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RU2003102607A - METHODS FOR DELIVERY OF MEDICINE TO HEPATOCYTES AND TREATMENT OF FLAVIVIRUS INFECTIONS - Google Patents

METHODS FOR DELIVERY OF MEDICINE TO HEPATOCYTES AND TREATMENT OF FLAVIVIRUS INFECTIONS Download PDF

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Publication number
RU2003102607A
RU2003102607A RU2003102607/15A RU2003102607A RU2003102607A RU 2003102607 A RU2003102607 A RU 2003102607A RU 2003102607/15 A RU2003102607/15 A RU 2003102607/15A RU 2003102607 A RU2003102607 A RU 2003102607A RU 2003102607 A RU2003102607 A RU 2003102607A
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Russia
Prior art keywords
compound
hepatocyte
carrier
carboxamidine
group
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RU2003102607/15A
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Russian (ru)
Inventor
Джонсон ЛО (US)
Джонсон ЛО
Жи ХОНГ (US)
Жи ХОНГ
Original Assignee
Рибафарм Инк. (US)
Рибафарм Инк.
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Publication of RU2003102607A publication Critical patent/RU2003102607A/en

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    • 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
    • A61K31/7052Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/7056Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • 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
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • 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

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Virology (AREA)
  • Molecular Biology (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Saccharide Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)

Claims (24)

1. Способ доставки лекарства в гепатоцит, при котором берут соединение, имеющее карбоксамидиновую группу, которое обладает активностью, выбранной из группы, состоящей из противовирусной активности и противоопухолевой активности, устанавливают, что гепатоцит содержит переносчик, который транспортирует это соединение через плазматическую мембрану гепатоцита, причем транспорт этого соединения по существу не ингибируется рибавирином, и предоставляют указанному переносчику указанное соединение, причем переносчик представляет собой мембранносвязанный белок или белковый комплекс, который способствует проникновению этого соединения через плазматическую мембрану в гепатоцит.1. A method of delivering a drug to a hepatocyte in which a compound having a carboxamidine group that has an activity selected from the group consisting of antiviral activity and antitumor activity is taken, it is established that the hepatocyte contains a carrier that transports this compound through the plasma membrane of the hepatocyte, the transport of this compound is not substantially inhibited by ribavirin, and provide the indicated carrier with said compound, the carrier being a meme rannosvyazanny protein or protein complex that facilitates penetration of the compound through the plasma membrane into the hepatocyte. 2. Способ по п.1, где соединение включает в себя нуклеозид, имеющий основание, связанное с сахаром.2. The method according to claim 1, where the compound includes a nucleoside having a base associated with sugar. 3. Способ по п.2, где основание представляет собой моноциклическое основание.3. The method according to claim 2, where the base is a monocyclic base. 4. Способ по п.3, где моноциклическое основание представляет собой 1,2,4-триазол.4. The method according to claim 3, where the monocyclic base is a 1,2,4-triazole. 5. Способ по п.2, где сахар представляет собой β-рибофуранозу.5. The method according to claim 2, where the sugar is β-ribofuranose. 6. Способ по п.2, где нуклеозид представляет собой 1-бета-D-рибофуранозил-1,2,4-триазол-3-карбоксамидин.6. The method according to claim 2, where the nucleoside is 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamidine. 7. Способ по п.2, где нуклеозид представляет собой 1-бета-L-рибофуранозил-1,2,4-триазол-3-карбоксамидин.7. The method according to claim 2, where the nucleoside is 1-beta-L-ribofuranosyl-1,2,4-triazole-3-carboxamidine. 8. Способ по п.1, где карбоксамидиновая группа превращается в карбоксамидную группу в гепатоците.8. The method according to claim 1, where the carboxamidine group is converted into a carboxamide group in the hepatocyte. 9. Способ по п.8, где карбоксамидная группа претерпевает ферментативное фосфорилирование и посредством этого накапливается в гепатоците.9. The method of claim 8, wherein the carboxamide group undergoes enzymatic phosphorylation and thereby accumulates in the hepatocyte. 10. Способ по п.1, где противовирусная активность представляет собой противовирусную активность в отношении флавивирусов.10. The method according to claim 1, where the antiviral activity is an antiviral activity against flaviviruses. 11. Способ по п.10, где противовирусная активность в отношении флавивирусов представляет собой противовирусную активность в отношении пестивируса и вируса гепатита С.11. The method of claim 10, where the antiviral activity against flaviviruses is an antiviral activity against pestivirus and hepatitis C. 12. Способ по п.1, где противоопухолевая активность включает в себя противоопухолевую активность в отношении неопластических гепатоцитов.12. The method according to claim 1, where the antitumor activity includes antitumor activity against neoplastic hepatocytes. 13. Способ по п.1, где переносчик представляет собой АТФ-зависимый переносчик.13. The method according to claim 1, where the carrier is an ATP-dependent carrier. 14. Способ по п.1, где переносчик включает в себя трансмембранный белок.14. The method according to claim 1, where the carrier includes a transmembrane protein. 15. Способ по п.1, где гепатоцит поражен заболеванием.15. The method according to claim 1, where the hepatocyte is affected by the disease. 16. Способ по п.1, где транспорт соединения представляет собой транспорт, который ингибируется вторым соединением, имеющим карбоксамидиновую группу.16. The method according to claim 1, where the transport of the compound is a transport that is inhibited by the second compound having a carboxamidine group. 17. Способ ингибирования репликации вируса, принадлежащего к семейству флавивирусов, в системе, содержащей клетки, при котором берут фармацевтическую композицию, имеющую карбоксамидиновую группу, и предоставляют клетке в системе, содержащей клетки, эту фармацевтическую композицию, причем указанное соединение транспортируется через плазматическую мембрану клетки, при этом транспорт соединения по существу не ингибируется рибавирином, и причем переносчик представляет собой мембранносвязанный белок или белковый комплекс, который способствует проникновению этого соединения через плазматическую мембрану в гепатоцит.17. A method of inhibiting the replication of a virus belonging to the flavivirus family in a system containing cells, in which a pharmaceutical composition having a carboxamidine group is taken, and providing the cell in the system containing cells with this pharmaceutical composition, said compound being transported through the plasma membrane of the cell, wherein the transport of the compound is not substantially inhibited by ribavirin, and wherein the carrier is a membrane-bound protein or protein complex, which method prevents the penetration of this compound through the plasma membrane into the hepatocyte. 18. Способ по п.17, где вирус представляет собой вирус Западного Нила.18. The method according to 17, where the virus is a West Nile virus. 19. Способ по п.17, где вирус представляет собой вирус гепатита С.19. The method according to 17, where the virus is a hepatitis C. 20. Способ по п.17, где система, содержащая клетки, представляет собой систему in vitro.20. The method according to 17, where the system containing cells is an in vitro system. 21. Способ по п.17, где система, содержащая клетки, представляет собой систему in vivo.21. The method according to 17, where the system containing cells is an in vivo system. 22. Способ по п.17, где система in vivo имеет по меньшей мере один гепатоцит, который инфицирован вирусом.22. The method according to 17, where the in vivo system has at least one hepatocyte that is infected with a virus. 23. Способ по п.17, где фармацевтическое соединение представляет собой 1-бета-D-рибофуранозил-1,2,4-триазол-3-карбоксамидин-HCl.23. The method of claim 17, wherein the pharmaceutical compound is 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamidine-HCl. 24. Способ по п.17, где фармацевтическое соединение находится в L-конфигурации.24. The method according to 17, where the pharmaceutical compound is in the L-configuration.
RU2003102607/15A 2000-08-22 2001-08-21 METHODS FOR DELIVERY OF MEDICINE TO HEPATOCYTES AND TREATMENT OF FLAVIVIRUS INFECTIONS RU2003102607A (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US22686900P 2000-08-22 2000-08-22
US60/226,869 2000-08-22
US24062700P 2000-10-13 2000-10-13
US60/240,627 2000-10-13

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Country Link
EP (1) EP1313469A1 (en)
JP (1) JP2004506684A (en)
KR (1) KR20030040416A (en)
CN (1) CN1447692A (en)
AU (1) AU2001292557A1 (en)
BR (1) BR0113388A (en)
CA (1) CA2415793A1 (en)
CZ (1) CZ2003308A3 (en)
HU (1) HUP0302884A2 (en)
IL (1) IL154167A0 (en)
MX (1) MXPA03001529A (en)
NO (1) NO20030794L (en)
PL (1) PL365744A1 (en)
RU (1) RU2003102607A (en)
WO (1) WO2002015904A1 (en)

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WO2003037908A1 (en) * 2001-10-31 2003-05-08 Ribapharm Inc. Antiviral combination therapy and compositions
US6811777B2 (en) 2002-04-13 2004-11-02 Allan Mishra Compositions and minimally invasive methods for treating incomplete connective tissue repair
US7608258B2 (en) 2002-04-13 2009-10-27 Allan Mishra Method for treatment of tendinosis using platelet rich plasma
US20050182252A1 (en) 2004-02-13 2005-08-18 Reddy K. R. Novel 2'-C-methyl nucleoside derivatives
US20100112081A1 (en) 2008-10-07 2010-05-06 Bioparadox, Llc Use of platelet rich plasma composition in the treatment of cardiac conduction abnormalities
US20140356893A1 (en) 2013-06-04 2014-12-04 Allan Mishra Compositions and methods for using platelet-rich plasma for drug discovery, cell nuclear reprogramming, proliferation or differentiation
WO2015123352A1 (en) 2014-02-13 2015-08-20 Ligand Pharmaceuticals, Inc. Prodrug compounds and their uses
US9994600B2 (en) 2014-07-02 2018-06-12 Ligand Pharmaceuticals, Inc. Prodrug compounds and uses therof

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US3984396A (en) * 1971-06-01 1976-10-05 Icn Pharmaceuticals, Inc. 1-(β,-D-ribofuranosyl)-1,2,4-triazole acid esters
US5959077A (en) * 1993-05-26 1999-09-28 Laboratori Balducci S.P.A. Hepatotropic conjugates of antiviral drugs carriers thereof and pharmaceutical compositions containing them

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AU2001292557A1 (en) 2002-03-04
WO2002015904A1 (en) 2002-02-28
BR0113388A (en) 2004-02-25
WO2002015904B1 (en) 2002-07-04
EP1313469A1 (en) 2003-05-28
KR20030040416A (en) 2003-05-22
CN1447692A (en) 2003-10-08
IL154167A0 (en) 2003-07-31
NO20030794L (en) 2003-04-22
MXPA03001529A (en) 2004-04-02
JP2004506684A (en) 2004-03-04
CZ2003308A3 (en) 2004-03-17
NO20030794D0 (en) 2003-02-20
CA2415793A1 (en) 2002-02-28
HUP0302884A2 (en) 2003-12-29
PL365744A1 (en) 2005-01-10

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Effective date: 20050527