Boston Scientific Scimed, Inc.

Scimed Life Systems, Inc.

Robert Herrmann

David Knapp

Wendy Naimark

Young-Ho Song

Yixin Xu

Anurag Singhal

Jan Weber

Aiden Flanagan

Peter L Dayton

Scott Schewe

Torsten Scheuermann

Frederick H Strickler

Barry J O'Brien

Michael Kuehling

Ken Merdan

Rajesh Radhakishnan

Mary Joe Timm

An implantable medical device for releasing therapeutic agent having a medical device body and a plurality of reservoir-defining structures disposed on a surface of the body. A reservoir can be defined by the reservoir-defining structures and therapeutic agent may be located in the reservoir. A cover may extend over the reservoir so that the therapeutic agent is released from the reservoir when the medical device implanted. Methods for making the medical device may also include providing a medical device body, positioning a plurality of reservoir-defining structures on a surface of the body to form a reservoir, loading therapeutic agent into the reservoir, and covering the reservoir so that the therapeutic agent may release when the medical device is implanted. Alternatively, the reservoir may be covered with a cover and an opening formed in the cover so that the therapeutic agent may release when the medical device is implanted.

Medical devices for releasing therapeutic agent and methods of making the same

A medical device is provided which is adapted for implantation or insertion into the vasculature. The medical device has (a) a medical device substrate; (b) a lower polymeric layer, provided over the substrate made of a nitric oxide donor and a polymer; and (c) an upper polymeric layer, provided over the lower polymer layer, made of a polymer and an anti-restenotic agent.

Anti-thrombogenic and anti-restenotic vascular medical devices

According to an aspect of the present invention, implantable or insertable medical devices are provided which contain the following: (a) substrate having one or more depressions that contain at least one therapeutic agent and (b) a porous membrane disposed over the substrate and the one or more depressions, which regulate transport of chemical species between the therapeutic-agent-containing depressions and the exterior of the device. The substrate and the porous membrane are formed of different materials each with a different thermal expansion coefficient. Moreover, one of the substrate and the porous membrane at least partially surrounds the other. Other aspects of the present invention are directed to methods of making such medical devices, and methods of treatment using such medical devices.

Medical devices having porous component for controlled diffusion

A medical device with a therapeutic agent-releasing polymer coating. The medical device is provided by a method that comprises: (a) attaching at least one reactive species to a medical device surface, which reactive species leads to chain growth polymerization in the presence of monomer; (b) contacting the reactive species with at least one monomer species, thereby forming a polymer coating on the surface of the medical device; and (c) providing at least one therapeutic agent within the polymer coating. The therapeutic agent may be incorporated during formation of the polymer coating or after formation of the polymer coating. The at least one reactive species can comprise, for example, a free radical species, a carbanion species, a carbocation species, a Ziegler-Natta polymerization complex, a metallocene complex, and/or an atom transfer radical polymerization initiator. Alternatively, the medical device is provided by a process comprising: (a) immobilizing least one polymerization catalyst at a medical device surface, which polymerization catalyst leads to polymerization in the presence of monomer; (b) contacting the medical device surface with at least one monomer species, thereby forming a polymer coating at the surface of the medical device; and (c) providing at least one therapeutic agent within the polymer coating.

Processes for producing polymer coatings through surface polymerization

This invention relates to devices and methods for the local, differential delivery of nitric oxide within the body. The devices include devices having at least two differing nitric oxide donor compounds, such as nitric oxide donor compounds having differing half-lives and nitric oxide donor compounds having different release mechanisms. The devices also include devices having at least two chemically distinct compositions to which nitric oxide donor compounds are adsorbed or attached or within which the donor compounds are disposed. The devices are typically used to increase local nitric oxide concentration in the body upon placement of the medical article at a delivery position on or within a patient. The methods of the present invention include a method of treating an atherosclerotic lesion which comprises: exposing the lesion to a first higher concentration of nitric oxide effective to reduce the number of cells within the lesion; and subsequently exposing the lesion to a second lower concentration of nitric oxide effective to inhibit restenosis. The methods of the present invention also include methods for preferentially providing differing nitric oxide donor compounds within different tissues to effect therapy.

Differential delivery of nitric oxide

Novel nitric-oxide releasing lipid molecules are provided which comprise a lipid molecule selected from (a) phosphoglycerides, (b) lipids having a sphingosine base as a backbone, (c) monoacylglyerols, (d) diacylglycerols, (e) glycosylacylglycerols, and (f) sterol compounds of the formula: where R is a branched aliphatic chain of eight or more carbon atoms, wherein the lipid molecule is provided with a nitric-oxide containing group which comprises (a) a &#x2014;S&#x2014;N&#x2550;O moiety, (b) a &#x2014;O&#x2014;N&#x2550;O moiety, or (c) a a moiety. Also provided are methods of forming such nitric oxide releasing lipid molecules. Various pharmaceutical compositions, topical liquids and drug delivery systems comprising the nitric-oxide releasing lipid molecules are also described. Further provided are methods for therapeutically administering nitric oxide to patients, methods of treating or preventing various conditions, methods for promoting wound healing and methods of reducing the cells present in an atherosclerotic lesion, which methods utilize the nitric-oxide releasing lipid molecules.

Lipid-based nitric oxide donors

A method for producing a S-nitrosylated species is provided. The method comprises: (a) providing a deoxygenated, alkaline aqueous solution comprising a thiol and a nitrite-bearing species; (b) acidifying the solution by adding acid to the solution while concurrently mixing the solution (e.g., by vigorously stirring the solution) to produce the S-nitrosylated species; and (c) isolating the S-nitrosylated species. The nitrite-bearing species can be, for example, an inorganic nitrite, such as an alkali metal nitrite, or an organic nitrite, such as an alkyl nitrite (e.g., ethyl nitrite, amyl nitrite, isobutyl nitrite or t-butyl nitrite). The thiol is preferably a thiol-containing polysaccharide, a thiol-containing lipoprotein, a thiol-containing amino acid or a thiol-containing protein, and more preferably a thiol-containing polysaccharide such as thiolated cyclodextrin. In many preferred embodiments, the S-nitrosylated species is insoluble in the acidified solution, precipitating upon formation. The S-nitrosylated species can be isolated, for example, by a process in which the precipitate is removed from the solution (e.g., by centrifugation) and the aqueous solvent remaining in the precipitate is sublimated (e.g., by freezing the precipitate and subjecting it to a vacuum). The isolated S-nitrosylated product is preferably protected from heat, light, moisture and oxygen.

High yield S-nitrosylation process

An implantable or insertable medical device is provided which comprises (a) a superoxide dismutase mimic and (b) a polymeric release region. Upon administration to a patient, the polymeric release region controls the release of the superoxide dismutase mimic, which is beneficially selected from a metal-chelate superoxide dismutase mimic and a nitroxide superoxide dismutase mimic. Also provided is a method of making an implantable or insertable medical device.

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Boston, MA, United States of America

Robert Herrmann