Methods of treating arthritis
The present invention provides methods of treating arthritis. A sustained release composition comprising liposomes and one or more therapeutic agent or a pharmaceutically acceptable salt thereof is administered to a subject in need thereof. The liposomes may be in an aqueous suspension. The sustained release composition can be administered intraarticularly.
1. A method of treating arthritis, comprising:
intraarticularly injecting a composition into a joint of a subject in need of treatment for arthritis, said composition comprising:
liposomes comprising 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC), dipalmitoylphosphatidylglycerol (DOPG), and cholesterol, wherein the mole percent ratio of DOPC:DOPG:cholesterol is about 29.5 to 90 (DOPC):3 to 37.5 (DOPG):10 to 33 (cholesterol) based on the total amount of the phospholipids and cholesterol; and
one or more therapeutic agents, wherein the therapeutic agent is not covalently bound to a phospholipid.
2. The method of claim 1 , wherein the composition is prepared by reconstituting a lyophilized lipid cake comprising DOPC and DOPG, and said cholesterol with an aqueous solution comprising said one or more therapeutic agents to form an aqueous suspension.
3. The method of claim 1 , wherein the composition is prepared by reconstituting a lyophilized combination of said one or more therapeutic agents and a lipid cake comprising DOPC and DOPG, and said cholesterol with an aqueous solution to form an aqueous suspension.
4. The method of claim 1 , wherein the therapeutic agent comprises a water-soluble steroid or a pharmaceutically acceptable salt thereof.
5. The method of claim 4 , wherein the water-soluble steroid is dexamethasone sodium phosphate (DSP).
6. The method of claim 1 , wherein the therapeutic agent comprises a nonsteroidal anti-inflammatory drug or a pharmaceutically acceptable salt thereof.
7. The method of claim 6 , wherein the nonsteroidal anti-inflammatory drug is indomethacin.
8. The method of claim 6 , wherein the therapeutic agent is indomethacin sodium.
9. The method of claim 6 , wherein the concentration of the nonsteroidal anti-inflammatory drug or its pharmaceutically acceptable salt is 4.65 to 5 mg/ml.
10. The method of claim 1 , wherein the therapeutic agent comprises a disease modifying anti-rheumatic drug (DMARD).
11. The method of claim 10 , wherein the DMARD comprises a TNF-a antagonist.
12. The method of claim 11 , wherein the TNF-a antagonist is etanercept.
13. The method of claim 12 , wherein the concentration of etanercept in the composition is 42.8 mg/ml to 50 mg/ml.
14. The method of claim 11 , wherein the TNF-a antagonist is adalimumab.
15. The method of claim 10 , wherein the DMARD comprises methotrexate or a pharmaceutically acceptable salt thereof.
16. The method of claim 15 , wherein the pharmaceutically acceptable salt of methotrexate is methotrexate sodium.
17. The method of claim 15 , wherein the concentration of methotrexate or its pharmaceutically acceptable salt is 2.3 to 2.5 mg/ml.
18. The method of claim 1 , wherein the therapeutic agent is encapsulated in an aqueous medium of the liposomes.
19. The method of claim 5 , wherein the dose of the DSP is about 0.2 mg to about 6 mg.