Abstract: The invention provides a method for adjusting, i.e., varying, the rate of delivery of a therapeutic agent through a body surface from an electrotransport assembly of the type which includes a predetermined, e.g., fixed, output electronic controller and a detachable therapeutic agent source. The method provides a plurality of therapeutic agent sources in which a single parameter or a series of parameters has been varied. The plurality of agent sources are supplied, one at a time, to the controller of the electrotransport assembly, so that together (i.e., source and controller) the agent delivery rate is varied.
Abstract: A composition for administration of a therapeutically effective dose of a topoisomerase inhibitor I or topoisomerase I/II inhibitor is described. The composition includes liposomes having an outer surface and an inner surface defining an aqueous liposome compartment, and being composed of a vesicle-forming lipid and of a vesicle-forming lipid derivatized with a hydrophilic polymer to form a coating of hydrophilic polymer chains on both the inner and outer surfaces of the liposomes. Entrapped in the liposomes is the topoisomerase inhibitor at a concentration of at least about 0.10 &mgr;mole drug per &mgr;mole lipid.
Type:
Grant
Filed:
October 15, 1999
Date of Patent:
March 12, 2002
Assignee:
Alza Corporation
Inventors:
James L. Slater, Gail T. Colbern, Peter K. Working
Abstract: Adhesive transdermal drug delivery devices may be removed and subsequently reapplied to an area of skin if the adhesive has an initial adhesive/skin bond strength sufficient to maintain said transdermal drug delivery device on the skin to which it is applied for the entire predetermined administration period; and an adhesive/skin bond strength upon replacement on the skin after removal therefrom which is adequate to retain the device on the skin for the balance of the administration period.
Abstract: A compound comprised of a hydrophilic polymer covalently yet reversibly linked to a amine-containing ligand through a dithiobenzyl linkage is described.
Abstract: Controlled release of liquid, active agent formulations is provided by dispersing porous particles containing the liquid active agent formulation in osmotic, push-layer dosage forms. The dosage forms may provide for continuous or pulsatile delivery of active agents.
Type:
Grant
Filed:
December 22, 1999
Date of Patent:
January 29, 2002
Assignee:
Alza Corporation
Inventors:
Patrick S. -L. Wong, David E. Edgren, Liang C. Dong, Crystal Pollock-Dove
Abstract: The present invention is directed to an oral active agent delivery system and method for delivering discrete units of an active agent formulation to a patient. An active agent formulation chamber containing the active agent formulation and having a fluid passing active agent formulation retainer is placed at a first end into a fluid and at a second end into a patient's mouth. The active agent is delivered when the patient sips on the second end of the chamber.
Type:
Grant
Filed:
January 19, 2001
Date of Patent:
December 25, 2001
Assignee:
Alza Corporation
Inventors:
Patrick S.-L. Wong, Howard B. Rosen, Nathan Roth, Phyllis I. Gardner
Abstract: Method of making an electrotransport device containing an analog of a parent polypeptide having one or more amino acid residues substituted relative to the parent polypeptide with an amino acid residue selected from the group consisting of proline, glycine and asparagine.
Abstract: An injectable depot gel composition containing a polymer, a solvent that can dissolve the polymer and thereby form a viscous gel, a beneficial agent; and an emulsifying agent in the form of a dispersed droplet phase in the viscous gel. The injectable depot gel composition can be prepared by mixing the polymer and the solvent so that the solvent dissolves the polymer and forms a viscous gel. The beneficial agent is dissolved or dispersed in the viscous gel and the emulsifying agent is mixed with the beneficial agent containing viscous gel. The emulsifying agent forms a dispersed droplet phase in the viscous gel to provide the injectable depot gel composition. The injectable depot gel composition can deliver a beneficial agent to a human or animal with a desired release profile.
Abstract: A liposome composition for localizing an anti-tumor compound to a solid tumor via the bloodstream. The liposomes, which contain the agent in entrapped form, are composed of vesicle-forming lipids and between 1-20 mole percent of a vesicle-forming lipid derivatized with hydrophilic biocompatible polymer, and have sizes in a selected size range between 0.07 and 0.12 microns. After intravenous administration, the liposomes are taken up by the tumor within 24-48 hours, for site-specific release of entrapped compound into the tumor. In one composition for use in treating a solid tumor, the compound is an anthracycline antibiotic drug which is entrapped in the liposomes at a concentration of greater than about 50 &mgr;g agent/&mgr;mole liposome lipid. The method results in regression of solid colon and breast carcinomas which are refractory to anthracycline antibiotic drugs administered in free form or entrapped in conventional liposomes.
Type:
Application
Filed:
April 26, 2001
Publication date:
December 13, 2001
Applicant:
Alza Corporation
Inventors:
Francis J. Martin, Martin C. Woodle, Carl Redemann, Annie Yau-Young
Abstract: An electrotransport device (10) for the electrotransport delivery of agents having at least one hydrophobic site thereon, such as peptides and proteins, contains donor and counter electrodes (12, 16 and 14, 18), a power source and electrical control circuitry (24). The donor electrode (12, 16) contains, in addition to the agent, an electrotransport enhancer such as non-ionic surfactants or zwitterionic surfactants without a net charge. A method of increasing electrotransport flux of agent shaving at least one hydrophobic site thereon utilizes non-ionic or zwitterionic surfactants in the solution or suspension containing the agent. A method for the electrotransport delivery of an agent with at least one hydrophobic site through a body surface relies on the incorporation of a non-ionic surfactant or a zwitterionic surfactant without a net charge, into the solution or suspension containing the agent to decrease its hydrophobicity.
Type:
Grant
Filed:
June 18, 1997
Date of Patent:
December 11, 2001
Assignee:
Alza Corporation
Inventors:
Leslie A. Holladay, Lynda G. Treat-Clemons, Patricia Margaret Bassett
Abstract: A device (3) comprising a sheet member (6) having a plurality of microprotrusions (4) for penetrating the skin and a rigid support (15) contacting and extending across the sheet member (6) for transmitting an applied force evenly across the length and width of the sheet member (6) to reproducibly and reliably penetrate the skin with the microprotrusions (4).
Type:
Grant
Filed:
December 9, 1998
Date of Patent:
November 27, 2001
Assignee:
ALZA Corporation
Inventors:
Joseph Creagan Trautman, Patrick S.-L. Wong, Peter E. Daddona, Hyunok Lynn Kim, Michael G. Zuck
Abstract: The invention is directed to a composition and product for use in an electrotransport device. The composition includes an ionized drug, an anti-inflammatory agent and a solvent. Preferably, the anti-inflammatory agent is hydrocortisone or esters thereof, and the solvent is water and a material such as an alcohol, a glycol, a glycerol, a cyclodextrin, a nonionic surfactant and/or mixtures thereof.
Type:
Grant
Filed:
June 26, 1998
Date of Patent:
November 27, 2001
Assignee:
ALZA Corporation
Inventors:
Philip W. Ledger, Michel J. N. Cormier, Patricia S. Campbell
Abstract: A liposome composition comprising small, surface-bound effector molecules is disclosed. The liposomes have a surface layer of hydrophilic polymer chains, for enhanced circulation time in the bloodstream. The effector molecules are attached to the distal ends of the polymer chains. In one embodiment, the effector is polymyxin B, for treatment of septic shock.
Type:
Application
Filed:
June 8, 2001
Publication date:
November 22, 2001
Applicant:
Alza Corporation
Inventors:
Samuel Zalipsky, Martin C. Woodle, Francis J. Martin, Yechezkel Barenholz, Herve Bercovier
Abstract: An iontophoretic delivery device (10) is provided. Device (10) has an electronic circuit (32) having electronic components such as batteries (30) mounted thereon. Device (10) also includes a pair of electrode assemblies (18, 19). The electronic circuit (32) is electrically connected to the electrode assemblies (18, 19) using an electrically conductive adhesive (34). The adhesive can also be used to electrically connect two or more electronic components within circuit (32) or to connect an electronic component to the electronic circuit (32). In one practice of the invention, the electrically conductive adhesive (44) functions as an electrode and electrically connects the circuit (32) to an agent-containing reservoir (24, 25). In a further practice of the invention, the electrically conductive adhesive (93) functions as an agent reservoir and contains the agent to be iontophoretically delivered.
Type:
Grant
Filed:
December 2, 1994
Date of Patent:
November 13, 2001
Assignee:
Alza Corporation
Inventors:
Ronald P. Haak, J. Richard Gyory, Robert M. Myers, Felix A. Landrau, Harold F. Sanders, Lothar W. Kleiner, Linda M. Hearney
Abstract: Reagents for use in preparing a therapeutic liposome composition sensitized to a target cell are described. The reagents include a liposomal composition composed of pre-formed liposomes having an entrapped therapeutic agent and a plurality of targeting conjugates composed of a lipid, a hydrophilic polymer and a targeting ligand. The therapeutic, target-cell sensitized liposome composition is formed by incubating the liposomal composition with a selected conjugate.
Type:
Application
Filed:
June 7, 2001
Publication date:
November 8, 2001
Applicant:
Alza Corporation
Inventors:
Theresa M. Allen, Paul Uster, Francis J. Martin, Samuel Zalipsky
Abstract: Methods for modifying polypeptide agents to enhance their transdermal electrotransport flux are provided. The polypeptide is modified by reducing the potential of the polypeptide for forming &agr;-helical or &bgr;-sheet segments. In particular, amino acid residues known to stabilize &agr;-helical and &bgr;-sheet segments can be replaced with destabilizing residues and known helix breakers. Modified molecules and compositions including the molecules are also provided.
Abstract: The invention relates to formulations for the electrically assisted transdermal delivery of lidocaine and epinephrine. The present invention further provides methods and devices for the electrically assisted delivery of local anesthetics, preferably lidocaine.
Type:
Grant
Filed:
November 14, 1997
Date of Patent:
September 25, 2001
Assignee:
Alza Corporation
Inventors:
Andreas Linkwitz, Ivan W. Chin, J. Richard Gyory, Ronald V. Thompson, Paul J. Urbanski
Abstract: This invention pertains to a dosage form for the management of epilepsies wherein the dosage form comprises administering valproic acid or a valproic acid derivative at a continuous rate over an extended time.
Type:
Grant
Filed:
May 28, 1993
Date of Patent:
September 11, 2001
Assignee:
Alza Corporation
Inventors:
Atul Devatt Ayer, Richard L.-C. Yieh, Brenda J. Pollock, Patrick S.-L. Wong
Abstract: Osmotic delivery system semipermeable body assemblies that control the delivery rate of a beneficial agent from an osmotic delivery system incorporating one of the semipermeable body assemblies. A semipermeable body assembly or plug includes a semipermeable body which is positionable in an opening of an osmotic delivery system. The semipermeable body has a hollow interior portion having a size selected to obtain a predetermined liquid permeation rate through the semipermeable body. Because the beneficial agent in the osmotic delivery system is delivered at substantially the same rate the osmotic agent imbibes liquid which has permeated through the plug from a surrounding environment, the liquid permeation rate through the plug controls the delivery rate of the beneficial agent from the osmotic delivery system.
Type:
Grant
Filed:
July 24, 1998
Date of Patent:
September 11, 2001
Assignee:
Alza Corporation
Inventors:
Guohua Chen, Scott D. Lautenbach, Keith E. Dionne, Scott D. Jordan, Steve A. Berry, Craig I. Rodenberger, Rupal Ayer