Regimens for intra-articular viscosupplementation

Abstract

The invention provides viscosupplementation methods for treating osteoarthritis and joint injury with HA-based viscosupplements, particularly viscosupplements with an intra-articular residence half-life shorter than 3 weeks. Viscosupplements for use in the methods of the invention may be further characterized in that they contain less than 20 mg/ml HA, at least 5% (w/w) of which is in a gel form, such as, e.g., hylan B. In an illustrative embodiment, hylan G-F 20 (Synvisc®) is administered in a single intra-articular knee injection of 6±2 ml.

1 . A viscosupplementation method for treating a knee joint of a subject, the method consisting of a single intra-articular administration of 4 ml or more. 
     
     
         2 . The method of  claim 1 , wherein the viscosupplement contains less than 20 mg/ml HA. 
     
     
         3 . The method of  claim 1 , wherein the subject is human. 
     
     
         4 . The method of  claim 3 , wherein the total volume of the viscosupplement in the single administration is 6±2 ml or more. 
     
     
         5 . The method of  claim 4 , wherein the amount is 6 ml. 
     
     
         6 . The method of  claim 1 , wherein the viscosupplement is administered to a subject in need of treatment of joint pain. 
     
     
         7 . The method of  claim 1 , wherein the single administration of the viscosupplement is therapeutically effective for at least 4 months. 
     
     
         8 . The method of  claim 1 , wherein the viscosupplement is characterized by one or more features as follows:
 (i) the viscosupplement has a residence half-life of less than 3 weeks;   (ii) the viscosupplement contains less than 20 mg/ml HA;   (iii) 5% (w/w) or more of HA in the viscosupplement is in a gel form.   
     
     
         9 . The method of  claim 8 , wherein the residence half-life is more than 3 days. 
     
     
         10 . The method of  claim 1 , wherein the viscosupplement contains 8±2 mg/ml HA. 
     
     
         11 . The method of  claim 1 , wherein the HA in the viscosupplement is of animal origin. 
     
     
         12 . The method of  claim 11 , wherein the viscosupplement is produced from rooster combs. 
     
     
         13 . The method of  claim 1 , wherein the HA in the viscosupplement is of bacterial origin. 
     
     
         14 . The method of  claim 1 , wherein at least a fraction of the viscosupplement has been crosslinked. 
     
     
         15 . The method of  claim 14 , wherein the crosslinker is formaldehyde. 
     
     
         16 . The method of  claim 15 , wherein the viscosupplement comprises hylan A. 
     
     
         17 . The method of  claim 16 , wherein an average molecular weight of HA in hylan A is 6,000 kDa. 
     
     
         18 . The method of  claim 14 , wherein the crosslinker is divinyl sul one. 
     
     
         19 . The method of  claim 18 , wherein the viscosupplement comprises hylan B. 
     
     
         20 . The method of  claim 14 , wherein the viscosupplement comprises hylan A and hylan B. 
     
     
         21 . The method of  claim 20 , wherein the hylan A/hylan B ratio is 9:1 by weight of HA. 
     
     
         22 . The method of  claim 1 , wherein the viscosupplement contains 8±2 mg/ml HA, of which 10% by weight is in a gel form. 
     
     
         23 . The method of  claim 1 , wherein the viscosupplement is Synvisc®. 
     
     
         24 . The method of  claim 23 , wherein the viscosupplement further comprises a component selected from the group consisting of nonsteroidal anti-inflammatory drug, anaesthetic, opioid analgesics, corticosteroids, antineoplastic agent, and anti-viral agent. 
     
     
         25 . A viscosupplementation method for treating a knee joint of a human subject, the method consisting of a single intra-articular administration of 6±2 ml Synvisc®. 
     
     
         26 . The method of  claim 25 , wherein the amount administered is 6 ml. 
     
     
         27 . A method of treating a joint pathology comprising the viscosupplementation method of  claim 1 . 
     
     
         28 . The method of  claim 27 , wherein the joint pathology is associated with osteoarthritis. 
     
     
         29 . A method of treating osteoarthritic pain in a knee joint of a human subject, the method comprising administering a single intra-articular injection of 6±2 ml Synvisc®. 
     
     
         30 . The method of  claim 31 , wherein the amount is 6 ml. 
     
     
         31 . A viscosupplementation device, comprising a syringe containing 4 ml or more of Synvisc®. 
     
     
         32 . The device of  claim 31 , which is sterile. 
     
     
         33 . The device of  claim 31 , wherein the syringe contains 6±2 ml of Synvisc®. 
     
     
         34 . The device of  claim 31 , wherein the amount of Synvisc® in the syringe is 6 ml. 
     
     
         35 . The device of  claim 31 , wherein Synvisc® further comprises a component selected from the group consisting of non-steroidal anti-inflammatory drug, anesthetic, opioid analgesics, corticosteroids, antineoplastic agent, anti-viral agent, and cells.