Aciont, Inc.

University of Utah Research Foundation

Theratech, Inc.

Spriaso LLC

Stanley Research Foundation

William I Higuchi

S Kevin Li

David J Miller

Kevin Li

Yang Song

Honggang Zhu

Matthew S Hastings

Charles D Ebert

Jie Zhang

Theodore H Stanley

Daniel Mufson

Gordon L Flynn

John W Higuchi

Jeffrey I Fox

Firoozeh Aminian Patel

Michael Delmage

G Lynn Powell

Anthony Tuitupou

Rajan Kochambilli

Described are compositions that may be orally administered that comprise a bioreversible derivative of hydroxy N-substituted-2-aminotetralin or an enantiomer or salt or prodrug thereof, and a pharmaceutically acceptable carrier suitable for oral administration in the amount present, wherein the composition is orally bioavailable when administered to a subject. The bioreversible derivative has an intrinsic lipophilicity C log P value of about 7 to about 11.5. A method comprises oral administering such composition to a human subject in need of hydroxy N-substituted-2-aminotetralin therapy.

Compositions comprising bioreversible derivatives of hydroxy N-substituted-2-aminotetralins, and related dosage forms

The present invention includes methods and devices for providing sustained in-vivo release of an active agent to a subject. In some aspects, such release may be achieved by reacting an active agent in-vivo with a depot forming agent in order to form a sustained release active agent depot inside the subject. The depot can then release the active agent over a sustained period of time.

Methods and devices for sustained in-vivo release of an active agent

The present invention is drawn to a pharmaceutical compound for the treatment of posterior retinal diseases through topical application of the compound. The compound includes an effective amount of a therapeutic compound, and at least one additional agent that helps to prolong the residence time of the therapeutic compound within the extraocular space, or increase the transport of the therapeutic compound across a tissue of an eye toward and into a posterior ocular region, or both. The invention is additionally drawn to a device and method for delivering the compound.

Non-invasive ocular drug delivery

An iontophoretic method for transporting compounds of interest across a body tissue is provided. The method utilizes an AC signal in conjunction with a barrier-modifying agent such as a fatty acid, fatty alcohol, bile acid, surfactant, or the like. The method enables the maintenance of a substantially constant electrical state in a localized region of the tissue through which transport occurs, thereby allowing a compound of interest to be transported across the tissue in a controlled and predictable manner. The barrier-modifying agent reduces the time as well as the voltage level required to achieve a target electrical resistance, thereby reducing patient discomfort and increasing the battery life of the iontophoresis device.

Method for increasing the battery life of an alternating current iontophoresis device using a barrier-modifying agent

The invention provides a device for iontophoretically transporting a compound through a localized region of an individual's body tissue. The device comprises first and second iontophoretic electrodes, a reference electrode, a current source, and a monitoring means. The first electrode is placed in ion-conducting relation with the localized region to allow iontophoretic transport of a compound therethrough. The second and transport electrodes are each placed in contact with the individual's body tissue, and all electrodes are spaced apart from each other. The current source is electrically connected to the first and second electrodes and applies a current to the localized region of body tissue to effect iontophoretic transport. The monitoring means monitors the electrical resistance of the localized region by measuring any voltage difference between the reference electrode and the first and/or second electrodes. Methods for using a reference electrode to monitor and control iontophoresis are also provided.

Device and method for monitoring and controlling electrical resistance at a tissue site undergoing iontophoresis

A device and method are provided that minimize the changes in flux encountered during iontophoresis and reduce inter-subject variability. For drug delivery, the active agent to be delivered is administered in conjunction with at least one background ion having a hindrance factor that changes at a faster rate than the hindrance factor of the active agent when an electrical current is applied. For analyte extraction, the extraction reservoir contains at least one background ion having a hindrance factor that changes at a faster rate than the hindrance factor of the background ions of the analyte in the tissue when an electrical current is applied.

Use of background electrolytes to minimize flux variability during iontophoresis

A variety of methods for transporting different agents such as pharmaceutical agents, nutrients and genetic materials across a tissue are provided. The methods utilize an AC signal to maintain a substantially constant electrical state in a region of the tissue through which transport occurs, thereby allowing agent to be transported across the tissue in a controlled and predictable manner. Certain methods include an optional AC or DC prepulse signal to initially achieve the target electrical state. An optional DC offset signal can also be included to assist in promoting transfer of the agent. The methods have utility in a variety of different clinical settings and applications.

Methods for delivering agents using alternating current

A variety of methods for extracting different substances such as endogenous substances, pharmaceutical substances, markers of disease, and their metabolites across a tissue are provided. The methods utilize an AC signal to maintain a substantially constant electrical state in a region of the tissue through which extraction occurs, thereby allowing substances to be transported across the tissue in a controlled and predictable manner. Certain methods include an optional AC or DC prepulse signal to initially achieve the target electrical state. An optional DC offset signal can also be utilized to assist in promoting extraction of the substance. The methods have utility in a variety of different clinical settings and applications.

Methods for extracting substances using alternating current

The present invention is directed to novel methods and apparatus for noninvasive blood glucose monitoring. Blood glucose is monitored noninvasively by correlation with amount of glucose which permeates an epithelial membrane, such as skin or a mucosal membrane, into a glucose receiving medium over a specified time period. The glucose receiving medium preferably includes a glucose permeation enhancer capable of increasing the glucose permeability across the epithelial membrane. The glucose receiving medium is positioned against the epithelial membrane so that the permeation enhancer alters the permeability of the membrane. After sufficient time delay, the glucose receiving medium is removed and analyzed for the presence of glucose using conventional analytical techniques. The apparatus within the scope of the present invention includes means for supporting the glucose receiving medium. Such means for supporting the glucose receiving medium may include a housing defining a receiving chamber therein which holds the glucose receiving medium and an opening to the receiving chamber. The means for supporting the glucose receiving medium may also include a hydrogel. The apparatus also preferably includes means for temporarily positioning the glucose receiving medium against the epithelial membrane.

Apparatus and method for noninvasive blood glucose monitoring

A method for preventing tooth decay comprising: (1) laser irradiation of the tooth's surface with a carbon dioxide laser (wavelength=10.6 microns) at 20 to 50 watts for 1 to 400 seconds, and (2) subsequent chemical treatment of the tooth with a chemical agent such as ethane-1-hydroxy-1, 1-diphosphonic acid at concentrations greater than about 0.00001 molar. The resulting tooth has a reduced dissolution rate in acid and increased resistivity to cavities.

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Salt Lake City, UT, United States of America

William I Higuchi