Becton Dickinson and Company Limited

Other

North Carolina State University

Corning Glass Works

Vyteris, Inc.

Becton Dickinson Research Center

Burton H Sage

Carl Randolph Bock

Philip G Green

Ronald J Flower

John L Haynes

Randal A Hoke

Robert I Connelly

Jim E Riviere

Robert F Adrion

C Randolph Bock

Munir A Hussain

Arnold J Repta

Charles H Rogers

James P O'Connell

Thomas H Schulte

James D Mansour

John R DeNuzzio

Michael W Malpass

Hai-Ping Wu

Vilambi Reddy

A device includes a plurality of microneedles for abrading the stratum corneum of the skin to form a plurality of grooves in the tissue having a controlled depth and width. The microneedles have a length of about 5-250 microns and generally about 5-200 microns. The device is rubbed over the skin to prepare an abraded site after which a transdermal delivery or sampling device is applied to the abraded delivery site. The abrasion increases the permeability of the skin and the rate of delivery and extraction of a substance without pain or irritation to the patient.

Method and device for abrading skin

The present invention claims an apparatus for transdermal delivery of medicaments, with novel electrode systems, which avoids burns caused by changes in pH or excessive current applied at the sight of delivery, which is low in cost and easy to manufacture. In the present invention, preferably, the anode of the electrode system is predominantly formed from a low-cost bulk base metal which includes a coating of a precious metal thereon. The cathode of the electrode system is preferably formed from an chemically inert material which is a poor electron condutor and is coated on a good electron conductive material which has poor chemical stability. The electrode system of the present invention is highly efficient, easy to manufacture and cost-effective.

Low cost electrodes for an iontophoretic device

A device for delivering a liquid therapeutic preparation into the body of a patient by injection into or through the skin of the patient comprises a low-profile housing having a bottom surface adapted to be brought into contact with the skin of the patient. A reservoir is disposed within the housing for containing a liquid therapeutic preparation to be administered. An injection needle is disposed generally horizontally in the housing, and is adapted to communicate with the reservoir. The injection needle has a bent injection end which is adapted to project through a needle aperture in the bottom surface of the housing. A movable needle carrier is disposed in the housing for carrying the injection needle and for causing the injection end of the needle to project through the needle aperture upon movement of the needle carrier. The needle carrier and the injection needle are disposed in a side-by-side relationship with the reservoir in the housing in order to minimize the height of the housing above the bottom surface. As a result, the housing is sufficiently low in height to allow the device to be worn inconspicuously under the clothing of the patient.

Low-profile automatic injection device with self-emptying reservoir

This invention relates to novel methods and devices for iontophoretically administering therapeutic doses of cell adhesion receptor antagonists in a controlled manner through the skin. Such antagonist compounds include but are not limited to antagonists of the IIb/IIIa and .alpha..sub.v .beta..sub.3 integrins and related cell surface adhesive protein receptors. The present invention includes iontophoretic delivery devices comprising cell adhesion receptor antagonists. Such methods and devices are useful, alone or in combination with other therapeutic agents, for the treatment of thromboembolic disorders, angiogenic disorders, inflammation, bone degradation, cancer metastasis, diabetic retinopathy, restenosis, macular degeneration, and other conditions mediated by cell adhesion and/or cell migration and/or angiogenesis.

Iontophoretic delivery of cell adhesion inhibitors

A device for delivering a liquid theraputic preparation into the body of a patient by injection into or through the skin of the patient comprises a low-profile housing having a bottom surface adapted to be brought into contact with the skin of the patient. A reservoir is disposed within the housing for containing a liquid theraputic preparation to be administered. An injection needle is disposed generally horizontally in the housing, and is adapted to communicate with the reservoir. The injection needle has a bent injection end which is adapted to project through a needle aperture in the bottom surface of the housing. A movable needle carrier is disposed in the housing for carrying the injection needle and for causing the injection end of the needle to project through the needle aperture upon movement of the needle carrier. The needle carrier and the injection needle are disposed in a side-by-side relationship with the reservoir in the housing in order to minimize the height of the housing above the bottom surface. As a result, the housing is sufficiently low in height to allow the device to be worn inconspicuously under the clothing of the patient.

An iontophoretic drug delivery device of the present invention includes a power source and an electrode assembly containing at least two electrodes, in electrical contact with a first reservoir and a second reservoir. The present invention also includes at least three electrodes in a three electrode embodiment, with the third electrode in electrical contact with a third reservoir. In either embodiment, the first reservoir and the second reservoir contain an active agent to be delivered to an applied area of a patient. The present invention also includes in its two electrode embodiment a switch for reversing the flow of current or in its three electrode embodiment a switch for switching the flow of current, so as to reduce sensation. The devices also include a timer for controlling the amount of time the electrical current flows in each direction. In this way, the devices are suitable for use to deliver an active agent to the applied area approximate the first reservoir when the electrical current flows in one direction for a first period of time and to deliver an active agent to the applied area approximate the second reservoir when the electrical current flows in the other direction during a second period of time. Thus, reversing polarity or switching the flow of current between electrodes, and iontophoresing thereunder below the sensation threshold results in sensation anesthesia so that the current can be raised to deliver the drug without sensation.

Iontophoretic drug delivery system and method for using same

This invention relates to novel methods and devices for iontophoretically administering therapeutic doses of cell adhesion receptor antagonists in a controlled manner through the skin. Such antagonist compounds include but are not limited to antagonists of the IIb/IIIa and .alpha..sub.v .beta..sub.3 inter and related cell surface adhesive protein receptors. The present invention includes iontophoretic delivery devices comprising cell adhesion receptor antagonists. Such methods and devices are useful, alone or in combination with other therapeutic agents, for the treatment of thromboembolic disorders, angiogenic disorders, inflammation, bone degradation, cancer metastasis, diabetic retinopathy, restenosis, macular degeneration, and other conditions mediated by cell adhesion and/or cell migration and/or angiogenesis.

The present invention relates to a method for preparing proteins or peptides for iontophoretic delivery by modifying said proteins or peptides, by hydrophobic bonding of acharged molecule to a hydrophobic region of the protein or peptide, to have an isoelectric point of less than about 4.0 or greater than about 7.3 with an electrostatic charge of at least plus or minus 1 over the pH range of about 4.0 to about 7.3. Another embodiment of the present invention relates to a device for delivery of a protein or peptide having an isoelectric point of less than about 4.0 or greater than about 7.3 with an electrostatic charge of at least plus or minus 1 over the pH range of about 4.0 to about 7.3.

Molecules for iontophoretic delivery

The present invention relates to a method and device for the iontophoretic delivery of a therapeutic dose range of bisphosphonate to be delivered to a patient over a period of lime to prevent the onset for advancement of osteoporosis and other metabolic bone diseases for a selected period of time.

Device for the iontophoretic administration of bisphosphonates

A method for preventing the onset or advancement of osteoporosis or other metabolic bone disorders in a patient by iontophoretically administering to the patient an effective amount of a bisphosphonate which would be effective for preventing the onset or advancement of osteoporosis or other bone disorders and wherein the effective amount of bisphosphonate is delivered over a period of from about four (4) hours to about forty-eight (48) hours, at intervals of from about once a week to about twice a year and wherein the effective amount of bisphosphonate also contains an agent capable of chelating calcium.

Method for the iontophoretic administration of bisphosphonates

An iontophoretic drug delivery device of the present invention includes a power source and an electrode assembly in electrical contact with at least three reservoirs, with at least two of the reservoirs containing an active formulation to be delivered to an applied area of a patient, with a switch for switching the flow of current from between the first electrode and the third electrode and between the second electrode and the first electrode so as to reduce sensation. The device also includes a timer for controlling the amount of time the electrical current flows between a pair of electrodes. In the preferred embodiment, the active formulation includes a local anesthetic such as Lidocaine and a vasoconstrictor such as Epinephrine. In this way, the device is suitable for use to deliver the local anesthetic to the applied area approximate the first reservoir for a first period of time and to deliver the local anesthetic to the applied area approximate the second reservoir during a second period of time. Thus, switching between pairs of electrodes and iontophoresing thereunder below the sensation threshold results in sensation anesthesia so that the current can be raised to deliver the drug without sensation.

The invention discloses peptides and proteins for iontophoretic delivery. Specifically disclosed are methods for iontophoretic delivery of assemblages of amino acids which comprises modifying said assemblages of amino acids to an isoelectric point less than about 4.0 or greater than about 7.3 with an electrostatic charge of plus or minus 1 and patches with assemblages of amino acids with isoelectric points less than about 4.0 or greater than about 7.3 with an electrostatic charge of plus or minus 1.

The invention discloses methods and compositions for enhanced skin concentration of iontophoretic delivered active agents. The compositions are pharmaceutically acceptable compositions for iontophoretic delivery which comprise a skin concentration enhancing amount of a vasoconstrictor and active agent. Methods comprise adding a skin concentration enhancing amount of a vasoconstrictor to an active agent and delivering by iontophoresis.

Method and composition for increased skin concentration of active agents

The present invention provides an iontophoretic drug delivery device having electrode renewing features includes a housing having a first electrode, a second electrode, a circuit for providing electrical communication between the first and second electrodes. The circuit is capable of engaging a source of current. Control means is provided for effecting the amount of current passing between the electrodes. A removable electrolyte reservoir is capable of holding electrolyte and removably engaging the housing so that one of the electrodes can contact electrolyte contained within the reservoir. A removable active agent reservoir is capable of holding an active agent for iontophoretic delivery. The active agent reservoir is capable of removably engaging the housing so that the active agent contacts one of the electrodes. The present invention also provides a method for renewing electrodes during delivery of an active agent from an iontophoretic system which comprises at least two electrodes and means for containing an active agent, which method comprises:

Device and method for renewing electrodes during iontophoresis

The invention discloses methods and compositions for enhanced iontophoretic delivery of active agents. The compositions are pharmaceutically acceptable compositions for iontophoretic delivery comprising a delivery enhancing amount of a vasodilator and active agent. Methods comprise adding a delivery enhancing amount of a vasodilator to an active agent and delivering by iontophoresis.

Growing community of inventors

Raleigh, NC, United States of America

Burton H Sage