TGF-beta enhancing compositions for cartilage repair and methods related thereto
Inventors
Boden, Scott D • Sangadala, Sreedhara
Assignees
Emory University • US Department of Veterans Affairs
Publication Number
US-10322125-B2
Publication Date
2019-06-18
Expiration Date
2034-02-18
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Abstract
This disclosure relates to compounds and compositions for cartilage repair and methods related thereto. In certain embodiments, the disclosure relates to methods of inducing cartilage growth and regeneration comprising administering an effective amount of a composition comprising a compound disclosed herein to the subject or implanting a cartilage matrix comprising a compound disclosed herein in the subject. In certain embodiments, the compound is used locally such as injection at any desired site of cartilage formation.
Core Innovation
This disclosure relates to compounds and compositions for cartilage repair and methods related thereto, specifically methods of inducing cartilage growth and regeneration. The invention involves administering an effective amount of a pharmaceutical composition comprising selected compounds or implanting a cartilage matrix comprising such compounds into a subject. The compounds may be used locally, for example by injection at any desired site of cartilage formation, and the compositions may be delivered through devices such as syringes or catheters.
The problem addressed is the lack of effective disease-modifying treatments for osteoarthritis, a condition resulting in cartilage degeneration common in the aging population. Current treatments focus primarily on symptom management, with joint replacement surgery as a last resort. There is a recognized need for improved therapies that promote cartilage growth and repair, as articular cartilage damage leads to joint dysfunction and currently available treatments do not adequately regenerate damaged cartilage tissue.
The invention includes pharmaceutical compositions comprising TGF-β enhancing compounds or their salts and pharmaceutically acceptable excipients. These compounds include specific chemical classes such as 1-ethylidene-2-phenylhydrazine derivatives, pyrimidine-2,4-diamine derivatives, 3-benzylideneindolin-2-one derivatives, quinolin-4-amine derivatives, and quinazolin-4-amine derivatives. The compositions can be formulated for controlled release over variable time periods and may be administered by various routes including local injection or systemic delivery.
Claims Coverage
The claims define eight main inventive features across pharmaceutical compositions, methods of treatment, cartilage matrices, and kits, focusing on specific compounds to promote cartilage repair and regeneration.
Pharmaceutical composition comprising selected compounds
A pharmaceutical composition comprising a compound selected from a group of specified hydrazine derivatives or their salts, combined with a pharmaceutically acceptable excipient.
Method of treating damaged cartilage by administering a compound
A method of treating damaged cartilage from physical injury or chondrodystrophies by administering an effective amount of a specified compound to a human subject in need thereof.
Method of administering composition using injection devices
Administering the pharmaceutical composition by injection using a syringe or catheter with a lumen, slid through an incision at the site of damaged cartilage.
Method of co-administration with progenitor or stem cells and growth factors
Administering the compound in combination with progenitor cells, autologous mesenchymal stem cells, peripheral blood progenitor cells, chondrocytic cells, TGF-β proteins, hyaluronic acid, proteoglycans, growth factors, or combinations thereof.
Method of treating cartilage damage by surgically creating lesions and administering compounds
Treating damaged cartilage by surgically creating lesions extending into subchondral bone and administering a specified compound at the site of the lesions.
Method of treating cartilage damage by lesion creation and implanting a matrix with compound
Treating damaged cartilage by surgically creating lesions and implanting a cartilage matrix comprising the specified compound in the area of created lesions.
Method combining matrix implantation and compound administration
Treating damaged cartilage by creating lesions, implanting a matrix in the lesion area, and administering the specified compound at the same site.
Cartilage matrix and kit comprising compound and optional cells or growth factors
A cartilage matrix comprising collagen, hydrogel, or similar materials and the specified compound; and kits comprising the matrix and compound, optionally including progenitor cells, mesenchymal stem cells, TGF-β proteins, hyaluronic acid, proteoglycans, or growth factors, and transfer devices such as syringes or catheters.
The claims cover pharmaceutical compositions comprising specific TGF-β enhancing compounds, methods of treating damaged cartilage via local or systemic administration of these compounds, methods involving surgical lesion creation with compound administration and implanting cartilage matrices, as well as cartilage matrices and kits incorporating these compounds with optional biological components. Together, these claims define a comprehensive approach to cartilage repair and regeneration using the disclosed compounds.
Stated Advantages
The compositions and methods provide improved therapies for cartilage repair and regeneration, addressing the lack of effective disease-modifying treatments for osteoarthritis and related cartilage damage.
Localized administration and controlled release formulations enable targeted treatment at the site of cartilage damage, potentially enhancing efficacy and reducing systemic effects.
Combination with progenitor cells, stem cells, chondrocytic cells, TGF-β proteins, and other growth factors supports enhanced cartilage growth and integration of grafts.
Use in surgical methods involving lesion creation and cartilage matrix implantation optimizes the regeneration environment for damaged cartilage tissue.
Documented Applications
Treatment of damaged cartilage from physical injury or chondrodystrophies such as osteoarthritis, achondroplasia, costochondritis, spinal disc herniation, and polychondritis.
Articular cartilage repair and regeneration, including autologous chondrocyte implantation and marrow-stimulating procedures like microfracture surgery.
Regeneration of intervertebral disc cartilage, including annulus fibrosus and nucleus pulposus tissue, optionally using fabricated intervertebral disc implants.
Use in cartilage matrix or scaffold formations comprising hydrogels, collagen, agarose, alginate, hyaluronic acid, fibrin, or polyglycolic acid, optionally with stem or progenitor cells and growth factors.
Pharmaceutical compositions for oral, intravenous, parenteral, intradermal, percutaneous, subcutaneous, and localized injection administration routes for cartilage growth and repair.
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