Prostacyclin compositions for regulation of fracture repair and bone formation

Abstract

The present disclosure provides a prostacyclin coated implant to enhance fracture repair and bone formation comprising: an implant; and a prostacyclin coating comprising a prostacyclin compound disposed in a polymer coating the implant, wherein the prostacyclin coating releases the prostacyclin compound which enhances fracture repair and bone formation.

What is claimed is: 
     
         1 . A composition that enhances fracture repair and bone formation comprising:
 an extended release polymer; and   a prostacyclin disposed in the extended release polymer, wherein the prostacyclin is provided in an amount sufficient to enhance fracture repair and bone formation in situ.   
     
     
         2 . The composition of  claim 1 , wherein the extended release polymer is a hydrogel. 
     
     
         3 . The composition of  claim 1 , wherein the extended release polymer is a hydrogel selected from crosslinked poly(vinyl alcohol) and poly(hydroxy ethylmethacrylate), acyl substituted cellulose acetates and alkyl derivatives thereof, partially and completely hydrolyzed alkylene-vinyl acetate copolymers, polyvinyl chloride, homo- and copolymers of polyvinyl acetate, polyethylene, polypropylene, crosslinked polyesters of acrylic acid and/or methacrylic acid, alkyl acrylates such as methyl methacrylate or methyl acrylate, polyacrylic acid, polyalkacrylic acids such as polymethacrylic acid, polyvinyl alkyl ethers, polyvinyl fluoride, polytetrafluoroethylene, polycarbonate, polyurethane, polyamide, polysulphones, polystyrene, styrene acrylonitrile copolymers, poly(ethylene oxide), poly(alkylenes), poly(vinyl imidazole), poly(esters), poly(ethylene terephthalate), polyphosphazenes, and chlorosulphonated polyolefins, and combinations thereof. 
     
     
         4 . The composition of  claim 1 , wherein the extended release polymer provides a release of the prostacyclin compound over less than 6 months. 
     
     
         5 . The composition of  claim 1 , wherein the extended release polymer comprises multiple layers of polymer coatings to provide a specific release regime over an extended period of time. 
     
     
         6 . The composition of  claim 1 , wherein the composition further comprises bone fragments. 
     
     
         7 . The composition of  claim 1 , wherein the composition is provided in an implant, and wherein the implant is a cage, a wire, a staple, a plate, a screw, a rod, a tubular structure, a scaffold, an external fixation device or a combination thereof. 
     
     
         8 . The composition of  claim 7 , wherein the implant comprises stainless steel, titanium, polyether ether ketone, polyethelene or a combination thereof. 
     
     
         9 . The composition of  claim 1 , wherein the extended release polymer is a biodegradable polymer. 
     
     
         10 . The composition of  claim 1 , wherein the prostacyclin compound is (Z)-5-[(4R,5R)-5-hydroxy-4-((S,E)-3-hydroxyoct-1-enyl)hexahydro-2H-cyclopenta[b]furan-2-ylidene]pentanoic acid or (5E)-5-[(3aS,4R,5R,6aS)-5-hydroxy-4-[(E,3S)-3-hydroxyoct-1-enyl]-3,3a,4,5,6,6a-hexahydro-1H-pentalen-2-ylidene]pentanoic acid. 
     
     
         11 . The composition of  claim 1 , wherein the composition is adapted for administration parenterally, enterally, injected (intravenous (IV), intramuscular (IM), and subcutaneous (SC)), topically, intraarticularly, or via intraosseous infusion. 
     
     
         12 . A device for enhancing fracture repair and bone formation comprising:
 an implant; and   a prostacyclin disposed in a polymer coating the implant, wherein the prostacyclin coating releases the prostacyclin compound which enhance fracture repair and bone formation.   
     
     
         13 . The device of  claim 12 , wherein the polymer coating is an extended release polymer that provides a release of the prostacyclin compound over less than 6 months. 
     
     
         14 . The device of  claim 12 , wherein the polymer coating comprises multiple layers of polymer coatings to provide a specific release regime over an extended period of time. 
     
     
         15 . The device of  claim 12 , wherein the extended release polymer is a hydrogel. 
     
     
         16 . The device of  claim 12 , wherein the extended release polymer is a hydrogel selected from crosslinked poly(vinyl alcohol) and poly(hydroxy ethylmethacrylate), acyl substituted cellulose acetates and alkyl derivatives thereof, partially and completely hydrolyzed alkylene-vinyl acetate copolymers, polyvinyl chloride, homo- and copolymers of polyvinyl acetate, polyethylene, polypropylene, crosslinked polyesters of acrylic acid and/or methacrylic acid, alkyl acrylates such as methyl methacrylate or methyl acrylate, polyacrylic acid, polyalkacrylic acids such as polymethacrylic acid, polyvinyl alkyl ethers, polyvinyl fluoride, polytetrafluoroethylene, polycarbonate, polyurethane, polyamide, polysulphones, polystyrene, styrene acrylonitrile copolymers, poly(ethylene oxide), poly(alkylenes), poly(vinyl imidazole), poly(esters), poly(ethylene terephthalate), polyphosphazenes, and chlorosulphonated polyolefins, and combinations thereof. 
     
     
         17 . The device of  claim 12 , wherein the implant is a cage, a wire, a staple, a plate, a screw, a rod, a tubular structure, a scaffold, an external fixation device or a combination thereof. 
     
     
         18 . The device of  claim 12 , wherein the implant comprises stainless steel, titanium, polyether ether ketone, polyethelene or a combination thereof. 
     
     
         19 . The device of  claim 12 , wherein the implant is a biodegradable polymer. 
     
     
         20 . The device of  claim 12 , wherein the prostacyclin is (Z)-5-[(4R,5R)-5-hydroxy-4-((S,E)-3-hydroxyoct-1-enyl)hexahydro-2H-cyclopenta[b]furan-2-ylidene]pentanoic acid or (5E)-5-[(3aS,4R,5R,6aS)-5-hydroxy-4-[(E,3S)-3-hydroxyoct-1-enyl]-3,3a,4,5,6,6a-hexahydro-1H-pentalen-2-ylidene]pentanoic acid. 
     
     
         21 . The device of  claim 12 , wherein the composition is adapted for administration parenterally, enterally, injected (intravenous (IV), intramuscular (IM), and subcutaneous (SC)), topically, intraarticularly, or via intraosseous infusion 
     
     
         22 . A scaffold for accelerating bone healing comprising:
 an extended release polymer and a prostacyclin in, on, or about the scaffold, wherein the prostacyclin provided in an amount that enhances bone formation about the scaffold.   
     
     
         23 . The scaffold of  claim 22 , wherein the prostacyclin is disposed in an extended release polymer to provide a release of the prostacyclin compound over less than 6 months. 
     
     
         24 . The scaffold of  claim 22 , wherein the extended release polymer comprising multiple layers that provide a specific release regime over an extended period of time. 
     
     
         25 . The scaffold of  claim 22 , wherein the prostacyclin is (Z)-5-[(4R,5R)-5-hydroxy-4-((S,E)-3-hydroxyoct-1-enyl)hexahydro-2H-cyclopenta[b]furan-2-ylidene]pentanoic acid or (5E)-5-[(3aS,4R,5R,6aS)-5-hydroxy-4-[(E,3S)-3-hydroxyoct-1-enyl]-3,3a,4,5,6,6a-hexahydro-1H-pentalen-2-ylidene]pentanoic acid. 
     
     
         26 . The scaffold of  claim 22 , further comprising a coating comprising silver ions, zinc ions, or silver ions and zinc ions to prevent or treat infection. 
     
     
         27 . The scaffold of  claim 22 , wherein the composition is adapted for administration parenterally, enterally, injected (intravenous (IV), intramuscular (IM), and subcutaneous (SC)), topically, intraarticularly, or via intraosseous infusion 
     
     
         28 . A method for treating and enhancing fracture repair and bone formation comprising the steps of:
 providing an implant having a prostacyclin disposed in a polymer; and   positioning the implant in a position to provide prostacyclin at a bone healing interface, wherein the prostacyclin about the bone healing interface to enhance fracture repair and bone formation.