Therapeutic effect of an injectable sustained-release sinomenine hydrochloride and sodium hyaluronate compound in a rabbit model of osteoarthritis

摘要

Background While intra-articular injection of sinomenine hydrochloride has a therapeutic effect on osteoarthritis,it has a short half-life,and is thermolabile and photolabile.The aim of this research was to evaluate the sustained-release of sinomenine hydrochloride from an injectable sinomenine hydrochloride and sodium hyaluronate compound (CSSSI) and its therapeutic effect in a rabbit model of osteoarthritis following intra-articular injection.Methods An injectable compound consisting of 1％ sodium hyaluronate and 2.5％ sinomenine hydrochloride was prepared and kept as the experiment group,and 2.5％ sinomenine hydrochloride was prepared and kept as the control group.The cumulative mass release was measured at different time points in each group in vitro.Sixty-five male Zelanian rabbits were randomly divided into five groups:15 (30 knees) each for the control,sodium hyaluronate,sinomenine hydrochloride,and CSSSI groups respectively,and five (10 knees) for the modeling group.Papain was injected into both knees of each rabbit for model establishment.Subsequently,0.2 ml of the corresponding drugs was injected into the articular cavities of the remaining experiment groups,while the control group was treated with 0.2 ml normal saline.All groups were treated once a week for 4 weeks.Seven days after the last treatment,knees were anatomized to perform pathological observations and Mankin's evaluation of the synovium.Four groups were compared using the SPSS 13.0 software package.Results In the in vitro sustained-release experiments,90％ of the drug was released in the experiment group 360minutes following the injection.Comparison of the Mankin's evaluations of the four groups illustrated statistical discrepancies (P＜0.05).In further paired comparisons of the CSSSI group vs.modeling control/sodium hyaluronate/sinomenine hydrochloride groups,statistical significance was uniformly obtained.Moreover,sodium hyaluronate and sinomenine hydrochloride treatments showed significant improvement over the modeling control (P＜0.05),whereas sodium hyaluronate vs.sinomenine hydrochloride comparison failed to reach significance (P ＞0.05).Conclusions CSSSI has a sustained-release effect on sinomenine hydrochloride.Intra-articular injection of CSSSI was significantly better than the sole sodium hyaluronate or sinomenine hydrochloride for the treatment of osteoarthritis in a rabbit model.