Therapy for post-traumatic osteoarthritis
Compositions comprising a reverse-temperature sensitive hydrogel comprising a biopolymer such as a polysaccharide and a synthetic polymer, and a compound in an amount that reversibly inhibits respiratory enzyme complex I, and methods of using the composition, are provided.
1. An injectable composition comprising a hydrogel comprising a cross-linked polysaccharide comprising hyaluronic acid having a molecular weight (MW) of 1 million Da or greater and an amount of amobarbital or a derivative thereof effective to inhibit post-traumatic osteoarthritis, wherein the hydrogel has an initial viscosity of about 80 to about 200 Pascal Seconds.
2. The composition of claim 1 wherein the hyaluronic acid has a MW of about 1,600,000 to 3,200,000.
3. The composition of claim 1 wherein the derivative comprises pentobarbital, secobarbital, phenobarbital, or barbital.
4. The composition of claim 1 wherein the hydrogel has an initial viscosity of about 120 to about 140 Pascal Seconds.
5. A method to inhibit post-traumatic osteoarthritis after injury in a mammal, comprising administering to an injured joint of the mammal an effective amount of the composition of claim 1 .
6. The method of claim 5 wherein the mammal is a human.
7. The method of claim 5 wherein the administration is within 4 days of the injury.
8. The method of claim 5 wherein the mammal has an injured joint.
9. The method of claim 5 wherein the administration is with 12 hours of the injury.
10. The method of claim 5 wherein the composition is injected.
11. A method of treating articular injury in a mammal, comprising: injecting into an injured joint of a mammal an effective amount of the composition of claim 1 .
12. The method of claim 11 wherein the injury is a knee, hip, ankle or elbow injury.
13. The composition of claim 1 wherein the hyaluronic acid is present in the composition from about 0.01% wt/vol and up to about 2.0% wt/vol.
14. The composition of claim 1 wherein the hyaluronic acid is present at about 0.2% wt/vol to about 1.0% wt/vol.
15. The composition of claim 1 wherein the hyaluronic acid is present at about 0.2 wt/vol to about 4% wt/vol.
16. The composition of claim 1 wherein the hyaluronic acid has a MW of 1.5 M Dalton or greater.
17. An injectable composition comprising a hydrogel consisting of a cross-linked hyaluronic acid having a molecular weight (MW) of 1 million Da or greater and an amount of amobarbital, pentobarbital, secobarbital, phenobarbital, barbital, adenosine diphosphate ribose, or metformin, and optionally a carrier, effective to inhibit post-traumatic osteoarthritis.