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-9511071-B2
Publication Date
2016-12-06
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, particularly 2,4-diamino-1,3,5-triazine derivatives or salts thereof, for forming bone. The compositions comprise these compounds, optionally combined with bone morphogenetic proteins (BMPs) or other growth factors, in matrices such as collagen sponges, hydrogels, and calcium phosphates, which are implanted in a subject at sites of desired bone growth. The disclosed compounds modulate Smurf1 interactions with natural target proteins, enhancing BMP-mediated osteoblastic differentiation and ossification processes.
Bone grafting traditionally relies on autologous grafts from the iliac crest, which carries risks including pain, nerve damage, hematoma, and cosmetic deformity. Synthetic bone grafts use matrices and BMPs to induce ossification but face challenges such as high cost and the need for large BMP-2 concentrations. Thus, the invention addresses the need for alternative compositions that substitute or complement BMPs for bone growth and repair without the drawbacks of harvesting bone or extensive BMP use.
Claims Coverage
The claims disclose multiple inventive features centered on bone graft compositions comprising 2,4-diamino-1,3,5-triazine derivatives or salts and various matrices, optionally including growth factors such as BMPs, and methods related thereto.
Bone graft composition comprising 2,4-diamino-1,3,5-triazine derivatives and collagen
A composition including a compound of specified formula as a 2,4-diamino-1,3,5-triazine derivative or salt thereof, further comprising collagen.
Selection of specific 2,4-diamino-1,3,5-triazine derivative compounds
The bone graft composition where the 2,4-diamino-1,3,5-triazine derivative is selected from a defined group of specified substituted 1,3,5-triazine compounds or salts thereof.
Inclusion of growth factors in the bone graft composition
The bone graft composition further comprises a growth factor, specifically bone morphogenetic proteins such as BMP-2, BMP-7, BMP-6, or BMP-9.
Bone graft composition comprising 2,4-diamino-1,3,5-triazine derivatives and calcium phosphates
A composition including a compound of specified formula as a 2,4-diamino-1,3,5-triazine derivative or salt thereof, further comprising calcium phosphates, namely hydroxyapatite and tricalcium phosphate, optionally in physiologically compatible bone granules.
Bone graft composition wherein calcium phosphates are present with specific compounds and growth factors
The composition further includes growth factors, specifically bone morphogenetic proteins (BMP-2, BMP-7, BMP-6, BMP-9), and optionally a hydrogel polymer.
Bone graft composition comprising 2,4-diamino-1,3,5-triazine derivatives and bioglass
A composition comprising a specified 2,4-diamino-1,3,5-triazine derivative or salt and bioglass, optionally including growth factors including bone morphogenetic proteins.
The claims cover bone graft compositions containing specific 2,4-diamino-1,3,5-triazine derivatives combined with various biologically compatible matrices such as collagen, calcium phosphates, or bioglass, optionally comprising bone morphogenetic proteins or other growth factors, to enhance or induce bone formation.
Stated Advantages
Provides materials and methods to form bone without the need to harvest bone from remote sites, avoiding complications associated with autologous grafts.
Offers compositions that potentiate BMP activity, allowing for potentially lower doses of BMPs to be used, reducing treatment cost and barriers to clinical use.
Includes compounds that modulate Smurf1 interaction, enhancing BMP signaling and promoting osteoblastic differentiation and bone formation.
Documented Applications
Bone grafting for spinal fusion, cancerous bone removal repair, plastic surgery, and other bone defects.
Treatment of bone fractures, including preventative and therapeutic use for subjects with symptoms or diagnosed fractures.
Treatment of bone degenerative diseases such as osteoporosis, osteitis deformans, bone metastasis, multiple myeloma, primary hyperparathyroidism, and osteogenesis imperfecta.
Methods of forming bone or cartilage by implanting graft compositions at voids in bony structures including extremities, maxilla, mandible, pelvis, spine, or cranium.
Spinal fusion methods to immobilize vertebrae and promote bone growth between vertebrae, including treatment of degenerative disc disease and back pain.
Preparation and insertion of prosthetic devices or anchors by implanting graft compositions in contact with bone to promote integration.
Use of bone graft compositions in sinus augmentation, alveolar ridge augmentation, and dental implant preparation.
Pharmaceutical compositions and dosing regimens for systemic or localized administration including oral, intravenous, intradermal, subcutaneous, or direct injection routes.
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