Compositions and products for use in the treatment of bone fractures and defects
Inventors
Assignees
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Publication Number
US-11541063-B2
Publication Date
2023-01-03
Expiration Date
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.
Core Innovation
The invention relates to local treatment of a bone fracture or bone defect in a patient by applying onto or into the site a formulation comprising at least one biodegradable polymer, a testosterone, dihydrotestosterone or an ester thereof, and an alendronate or pharmaceutically acceptable salt thereof. The formulation stimulates formation of new bone at the site by inducing osteoblast activity, and the local application is directed to a fracture or defect site rather than systemic administration.
The disclosed formulations combine an anabolic androgen receptor agonist component with an anti-catabolic bisphosphonate component, and this combination is framed as a synergistic approach that enhances osteoblast activity and promotes new bone formation. Controlled/zero-order release concepts are discussed in connection with biodegradable polymers, including amino-acid based polyester urethanes, polyesteramides (PEAs), and multi-block copolymers for erosion-driven release.
The invention further discloses multiple delivery formats for local administration at the fracture/defect site, including injectable in situ depot-forming formulations, one-directional-release patches with an essentially impermeable outer layer, bone fillers optionally containing microspheres, and coated implants/devices. A preclinical in-vitro osteoblast study is described showing stronger ALP induction with alendronate plus Stanolone than alendronate alone, supporting the osteoblast activity induction concept.
Claims Coverage
The independent claim covers a local bone-treatment method with a formulation containing a biodegradable polymer, an androgen receptor agonist component, and alendronate or a pharmaceutically acceptable salt, where osteoblast activity induction stimulates new bone formation. The claim set includes further refinements through dependent claims that narrow polymer selection, application format, target fracture type, and quantitative ranges for the drug components.
Local biodegradable-polymer testosterone/dihydrotestosterone-alendronate bone treatment
A method for local treatment of a bone fracture or bone defect in a patient by applying onto or into the site a formulation comprising at least one biodegradable polymer, a testosterone, dihydrotestosterone or an ester thereof, and an alendronate or pharmaceutically acceptable salt thereof, wherein the method stimulates formation of new bone at the site by inducing osteoblast activity.
Drug amount constraints for testosterone component
The formulation comprises testosterone, dihydrotestosterone, or an ester thereof in an amount equivalent to 20 μg to 2.5 mg of testosterone.
Drug amount constraints for alendronate component
Alendronate or a salt thereof is included in the formulation in an amount of 1 μg to 250 μg.
Selection of biodegradable polymer from defined biodegradable polymer classes
The biodegradable polymer is chosen from biodegradable polymers including polylactides, polyglycolides, polycaprolactones, and related polymers and copolymers, including block copolymers and branched copolymers, and mixtures thereof.
Application as a coating
The formulation is applied as a coating.
Treatment of complicated or pathological fractures/defects
The method is applied to a complicated fracture or a pathological bone fracture or bone defect.
Overall, the claim coverage centers on local application of a biodegradable-polymer formulation combining testosterone/dihydrotestosterone or esters with alendronate or salts to induce osteoblast activity and stimulate new bone formation. Dependent claims further narrow biodegradable-polymer selection, application as a coating, the fracture or defect being complicated or pathological, and specified quantitative ranges for the androgenic and bisphosphonate components.
Stated Advantages
Stimulates formation of new bone at the site of the bone fracture or bone defect by inducing osteoblast activity.
Stronger osteoblast activity indication as supported by increased ALP induction in an in-vitro osteoblast study with alendronate plus Stanolone than with alendronate alone.
Documented Applications
Local treatment of a bone fracture or bone defect in a patient, including complicated fractures and pathological bone fractures or bone defects.
Use in delivery formats including injectable in situ depot-forming formulations, one-directional-release patches, bone fillers optionally containing microspheres, and coated implants/devices for local fracture or defect site treatment.
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