Liponucleotide-containing liposomes

Details Liponucleotide-containing liposomes Liponucleotide-containing liposomes

1989-06-28

1993-06-29

Brown, Johnnie R.

Drug, bio-affecting and body treating compositions

Preparations characterized by special physical form

Liposomes

514 45, 514 49, 514 50, 514 51, 544276, 544277, 536 267, 536 268, 536 269, 536 2623, 536 265, 536 2671, A61K 3722, C07H 1906, C07H 1910, C07H 1916

Patent

active

052232638

ABSTRACT:
Compounds are disclosed for treating AIDS, herpes, and other viral infections by means of lipid derivatives of antiviral agents. The compounds consist of nucleoside analogues having antiviral activity which are linked, commonly through a phosphate group at the 5' position of the pentose residue, to one of a selected group of lipids. The lipophilic nature of these compounds provide advantages over the use of the nucleoside analogue alone. It also makes it possible to incorporate them into the lamellar structure of liposomes, either alone or combined with similar molecules. In the form of liposomes, these antiviral agents are preferentially taken up by macrophages and monocytes, cells which have been found to harbor the target HIV virus. Additional site specificity may be incorporated into the liposomes with the addition of ligands, such as monoclonal antibodies or other peptides or proteins which bind to viral proteins. Effective nucleoside analogues are dideoxynucleosides, azidothymine (AZT), and acyclovir; lipid groups may be glycolipids, sphingolipids, phospholipids or fatty acids. The compounds persist, after intracellular hydrolysis, as phosphorylated or non-phosphorylated antiviral nucleosides. The compounds are effective in improving the efficacy of antiviral nucleoside analogues by prolonging the antiviral activity after the administration of the drug has ended, and in preventing retroviral replication in HIV infections which have become resistant to therapy with conventional forms of the antiretroviral agents.

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