Medical implants containing adenosine receptor agonists and methods for inhibitiing medical implant loosening

The invention provides methods and compositions for reducing or inhibiting bone resorption, osteoclast differentiation and stimulation and the loosening of medical prostheses by administering a compound or agent that modulates an adenosine receptor such as the adenosine A 2A receptor, in particular, an agonist of an adenosine A 2A receptor. The invention also extends to pharmaceutical compositions comprising such an agent that modulates an adenosine receptor such as an adenosine A 2A agonist and to prosthetic devices containing such an agent that modulates an adenosine receptor such as an A 2A agonist on one or more surfaces or within the prosthetic device such as, for example, suspended in the cement forming the prosthetic device.

Methods for Inhibiting Osteolysis

The invention provides methods and compositions for reducing or inhibiting osteolysis, bone resorption, osteoclast differentiation and stimulation and the loosening of medical prostheses by administering a compound or agent that inhibits the biological activity of an axon guidance protein. The compound or agent my inhibit transcription or translation of or bind to an axon guidance protein, such as, for instance, a netrin like netrin-1. Likewise, the compound or agent may inhibit transcription or translation of or bind to a receptor of an axon guidance protein, such as, for instance, a netrin receptor such as unc5b. In some instances, the compound or agent is an agonist of an adenosine Areceptor. The invention also extends to pharmaceutical compositions comprising such compounds and agents. 1. A method for inhibiting , reducing or slowing osteolysis comprising administering to a subject a therapeutically effective amount of an agent effective to inhibit or reduce the biological activity of an axonal guidance protein or a receptor of the axonal guidance protein , or an analog , derivative or a combination thereof.2. The method according to wherein the axonal guidance protein is selected from the group consisting of sema4D claim 1 , plexin A1 claim 1 , and netrin-1.3. The method according to wherein the agent effective to inhibit or reduce the biological activity of an axonal guidance protein or a receptor of the axonal guidance protein is selected from the group consisting of an antibody claim 1 , a peptide claim 1 , a nucleic acid claim 1 , an interfering RNA and a small molecule.4. The method according to wherein the axonal guidance protein is netrin-1 and the axonal guidance protein receptor is unc5b.5. The method according to further comprising administering one or more other agents effective to inhibit bone resorption or differentiation or stimulation of osteoclasts.6. The method according to wherein the one or more other agents are selected from the group ...

METHODS AND COMPOSITIONS FOR TREATING OSTEOARTHRITIS AND PROMOTING CARTILAGE FORMATION

The invention provides methods and compositions for treating or inhibiting the development of osteoarthritis in a subject having osteoarthritis or at risk for developing osteoarthritis and for stimulating or increasing cartilage production or formation in a subject. The methods feature administering to the subject a therapeutically effective amount of a composition comprising one or more agent from among adenosine, an adenosine receptor agonist, and an agent that upregulates or increases the amount of or the biological activity of adenosine, or an analog or derivative thereof. The adenosine receptor may be an A, A, Aand Aadenosine receptor. The agent that upregulates or increases the amount of or the biological activity of adenosine may be dipyridamole or ticagrelor. The composition may be administered via intraarticular injection such as injection into the synovial fluid of a joint. The composition may be effective to reduce or inhibit degeneration or damage to cartilage or to stimulate or increase cartilage production or formation. The composition may be a liposomal composition or contain a liposome. 1. A method for treating or inhibiting the development of osteoarthritis in a subject having osteoarthritis or at risk for developing osteoarthritis , comprising administering to the subject a therapeutically effective amount of a composition comprising one or more agent selected from the group consisting of adenosine , an adenosine receptor agonist , and an agent that upregulates or increases the amount of or the biological activity of adenosine , or an analog or derivative thereof.2. The method of wherein the adenosine receptor is selected from the group consisting of an A claim 1 , A claim 1 , Aand Aadenosine receptor.3. The method of wherein and the adenosine receptor agonist is an adenosine receptor Aagonist.4. The method of wherein and the adenosine receptor agonist is a selective adenosine receptor agonist.5. The method of wherein the agent that upregulates or ...

Methods and compositions for stimulating bone regeneration

The invention provides methods and compositions for stimulating or promoting bone regeneration or repairing bone fracture or for stimulating or increasing differentiation or activation of osteoblasts by administering to a subject a therapeutically effective amount of an adenosine receptor agonist, or an analog, derivative or combination thereof, an adenosine receptor antagonist, or an analog, derivative or combination thereof, or adenosine or a compound that upregulates, increases the amount of or increases the biological activity of adenosine. The invention also extends to pharmaceutical compositions such as those comprising an agent that modulates an adenosine receptor such as an adenosine A 2A agonist or A 1 antagonist.

LIPOSOMES ENCAPSULATING ADENOSINE

Provided are liposomes that encapsulate adenosine. The liposomes may be formed from sphingomyelin or a combination of sphingomyelin and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) or a combination of sphingomyelin and 1,2-dimyristoyl-sn-glycero-3-phosphorylglycerol (DMPG) or a combination of sphingomyelin, DMPG, and DMPC. The liposomes encapsulating adenosine may be used to induce cartilage regeneration, treat osteoarthritis, alleviate joint pain, and/or slow, arrest, and/or reverse progressive structural tissue damage associated with osteoarthritis or treat osteoarthritis, rheumatoid arthritis, acute gouty arthritis, and/or synovitis. The liposomes may release adenosine for up to two weeks. 1. An injectable formulation comprising saline and liposomes comprising one or more lamellae , wherein the liposome lamellae comprise 70 to 100% by mass sphingomyelin and when there is less than 100% by mass sphingomyelin the remainder is 1 ,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) or 1 ,2-dimyristoyl-sn-glycero-3-phosphorylglycerol (DMPG) or DMPC and DPMG together , wherein the liposomes(a) have a diameter of 50 nm to 150 μm; and(b) encapsulate adenosine in the aqueous compartment of the liposome.2. The injectable formulation of claim 1 , wherein the liposomes are metastable.3. The injectable formulation of claim 1 , wherein the adenosine or a portion thereof is released for up to two weeks4. The injectable formulation of claim 1 , further comprising an excipient.5. The injectable formulation of claim 1 , wherein the formulation is suitable for intra-articular injection.6. The injectable formulation of claim 1 , wherein the adenosine concentration is 0.1 to 7 mg/mL.7. The injectable formulation of claim 5 , wherein the adenosine concentration is 0.1 to 4 mg/mL.8. The injectable formulation of claim 1 , wherein the ratio of DMPC and DMPG is from 6:4 to 8:2.9. The injectable formulation of claim 8 , wherein the ratio of DMPC and DMPG is 7:3.10. The injectable ...

METHODS AND COMPOSITIONS FOR TREATING BONE DISEASES

The invention provides methods and compositions for stimulating or promoting bone generation and regeneration, for stimulating or increasing differentiation, activation or function of osteoblasts, for inhibiting or decreasing differentiation, activation or function of osteoclasts, and for treating bone diseases such as osteonecrosis by administering to a subject a therapeutically effective amount of a pro-nerve growth factor (proNGF) or a pro-brain derived neurotrophic factor (proBDNF) or an analog, homolog, fragment or derivative thereof. The pro-nerve growth factor (proNGF) or a pro-brain derived neurotrophic factor (proBDNF) or an analog, homolog, fragment or derivative thereof may be a mutated or poorly hydrolyzed form of proNGF or proBDNF. 1. A method for stimulating or promoting bone growth , bone density or bone regeneration comprising administering to a subject a therapeutically effective amount of a pro-nerve growth factor (proNGF) or a pro-brain derived neurotrophic factor (proBDNF) or a biologically active analog , homolog , fragment or derivative thereof.2. The method according to wherein the pro-nerve growth factor (proNGF) or the pro-brain derived neurotrophic factor (proBDNF) is a mutated or a poorly hydrolyzed form of proNGF or proBDNF.3. The method according to wherein the pro-nerve growth factor (proNGF) or the pro-brain derived neurotrophic factor (proBDNF) stimulates osteoblast differentiation or activation or inhibits osteoclast differentiation or activation.4. A method for stimulating differentiation or activation of osteoblasts or increasing function of osteoblasts comprising administering to a subject a therapeutically effective amount of a pro-nerve growth factor (proNGF) or a pro-brain derived neurotrophic factor (proBDNF) or a biologically active analog claim 1 , homolog claim 1 , fragment or derivative thereof.5. The method according to wherein the pro-nerve growth factor (proNGF) or the pro-brain derived neurotrophic factor (proBDNF) is ...

TISSUE REPAIR DEVICES AND SCAFFOLDS

The present invention relates to multiphasic, three-dimensionally printed, tissue repair devices or scaffolds useful for promoting bone growth and treating bone fracture, defect or deficiency, methods for making the same and methods for promoting bone growth and treating bone fracture, defect or deficiency using the same. The scaffold has a porous bone ingrowth area containing interconnected struts surrounded by a microporous shell. At the ends of the scaffold, the shell may be extended as a guide flange to stabilize the scaffold between ends of bone. The center of the scaffold may be empty and may serve as a potential marrow space. 1. A tissue repair device or scaffold having a porous bone ingrowth structure containing interconnected struts surrounded by a microporous shell wherein the tissue repair device or scaffold contains therein or thereon a therapeutically effective amount of an adenosine receptor agonist , an adenosine receptor antagonist , or an agent that upregulates , increases the amount of or increases the biological activity of adenosine or an analog or derivative thereof.2. A tissue repair device or scaffold according to wherein the adenosine receptor agonist is an adenosine Aor adenosine Areceptor agonist.3. A tissue repair device or scaffold according to wherein the adenosine receptor antagonist is an adenosine Areceptor antagonist.4. A tissue repair device or scaffold according to wherein the agent that upregulates claim 1 , increases the amount of or increases the biological activity of adenosine is dipyridamole.5. A tissue repair device or scaffold according to wherein the adenosine receptor agonist claim 1 , an adenosine receptor antagonist claim 1 , or an agent that upregulates claim 1 , increases the amount of or increases the biological activity of adenosine or an analog or derivative thereof is provided in a sustained release formulation.6. A tissue repair device or scaffold according to wherein the microporous shell is extended as a guide ...

Methods and compositions for treating osteoarthritis and promoting cartilage formation

The invention provides methods and compositions for treating or inhibiting the development of osteoarthritis in a subject having osteoarthritis or at risk for developing osteoarthritis and for stimulating or increasing cartilage production or formation in a subject. The methods feature administering to the subject a therapeutically effective amount of a composition comprising one or more agent from among adenosine, an adenosine receptor agonist, and an agent that upregulates or increases the amount of or the biological activity of adenosine, or an analog or derivative thereof. The adenosine receptor may be an A1, A2A, A2B and A3 adenosine receptor. The agent that upregulates or increases the amount of or the biological activity of adenosine may be dipyridamole or ticagrelor. The composition may be administered via intraarticular injection such as injection into the synovial fluid of a joint. The composition may be effective to reduce or inhibit degeneration or damage to cartilage or to stimulate or increase cartilage production or formation. The composition may be a liposomal composition or contain a liposome.

Adenosine a2a receptor antagonists for treating and preventing hepatic fibrosis,cirrhosis and fatty liver

Methods and compositions for treating hepatic diseases

Liposomes encapsulating adenosine

Provided are liposomes that encapsulate adenosine. The liposomes may be formed from sphingomyelin or a combination of sphingomyelin and l,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) or a combination of sphingomyelin and l,2-dimyristoyl-sn-glycero-3-phosphorylglycerol (DMPG) or a combination of sphingomyelin, DMPG, and DMPC. The liposomes encapsulating adenosine may be used to induce cartilage regeneration, treat osteoarthritis, alleviate joint pain, and/or slow, arrest, and/or reverse progressive structural tissue damage associated with osteoarthritis or treat osteoarthritis, rheumatoid arthritis, acute gouty arthritis, and/or synovitis. The liposomes may release adenosine for up to two weeks.

Pharmaceutical compositions containing tsg-6 for treating inflammatory diseases and cancer-related pathologies and methods

Medical implants containing adenosine receptor agonists and methods for inhibiting medical implant loosening

The invention provides methods and compositions for reducing or inhibiting bone resorption, osteoclast differentiation and stimulation and the loosening of medical prostheses by administering a compound or agent that modulates an adenosine receptor such as the adenosine A2A receptor, in particular, an agonist of an adenosine A2A receptor. The invention also extends to pharmaceutical compositions comprising such an agent that modulates an adenosine receptor such as an adenosine A2A agonist and to prosthetic devices containing such an agent that modulates an adenosine receptor such as an A2A agonist on one or more surfaces or within the prosthetic device such as, for example, suspended in the cement forming the prosthetic device. The compounds are CGS-21680, IB-MECA and R-PIA.

Methods and compositions for treating hepatic diseases

The invention provides methods and compositions for treating a hepatic disease, for reducing fat deposition in the liver and for inhibiting fibrosis of the liver by administering a compound or agent that modulates an adenosine receptor, in particular, an inhibitor or antagonist of an adenosine receptor, especially an A1 or A2B adenosine receptor antagonist.

Methods and compositions for treating bone diseases

The invention provides methods and compositions for stimulating or promoting bone generation and regeneration, for stimulating or increasing differentiation, activation or function of osteoblasts, for inhibiting or decreasing differentiation, activation or function of osteoclasts, and for treating bone diseases such as osteonecrosis by administering to a subject a therapeutically effective amount of a pro-nerve growth factor (proNGF) or a pro-brain derived neurotrophic factor (proBDNF) or an analog, homolog, fragment or derivative thereof. The pro-nerve growth factor (proNGF) or a pro-brain derived neurotrophic factor (proBDNF) or an analog, homolog, fragment or derivative thereof may be a mutated or poorly hydrolyzed form of proNGF or proBDNF.