The present invention generally relates to nitric oxide releasing pharmaceutical compositions and methods of using the same.

Nitric oxide-releasing materials, methods of making nitric oxide-releasing materials, and uses of nitric oxide-releasing materials are provided. The nitric oxide-releasing materials include a mesoporous silica core and an outer surface having a plurality of nitric oxide donors. In an exemplary aspects, the nitric oxide-releasing material includes a mesoporous diatomaceous earth core, and an outer surface having a plurality of S-nitroso-N-acetyl-penicillamine groups covalently attached thereto. Uses of the nitric oxide-releasing materials can include coatings for medical devices such as catheters, grafts, and stents; wound gauzes; acne medications; and antiseptic mouthwashes; among others.

The present invention generally relates to nitric oxide releasing pharmaceutical compositions and methods of using the same.

A variety of nitric oxide-releasing vascular grafts and prostheses are provided. Methods of making the nitric oxide-releasing vascular grafts and prostheses are also provided. Methods of administering the nitric oxide-releasing vascular grafts and prostheses to a subject in need thereof are also provided. The nitric oxide-releasing vascular grafts and prostheses have a base layer made of a graft material and a nitric oxide-releasing layer made from a polymer matrix including a plurality of polysiloxanes and a plurality of nitric oxide-donating crosslinking moieties covalently crosslinking polysiloxanes in the plurality of polysiloxanes. In some aspects, the vascular grafts and prostheses can provide for reduced infection rates and increased patency by providing for prolonged local delivery of nitric oxide when implanted in a vessel of a subject in need thereof.

A self-activating dressing for use with a medical device inserted into a skin surface of a patient via a skin insertion site. The dressing includes a dressing body impregnated with a nitric oxide releasing compound which reacts in the presence of a physiological fluid to release nitric oxide. Nitric oxide provides antimicrobial activity and promotes wound healing. The nitric oxide releasing compound may include s-nitroso-n-acetyl penicillamine (SNAP), s-nitrosoglutathione (GSNO), and mixtures thereof. A slit defined in the dressing body enables the dressing body to be placed around a perimeter of the medical device on the skin surface at the skin insertion site such that the dressing body surrounds and contacts skin insertion site. The dressing body may be further impregnated with a catalyst, such as copper, iron, zinc, selenium, and silver, to facilitate release of nitric oxide. The dressing body may be further impregnated with an additional antimicrobial agent.

Coating compositions, coated articles including the coating compositions, and methods of making the coating compositions and coated articles are provided. In some aspects, the coating compositions are applied to a substrate having nitric oxide-releasing properties. The coating compositions can include copolymers having crosslinking agents that can be activated with mild UV light (about 345 nm to 365 nm) to avoid damaging the substrate while creating strong covalent bonds to the substrate. The copolymers can include hydrophilic repeat units, and in particular zwitterionic repeat units such as repeat units containing phosphorylcholine groups. In some aspects, the coating compositions are applied to a surface of a polymer substrate, wherein the polymer substrate had nitric oxide releasing properties. The coating compositions and the coated articles can have antifouling, antithrombotic, and/or antibacterial properties.

Described herein are nitric oxide releasing materials, methods of making nitric oxide releasing materials, and devices including nitric oxide releasing materials. The nitric oxide releasing material includes a polymer matrix having a plurality of polysiloxanes and nitric oxide-donating crosslinking moieties that covalently crosslink the polysiloxanes. Blood clotting or adhesion of a bio-material to a surface, as well as biofilm formation can be prevented using the methods and materials described.

The present disclosure relates to a method for immobilizing heparin and a NO-generating catalyst and a cardiovascular device having a surface modified using the same, and more particularly, to a method of co-immobilizing a heparin-phenol derivative and copper nanoparticles as a NO-generating catalyst on the surface of a material by a polyphenol oxidase-mediated reaction, a material having a surface with heparin and a NO-generating catalyst co-immobilized thereon by using the method, and a cardiovascular device including the material. It has been confirmed that a surface having heparin and the NO-generating catalyst co-immobilized thereon by the method of the present disclosure has high in vivo stability, continuously generates NO, and also promotes the proliferation of endothelial cells while significantly inhibiting the adhesion and activation of platelets and smooth muscle cells. Thus, the method may be advantageously applied to cardiovascular devices for inhibiting thrombosis and restenosis.

A catheter configured to release nitric oxide and chlorhexidine providing anti-platelet and antimicrobial properties is manufactured by impregnating a thermoplastic polyurethane catheter extrusion with a nitric oxide releasing compound and with chlorhexidine. Thereafter, the impregnated catheter extrusion is coated with a polyurethane coating comprising chlorhexidine and/or a nitric oxide releasing compound. In the impregnating step, the catheter extrusion may be exposed to a solvent having the nitric oxide releasing compound and chlorhexidine dissolved therein. The solvent is removed from the catheter extrusion. In the coating step, the impregnated catheter extrusion may be dip coated in a polymer solution comprising polyurethane and chlorhexidine and/or a nitric oxide releasing compound in a suitable solvent. The nitric oxide releasing compound, impregnated and/or coated, may be selected from s-nitroso-n-acetylpenicillamine (SNAP), s-nitrosoglutathione (GSNO), and mixtures thereof. The chlorhexidine, impregnated and/or coated, may be selected from chlorhexidine diacetate, chlorhexidine base, chlorhexidine gluconate, and mixtures thereof.

Methods of preparing nitric oxide-releasing silica particles are provided, including the steps of functionalizing a silica particle with a linker moiety; and reacting a functional group on a nitric oxide storage/release compound with the linker moiety to attach the nitric oxide storage/release compound to the silica particle via the linker moiety. The disclosure also provides certain nitric oxide-releasing silica particles and precursors thereof, as well as compositions containing such particles.