Compositions and methods for the treatment of bone voids and open fractures
Inventors
Assignees
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Publication Number
US-9173976-B2
Publication Date
2015-11-03
Expiration Date
Abstract
The present invention relates to compositions, methods and medical devices for the treatment of bone voids and bone defects. The methods of the invention comprise the step of applying to a bone void or bone defect site a composition comprising a matrix which provides local prolonged release of at least one antibiotic agent at the bone void site.
Core Innovation
The patent discloses a medical device for treatment of bone voids or bone defects, including open bone fractures, using coated and non-coated bone filler particles implanted at a site requiring bone repair. The device includes coated bone filler particles that contain a biodegradable, lipid-saturated matrix composition together with non-coated bone filler particles mixed in a specified coated-to-non-coated weight ratio. The disclosed compositions use a biodegradable polyester matrix and lipid components to form a substantially water-free multilayer structure supporting local controlled sustained antibiotic delivery while also providing osteoconductive healing support from the bone filler particles.
The matrix composition comprises PLGA, cholesterol, and a mixture of DPPC and DSPC with a defined DPPC:DSPC ratio, together with doxycycline or doxycycline hyclate. The patent further describes local controlled prolonged antibiotic release as providing controlled release with zero-order kinetics over prolonged periods and with limited initial burst, supported by in vitro release profile and stability/antimicrobial activity data. The coated bone filler is described as preventing or eradicating infection at the implantation site while supporting osteoconductive healing.
The document also describes treatment outcomes using coated bone filler in preclinical and clinical settings, including an in vivo rabbit model and human clinical results in open fractures, including Gustilo II through Gustilo IIIB categories. The disclosed results include reported lack of infection at target sites over months in the referenced clinical context. The patent context further relates the device use to implantation at a location where bone growth is desired, including in open long bone fractures, and specifies examples where bone filler components can include synthetic tri-calcium phosphate (β-TCP) and related constraints.
Claims Coverage
The partial content provides three independent claims. Across these claims, the inventive coverage focuses on the specific coated and non-coated bone filler particle device composition and ratio, the biocompatible matrix composition, and use of the device in treating an open bone fracture at the fracture site.
Coated and non-coated bone filler particle device with defined coated-to-non-coated ratio and matrix composition
Coated and non-coated bone filler particles at a ratio of between about 1:3-10:1, wherein the coated bone filler particles comprise between about 80-90% (w/w) of bone filler and between about 10-20% (w/w) of a matrix composition which comprises 15-25% (w/w) PLGA; 5-15% (w/w) cholesterol; 50-70% (w/w) of a mixture of DPPC and DSPC, wherein the ratio of DPPC to DSPC is between 5:1 and 2:1; and 7-12% (w/w) of doxycycline or doxycycline hyclate.
Biocompatible matrix composition with defined PLGA, cholesterol, DPPC/DSPC ratio, and doxycycline component
A biocompatible matrix composition comprising 15-25% (w/w) PLGA; 5-15% (w/w) cholesterol; 50-70% (w/w) of a mixture of DPPC and DSPC, wherein the ratio of DPPC to DSPC is between 5:1 and 2:1; and 7-12% (w/w) of doxycycline or doxycycline hyclate.
Method for treating an open bone fracture by implanting the coated and non-coated bone filler particle device
A method for treating an open bone fracture in a patient comprising implanting at the fracture site a medical device comprising coated and non-coated bone filler particles at a ratio of between about 1:3-10:1, wherein the coated bone filler particles comprise between about 80-90% (w/w) of bone filler and between about 10-20% (w/w) of a matrix composition which comprises 15-25% (w/w) PLGA; 5-15% (w/w) cholesterol; 50-70% (w/w) of a mixture of DPPC and DSPC, wherein the ratio of DPPC to DSPC is between 5:1 and 2:1; and 7-12% (w/w) of doxycycline or doxycycline hyclate.
Across the independent claims, the patent coverage centers on a device of coated and non-coated bone filler particles mixed at a specified weight ratio, a specific biodegradable polyester and lipid matrix with defined DPPC:DSPC ratio and doxycycline or doxycycline hyclate content, and implanting that device at the fracture site to treat an open bone fracture.
Stated Advantages
Local controlled prolonged antibiotic release at the fracture site, including zero-order kinetics over prolonged periods with limited initial burst.
Support of osteoconductive healing from the bone filler while preventing or eradicating infection at the implantation site.
Reported lack of infection at target sites in referenced clinical and preclinical contexts.
Documented Applications
Treatment of bone voids or bone defects, including open bone fractures, by implanting the disclosed medical device at the fracture site.
Treatment of open long bone fractures, including fractures selected by Gustillo grade II through IIIb categories, using the disclosed medical device.
Implantation at a location where bone growth is desired.
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