45 results about "Cartilage degradation" patented technology

Methods and compositions for inhibiting articular cartilage degradation. The compositions preferably include multiple chondroprotective agents, including at least one agent that promotes cartilage anabolic activity and at least one agent that inhibits cartilage catabolism. The compositions may also include one or more pain and inflammation inhibitory agents. The compositions may be administered systemically, such as to treat patients at risk of cartilage degradation at multiple joints, and suitably may be formulated in a carrier or delivery vehicle that is targeted to the joints. Alternatively the compositions may be injected or infused directly into the joint.

[1,2,4]Triazolo[1,5-a]pyridine compounds are disclosed that have a formula represented by the formula (I). The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, diseases involving cartilage degradation, bone and / or joint degradation, for example osteoarthritis; and / or conditions involving inflammation or immune responses, such as Crohn's disease, rheumatoid arthritis, psoriasis, allergic airways disease (e.g. asthma, rhinitis), juvenile idiopathic arthritis, colitis, inflammatory bowel diseases, endotoxin-driven disease states (e.g. complications after bypass surgery or chronic endotoxin states contributing to e.g. chronic cardiac failure), diseases involving impairment of cartilage turnover (e.g diseases involving the anabolic stimulation of chondrocytes), congenital cartilage malformations, diseases associated with hypersecretion of IL6, transplantation rejection (e.g. organ transplant rejection) and proliferative diseases.

The change in tissue impedance due to the change in the extracellular matrix that results from the degradation of cartilage is utilized to detect degradation of articular cartilage. A probe includes electrodes that apply a current to the articular cartilage which results in a current distribution and electric field within the cartilage, along with an associated voltage drop across the electrodes. The amplitude of this voltage drop is then measured and divided by the current applied to determine the tissue impedance. By measuring the impedance of patient tissue and comparing the detected patient impedance to a normal value for the tissue from clinically normal tissue, a determination of whether the patient tissue is degraded, and a determination of the extent of degradation is possible. Preferably, the impedance is measured using a probe with interdigitated electrodes. By changing which electrodes are utilized, the wavelength of the current distribution changes, allowing the probe to image depth dependent focal lesions.

A compound of formula (I), or a pharmaceutically acceptable salt, hydrate, complex or pro-drug thereof,wherein: one of R1 and R2 is H, and the other is selected from OR6, SR6, NR6R7, N3, Me, Et, CF3, SOR8 and SO2R8; orR1 and R2 are both H;one of R3 and R4 is H, and the other is selected from tert-butylmethyl, iso-propylmethyl, sec-butyl, tert-butyl, cyclopentyl and cyclohexyl; orR3 and R4 are joined together with the adjacent backbone carbon atom to form a spiro-C5-C6 cycloalkyl group;R6 and R7 are each independently selected from H, C1-8-alkyl and C3-8-cycloalkyl; orR6 and R7 are linked to form a cyclic group together with the nitrogen to which they are attached;R8 is C1-8-alkyl or C3-8-cycloalkyl;R9 is a para-substituted 6-membered monocyclic aryl or heteroaryl ring which includes up to five heteroatoms.The invention further relates to pharmaceutical compositions comprising compounds of formula (I), and the use of such compounds in the treatment of a disease selected from osteoporosis, Paget's disease, Chagas's disease, malaria, gingival diseases, hypercalaemia, metabolic bone disease, diseases involving matrix or cartilage degradation, and bone cancer disorders such as bone metastases and associated pain.

The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts thereof,wherein:X is CH or N; andR4 is optionally substituted C3-8 alkyl or optionally substituted C3-8 cycloalkyl.The invention further relates to pharmaceutical compositions comprising compounds of formula (I), and the use of such compounds in the treatment of a disease selected from osteoporosis, Paget's disease, Chagas's disease, malaria, gingival diseases, hypercalaemia, metabolic bone disease, diseases involving matrix or cartilage degradation, and bone cancer disorders such as bone metastases and associated pain.

The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts thereof,wherein:X is CH or N;one of R1 and R2 is H, and the other is selected from OR6, SR6, NR6R7, N3, Me, Et, CF3, SOR8 and SO2R8;R3 is selected from tert-butylmethyl, iso-propylmethyl, sec-butyl, tert-butyl, cyclopentyl and cyclohexyl;R4 is optionally substituted C1-8 alkyl or optionally substituted C3-8 cycloalkyl;R6 and R7 are each independently selected from H, C1-8-alkyl and C3-8-cycloalkyl, or R6 and R7 are linked to form a cyclic group together with the nitrogen to which they are attached; andR8 is C1-8-alkyl or C3-8-cycloalkyl.The invention further relates to pharmaceutical compositions comprising compounds of formula (I), and the use of such compounds in the treatment of a disease selected from osteoporosis, Paget's disease, Chagas's disease, malaria, gingival diseases, hypercalaemia, metabolic bone disease, diseases involving matrix or cartilage degradation, and bone cancer disorders such as bone metastases and associated pain.

A method for decreasing cartilage abnormalities and preventing cartilage degradation in an animal using a combination at least one sulfur containing amino acid and manganese.

The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts thereof, A compound of formula (I), or a pharmaceutically acceptable salt, hydrate, complex or pro-drug thereof (I), wherein: one of R1 and R2 is H, and the other is selected from F and Cl, or R1 and R2 are both F; R3 is selected from cyclopentyl and cyclohexyl; R4 is an optionally substituted 5- or 6-membered monocyclic or an 8- to 10-membered bicyclic aryl or heteroaryl ring which includes up to four heteroatoms. The invention further relates to pharmaceutical compositions comprising compounds of formula (I), and the use of such compounds in the treatment of a disease selected from osteoporosis, Paget's disease, Chagas's disease, malaria, gingival diseases, hypercalaemia, metabolic bone disease, diseases involving matrix or cartilage degradation, and bone cancer disorders such as bone metastases and associated pain.

The present invention relates to compounds of formula (I), and pharmaceutically acceptable salts thereof (I), wherein: R3 is cyclopentyl or cyclohexyl; X is CH or N; and R4 is optionally substituted C1-8 alkyl or optionally substituted C3-8 cycloalkyl. The invention further relates to pharmaceutical compositions comprising compounds of formula (I), and the use of such compounds in the treatment of a disease selected from osteoporosis, Paget's disease, Chagas's disease, malaria, gingival diseases, hypercalaemia, metabolic bone disease, diseases involving matrix or cartilage degradation, and bone cancer disorders such as bone metastases and associated pain.