JPWO2020206314A5 - - Google Patents

Claims (23)

An injectable formulation comprising saline and liposomes containing one or more layers, wherein the layers of the liposomes comprise 70-100% by weight sphingomyelin and less than 100% by weight sphingomyelin then the balance is 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) or 1,2-dimyristoyl-sn-glycero-3-phosphorylglycerol (DMPG); or DMPC and DMPG,
Here, the liposome is
(a) have a diameter of 50 nm to 150 μm; and (b) encapsulate adenosine in the aqueous compartment of the liposome;
Injectable formulation. 2. The injectable formulation of claim 1, wherein the liposomes are metastable. 2. The injectable formulation of claim 1, wherein adenosine or a portion thereof is released for up to two weeks. 2. The injectable formulation of claim 1, further comprising an excipient. 2. The injectable formulation of claim 1, suitable for intra-articular injection. The injectable formulation according to claim 1, wherein the adenosine concentration is 0.1-7 mg/mL. The injectable formulation according to claim 5, wherein the adenosine concentration is 0.1-4 mg/mL. The injectable formulation according to claim 1, wherein the ratio of DMPC and DMPG is 6:4-8:2. 9. The injectable formulation according to claim 8, wherein the ratio of DMPC and DMPG is 7:3. The injectable formulation of claim 1, wherein the total lipid concentration is 7-12 mg/mL. 2. The injectable formulation of claim 1, wherein one or more of the liposomes has a diameter of 50 nm-100 μm. 7. The injectable formulation of claim 6, wherein one or more of the liposomes has a diameter of 100 nm-150 μm. The injectable formulation according to claim 1, wherein the liposomes disintegrate at a temperature of 35-45°C. 2. The injectable formulation of claim 1, wherein at least a portion of the adenosine is released within 1 second to 1 hour after administration to the joint of the individual. 15. The injectable formulation of claim 14, wherein at least a portion of the adenosine is released within 1 minute to 1 hour after administration to the joint of the individual. 16. The injectable formulation of claim 15, wherein at least 1-20% of the adenosine is released within 1 minute to 1 hour after administration to the joint of the individual. 15. The injectable formulation of claim 14, wherein at least a portion of the adenosine, or at least 1-20% of the adenosine, is released within 1 second to 10 minutes after administration to the joint of the individual. The injectable formulation i) induces cartilage regeneration and/or ii) reduces joint pain and/or inflammation and/or iii) delays and/or stops progressive structural tissue damage The injectable formulation according to any one of claims 1 to 17, which is administered to an individual for and/or reversal. 19. The injectable formulation of any one of claims 1-18, wherein the injectable formulation is administered by intra-articular injection into a joint of the individual. 20. The injectable formulation of any one of claims 1-19, wherein the injectable formulation is administered in one or more injections. 21. The injectable formulation of any one of claims 1-20, wherein the injectable formulation is administered multiple times, each administration occurring once every 10 days. 22. The injectable formulation of any one of claims 1-21, which is administered to an individual with osteoarthritis , rheumatoid arthritis, acute gouty arthritis, and/or synovitis. The injectable formulation according to any one of claims 1 to 22, which is administered to an individual selected from human or non-human mammals.