Abstract: A new class of neuramidase inhibitor prodrugs is provided characterized by a prodrug moiety of a carboxyl group modified to form a carbonyl ethoxy amino acid, a carbonyl ethoxy dipeptide or a carbonyl ethoxy tripeptide, a guanidine group modified to form a carbonyl ethoxy amino acid, a carbonyl ethoxy dipeptide, a carbonyl ethoxy tripeptide; a primary alcohol modified to form an esterified single amino acid, dipeptide or tripeptide of zanavimir of the unaltered therapeutic agent. Exemplary therapeutic agents so modified to form prodrugs include zanavimir, oseltamivir and peramivir. The prodrug has increased oral bioavailability relative to the unaltered neuraminidase inhibitor and is effective in the inhibition of viral infections involving neuraminidase in the viral reproductive cycle.

Abstract: Disclosed are neuraminidase inhibitor compounds and pharmaceutical compositions with improved bioavailability and/or improved efficacy and methods of treating influenza using the compounds and pharmaceuticals compositions.

Abstract: A new class of neuramidase inhibitor prodrugs is provided characterized by a prodrug moiety of a carboxyl group modified to form a carbonyl ethoxy amino acid, a carbonyl ethoxy dipeptide or a carbonyl ethoxy tripeptide, a guanidine group modified to form a carbonyl ethoxy amino acid, a carbonyl ethoxy dipeptide, a carbonyl ethoxy tripeptide; a primary alcohol modified to form an esterified single amino acid, dipeptide or tripeptide of zanavimir of the unaltered therapeutic agent. Exemplary therapeutic agents so modified to form prodrugs include zanavimir, oseltamivir and peramivir. The prodrug has increased oral bioavailability relative to the unaltered neuraminidase inhibitor and is effective in the inhibition of viral infections involving neuraminidase in the viral reproductive cycle.

Abstract: A pharmaceutical composition is provided that includes an active ingredient in the form of a powder or granule, a water soluble high molecular weight excipient and a water insoluble hydrophilic amphiphilic excipient. These ingredients are solution mixed and dried to form a modified pharmaceutical ingredient in simultaneous contact with both the water soluble high molecular weight excipient and the water insoluble hydrophilic amphiphilic excipient. Adjuvants are compacted about the modified pharmaceutical ingredient as well as a release control agent. The release control agent being present at levels from 1 to 40 total weight percent of the pharmaceutical composition.

Abstract: Disclosed are neuraminidase inhibitor compounds and pharmaceutical compositions with improved bioavailability and/or improved efficacy and methods of treating influenza using the compounds and pharmaceuticals compositions.

Abstract: A new class of neuramidase inhibitor prodrugs is provided characterized by a prodrug moiety of a carboxyl group modified to form a carbonyl ethoxy amino acid, a carbonyl ethoxy dipeptide or a carbonyl ethoxy tripeptide, a guanidine group modified to form a carbonyl ethoxy amino acid, a carbonyl ethoxy dipeptide, a carbonyl ethoxy tripeptide; a primary alcohol modified to form an esterified single amino acid, dipeptide or tripeptide of zanavimir of the unaltered therapeutic agent. Exemplary therapeutic agents so modified to form prodrugs include zanavimir, oseltamivir and peramivir. The prodrug has increased oral bioavailability relative to the unaltered neuraminidase inhibitor and is effective in the inhibition of viral infections involving neuraminidase in the viral reproductive cycle.

Abstract: Cidofovir or foscarnet based compounds having an amino acid or dipeptide esters are provided as prodrugs.

Abstract: A new class of neuramidase inhibitor prodrugs is provided characterized by a prodrug moiety of a carboxyl group modified to form a carbonyl ethoxy amino acid, a carbonyl ethoxy dipeptide or a carbonyl ethoxy tripeptide, a guanidine group modified to form a carbonyl ethoxy amino acid, a carbonyl ethoxy dipeptide, a carbonyl ethoxy tripeptide; a primary alcohol modified to form an esterified single amino acid, dipeptide or tripeptide of zanavimir of the unaltered therapeutic agent. Exemplary therapeutic agents so modified to form prodrugs include zanavimir, oseltamivir and peramivir. The prodrug has increased oral bioavailability relative to the unaltered neuraminidase inhibitor and is effective in the inhibition of viral infections involving neuraminidase in the viral reproductive cycle.

Abstract: The invention relates to synthetic peptide analogs of D-Arg-Oic-Pro-Gly-Phe and methods of their use to inhibit human platelet aggregation, thrombosis and cell activation mediated by PAR1 and PAR4.

Abstract: A prodrug composition is provided which includes a pharmaceutical species and an amino acid having a covalent bond to the pharmaceutical species. Particular pharmaceutical species are 6-amino-4-methyl-8-(beta.-D-ribofuranosyl)pyrrolo[4,3,2-de]pyrimido[4,5-c]pyridazine, also known as TCN and by the trade name triciribine; as well as the 5?phosphate of triciribine. TCN and TCNP prodrugs of the present invention have increased bioavailability compared to the parent TCN and TCNP. The inventive prodrug is transported from the gastrointestinal lumen by a specific transporter and is enzymatically cleaved to yield TCN or TCNP, such that TCN or TCNP is delivered to the individual.

Abstract: Cidofovir or foscarnet based compounds having an amino acid or dipeptide esters are provided as prodrugs.

Abstract: Cidofovir-based compounds having an amino acid, dipeptide or tripeptide attached to a cidofovir or cyclic cidofovir framework. The compounds show enhanced oral bioavailability and increased binding to the PepT1 transporter. The present invention also provides compositions and methods for treating virus infections, and a method of preparing cidofovir.

Abstract: A method is provided for the delivery of a therapeutic to epithelial cells through the use of a bile acid conjugated to a peptide, the peptide being ionically charged at physiological pH. The complex is well suited for oral and other forms of therapeutic administration of therapeutic drugs known in the art in order to exact systemic and/or localized effect. Intestinal epithelial cells, as well as non-epithelial cells within the gastrointestinal tract and other target cells receive with greater efficiency a charged therapeutic when delivered with an oppositely charged bile acid conjugate (BAC) through oral administration, direct injection, or infusive administrations, thereby increasing bioavailability.

Abstract: A prodrug composition is provided which includes a pharmaceutical species and an amino acid having a covalent bond to the pharmaceutical species. A particular pharmaceutical species is adenosine arabinoside, also known as Ara A and by the trade name vidarabine. Ara A prodrugs of the present invention have increased bioavailability compared to the parent compound Ara A. The inventive prodrug is transported from the gastrointestinal lumen by a specific transporter and is enzymatically cleaved to yield Ara A, such that Ara A is delivered to the individual.

Abstract: A dipeptide or tripeptide carrier system for active agent delivery to cells has an N-terminus natural amino acid and an active agent covalently bonded to a side chain of one of the remaining amino acid bases. The system is amenable to formulation as an oral administrant. The active agent being a therapeutic, a fluorescent dye, or contrast agent where the active agent has a molecular weight of less than 500 atomic mass units. An optional linker is provided intermediate between the active agent and the linking side chain.

Abstract: The invention relates to synthetic peptide analogs of D-Arg-Oic-Pro-Gly-Phe and methods of their use to inhibit human platelet aggregation, thrombosis and cell activation mediated by PAR1 and PAR4.

Abstract: A pharmaceutical composition is provided that includes an active ingredient in the form of a powder or granule, a water soluble high molecular weight excipient and a water insoluble hydrophilic amphiphilic excipient. These ingredients are solution mixed and dried to form a modified pharmaceutical ingredient in simultaneous contact with both the water soluble high molecular weight excipient and the water insoluble hydrophilic amphiphilic excipient. Adjuvants are compacted about the modified pharmaceutical ingredient as well as a release control agent. The release control agent being present at levels from 1 to 40 total weight percent of the pharmaceutical composition.

Abstract: A dipeptide or tripeptide carrier system for active agent delivery to cells has an N-terminus natural amino acid and an active agent covalently bonded to a side chain of one of the remaining amino acid bases. The system is amenable to formulation as an oral administrant. The active agent being a therapeutic, a fluorescent dye, or contrast agent where the active agent has a molecular weight of less than 500 atomic mass units. An optional linker is provided intermediate between the active agent and the linking side chain.

Abstract: A prodrug composition is provided which includes a pharmaceutical species and an amino acid having a covalent bond to the pharmaceutical species. The pharmaceutical species is characterized by bioavailability of 30% or less and a molecular weight in the range of 100-1000 Daltons. The composition is characterized further in that the pharmaceutical species is not acyclovir, ganciclovir, BRL44385, or penciclovir. Also described is an inventive method of delivering a pharmaceutical species to an individual including the step of orally administering an inventive prodrug to an individual. In one embodiment the prodrug includes a pharmaceutical species characterized by bioavailability of 30% or less, wherein the pharmaceutical species has a molecular weight in the range of 100-1000 Daltons. The inventive prodrug is transported from the gastrointestinal lumen by a specific transporter and is enzymatically cleaved to yield the pharmaceutical species, such that the pharmaceutical species is delivered to the individual.

Abstract: A method is provided for the packaging of a nucleic acid with a chelating agent having a coordinating moiety linked to a central hydrophobic moiety that terminates in a hydrophilic moiety. The complex is well suited for oral and other forms of therapeutic administration of nucleic acids in order to exact systemic and/or localized gene delivery therapy. Intestinal epithelial cells, as well as non-epithelial cells within the gastrointestinal tract and other target cells, are transformed for short or long-term therapies through oral administration, direct injection, or infusive administrations. A nucleic acid conjugating agent particulate composition amenable for administration as a gene therapy composition is provided. The composition is readily adjusted to create a particle having a controlled size and net-zero, -positive, or -negative charge.