Method of Enhancing Electrotransport Polypeptide Flux By Amino Acid Substitution with Histidine
AssigneeAlza Corporation
InventorLeslie A. Holladay
Life of this patent
Estimating the term…
Abstract
Methods of modifying polypeptide drugs in order to enhance their transdermal electrotransport flux are provided. The polypeptide is modified by substituting a histidine residue (His) for one or more glutamine (Gln), threonine (Thr) and/or asparagine (Asn) residue(s). The His for Gln substitution is particularly preferred from the standpoint of retaining biological activity of the parent polypeptide. Compositions containing the modified polypeptide, which are useful for transdermal electrotransport delivery, are also provided.
Claims25
1-16. (canceled)
An electrotransport device for delivering a pharmaceutical polypeptide agent through a body surface, comprising:
- a donor electrode assembly comprising a donor electrode and an agent reservoir, wherein the agent reservoir comprises a synthetic analog of a parent polypeptide in which at least one amino acid residue of the parent polypeptide has been replaced with a histidine residue;
- a counter electrode assembly comprising a counter electrode and an electrolyte reservoir;
- and
- an electrical power source, wherein the donor and counter electrode assemblies are electrically connected to the electrical power source.
An electrotransport device for delivering a hormone through a body surface, comprising:
- a donor electrode assembly comprising a donor electrode and an agent reservoir, wherein the agent reservoir comprises a synthetic analog of a parent hormone in which at least one amino acid residue of the parent hormone has been replaced with a histidine residue;
- a counter electrode assembly comprising a counter electrode and an electrolyte reservoir;
- and
- an electrical power source, wherein the donor and counter electrode assemblies are electrically connected to the electrical power source.
Dependencies are inferred from the claim text.