Compounds and compositions for ossification and methods related thereto
Inventors
Boden, Scott D. • Sangadala, Sreedhara
Assignees
Emory University • US Department of Veterans Affairs
Publication Number
US-10537577-B2
Publication Date
2020-01-21
Expiration Date
2031-08-18
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Abstract
The disclosure relates to compounds and compositions for forming bone and methods related thereto. In one embodiment, the disclosure relates to a composition comprising a compound disclosed herein, such as 2,4-diamino-1,3,5-triazine derivatives or salts thereof, for use in bone growth processes. In a typical embodiment, a bone graft composition is implanted in a subject at a site of desired bone growth or enhancement.
Core Innovation
The invention relates to compounds and compositions for ossification and methods related thereto, specifically involving 2,4-diamino-1,3,5-triazine derivatives or salts thereof used in bone growth processes. Bone graft compositions comprising these compounds are implanted in subjects at sites where bone growth or enhancement is desired. The compounds modulate Smurf1 interaction with its natural target proteins in cells, thereby potentiating bone morphogenetic protein (BMP) signaling to induce osteoblastic differentiation and bone formation.
The problem being solved arises from the complications and limitations associated with traditional bone grafting methods, such as harvesting bone from the iliac crest, which can cause pain, nerve damage, hematoma, and cosmetic deformity. Synthetic bone grafts often require high concentrations of expensive BMPs, such as BMP-2, limiting routine clinical use. There is a need to develop additional compounds and compositions that can substitute or complement BMP usage to improve bone formation while reducing costs and complications.
Claims Coverage
The patent includes multiple independent claims encompassing bone graft compositions, kits, and methods involving specific compounds and compositions.
Bone graft composition comprising specific polymers and substituted biguanides
A bone graft composition comprising collagen, calcium phosphates, bioglass, or hydrogel polymer; and a 1-(phenyl)-5-isopropyl-biguanide or salt thereof optionally substituted with one or more substituents.
Bone graft composition comprising a compound of formula II
A bone graft composition comprising collagen, calcium phosphates, bioglass, or hydrogel polymer; and a compound of formula II as defined in the claims.
Kit comprising substituted biguanides and a graft composition
A kit comprising a 1-(phenyl)-5-isopropyl-biguanide or salt thereof optionally substituted with one or more substituents; and a graft composition comprising collagen, calcium phosphates, bioglass, or hydrogel polymer.
Method of forming bone or cartilage by implanting graft compositions
A method of forming bone or cartilage, comprising implanting a graft composition comprising 1-(phenyl)-5-isopropyl-biguanide or salt thereof optionally substituted with one or more substituents in a subject under conditions such that bone or cartilage forms in the graft composition.
Bone graft compositions also comprising growth factors
Bone graft compositions comprising a growth factor, specifically bone morphogenetic proteins such as BMP-2, BMP-7, BMP-6, or BMP-9, together with 1-(phenyl)-5-isopropyl-biguanide or compound of formula II or their salts.
The claims collectively cover bone graft compositions and kits comprising specific 2,4-diamino-1,3,5-triazine derivatives or salts thereof in polymeric matrices with or without bone morphogenetic proteins, as well as methods of implanting such compositions to form bone or cartilage.
Stated Advantages
The compounds potentiate BMP-induced osteoblastic differentiation and bone formation.
The compositions avoid the need for bone harvesting from donor sites, reducing complications.
The compounds enable lower BMP doses, addressing cost and safety concerns associated with high BMP concentrations.
Documented Applications
Bone grafting for spinal fusions, post-cancerous bone removal, plastic surgery, and filling bone voids.
Forming bone or cartilage in voids in extremities, maxilla, mandible, pelvis, spine, and cranium.
Spinal fusion procedures for conditions such as degenerative disc disease and back pain.
Inserting prosthetic devices or anchors with enhanced bone integration.
Treating and preventing bone fractures using pharmaceutical compositions with the compounds disclosed.
Treating bone degenerative diseases such as osteoporosis, osteitis deformans, bone metastasis, multiple myeloma, primary hyperparathyroidism, and osteogenesis imperfecta.
Use in kits comprising bone graft materials, compounds disclosed, and optionally BMPs or other growth factors.
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