Pacesetter, Inc.

Minimed, Inc.

Medtronic Minimed, Inc.

Other

Aegis Biosciences, L.l.c.

Siemens-pacesetter, Inc.

Dais Analytic Corporation

David J Vachon

Shahram Moaddeb

Glenn Noronha

Bill C Ponder

Aaron M Heiss

Joseph C Walsh

Gene A Bornzin

William P Van Antwerp

Kevin L Morgan

Gary E Wnek

Jenn-Hann Larry Wang

Brooks B Cochran

Jonathan Reilly

Anne Margaret Pianca

Joseph J Florio

John Joseph Mastrototaro

John R Helland

Thomas Arnold Peyser

Joe H Satcher, Jr

Stephen M Lane

Liwei Cao

Compositions are provided for promoting healing of tissue of a vertebrate organism. The compositions can be for internal administration of a therapeutically effective amount of pharmacologically active, protease inhibiting, aqueous media soluble polysulfonated materials in salt form and associated with a secondary material to reduce one or more of inflammation, bacterial proliferation, proteolytic activity, and cancerous cell growth. The compositions may additionally or alternatively be cross-linked so as to alter the solubility of these pharmacologically active salts or slow dissolution by providing biodegradable cross-linkers. Compositions for healing the tissue of a multicellular organism are provided that can include a polysulfonated material in a liquid mixture, as solid particles or constructs that may or may not biodegrade or deliver a pharmacologically relevant value. Some of the compositions are also provided for inclusion into a device for preventing infection, reducing inflammation, and preserving the activity of a protein or protein drug.

Compositions and methods for promoting the healing of tissue of multicellular organisms

The present invention pertains to products and processes relating to compatible polymer blends comprising at least one sulfonated polymer and at least one non-sulfonated polymer. The sulfonated polymers may be produced using a number of sulfonating agents including a coordination complex of sulfur trioxide. The polymeric blended materials described herein are useful in a variety of applications, including as coatings for medical devices, protective clothing and fabric, laboratory equipment, vascular stents and shunts, absorbent materials and separation membranes, three-dimensional constructs, devices, and other uses.

Stable and compatible polymer blends

An implantable cardiac lead system suitable for placement in the coronary sinus region of the heart. The lead system comprises a lead having two or more non-helical bends in its distal portion. The two or more non-helical bends cooperate to prevent the lead from dislodgment or displacement inside the coronary sinus. The lead system may further comprise a stylet suitable for steering the lead into at least one of the coronary sinus vein, great cardiac vein, left marginal vein, left posterior ventricular vein, and small cardiac vein. The stylet is tapered in its distal portion to provide enhanced maneuverability and steerability inside the coronary sinus region. The lead system may also comprise an introducer which aids in introducing the lead into the heart.

Self-anchoring coronary sinus lead

A biosensor including an external surface, and an accessory material in close proximity to the external surface. The accessory material includes a coating containing a hydrophilic material and/or a fiber modified to deliver a therapeutic agent. The biosensor modifies a biological response to the biosensor upon contact with a tissue, such as upon implantation into the skin of a subject, thereby reducing biofouling, inflammation and other undesirable tissue responses that interfere with biosensor performance. The biosensor can be any biocompatible sensor, suitable for short- or long-term use. Preferably, the biosensor is an enzymatic or electrochemical sensor, such as a glucose sensor. Also provided are a method of producing a biosensor and a method of delivering a biologically active substance to a subject.

Anti-inflammatory biosensor for reduced biofouling and enhanced sensor performance

Fluorescent biosensor molecules, fluorescent biosensors and systems, as well as methods of making and using these biosensor molecules and systems are described. These biosensor molecules address the problem of obtaining fluorescence emission at wavelengths greater than about 500 nm. Biosensor molecules generally include an (1) an acridine-based fluorophore, (2) a linker moiety and (3) a boronate substrate recognition/binding moiety, which binds polyhydroxylate analytes, such as glucose. These biosensor molecules further include a 'switch' element that is drawn from the electronic interactions among these submolecular components. This fluorescent switch is generally 'off' in the absence of bound polyhydroxylate analyte and is generally &#x201c;on&#x201d; in the presence of bound polyhydroxylate analyte. Thus, the reversible binding of a polyhydroxylate analyte essentially turns the fluorescent switch &#x201c;on&#x201d; and &#x201c;off&#x201d;. This property of the biosensor molecules, as well as their ability to emit fluorescent light at greater than about 500 nm, renders these biosensor molecules particularly well-suited for detecting and measuring in-vivo glucose concentrations.

Analyte sensing via acridine-based boronate biosensors

Improved polymer matrices which incorporate fluorescent biosensor molecules as well as methods of making and using these polymer matrices are described. Such matrices can be used in fluorescent biosensors and biosensor systems, including those which are used in the detection of polyhydroxylated analytes such as glucose. The properties of the polymer matrices of the invention renders biosensors utilizing such matrices particularly well-suited for detecting and measuring in-vivo glucose concentrations.

Polymers functionalized with fluorescent boronate motifs and methods for making them

Disclosed is a method for microelectrogravimetrically depositing an electroactive species onto an electrode or a plurality of electrodes comprising dispensing a solution containing the electroactive species from a microdispenser to form a hanging drop of the solution and contacting the electrode with the hanging drop of the solution, wherein the electrode is electrically coupled with the microdispenser to form an electrochemical cell, and applying a potential to the electrochemical cell. The application of the potential effects deposition of the electroactive species onto the electrode. The method of the invention eliminates the need for immersion of the electrode in a bath, reduces the volume of solution required by a factor of at least 10-100, and avoids uneven depletion of various components of the solution over successive applications. The method reduces costs, provides for increased reproducibility in the plating process and avoids contamination of the solution, and is particularly suited for plating of enzymes, such as glucose oxidase, or metals, such as platinum, onto electrodes for use as biosensors.

Microelectrogravimetrically plated biosensors and apparatus for producing same

Fluorescent biosensor molecules, fluorescent biosensors and systems, as well as methods of making and using these biosensor molecules and systems are described. Embodiments of these biosensor molecules exhibit fluorescence emission at wavelengths greater than about 650 nm. Typical biosensor molecules include a fluorophore that includes an iminium ion, a linker moiety that includes a group that is an anilinic type of relationship to the fluorophore and a boronate substrate recognition/binding moiety, which binds glucose. The fluorescence molecules modulated by the presence or absence of polyhydroxylated analytes such as glucose. This property of these molecules of the invention, as well as their ability to emit fluorescent light at greater than about 650 nm, renders these biosensor molecules particularly well-suited for detecting and measuring in-vivo glucose concentrations.

Long wave fluorophore sensor compounds and other fluorescent sensor compounds in polymers

Disclosed is a biocompatible membrane comprising a hydrophilic polyurea composition. The hydrophilic polyurea composition comprises the product of a reaction mixture comprising (a) an amino terminated polysiloxane, (b) a hydrophilic polymer selected from the group consisting of a diamino terminated copolymer of polypropylene glycol and polyethylene glycol, polyethylene glycol, polypropylene glycol and diamino polyethylene glycol having an average molecular weight of from about 400 to about 2000, and (c) a diisocyanate selected from the group consisting of hexamethylene-1,6-diisocyanate, dicyclohexylmethane 4,4&prime;-diisocyanate, and isophorone diisocyanate, and constituting about 50 mole % of the reaction mixture. In this mixture, (a) and (b) constitute a polymeric portion of the reaction mixture, and the hydrophilic polyurea composition has a ratio of its diffusion coefficient for oxygen to its diffusion coefficient for glucose of from about 2,000 to about 10,000. Also provided are biosensors coated with a membrane of the invention, and methods of using such biosensors to measure an analyte in a tissue of a subject.

Hydrophilic polymeric material for coating biosensors

Provided is an infusion cannula modified to incorporate one of more medicinal agents. The infusion cannula has a tube having an inner lumen and an external surface, and is made of a flexible, biologically compatible elastomeric material, with a coating adhered to the external surface of the tube. The coating contains a medicinal agent in a polymer matrix. Preferably, the polymer is capable of sustained release of the medicinal agent. The infusion cannula can be produced by coating a tube with a medicinal agent in a polymer matrix. In some embodiments, the coating involves dipping the tube into the polymer matrix, or spraying or painting the polymer matrix onto the tube. Additionally provided is a method for infusing a substance into a subject by inserting the cannula into subcutaneous tissue of the subject and delivering the substance into the cannula, thereby infusing the substance into the subject through the cannula.

Subcutaneous infusion cannula

A passive fixation, body implantable lead assembly has a cylindrical tip electrode whose outer side surface is covered with a thin dielectric insulating layer so as to mask an active, disk-shaped electrode surface at the distal extremity of the tip electrode. The active electrode surface preferably has an area less than about 1 mm . An MCRD, in the form of a collar, may be carried by a proximal portion of the tip electrode. Supplementing a set of main tines projecting from the distal end portion of an insulating sheath housing the lead assembly is a set of nubby auxiliary tines extending from the sheath immediately adjacent the distal extremity thereof.

Lead assembly with masked microdisk tip electrode and monolithic controlled release device

Disclosed is a method for microelectrogravimetrically depositing an electroactive species onto an electrode or a plurality of electrodes comprising dispensing a solution containing the electroactive species from a microdispenser to form a hanging drop of the solution and contacting the electrode with the hanging drop of the solution, wherein the electrode is electrically coupled with the microdispenser to form an electrochemical cell, and applying a potential to the electrochemical cell. The application of the potential effects deposition of the electroactive species onto the electrode. The method of the invention eliminates the need for immersion of the electrode in a bath, reduces the volume of solution required by a factor of at least 10-100, and avoids uneven depletion of various components of the solution over successive applications. The method reduce costs, provides increased reproducibility in the plating process and avoids contamination of the solution, and is particularly suited for plating of enzymes, such as glucose oxidase, or metals, such as platinum, onto electrodes for use as biosensors.

Microelectrogravimetric method for plating a biosensor

Wound dressings and coated implantable medical devices include a styrene sulfonate polymer. Organic and inorganic therapeutic agents may be incorporated in the copolymer. Inorganic therapeutic agents are oligodynamic metals, especially silver.

Medical uses of styrene sulfonate polymers

An implantable cardiac stimulation lead comprises an elongated electrical conductor with an electrode configured to deliver a tiered level of drug therapy to a patient. An insulative electrical sheath covers the electrical conductor and an electrical connector is coupled to the proximal end of the electrical conductor, adapted for connection with the pulse generator. An electrically conductive electrode is located at a distal end of the electrical conductor whose proximal end is adapted for connection to an implantable stimulation device, the electrode having an interior cavity and an axial bore extending between an exterior surface and the interior cavity. A matrix member, preferably composed of silicon rubber, is received within the interior cavity and contains a therapeutic drug. The exterior surface is coated and the bore is filled with a therapeutic drug-hydrophilic wetting agent compound and the bore is filled with a wetting agent compounded with the therapeutic drug such that tiered delivery to a recipient of the therapeutic drug is achieved first from the exterior electrode surface, then from the bore, and finally from the matrix member. The opening of the bore at the exterior surface of the electrode is between about 0.1% and 50% of the entire surface area of the electrode and is insufficient to allow the intrusion of body fluid from the recipient into the cavity in the absence of a wetting agent, a hydrophilic, water soluble, biocompatible polymer. The diameter of the bore is between about 0.001 inches and 0.035 inches.

Open bore electrode with a tiered drug therapy delivery system

An implantable lead includes a distal portion carrying a tissue-stimulating electrode having an outer surface and an inner surface, at least a portion of the outer surface of the electrode being adapted to stimulate cardiac tissue. At least one of the surfaces of the stimulating electrode includes an overlay of a sulfonated thermoplastic elastomer/rubber for minimizing adhesion and tissue ingrowth while passing sufficient electrical current to stimulate the tissue. The overlay may comprise a coating, film, tube, sleeve or other encapsulation. Sulfonated block copolymers of styrene-ethylene-butylene-styrene (SEBS), styrene-ethylene-propylene-styrene (SEPS), styrene-isoprene-styrene and styrene-isobutylene-styrene are effective to inhibit the formation of thrombus at the shocking electrode. In addition, when these copolymers absorb body fluids, they swell and infiltrate the interstices of the electrode coils thereby inhibiting tissue ingrowth. Furthermore, such materials, while non-porous, are conductive and thus do not impede the flow of electrical current at sulfonation levels above at least about 30%, with the optimal level residing between about 40% and about 70%. Although the above-described sulfonated block copolymers are preferred, other hydrogel-like materials may be employed including p-HEMA (polyhydroxymethacrylate), PEG (polyethylene glycol) acrylates, and cross-linked PVP (polyvinylpyrrolidone), and polyurethane hydrogels.

Growing community of inventors

Granada Hills, CA, United States of America

David J Vachon