sciences.
  • microRNA is a small RNA having a size of about 19 to 24 nucleotides, which causes RNA interference that regulates gene expression by decomposing mRNA that is complementary to a nucleotide sequence or inhibiting translation into a protein.
  • RNA interference is closely related to almost all biological processes such as development and physiology of living organisms, cell differentiation, proliferation and death, and genome stability, and is also closely related to virus resistance and various human diseases. Based on the association between RNA interference and disease, competitive studies for the development of therapeutic agents for human diseases are being conducted worldwide.
  • coronavirus was first discovered in chickens in 1937, followed by animals such as dogs, pigs, and birds, and was also discovered in humans in 1965. When infecting humans, the coronavirus is known to cause colds, upper respiratory tract infections, respiratory diseases, diarrhea in children, and other intestinal diseases. Severe acute respiratory syndrome (SARS) is a novel or mutated coronavirus-related disease that spread widely in China between November 2002 and June 2003, resulting in 8,096 infections and 774 deaths. In addition, Middle East respiratory syndrome (MERS) was first discovered in Saudi Arabia in 2012, and infected people were also confirmed in Jordan, Kuwait, the United Arab Emirates and Kuwait. According to the World Health Organization, 572 as of May 15, 2014 Three people were infected, of which 173 were reported to have died.
  • SARS Severe acute respiratory syndrome
  • MERS Middle East respiratory syndrome
  • Vaccine development for the novel coronavirus which occurred in 2019 and designated as a pandemic in early 2020 by the WHO, is being completed one after another, and treatments are being developed, but So far, there is no treatment that has a definitive effect.
  • Patent Document 1 Korean Patent No. 1919081 (2018.11.09)
  • Non-Patent Document 1 'Health and Welfare Issue & Focus' No. 373 (2020-04) issued by the Korea Institute for Health and Social Affairs Issue Date 2020.03.05. ISSN 2092-7117
  • an object of the present invention is to provide a novel antiviral composition having excellent antiviral activity.
  • Another object of the present invention is to provide a vaccine composition for preventing viral infection containing the antiviral composition as an active ingredient.
  • Another object of the present invention is to provide a health functional food composition for preventing or improving viral infection containing the antiviral composition as an active ingredient.
  • Another object of the present invention is to provide a cosmetic composition for preventing or improving viral infection containing the antiviral composition as an active ingredient.
  • the present invention uses one or more placental-derived substances selected from the group consisting of placental-derived exosomes, microparticles, total RNA, microRNA (miRNA), extracellular vesicles, placental-derived cells, and mesenchymal stem cells as an active ingredient. It provides an antiviral composition comprising.
  • the present invention also provides a vaccine composition containing the antiviral composition as an active ingredient.
  • the present invention also provides a pharmaceutical composition for the treatment or prevention of viral infections containing the antiviral composition as an active ingredient.
  • the present invention also provides a health functional food composition for preventing or improving viral infection containing the antiviral composition as an active ingredient.
  • the present invention also provides a cosmetic composition for preventing or improving viral infection containing the antiviral composition as an active ingredient.
  • the present invention also provides a method for treating or preventing a viral infection comprising administering the antiviral composition.
  • the present invention also provides the use of the antiviral composition for the treatment or prevention of a viral infection.
  • the present invention also provides the use of the antiviral composition for the manufacture of a medicament for the treatment or prevention of viral infections.
  • FIG. 5 shows the results of a CPE inhibition assay under virus 10 1 TCID 50 conditions for confirming the virus inhibitory effect of placental-derived exosomes.
  • FIG. 6 shows the results of a CPE inhibition assay under virus 10 2 TCID 50 conditions for confirming the virus inhibitory effect of placental-derived exosomes.
  • FIG. 7 shows the results of a CPE inhibition assay under the virus 10 1 TCID 50 condition for confirming the virus inhibitory effect of placental-derived total RNA.
  • the present invention is a placental-derived material selected from the group consisting of placental-derived exosomes, microparticles, total RNA, microRNA (miRNA), extracellular vesicles, placental-derived cells and mesenchymal stem cells as an active ingredient. It relates to an antiviral composition comprising.
  • the “placenta” is an organ that is created during pregnancy. It supplies nutrients and enzymes from the mother to the fetus, discharges waste products and carbon dioxide from the fetus to the mother, prevents the transfer of pathogens or drugs, which are foreign substances in the living body, to the fetus, and Functions such as endocrine regulation of the fetus.
  • the placenta contains amino acids, proteins, sugars, nucleic acids, lipids, minerals, enzymes, hormones, and the like.
  • the amino acids include aspartic acid, glutamic acid, leucine, lysine, glycine, alanine, serine, threonine, phenylalanine, tyrosine, methionine, histidine, and the like.
  • Proteins and enzymes include albumins, globulins, acidic and alkaline phosphatases, hyalonidases, and the like.
  • Sugars include glucose, galactose, ribose, and the like.
  • Nucleic acids include uracil, xanthine, hypoxanthine, and the like, and lipids include lauric acid, palmityl acid, and linoleic acid.
  • Minerals include Na, K, Ca, P, Fe, Cl, and the like, and hormones include gonadothrombin, lactogen, and steroid hormones.
  • placental-derived extracellular vesicles, exosomes, miRNAs or microparticles can be obtained through exosome separation equipment or other classical ultracentrifugation.
  • the virus to be prevented and/or treated is dengue virus, acute respiratory syndrome virus, coronavirus (Coronavirus), MERS coronavirus, SARS coronavirus, West Nile virus.
  • Herpes simplex virus Herpes zoster virus, Coxsackie virus, Enterovirus ( Enterovirus), influenza virus (Influenza), poliovirus, influenza A, influenza B, influenza C, human coronavirus (HCoV-229E), swine coronavirus, bovine coronavirus, SARS-CoV,
  • One or more viruses selected from the group consisting of herpes simplex type 1, herpes simplex type 2 and herpes zoster virus may be exemplified, but are not stable thereto.
  • Enteroviruses include polioviruses, kosakiviruses, enteroviruses, etc.
  • Influenza viruses include influenza A, B, and C viruses
  • coronaviruses include human coronavirus (HCoV-229E), swine coronavirus, Bovine coronavirus, SARS-CoV, and the like are included
  • the herpes virus includes herpes simplex type 1 and type 2 and herpes zoster virus.
  • the antiviral composition according to the present invention may be used for prevention and/or treatment of coronavirus, more preferably SARS-CoV, SARS-CoV-1, SARS-CoV-2, Middle East coronavirus (MERS-CoV) ) and may be used for the prevention and / or treatment of one or more coronavirus infections selected from the group consisting of the COVID-19 virus.
  • coronavirus more preferably SARS-CoV, SARS-CoV-1, SARS-CoV-2, Middle East coronavirus (MERS-CoV)
  • MERS-CoV Middle East coronavirus
  • the antiviral composition according to the present invention can be used for immunization against endemic, pre-pandemic or pandemic (pandemic, worldwide) virus infection.
  • anti-virus [anti-virus] activity or "antiviral (efficacious) ability” refers to the ability to inhibit the infection of various subtypes and mutant viral particles of the viruses exemplified above into a host cell, that is, the host cell. It refers to the ability of virus particles to adhere to the cell membrane and inhibit the influx into the cell As a result, the virus interferes with the mechanism necessary for replication or propagation of the virus particles using the host cell, and through this, the antiviral have activity.
  • placental-derived exosomes and placental-derived total RNA have antiviral efficacy against corona-19 virus in vitro
  • corona-19 virus, placenta-derived exosomes and placental-derived total RNA in Vero cells As a result of each RNA treatment, it was confirmed that virus proliferation was inhibited under both viral infection conditions of 10 1 TCID 50 and 10 2 TCID 50 in the placental-derived exosomes 5ug treatment group. In addition, it was confirmed that virus proliferation was inhibited in the 10 1 TCID 50 virus condition in the placental-derived total RNA 100ng treatment group.
  • the present invention relates to a vaccine composition containing the antiviral composition as an active ingredient.
  • the present invention is a viral infection containing the antiviral composition as an active ingredient, preferably SARS-CoV, SARS-CoV-1, SARS-CoV-2, Middle East coronavirus (MERS-CoV) and COVID -19 It relates to a pharmaceutical composition for the treatment or prevention of one or more viral infections selected from the group consisting of viruses.
  • the antiviral composition as an active ingredient, preferably SARS-CoV, SARS-CoV-1, SARS-CoV-2, Middle East coronavirus (MERS-CoV) and COVID -19 It relates to a pharmaceutical composition for the treatment or prevention of one or more viral infections selected from the group consisting of viruses.
  • An antiviral composition or vaccine composition comprising the placenta extract of the present invention may include a pharmaceutically acceptable carrier.
  • the carrier used in the composition of the present invention includes a pharmaceutically acceptable carrier, adjuvant and vehicle, and is collectively referred to as a “pharmaceutically acceptable carrier”.
  • Pharmaceutically acceptable carriers that may be used in the compositions of the present invention include, but are not limited to, ion exchange, alumina, aluminum stearate, lecithin, serum proteins (eg, human serum albumin), buffers (eg, various phosphates).
  • glycine sorbic acid, potassium sorbate, partial glyceride mixtures of saturated vegetable fatty acids
  • water salts or electrolytes (eg protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride and zinc salts), colloidal silica, magnesium trisilicate, polyvinyl pyrrolidone, cellulose-based substrates, polyethylene glycol, sodium carboxymethylcellulose, polyarylate, waxes, polyethylene-polyoxypropylene-barrier polymers, polyethylene glycols and wool paper, and the like.
  • salts or electrolytes eg protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride and zinc salts
  • colloidal silica eg protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride and zinc salts
  • colloidal silica eg protamine sulfate, disodium hydrogen phosphat
  • composition according to the present invention may be administered orally or parenterally, and parenteral administration is intranasal, intranasal, buccal, intravenous, intramuscular, intraarterial, intramedullary, intrathecal, intracardiac, transdermal, subcutaneous, or intradermal. , intraperitoneal, enteral, topical, sublingual or rectal dosage forms.
  • the composition for intranasal or intranasal administration is prepared according to techniques well known in the art of pharmaceuticals and includes benzyl alcohol or other suitable preservatives, absorption enhancers to enhance bioavailability, fluorocarbons and/or other solubilizing agents known in the art or It can be prepared as a solution in brine using a dispersing agent.
  • the composition comprising the placenta extract according to the present invention may be in the form of a sterile injectable preparation as a sterile injectable aqueous or oleaginous suspension.
  • a sterile injectable preparation as a sterile injectable aqueous or oleaginous suspension.
  • suspensions may be formulated according to techniques known in the art using suitable dispersing or wetting agents (eg, Tween 80) and suspending agents.
  • the sterile injectable preparation may also be a sterile injectable solution or suspension (eg, a solution in 1,3-butanediol) in a non-toxic parenterally acceptable diluent or solvent.
  • Vehicles and solvents that can be used permissibly include mannitol, water, Ringel's solution and isotonic sodium chloride solution.
  • sterile, non-volatile oils are conventionally employed as the solvent or suspending medium.
  • any non-volatile, less irritating oil may be used, including synthetic mono or diglycerides.
  • Fatty acids such as oleic acid and its glyceride derivatives are useful in injectable formulations as are pharmaceutically acceptable natural oils (eg olive oil or castor oil), especially their polyoxyethylated ones.
  • composition of the present invention may be orally administered in any orally acceptable dosage form including, but not limited to, capsules, tablets, and aqueous suspensions and solutions.
  • aqueous suspensions are administered orally, the active ingredient is combined with emulsifying and suspending agents. If desired, sweetening and/or flavoring and/or coloring agents may be added.
  • compositions of the present invention may also be administered in the form of suppositories for rectal administration.
  • These compositions can be prepared by mixing a compound of the present invention with a suitable non-irritating excipient that is solid at room temperature but liquid at rectal temperature.
  • suitable non-irritating excipient include, but are not limited to, cocoa butter, beeswax, and polyethylene glycol.
  • composition according to the present invention may be formulated as pills, dragees, capsules, solutions, gels, syrups, slurries, and suspensions.
  • the pharmaceutical composition for oral administration may be prepared by mixing the active ingredient with a solid excipient, and may be prepared in the form of granules for preparation in the form of tablets or dragees.
  • Suitable excipients include, but are not limited to, sugar forms such as lactose, sucrose, mannitol and sorbitol, or starch from corn, wheat flour, rice, potatoes or other plants, cellulose such as methyl cellulose, hydroxypropylmethyl-cellulose or sodium carboxymethylcellulose, ara Carbohydrates such as gums, including big gum and tagacanth gum, or protein fillers such as gelatin and collagen can be used.
  • disintegrants or solubilizers in the form of cross-linked polyvinylpyrrolidone, agar and their respective salts such as alginic acid or sodium alginic acid may be added.
  • the present invention is a viral infection containing the antiviral composition as an active ingredient, preferably SARS-CoV, SARS-CoV-1, SARS-CoV-2, Middle East coronavirus (MERS-CoV) and COVID -19 It relates to a health functional food composition for preventing or improving one or more viral infections selected from the group consisting of viruses.
  • the antiviral composition as an active ingredient, preferably SARS-CoV, SARS-CoV-1, SARS-CoV-2, Middle East coronavirus (MERS-CoV) and COVID -19 It relates to a health functional food composition for preventing or improving one or more viral infections selected from the group consisting of viruses.
  • the functional food of the present invention can be used in various ways, such as pharmaceuticals, foods and beverages for preventing oxidation.
  • the functional food of the present invention includes, for example, various foods, candy, chocolate, beverage, gum, tea, vitamin complex, health supplement, and the like, and may be used in powder, granule, tablet, capsule or beverage form.
  • the antiviral composition of the present invention may be added to food or beverage for the purpose of preventing or improving viral infection.
  • the amount of the extract in food or beverage is generally 0.01 to 50% by weight of the total food weight of the health functional food composition of the present invention, preferably 0.1 to 20% by weight, and the health drink composition is 100 ml It can be added in a ratio of 0.02 to 10 g, preferably 0.3 to 1 g, but is not limited thereto.
  • the health beverage composition of the present invention has no particular limitation on the liquid component except for containing the extract as an essential component in the indicated ratio, and may contain various flavoring agents or natural carbohydrates as additional components like a conventional beverage.
  • natural carbohydrates include monosaccharides, for example, disaccharides such as glucose and fructose, for example, polysaccharides such as maltose and sucrose, for example, conventional sugars such as dextrin, cyclodextrin, and the like. and sugar alcohols such as xylitol, sorbitol, and erythritol.
  • natural flavoring agents such as taumatine, stevia extract (for example, rebaudioside A, glycyrrhizin, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used.
  • the proportion of the natural carbohydrate is generally about 1 to 20 g, preferably about 5 to 12 g per 100 ml of the composition of the present invention.
  • composition of the present invention comprises various nutrients, vitamins, minerals (electrolytes), synthetic flavoring agents and flavoring agents such as natural flavoring agents, coloring agents and thickening agents (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids , protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohols, carbonation agents used in carbonated beverages, and the like.
  • the compositions of the present invention may contain natural fruit juice and pulp for the production of fruit juice beverages and vegetable beverages. These components may be used independently or in combination. The proportion of these additives is not critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.
  • the present invention is a virus containing the antiviral composition as an active ingredient, preferably SARS-CoV, SARS-CoV-1, SARS-CoV-2, Middle East coronavirus (MERS-CoV) and COVID- It relates to a cosmetic composition for preventing or improving one or more viral infections selected from the group consisting of 19 viruses.
  • the antiviral composition of the present invention forms a cosmetic composition together with a cosmetically useful substance.
  • Cosmetically useful substances include antioxidants, binders, bulking agents, chelating agents, colorants, emollients, emulsion stabilizers, film formers, fillers, fragrance ingredients, gelling agents, hair conditioners, hair fixatives, humectants, plasticizers. , preservatives, skin conditioners, solvents, sunscreens, surfactants, UV absorbers, viscosity modifiers, waxes, and the like.
  • CTFS Cosmetic Ingredient Handbook J.M. Nikitakis, Ed., 1st Edition, p.51-101 (1988), all of which are incorporated herein by reference.
  • the cosmetic composition of the present invention may be prepared in various forms such as solution (lotion-type composition), concentrated solution, gel, ointment, emulsion (cream, emulsion), vesicle dispersion, powder, dense powder, paste or solid. may be provided in the form. More specifically, the cosmetic composition of the present invention is a rouge, cream (face cream, hand cream, moisturizing cream, sun protection cream), cream powder, eye liner, eye shadow, eyebrow pencil, foundation, lotion, mascara, micro It may be dispersed in various forms such as emulsions, ointments, pomades and rouges, but is not limited thereto. They can be packaged in press packs with propellants that can be applied in the form of foam or spray.
  • the present invention relates to a method for treating or preventing a viral infection comprising administering the antiviral composition.
  • the present invention relates to the use of said antiviral composition for the treatment or prevention of viral infections.
  • the present invention relates to the use of the antiviral composition for the manufacture of a medicament for the treatment or prevention of viral infections.
  • Example 1 Preparation of placental-derived extracellular vesicles, exosomes, total RNA and microparticles
  • the human or animal placenta was washed with NaCl and distilled water, treated with acetone, degreased, and dried to obtain a dry placenta.
  • dry placenta is sufficiently hydrolyzed by treatment with pepsin or hydrochloric acid, and placental tissue-derived extracellular vesicles are obtained through appropriate enzymatic treatment and sterilization.
  • the process of obtaining exosomes, miRNAs or microparticles can be obtained by using exosome separation equipment or by traditional ultracentrifugation methods.
  • the size distribution of the exosome particles was 148 nm ⁇ 1.4 nm, and the total concentration was 7.99 x 10 10 particles/ml.
  • the equipment used in this experiment is a Malvern NanoSight.
  • ExoGlow-NTA The results of exosome analysis using the software ExoGlow-NTA are shown in FIG. 2 .
  • the size distribution of placental-derived exosome particles was 239 nm ⁇ 12.3 nm, and the total concentration was 2.2 x 1010 particles/ml.
  • ExoGlow-NTA Fluorescent Labeling Kit is known to have high quantification accuracy of extracellular antifoams. Malvern NanoSight (488 nm laser) was used, and NTA Version 2.3 Build 2.3.5.0033.7-Beta7 software was used.
  • the amount of extracellular vesicles obtained by repeating twice in the present invention is as follows.
  • the amount of total RNA obtained by repeating 5 times in the present invention is as follows.
  • the samples of No. 1 and No. 2 correspond to the two-fold concentrated samples of Nos. 3-5, and in the present invention, all of the total RNA obtained 5 times was pooled and used.
  • the MTT assay method is a test that confirms cell viability in vitro.
  • Cell viability is determined by culturing the cells treated with serial dilution for a certain period of time and measuring the degree of color change using MTT, a reagent that reacts with the dehydrogenase of the mitochondria, an intracellular organ. way.
  • the unit of test result is expressed as cell viability (%).
  • MTT solution is 2 ⁇ 5mg/ml of MTT dissolved in PBS, filtered, and placed in a tube. After blocking the light, it was stored at 4°C.
  • a 96 well plate 1 ⁇ 10 4 cells of Vero cells were dispensed per well. (37°C 5% CO 2 , 24h culture) Placental-derived exosomes and total RNA to be measured are added to each well by serial dilution 2-fold for each concentration. In order to sufficiently expose the test substance, each was cultured in an incubator at 37° C. 5% CO 2 for 24 hours. The supernatant was removed and 2-5 mg/ml MTT solution was added to each well. At this time, the MTT solution is sensitive to light, so be careful to minimize light exposure. 37° C. 5% CO 2 It was left in an incubator for 4 hours.
  • DMSO DMSO was dispensed without removing or removing the MTT solution, and the plate roll was sufficiently shaken for 10 to 30 minutes while blocking light.
  • the absorbance of each well was measured at a wavelength of 500 nm to 600 nm using a plate reader. As a result of this experiment, it was confirmed that cytotoxicity was not observed in each sample as follows.
  • Vero cells were seeded at 1 ⁇ 10 4 per well in a 96-well plate (37° C. 5% CO 2 , cultured for 24 h). Cells were inoculated with 50 ⁇ L of each of the inoculation culture medium containing each sample and 50 ⁇ L of corona-19 virus at the MNTD concentration determined in the first step test and the dilution multiple concentration after the first step. Normal cells and virus-inoculated cells were used as controls. After 1 hour, the supernatant was removed and replaced with a fresh culture solution. Incubated in a 37° C. 5% CO 2 incubator for 72 hours. After removal of the supernatant, the cells were washed with PBS and the cells were fixed with 10% formalin.
  • the antiviral effect was measured by checking the TCID 50 value by the cell staining method as follows.
  • the virus titer 10 1 hayeoteumeuro observe the results of cell viability 66% at 100ng treated group at TCID 50 condition
  • the placenta-derived total RNA 100ng treated group is 10 1 TCID 50 It was possible to confirm the effect of inhibiting virus proliferation under viral conditions.
  • a composition comprising one or more placental-derived substances selected from the group consisting of placental-derived exosomes, microparticles, total RNA, microRNA (miRNA), extracellular vesicles, placental-derived cells, and mesenchymal stem cells according to the present invention Since it has a dose-dependent effect of inhibiting the proliferation of coronavirus in cells infected with coronavirus, it can be usefully used for prevention of infection with RNA viruses or other viruses, including coronavirus, and treatment after viral infection.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Virology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Developmental Biology & Embryology (AREA)
  • Epidemiology (AREA)
  • Cell Biology (AREA)
  • Zoology (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Biotechnology (AREA)
  • Oncology (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Dermatology (AREA)
  • Communicable Diseases (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Reproductive Health (AREA)
  • Polymers & Plastics (AREA)
  • Pregnancy & Childbirth (AREA)
  • Birds (AREA)
  • Nutrition Science (AREA)
  • Mycology (AREA)
  • Food Science & Technology (AREA)
  • Hematology (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Agronomy & Crop Science (AREA)
  • Wood Science & Technology (AREA)
  • Dentistry (AREA)
  • Environmental Sciences (AREA)

Abstract

La présente invention concerne une composition antivirale comprenant au moins une substance dérivée du placenta choisie dans le groupe constitué par des cellules dérivées du placenta, des cellules souches mésenchymateuses, des vésicules extracellulaires, des exosomes, des microparticules, de l'ARN total et du micro-ARN. Les cellules dérivées du placenta, cellules souches mésenchymateuses, vésicules extracellulaires, exosomes, microparticules, ARN total ou micro-ARN, lorsqu'ils sont administrés à des cellules infectées par un virus, inhibent la viabilité du virus d'une manière dépendante de la dose et, en tant que tels, peuvent être avantageusement utilisés pour prévenir ou traiter des infections virales.
PCT/KR2021/004465 2020-04-14 2021-04-09 Composition antivirale comprenant un matériel dérivé du placenta WO2021210852A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
KR1020227037509A KR20220167294A (ko) 2020-04-14 2021-04-09 태반 유래 물질을 포함하는 항바이러스 조성물

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US202063009640P 2020-04-14 2020-04-14
US63/009,640 2020-04-14
KR10-2020-0066577 2020-06-02
KR20200066577 2020-06-02

Publications (1)

Publication Number Publication Date
WO2021210852A1 true WO2021210852A1 (fr) 2021-10-21

Family

ID=78083842

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2021/004465 WO2021210852A1 (fr) 2020-04-14 2021-04-09 Composition antivirale comprenant un matériel dérivé du placenta

Country Status (2)

Country Link
KR (1) KR20220167294A (fr)
WO (1) WO2021210852A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2017536096A (ja) * 2014-10-09 2017-12-07 アントフロゲネシス コーポレーション 胎盤由来の接着細胞エクソソームおよびそれらの使用
CN108143750A (zh) * 2017-12-26 2018-06-12 湖北未来家园高科技农业股份有限公司 鹿胎盘外泌体的制备方法及应用
WO2020051362A1 (fr) * 2018-09-05 2020-03-12 Children's Medical Center Corporation Utilisation d'exosomes de cellules stromales mésenchymateuses en thérapie anténatale

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101919081B1 (ko) 2017-05-11 2018-11-16 (주)녹십자웰빙 인간 태반 추출물을 유효성분으로 포함하는 근 위축증 또는 근육감소증의 예방 또는 치료용 및 근육 기능 개선용 조성물

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2017536096A (ja) * 2014-10-09 2017-12-07 アントフロゲネシス コーポレーション 胎盤由来の接着細胞エクソソームおよびそれらの使用
CN108143750A (zh) * 2017-12-26 2018-06-12 湖北未来家园高科技农业股份有限公司 鹿胎盘外泌体的制备方法及应用
WO2020051362A1 (fr) * 2018-09-05 2020-03-12 Children's Medical Center Corporation Utilisation d'exosomes de cellules stromales mésenchymateuses en thérapie anténatale

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
JANE RIDLE: "Stem cells from a baby’s placenta may save life of coronavirus victim in NJ", 13 April 2020 (2020-04-13), pages 1 - 5, XP055857829, Retrieved from the Internet <URL:https://nypost.com/2020/04/13/could-stem-cells-from-a-babys-placenta-treat-covid-19/> *
MAAYAN JAFFE-HOFFMAN: "Israeli company uses placenta cells to treat critical COVID-19 patients", pages 1 - 3, XP055857841, Retrieved from the Internet <URL:www.jpost.com/health-science/israels-company-uses-placenta-cells-to-treat-critical-covid-19-patients-622960> *
MOTOHIRO KOMAKI, YURI NUMATA, CHIKAKO MORIOKA, IZUMI HONDA, MASAYUKI TOOI, NAOKI YOKOYAMA, HIROHITO AYAME, KENGO IWASAKI, ATSUKO T: "Exosomes of human placenta-derived mesenchymal stem cells stimulate angiogenesis", STEM CELL RESEARCH & THERAPY, vol. 8, 219, 1 December 2017 (2017-12-01), pages 1 - 12, XP055857846, DOI: 10.1186/s13287-017-0660-9 *

Also Published As

Publication number Publication date
KR20220167294A (ko) 2022-12-20

Similar Documents

Publication Publication Date Title
WO2022050516A1 (fr) Agent thérapeutique contre le coronavirus comprenant un extrait d&#39;elaeocarpus sylvestris en tant que principe actif
WO2019216603A1 (fr) Polypeptide dérivé du virus de l&#39;hépatite b et son utilisation antivirale
US20110098261A1 (en) Triterpenoid-based compounds useful as virus inhibitors
WO2017061769A1 (fr) Composition de prévention de l&#39;alopécie ou de stimulation de la croissance capillaire contenant un polysaccharide extracellulaire produit par ceriporia lacerata en tant qu&#39;ingrédient actif
WO2023249393A1 (fr) Composition pour la prévention, l&#39;atténuation ou le traitement d&#39;une infection à coronavirus, contenant un extrait d&#39;herbe médicinale utilisé en tant que principe actif
WO2021210852A1 (fr) Composition antivirale comprenant un matériel dérivé du placenta
KR102540814B1 (ko) 한약재 추출물을 유효성분으로 포함하는 코로나바이러스 감염증의 예방, 개선 또는 치료용 조성물
WO2021210851A1 (fr) Composition antivirale comprenant un extrait de placenta
WO2022131603A1 (fr) Composition antivirale contenant un extrait d&#39;herbe de géranium en tant que principe actif
WO2022031151A1 (fr) Composition antivirale comprenant un extrait de fougère aigle orientale ou une fraction de celle-ci
WO2021210853A1 (fr) Composition antivirale comprenant un micro-arn dérivé d&#39;extrait de placenta
WO2022215827A1 (fr) Composition d&#39;extrait de sanguisorba officinalis linné inhibant la protéase 3cl et l&#39;activité rdrp du sars-cov-2
WO2022065983A2 (fr) Composition de prévention ou de traitement d&#39;une infection à coronavirus comprenant un extrait de gynostemma pentaphyllum
CN112691094B (zh) 防治病毒的新型化合物及其应用
WO2023048334A1 (fr) Nouveau lactobacillus plantarum probio 88, son extrait et composition
WO2022211396A1 (fr) Composition pharmaceutique incluant un extrait de salvia plebeia r. br. ou un composé dérivé de celui-ci en tant que principe actif pour la prévention ou le traitement de la dystrophie musculaire
WO2023200064A1 (fr) Composition destinée à inhiber un virus grippal
WO2022065971A2 (fr) Composition pour la prévention ou le traitement d&#39;une infection à coronavirus, comprenant un extrait de hovenia dulcis thunb
WO2023055053A1 (fr) Peptide ayant une activité de prévention de la chute des cheveux ou de favorisation de la pousse des cheveux et son utilisation
WO2022065972A2 (fr) Composition pour la prévention ou le traitement d&#39;une infection à coronavirus comprenant un extrait d&#39;epimedium koreanum
WO2023055060A1 (fr) Peptide ayant une activité de prévention de la chute des cheveux ou de promotion de la pousse des cheveux, et son utilisation
WO2023055051A1 (fr) Peptide ayant une activité de prévention de la chute des cheveux ou de promotion de la pousse des cheveux, et son utilisation
KR102512522B1 (ko) 한약재 추출물을 유효성분으로 포함하는 코로나바이러스 감염증의 예방, 개선 또는 치료용 조성물
KR102526488B1 (ko) 한약재 추출물을 유효성분으로 포함하는 코로나바이러스 감염증의 예방, 개선 또는 치료용 조성물
WO2023200289A1 (fr) Composition pour la prévention, l&#39;atténuation ou le traitement d&#39;une infection à coronavirus, contenant un extrait d&#39;herbe médicinale utilisé en tant que principe actif

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 21788541

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 20227037509

Country of ref document: KR

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 21788541

Country of ref document: EP

Kind code of ref document: A1