RU2020113341A - METHOD AND COMPOSITION FOR VIRAL INFECTION TREATMENT - Google Patents

METHOD AND COMPOSITION FOR VIRAL INFECTION TREATMENT Download PDF

Info

Publication number
RU2020113341A
RU2020113341A RU2020113341A RU2020113341A RU2020113341A RU 2020113341 A RU2020113341 A RU 2020113341A RU 2020113341 A RU2020113341 A RU 2020113341A RU 2020113341 A RU2020113341 A RU 2020113341A RU 2020113341 A RU2020113341 A RU 2020113341A
Authority
RU
Russia
Prior art keywords
day
acid
prodrug
salt
mcg
Prior art date
Application number
RU2020113341A
Other languages
Russian (ru)
Other versions
RU2020113341A3 (en
Inventor
Роберт А. НЬЮМАН
Отис К. ЭДДИНГТОН
Original Assignee
Феникс Байотекнолоджи, Инк.
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
Priority claimed from PCT/US2017/051553 external-priority patent/WO2018053123A1/en
Application filed by Феникс Байотекнолоджи, Инк. filed Critical Феникс Байотекнолоджи, Инк.
Publication of RU2020113341A publication Critical patent/RU2020113341A/en
Publication of RU2020113341A3 publication Critical patent/RU2020113341A3/ru

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/56Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/58Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
    • A61K31/585Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin containing lactone rings, e.g. oxandrolone, bufalin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/24Apocynaceae (Dogbane family), e.g. plumeria or periwinkle
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0014Skin, i.e. galenical aspects of topical compositions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/10Dispersions; Emulsions
    • A61K9/107Emulsions ; Emulsion preconcentrates; Micelles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2009Inorganic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2013Organic compounds, e.g. phospholipids, fats
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2022Organic macromolecular compounds
    • A61K9/2031Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2022Organic macromolecular compounds
    • A61K9/205Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4816Wall or shell material
    • A61K9/4825Proteins, e.g. gelatin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841Filling excipients; Inactive ingredients
    • A61K9/4858Organic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841Filling excipients; Inactive ingredients
    • A61K9/4866Organic macromolecular compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/48Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4891Coated capsules; Multilayered drug free capsule shells
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • A61P31/14Antivirals for RNA viruses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/37Extraction at elevated pressure or temperature, e.g. pressurized solvent extraction [PSE], supercritical carbon dioxide extraction or subcritical water extraction
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
    • YGENERAL 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
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Claims (30)

1. Способ лечения вирусной инфекции, вызываемой филовирусом, эболавирусом или марбургвирусом, у субъекта, нуждающегося в этом, включающий введение субъекту одной или нескольких доз противовирусной композиции, содержащей комбинацию олеандрина и по меньшей мере двух тритерпенов, выбранных из группы, состоящей из олеаноловой кислоты (ее свободной кислоты, соли или пролекарственного средства), урсоловой кислоты (ее свободной кислоты, соли или пролекарственного средства) и бетулиновой кислоты (ее свободной кислоты, соли или пролекарственного средства). 1. A method of treating a viral infection caused by filovirus, ebolavirus or marburgvirus in a subject in need thereof, comprising administering to the subject one or more doses of an antiviral composition containing a combination of oleandrin and at least two triterpenes selected from the group consisting of oleanolic acid ( its free acid, salt or prodrug), ursolic acid (its free acid, salt or prodrug) and betulinic acid (its free acid, salt or prodrug). 2. Способ лечения вирусной инфекции, вызываемой эболавирусом, у субъекта, нуждающегося в этом, при этом указанный способ включает:2. A method of treating a viral infection caused by ebolavirus in a subject in need thereof, said method comprising: определение наличия или отсутствия у указанного субъекта вирусной инфекции; назначение введения противовирусной композиции, содержащей олеандрин и по меньшей мере два тритерпена, выбранных из группы, состоящей из олеаноловой кислоты (ее свободной кислоты, соли или пролекарственного средства), урсоловой кислоты (ее свободной кислоты, соли или пролекарственного средства) и бетулиновой кислоты (ее свободной кислоты, соли или пролекарственного средства); введение начальной дозы противовирусной композиции субъекту в соответствии с назначенным режимом введения начальной дозы в течение периода времени; периодическое определение адекватности клинического ответа субъекта и/или терапевтического ответа на лечение указанной противовирусной композицией; и, если клинический ответ и/или терапевтический ответ субъекта является адекватным, тогда продолжение лечения указанной противовирусной композицией по мере необходимости до достижения необходимого клинического результата; или, если клинический ответ и/или терапевтический ответ субъекта не является адекватным при указанной начальной дозе и начальном режиме введения, то увеличение или уменьшение указанной дозы до достижения необходимого клинического ответа и/или терапевтического ответа у субъекта. determining the presence or absence of a viral infection in the specified subject; the purpose of the administration of an antiviral composition containing oleandrin and at least two triterpenes selected from the group consisting of oleanolic acid (its free acid, salt or prodrug), ursolic acid (its free acid, salt or prodrug) and betulinic acid (its free acid, salt or prodrug); administering an initial dose of an antiviral composition to a subject in accordance with a designated initial dose regimen over a period of time; periodically determining the adequacy of the clinical response of the subject and / or therapeutic response to treatment with the specified antiviral composition; and, if the clinical response and / or therapeutic response of the subject is adequate, then continuing treatment with the specified antiviral composition as needed until the desired clinical result is achieved; or, if the clinical response and / or therapeutic response of the subject is not adequate at the specified initial dose and the initial mode of administration, then increase or decrease the specified dose until the desired clinical response and / or therapeutic response in the subject is achieved. 3. Способ по п. 1, отличающийся тем, что указанная противовирусная композиция содержит олеандрин, олеаноловую кислоту (ее свободную кислоту, соль или пролекарственное средство) и урсоловую кислоту (ее свободную кислоту, соль или пролекарственное средство).3. The method according to claim 1, wherein said antiviral composition comprises oleandrin, oleanolic acid (its free acid, salt or prodrug) and ursolic acid (its free acid, salt or prodrug). 4. Способ по п. 1, отличающийся тем, что указанная противовирусная композиция содержит олеандрин, олеаноловую кислоту (ее свободную кислоту, соль или пролекарственное средство) и бетулиновую кислоту (ее свободную кислоту, соль или пролекарственное средство).4. The method according to claim 1, wherein said antiviral composition comprises oleandrin, oleanolic acid (its free acid, salt or prodrug) and betulinic acid (its free acid, salt or prodrug). 5. Способ по любому из пп. 1-5, отличающийся тем, что указанная противовирусная композиция содержит олеандрин, олеаноловую кислоту (ее свободную кислоту, соль или пролекарственное средство), урсоловую кислоту (ее свободную кислоту, соль или пролекарственное средство) и бетулиновую кислоту (ее свободную кислоту, соль или пролекарственное средство).5. The method according to any one of claims. 1-5, characterized in that said antiviral composition contains oleandrin, oleanolic acid (its free acid, salt or prodrug), ursolic acid (its free acid, salt or prodrug) and betulinic acid (its free acid, salt or prodrug) means). 6. Способ по п.1, отличающийся тем, что титр указанного вируса в крови или плазме крови субъекта уменьшается или не увеличивается в результате лечения.6. The method according to claim 1, wherein the titer of said virus in the blood or plasma of the subject decreases or does not increase as a result of the treatment. 7. Способ по п.1, отличающийся тем, что одну или несколько доз вводят ежедневно, еженедельно или ежемесячно.7. The method of claim 1, wherein one or more doses are administered daily, weekly or monthly. 8. Способ по п.1, отличающийся тем, что указанное введение представляет собой парентеральное, буккальное, энтеральное, внутримышечное, подкожное, сублингвальное, пероральное, оральное введение или их комбинацию.8. The method of claim 1, wherein said administration is parenteral, buccal, enteral, intramuscular, subcutaneous, sublingual, oral, oral, or a combination thereof. 9. Способ по п.1, отличающийся тем, что олеандрин присутствует в чистом виде или как часть экстракта.9. The method according to claim 1, characterized in that the oleandrin is present in pure form or as part of the extract. 10. Способ лечения эболавирусной инфекции у субъекта, нуждающегося в этом, способ включает введение субъекту одной или нескольких доз противовирусной композиции, содержащей олеандрин.10. A method of treating an ebolavirus infection in a subject in need thereof, the method comprises administering to the subject one or more doses of an antiviral composition containing oleandrin. 11. Способ по п. 2, отличающийся тем, что указанная противовирусная композиция содержит олеандрин, олеаноловую кислоту (ее свободную кислоту, соль или пролекарственное средство) и урсоловую кислоту (ее свободную кислоту, соль или пролекарственное средство).11. The method according to claim 2, wherein said antiviral composition comprises oleandrin, oleanolic acid (its free acid, salt or prodrug) and ursolic acid (its free acid, salt or prodrug). 12. Способ по п. 2, отличающийся тем, что указанная противовирусная композиция содержит олеандрин, олеаноловую кислоту (ее свободную кислоту, соль или пролекарственное средство) и бетулиновую кислоту (ее свободную кислоту, соль или пролекарственное средство).12. The method according to claim 2, wherein said antiviral composition comprises oleandrin, oleanolic acid (its free acid, salt or prodrug) and betulinic acid (its free acid, salt or prodrug). 13. Способ по п. 2, отличающийся тем, что указанная противовирусная композиция содержит олеаноловую кислоту (ее свободную кислоту, соль или пролекарственное средство), урсоловую кислоту (ее свободную кислоту, соль или пролекарственное средство) и бетулиновую кислоту (ее свободную кислоту, соль или пролекарственное средство).13. The method according to claim 2, characterized in that said antiviral composition contains oleanolic acid (its free acid, salt or prodrug), ursolic acid (its free acid, salt or prodrug) and betulinic acid (its free acid, salt or a prodrug). 14. Способ по п.1, в котором доза составляет примерно 100-1000 мг или примерно 100-1000 мкг противовирусной композиции на кг веса тела указанного субъекта.14. The method of claim 1, wherein the dose is about 100-1000 mg or about 100-1000 μg of the antiviral composition per kg of body weight of said subject. 15. Способ по п.1, в котором количество олеандрина, как части указанной комбинации, вводимое в сутки, выбрано из группы, состоящей из от 140 мкг до 315 мкг, от 20 мкг до 750 мкг, от 12 мкг до 300 мкг, 12 мкг до 120 мкг, от 0,01 мкг до 100 мг, от 0,01 мкг до 100 мкг, от примерно 0,5 до примерно 100 мкг, от примерно 1 до примерно 80 мкг, от примерно 1,5 до примерно 60 мкг, от примерно 1,8 до примерно 60 мкг или от примерно 1,8 до примерно 40 мкг.15. The method of claim 1, wherein the amount of oleandrin administered per day as part of said combination is selected from the group consisting of 140 μg to 315 μg, 20 μg to 750 μg, 12 μg to 300 μg, 12 mcg to 120 mcg, 0.01 mcg to 100 mg, 0.01 mcg to 100 mcg, about 0.5 to about 100 mcg, about 1 to about 80 mcg, about 1.5 to about 60 mcg , from about 1.8 to about 60 μg, or from about 1.8 to about 40 μg. 16. Способ по п.1, в котором дозу указанной противовирусной композиции вводят дважды в день или примерно каждые 12 часов, а количество олеандрина в указанной дозе составляет от примерно 0,25 до примерно 50 мкг или от примерно 0,9 до 5 мкг.16. The method of claim 1, wherein the dose of said antiviral composition is administered twice a day, or about every 12 hours, and the amount of oleandrin in said dose is from about 0.25 to about 50 μg, or from about 0.9 to 5 μg. 17. Способ по п.1, в котором указанная одна или несколько доз указанной противовирусной композиции составляют примерно 0,05-0,5 мг/кг/день, примерно 0,05-0,35 мг/кг/день, примерно 0,05-0,22 мг/кг/день, примерно 0,05-0,4 мг/кг/день, примерно 0,05-0,3 мг/кг/день, примерно 0,05-0,5 мкг/кг/день, примерно 0,05-0,35 мкг/кг/день, примерно 0,05-0,22 мкг/кг/день, примерно 0,05-0,4 мкг/кг/день или примерно 0,05-0,3 мкг/кг/день из расчета количества единиц противовирусной композиции на кг веса тела субъекта в сутки.17. The method of claim 1, wherein said one or more doses of said antiviral composition are about 0.05-0.5 mg / kg / day, about 0.05-0.35 mg / kg / day, about 0, 05-0.22 mg / kg / day, about 0.05-0.4 mg / kg / day, about 0.05-0.3 mg / kg / day, about 0.05-0.5 mcg / kg / day, about 0.05-0.35 mcg / kg / day, about 0.05-0.22 mcg / kg / day, about 0.05-0.4 mcg / kg / day, or about 0.05- 0.3 μg / kg / day based on the number of units of antiviral composition per kg of body weight of the subject per day. 18. Способ по п.1, в котором указанная одна или несколько доз противовирусной композиции и молярное отношение олеандрина к указанным по меньшей мере двум тритерпенам выбирают из любого из следующего18. The method according to claim 1, wherein said one or more doses of antiviral composition and the molar ratio of oleandrin to said at least two triterpenes is selected from any of the following Антивирусная композицияAntivirus composition Олеандрин (моли)Oleandrin (moth) Олеаноловая кислота
(моли)
Oleanolic acid
(moths)
Урсоловая кислота (моли)Ursolic acid (moles) Бетулиновая кислота (моли)Betulinic acid (moles) Подходящая дозаSuitable dose
BB 0.5-1.50.5-1.5 4-64-6 4-64-6 -- от 0.05 до 0.35 мкг/кг/день 0.05 to 0.35 μg / kg / day C C 0.5-1.50.5-1.5 4-64-6 4-64-6 0.1-10.1-1 от 0.05 до 0.22 мкг/кг/день 0.05 to 0.22 μg / kg / day ACAC Около 1About 1 Около 4.7About 4.7 Около 4.5About 4.5 -- от 0.05 до 0.4 мкг/кг/день 0.05 to 0.4 μg / kg / day AD AD Около 1About 1 Около 4.7About 4.7 Около 4.5About 4.5 Около 0.6About 0.6 от 0.05 до 0.22 мкг/кг/день 0.05 to 0.22 μg / kg / day ....
19. Способ по п.1, в котором молярное отношение общего содержания тритерпена (олеаноловая кислота + урсоловая кислота + бетулиновая кислота) к олеандрину составляет от примерно 15:1 до примерно 5:1, или от примерно 12:1 до примерно 8:1, или от примерно 100: 1 до примерно 15:1, или от примерно 100:1 до примерно 50:1, или от примерно 100:1 до примерно 75:1, или от примерно 100:1 до примерно 80:1, или примерно 100:1 примерно до 90:1 или примерно до 10:1.19. The method of claim 1, wherein the molar ratio of total triterpene (oleanolic acid + ursolic acid + betulinic acid) to oleandrin is from about 15: 1 to about 5: 1, or from about 12: 1 to about 8: 1 , or from about 100: 1 to about 15: 1, or from about 100: 1 to about 50: 1, or from about 100: 1 to about 75: 1, or from about 100: 1 to about 80: 1, or about 100: 1 to about 90: 1 or about 10: 1. 20. Способ по п.1, в котором молярные отношения отдельных тритерпенов (олеаноловая кислота (OA):урсоловая кислота (UA):бетулиновая кислота (BA)) к олеандрину (OL) находятся в следующем диапазоне:2-8 (OA):2-8 (UA):0,1-1 (BA):0,5-1,5 (OL); или 3-6 (OA):3-6 (UA):0,3-8 (BA):0,7-1,2 (OL); или 4-5 (OA):4-5 (UA):0,4-0,7 (BA):0,9-1,1 (OL); 4,6 (OA):4,4 (UA):0,6 (BA):1 (OL); примерно 9-12 (ОА):примерно до 2 (UA):примерно до 2 или примерно 10 (OA):примерно 1 (UA):примерно 1 или примерно 9-12 (OA):примерно 0,1-2 (UA):примерно 0,1-2 (BA) или примерно 9-11 (OA):примерно 0,5-1,5 (UA):примерно 0,5-1,5 (BA) или примерно 9,5-10,5 (OA):примерно 0,75-1,25 (UA):около 0,75-1,25 (BA) или около 9,5-10,5 (OA):около 0,8-1,2 (UA):около 0,8-1,2 (BA) или около 9,75-10,5 (OA):около 0,9-1,1 (UA):около 0,9-1,1 (BA).20. The method of claim 1, wherein the molar ratios of the individual triterpenes (oleanolic acid (OA): ursolic acid (UA): betulinic acid (BA)) to oleandrin (OL) are in the following range: 2-8 (OA): 2-8 (UA): 0.1-1 (BA): 0.5-1.5 (OL); or 3-6 (OA): 3-6 (UA): 0.3-8 (BA): 0.7-1.2 (OL); or 4-5 (OA): 4-5 (UA): 0.4-0.7 (BA): 0.9-1.1 (OL); 4.6 (OA): 4.4 (UA): 0.6 (BA): 1 (OL); about 9-12 (OA): about 2 (UA): about 2 or about 10 (OA): about 1 (UA): about 1 or about 9-12 (OA): about 0.1-2 (UA) ): about 0.1-2 (BA) or about 9-11 (OA): about 0.5-1.5 (UA): about 0.5-1.5 (BA) or about 9.5-10 .5 (OA): about 0.75-1.25 (UA): about 0.75-1.25 (BA) or about 9.5-10.5 (OA): about 0.8-1.2 (UA): about 0.8-1.2 (BA) or about 9.75-10.5 (OA): about 0.9-1.1 (UA): about 0.9-1.1 (BA ). 21. Способ по п.1, в котором указанная противовирусная композиция содержит экстракт растительного материала видов Nerium или видов Thevetia.21. The method according to claim 1, wherein said antiviral composition comprises an extract of plant material of Nerium spp. Or Thevetia spp. 22. Способ по п.21, в котором указанный экстракт дополнительно содержит один или несколько предшественников сердечных гликозидов, один или несколько гликоновых компонентов сердечных гликозидов или их комбинацию.22. The method of claim 21, wherein said extract further comprises one or more precursors of cardiac glycosides, one or more glyconic components of cardiac glycosides, or a combination thereof. 23. Способ по п.21, в котором суточная доза указанного экстракта составляет максимум примерно 100 мкг/день, примерно 80 мкг/день, примерно 60 мкг/день, примерно 40 мкг/день, примерно 38,4 мкг/день или около 30 мкг/день экстракта олеандра, содержащего олеандрин.23. The method of claim 21, wherein the daily dose of said extract is a maximum of about 100 mcg / day, about 80 mcg / day, about 60 mcg / day, about 40 mcg / day, about 38.4 mcg / day, or about 30 μg / day oleander extract containing oleandrin. 24. Способ по п.21, в котором суточная доза указанного экстракта составляет минимум примерно 0,5 мкг/день, примерно 1 мкг/день, примерно 1,5 мкг/день, примерно 1,8 мкг/день, примерно 2 мкг/день, или около 5 мкг/день.24. The method of claim 21, wherein the daily dose of said extract is at least about 0.5 μg / day, about 1 μg / day, about 1.5 μg / day, about 1.8 μg / day, about 2 μg / day, or about 5 mcg / day. 25. Способ по п.1, в котором после введения указанной одной или нескольких доз концентрация олеандрина в плазме у указанного субъекта находится в диапазоне от примерно 0,05 до примерно 2 нг/мл, от примерно 0,005 до примерно 10 нг/мл, примерно от 0,005 до примерно 8 нг/мл, от примерно 0,01 до примерно 7 нг/мл, от примерно 0,02 до примерно 7 нг/мл, от примерно 0,03 до примерно 6 нг/мл, от примерно 0,04 до примерно 5 нг/мл или от примерно 0,05 до примерно 2,5 нг/мл в пересчете на количество олеандрина на мл плазмы.25. The method of claim 1, wherein after administration of said one or more doses, the plasma concentration of oleandrin in said subject ranges from about 0.05 to about 2 ng / ml, from about 0.005 to about 10 ng / ml, about 0.005 to about 8 ng / ml, about 0.01 to about 7 ng / ml, about 0.02 to about 7 ng / ml, about 0.03 to about 6 ng / ml, about 0.04 to about 5 ng / ml; or from about 0.05 to about 2.5 ng / ml, based on the amount of oleandrin per ml of plasma. 26. Способ по п.1, в котором указанную противовирусную композицию вводят в качестве первичной противовирусной терапии, дополнительной противовирусной терапии или совместной противовирусной терапии.26. The method of claim 1, wherein said antiviral composition is administered as primary antiviral therapy, adjunctive antiviral therapy, or antiviral co-therapy. 27. Способ по п.26, где указанное введение включает отдельное введение или совместное введение указанной противовирусной композиции по меньшей мере с одной другой противовирусной композицией или по меньшей мере с одной другой композицией для лечения симптомов, связанных с указанной вирусной инфекцией.27. The method of claim 26, wherein said administration comprises separately administering or co-administering said antiviral composition with at least one other antiviral composition or at least one other composition for treating symptoms associated with said viral infection. 28. Способ по п.27, где указанные симптомы выбраны из группы, состоящей из воспаления, рвоты, тошноты, головной боли, лихорадки, диареи, тошноты, крапивницы, конъюнктивита, недомогания, мышечной боли, боли в суставах, судорог и паралича.28. The method of claim 27, wherein said symptoms are selected from the group consisting of inflammation, vomiting, nausea, headache, fever, diarrhea, nausea, urticaria, conjunctivitis, malaise, muscle pain, joint pain, seizures, and paralysis.
RU2020113341A 2017-09-14 2018-07-16 METHOD AND COMPOSITION FOR VIRAL INFECTION TREATMENT RU2020113341A (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
PCT/US2017/051553 WO2018053123A1 (en) 2016-09-14 2017-09-14 Method and compositions for treating viral infection
USPCT/US2017/051553 2017-09-14
US201862698365P 2018-07-16 2018-07-16
US62/698,365 2018-07-16
PCT/US2018/042226 WO2019055119A1 (en) 2017-09-14 2018-07-16 Method and composition for treating viral infection

Publications (2)

Publication Number Publication Date
RU2020113341A true RU2020113341A (en) 2021-10-15
RU2020113341A3 RU2020113341A3 (en) 2021-10-15

Family

ID=65723839

Family Applications (1)

Application Number Title Priority Date Filing Date
RU2020113341A RU2020113341A (en) 2017-09-14 2018-07-16 METHOD AND COMPOSITION FOR VIRAL INFECTION TREATMENT

Country Status (9)

Country Link
EP (1) EP3681508A4 (en)
JP (3) JP6820450B2 (en)
KR (2) KR102295179B1 (en)
AU (2) AU2018334386B2 (en)
CA (1) CA3075729A1 (en)
IL (2) IL285232B (en)
MX (1) MX2020002883A (en)
RU (1) RU2020113341A (en)
WO (1) WO2019055119A1 (en)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112689510B (en) * 2020-03-31 2022-02-01 菲尼克斯生物技术公司 Methods and compositions for treating coronavirus infection
KR20220151038A (en) * 2020-03-31 2022-11-11 피닉스 바이오테크놀러지 인코포레이티드. Compositions for preventing coronavirus infection
US11806359B2 (en) 2020-03-31 2023-11-07 Phoenix Biotechnology, Inc. Method and compositions for treating Coronavirus infection
EP4009981B1 (en) 2020-03-31 2023-08-16 Phoenix Biotechnology, Inc. Method and compositions for treating coronavirus infection
FR3109297A1 (en) * 2020-04-19 2021-10-22 Ephyla "New non-protein furin inhibitor"
WO2022094816A1 (en) * 2020-11-04 2022-05-12 Janssen Pharmaceuticals, Inc. Solid formulation

Family Cites Families (62)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PT84857B (en) 1986-05-13 1990-02-08 Huseyin Ziya Ozel PROCESS FOR THE PREPARATION OF EXTRACTS OF NERIUM SPECIES AND PHARMACEUTICAL COMPOSITIONS THAT CONTAIN THEM
US5236132A (en) 1992-01-03 1993-08-17 Vortec, Inc. Gradient-force comminuter/dehydrator apparatus and method
US5598979A (en) 1995-04-20 1997-02-04 Vortec, Inc. Closed loop gradient force comminuting and dehydrating system
CA2191923C (en) 1996-12-03 2000-10-24 Ji-Won Yoon Portulaca oleracea and tumor cell growth
DK1079824T3 (en) 1998-05-19 2011-11-21 Res Dev Foundation Triterpene compositions and methods for their use
JP2002526452A (en) 1998-09-24 2002-08-20 オゼル・ファーマスーティカルズ・インコーポレイテッド Oleander extract, its pharmaceutical composition and its preparation method
US6517015B2 (en) 2000-03-21 2003-02-11 Frank F. Rowley, Jr. Two-stage comminuting and dehydrating system and method
NZ524087A (en) 2000-08-18 2004-08-27 Univ Illinois Prodrugs of betulinic acid derivatives for the treatment of cancer and HIV
US9931316B2 (en) * 2004-01-06 2018-04-03 Paul Edward Stamets Antiviral activity from medicinal mushrooms and their active constituents
US6715705B2 (en) 2001-03-16 2004-04-06 Frank F. Rowley, Jr. Two-stage comminuting and dehydrating system and method
ATE295087T1 (en) 2001-04-09 2005-05-15 Loders Croklaan Bv CONCENTRATE OF TRITERPENES
CA2446748C (en) 2001-05-11 2011-03-08 University Of Ottawa Anxiolytic marcgraviaceae compositions containing betulinic acid, betulinic acid derivatives, and methods
US20040082521A1 (en) 2002-03-29 2004-04-29 Azaya Therapeutics Inc. Novel formulations of digitalis glycosides for treating cell-proliferative and other diseases
WO2003099011A1 (en) * 2002-05-28 2003-12-04 Henry M. Jackson Foundation For The Advancement Of Military Medicine, Inc. Cardiac glycosides to treat cystic fibrosis and other il-8 dependent disorders
US7179484B2 (en) 2002-11-06 2007-02-20 Azaya Therapeutics, Inc. Protein-stabilized liposomal formulations of pharmaceutical agents
US20050026849A1 (en) 2003-03-28 2005-02-03 Singh Chandra U. Water soluble formulations of digitalis glycosides for treating cell-proliferative and other diseases
WO2005090380A1 (en) 2004-03-17 2005-09-29 Panacos Pharmaceuticals, Inc. Pharmaceuticals salts of 3-o-(3',3'-dimethylsuccinyl) betulinic acid
US7118508B2 (en) 2004-07-28 2006-10-10 General Motors Corporation Planetary transmissions having three interconnected gear members and clutched input members
CA2597300C (en) 2005-02-09 2012-11-27 Rama Mukherjee Novel betulinic acid derivatives
WO2006105354A1 (en) 2005-03-29 2006-10-05 Regents Of The University Of Minnesota Selective oxidation of triterpenes employing tempo
US20060252733A1 (en) 2005-04-07 2006-11-09 Novelix Pharmaceuticals, Inc. Betulin, betulin derivatives, betulinic acid and betulinic acid derivatives as novel therapeutics in the treatment of disease of lipid and/or glucose metabolism
US20090131714A1 (en) 2005-06-08 2009-05-21 Krasutsky Pavel A Synthesis of betulonic and betulinic aldehydes
CA2611435C (en) 2005-06-10 2013-01-08 Pola Chemical Industries Inc. Novel triterpenic acid derivative and preparation for external application for skin comprising the same
US7402325B2 (en) 2005-07-28 2008-07-22 Phoenix Biotechnology, Inc. Supercritical carbon dioxide extract of pharmacologically active components from Nerium oleander
ZA200805703B (en) 2005-12-16 2009-10-28 Panacos Pharmaceuticals Inc Preparation of pharmaceutical salts of 3-0-(3',3'-dimethyl-succinyl) betulinic acid
EP1803461A1 (en) * 2005-12-27 2007-07-04 Heinz-Herbert Fiebig Therapeutic use of an extract from the leaves of Nerium oleander
GB0604535D0 (en) 2006-03-07 2006-04-12 Sndv Sprl Betulonic acid derivatives
WO2008063318A2 (en) 2006-10-12 2008-05-29 The Texas A & M University System And Safe Et Al Betulinic acid, derivatives and analogs thereof and uses therefor
WO2008057420A2 (en) 2006-11-03 2008-05-15 Panacos Pharmaceuticals, Inc. Extended triterpene derivatives
WO2008091532A1 (en) 2007-01-19 2008-07-31 Panacos Pharmaceuticals, Inc. Salts of 3-o-(3',3'-dimethylsuccinyl)betulinic acid and solid state forms thereof
US8987212B2 (en) 2007-08-07 2015-03-24 Muhammed Majeed Oleanoyl peptide composition and method of treating skin aging
MX2010005081A (en) 2007-11-13 2010-06-23 Phoenix Biotechnology Inc Method of determining the probability of a therapeutic response in cancer chemotherapy with cardiac glycoside.
TWI442925B (en) 2008-04-18 2014-07-01 Reata Pharmaceuticals Inc Antioxidant inflammation modulators: oleanolic acid derivatives with saturation in the c-ring
SI2276493T1 (en) 2008-04-18 2019-04-30 Reata Pharmaceuticals, Inc. Antioxidant inflammation modulators: oleanolic acid derivatives with amino and other modifications at c-17
BRPI0911422B8 (en) 2008-04-18 2021-05-25 Reata Pharmaceuticals Inc inflammatory antioxidant modulating compounds, pharmaceutical composition and their uses
US8071632B2 (en) 2008-04-18 2011-12-06 Reata Pharmaceuticals, Inc. Antioxidant inflammation modulators: novel derivatives of oleanolic acid
EP2340257A4 (en) 2008-09-10 2012-09-26 Univ Quebec A Chicoutimi Bidesmosidic betulin and betulinic acid derivatives and uses thereof as antitumor agents
US8778990B2 (en) 2008-11-04 2014-07-15 Trustees Of Dartmouth College Betulinic acid derivatives and methods of use thereof
US8802727B2 (en) 2009-07-14 2014-08-12 Hetero Research Foundation, Hetero Drugs Limited Pharmaceutically acceptable salts of betulinic acid derivatives
CN101704872B (en) 2009-11-23 2012-06-27 张南 23-hydroxybetulinic acid derivatives as well as preparation methods and application thereof
US8685469B2 (en) 2009-11-30 2014-04-01 University Of Kwazulu-Natal In vitro anti-sickling activity of betulinic acid, oleanolic acid and their derivatives
US9011937B2 (en) 2010-11-22 2015-04-21 Phoenix Biotechnology, Inc. Method of treating neurological conditions with extract of Nerium species or Thevetia species
KR101811462B1 (en) 2010-01-11 2018-01-25 피닉스 바이오테크놀러지 인코포레이티드. Composition treating neurological conditions comprising nerium oleander
TWI386415B (en) 2010-02-02 2013-02-21 Univ Kaohsiung Medical Ursolic acid derivative and pharmaceutical composition thereof
TWI410431B (en) 2010-12-22 2013-10-01 Ind Tech Res Inst Use of oleanolic acid derivatives in the manufacture of a medicament to prevent or treat hepatitis c
US20140221328A1 (en) 2011-01-10 2014-08-07 Bandi Parthasaradhi Reddy Pharmaceutically acceptable salts of novel betulinic acid derivatives
ES2552512T3 (en) 2011-01-31 2015-11-30 Bristol-Myers Squibb Company C-28 amines of C-3 modified betulinic acid derivatives as inhibitors of human immunodeficiency virus maturation
CN102558280B (en) 2011-11-18 2014-09-17 温州大学 Method for producing 30-halogenated betulinic acid
WO2013079024A1 (en) 2011-12-01 2013-06-06 杭州本生药业有限公司 Oleanolic acid amidate derivatives, preparation methods and uses thereof
NO2786757T3 (en) 2011-12-01 2018-01-13
US20150119373A1 (en) 2012-04-24 2015-04-30 Hetero Research Foundation Novel betulinic acid derivatives as hiv inhibitors
US8921419B2 (en) 2012-05-08 2014-12-30 Trustees Of Dartmouth College Triterpenoids and compositions containing the same
CN104684883A (en) 2012-08-14 2015-06-03 内克索利戈有限公司 Novel ursolic acid derivative and method for preparing same
WO2014040073A1 (en) 2012-09-10 2014-03-13 Reata Pharmaceuticals, Inc. C13-hydroxy derivatives of oleanolic acid and methods of use thereof
NZ705213A (en) 2012-09-10 2018-07-27 Reata Pharmaceuticals Inc C17-heteroaryl derivatives of oleanolic acid and methods of use thereof
ES2731758T3 (en) 2012-09-10 2019-11-18 Reata Pharmaceuticals Inc C17 alkanediyl and alkenodiyl derivatives of oleanolic acid and methods of use thereof
US9637516B2 (en) 2012-12-31 2017-05-02 Hetero Research Foundation Betulinic acid proline derivatives as HIV inhibitors
EA027861B1 (en) 2013-02-25 2017-09-29 Бристол-Майерс Сквибб Компани C-3 alkyl and alkenyl modified betulinic acid derivatives or pharmaceutical salts thereof, antiviral pharmaceutical composition and pharmaceutical composition for the treatment of hiv based thereon
WO2015121168A1 (en) * 2014-02-12 2015-08-20 Organobalance Gmbh Yeast strain and microbial method for production of pentacyclic triterpenes and/or triterpenoids
WO2015195776A1 (en) 2014-06-19 2015-12-23 Bristol-Myers Squibb Company Betulinic acid derivatives with hiv maturation inhibitory activity
US9492438B2 (en) * 2014-07-25 2016-11-15 Bette Pollard Amphiphilic pyridinum compounds to treat epilepsy and other disorders of the nervous system
CN108348469A (en) * 2015-06-08 2018-07-31 德马克有限责任公司 Therapeutic composition

Also Published As

Publication number Publication date
JP2022075755A (en) 2022-05-18
JP7037673B2 (en) 2022-03-16
KR20210107904A (en) 2021-09-01
AU2018334386A1 (en) 2020-04-02
JP2021063105A (en) 2021-04-22
IL285232B (en) 2022-07-01
IL285232A (en) 2021-09-30
RU2020113341A3 (en) 2021-10-15
IL273162B (en) 2021-08-31
JP2020534293A (en) 2020-11-26
KR20200081356A (en) 2020-07-07
EP3681508A4 (en) 2021-05-19
AU2020204236B2 (en) 2020-12-10
KR102295179B1 (en) 2021-08-30
AU2018334386B2 (en) 2021-11-04
CA3075729A1 (en) 2019-03-21
IL273162A (en) 2020-04-30
JP6820450B2 (en) 2021-01-27
WO2019055119A1 (en) 2019-03-21
AU2020204236A1 (en) 2020-07-16
EP3681508A1 (en) 2020-07-22
MX2020002883A (en) 2020-10-05

Similar Documents

Publication Publication Date Title
RU2020113341A (en) METHOD AND COMPOSITION FOR VIRAL INFECTION TREATMENT
RU2010101892A (en) HYALURONIDASE AND METHOD OF ITS USE
MD4430B1 (en) Compositions and methods for treating hepatitis C virus
RU2009142940A (en) TAPENTADOL TITRATION
JP2010525050A5 (en)
HRP20192189T1 (en) Dosage forms and therapeutic uses l-4-chlorokynurenine
NZ598465A (en) Dosage regimens for hcv combination therapy comprising bi201335, interferon alpha and ribavirin
US11911467B2 (en) Composition comprising PIC for treatment of cancer
MX2022006742A (en) Use and pharmaceutical composition of phenylisoxazolyl methylene-naphthalene-ether derivatives.
RU2007103306A (en) COMPOSITIONS ON THE BASIS OF RIZEDRONATE AND WAYS OF THEIR APPLICATION
RU2017127509A (en) COMPOSITIONS AND METHODS FOR IMPROVED MUSCLE METABOLISM
JP2016505050A5 (en)
CA2491296A1 (en) Methods for treating psychosis associated with interferon-.alpha. therapy
WO2007129290A1 (en) Statins for the treatment of viral influenza infections
CA2435921A1 (en) Method of cancer therapy
EP3017816B1 (en) Diindolylmethane-based medicinal agent and use thereof to treat influenza and viral respiratory infections
RU2013120345A (en) NEW METHODS FOR TREATING INFECTIONS CAUSED BY HEPATITIS C VIRUS
CN111514290B (en) Cucurbitacin composition and application thereof
EP2595627A1 (en) Use of uleine for the prevention and/or the treatment of infectious diseases
JPWO2020202111A5 (en)
ES2806449T3 (en) Antitumor drug containing taxane compound and antitumor effect enhancer
CN113827604B (en) Application of adefovir in preparing medicine for treating tumor or resisting tumor metastasis
MD4177C1 (en) Method for vaccination against hepatitis B of persons with immunodeficiency
RU2013148539A (en) ALISPORIVIR FOR TREATMENT OF HEPATITIS C VIRUS INFECTION
US20220160741A1 (en) Method and Compositions for Treating Coronavirus Infection