Compositions and products for use in the treatment of bone fractures and defects

Abstract

The invention relates to methods for treatment of bone fractures and defects, in particular to method that accelerate fracture healing, and to compositions, injectable in situ depot forming formulations and patches comprising at least one biodegradable polymer, an androgen receptor agonist and a bisphosphonate or pharmaceutically acceptable salt thereof for use in such methods.

1 . A composition comprising at least one biodegradable polymer, an androgen receptor agonist and a bisphosphonate or pharmaceutically acceptable salt thereof, wherein said composition is a composition for local administration to bone and wherein the amount of said bisphosphonate or salt thereof is between 0.1 μg and 1 mg and the amount of said androgen receptor agonist is between 1 μg and 10 mg of testosterone or a derivative thereof or an equipotent amount of an androgen receptor agonist other than testosterone. 
     
     
         2 . A composition according to  claim 1  wherein the androgen receptor agonist is testosterone or a derivative thereof. 
     
     
         3 . A composition according to  claim 2  wherein the testosterone or derivative is testosterone, nandrolone or dihydrotestosterone. 
     
     
         4 . A composition according to  claim 1  wherein the bisphosphonate is selected from the group consisting of alendronate, risedronate, ibandronate, pamidronate, clodronate, zoledronate, etidronate, tiludronate, minodronate, olpadronate, neridronate, incadronate, and mixtures thereof. 
     
     
         5 . A composition according to  claim 1  wherein the bisphosphonate is alendronate or alendronate sodium. 
     
     
         6 . (canceled) 
     
     
         7 . A composition according to  claim 1 , wherein the at least one biodegradable polymer is selected from the group consisting of polylactides, polyglycolides, polycaprolactones, polydioxannones, polycarbonates, polyhydroxybutyrates, polyalkyene oxalates, polyanhydrides, polyamides, polyesteramides, polyurethanes, polyacetals, polyketals, polyorthocarbonates, polyphosphazenes, polyhydroxyvalerates, polyalkylene succinates, poly(malic acid), polyorthoesters, and copolymers, block copolymers, branched copolymers, and mixtures thereof, such as, poly-D, L-Lactide (PDLLA), copolymers of lactide and glycolide (PLGA), copolymers of lactide and s-caprolactone, poly(lactide-2-caprolactone) (PLA-2-CL) copolyesters and polylactide-trimethylenecarbonate copolymer and amino acid-based polymers such as tyrosine-based polyarylates and polycarbonates, and leucine and/or lysine-based polyester urethanes and polyester-amides. 
     
     
         8 . A patch, injectable in situ forming depot formulation or bone filler composition comprising a composition according to  claim 1 . 
     
     
         9 . A patch according to  claim 8  comprising a first layer comprising said composition according to  claim 1  and a biodegradable second layer which is essentially impermeable for said androgen receptor agonist and said bisphosphonate or pharmaceutically acceptable salt thereof. 
     
     
         10 . (canceled) 
     
     
         11 . A patch, injectable in situ forming depot formulation, or bone filler according to  claim 8  comprising testosterone in an amount of between 1 μg and 10 mg and alendronate or alendronate sodium in an amount of between 0.1 μg and 100 μg. 
     
     
         12 . (canceled) 
     
     
         13 . A coating for a bone filler, medical device and/or bone implant comprising a composition according to  claim 1 . 
     
     
         14 . A bone filler, medical device or bone implant provided with a coating according to  claim 13 . 
     
     
         15 .- 19 . (canceled) 
     
     
         20 . A method of treating a bone fracture or bone defect in a patient comprising administering to a site of fracture a composition according to  claim 1 . 
     
     
         21 . A method according to  claim 20  wherein said fracture is a complicated fracture or a pathological fracture. 
     
     
         22 . A method according to  claim 20  comprising administering to the site of fracture or defect a patch comprising said composition. 
     
     
         23 . A method according to  claim 20  comprising administering to the site of fracture or defect an injectable in situ forming depot formulation comprising said composition. 
     
     
         24 . A method according to  claim 20  comprising introducing a bone filler comprising said composition to or into a site of the bone fracture or bone defect. 
     
     
         25 . A method according to  claim 20  comprising introducing a bone filler, medical device or bone implant provided with a coating comprising said composition to or into a site of the bone fracture or bone defect. 
     
     
         26 . A method according to  claim 20  wherein bisphosphonate is alendronate or alendronate sodium and the androgen receptor agonist is testosterone, nandrolone or dihydrotestosterone. 
     
     
         27 . A composition according to  claim 2  wherein the testosterone or derivative is selected from the group consisting of testosterone, a testosterone ester, a testosterone precursor, a testosterone metabolite and a testosterone analogue.