(S)-(+)-氟比洛芬的合成

目的 采用新的方法合成非甾体抗炎镇痛药氟比洛芬并拆分得到S-异构体。方法 以国内价格较低廉的2-氟苯胺为起始原料，经1，3-二溴-5，5-二甲基海因溴代、与苯缩合、再与2-溴丙酸钠进行格氏反应，酸化后得到外消旋的氟比洛芬，再经葡辛胺拆分，得（S）-（＋）-氟比洛芬。结果 成功制备得到目标产物，其结构经mp，NMR等确证。结论 该制备方法具有工艺简单、得率高、试剂价格低廉等特点，适合于工业化生产。     

Effect of Flurbiprofen and S-Flurbiprofen Patches on Multimodal Pain Management After Total Knee Arthroplasty: A Prospective Randomized Controlled Trial

BackgroundTotal knee arthroplasty (TKA) is an established procedure for knee osteoarthritis. Multimodal analgesia is reportedly more effective for postoperative analgesia. We investigated the efficacy of 2 patches after TKA.MethodsSeventy-nine knees that underwent unilateral TKA for osteoarthritis were included. Oral administration, local periarticular analgesic injection, and patches were adopted for pain management. The knees were randomly assigned to the flurbiprofen patch (FPP), S-flurbiprofen patch (SFPP), and control (no patch) groups. Patch treatment was continued for 14 days. Pain according to the visual analog scale, knee flexion angle, renal dysfunction, gastrointestinal injury, duration of hospitalization, dermatitis, and the rate of using additional oral nonsteroidal anti-inflammatory drugs were compared (from preoperative to postoperative day 14).ResultsThe FPP, SFPP, and control groups included 29, 27, and 23 knees, respectively. Visual analog scale was lower in the FPP and SFPP groups than in the control group on days 1 and 3 (day 1: 24.4, 25.0, and 39.4, respectively; day 3: 25.5, 23.3, and 39.3, respectively). Knee flexion angle was larger in the SFPP group than in the control group on days 7 and 14 (day 7: 89.8° and 76.6°, respectively; day 14: 98.3° and 84.2°, respectively). Neither renal dysfunction nor gastrointestinal injury was confirmed. The duration of hospitalization did not differ among the groups. Dermatitis occurred only in the SFPP group. The rate of using additional oral nonsteroidal anti-inflammatory drugs was higher in the control group.ConclusionBoth patches were effective and safe as part of multimodal analgesia for postoperative TKA.     

Efficacy of S-flurbiprofen plaster in knee osteoarthritis treatment: Results from a phase III,randomized, active-controlled,adequate, and well-controlled trial

Objectives: S-flurbiprofen plaster (SFPP) is a novel non-steroidal anti-inflammatory drug (NSAID) patch, intended for topical treatment for musculoskeletal diseases. This trial was conducted to examine the effectiveness of SFPP using active comparator, flurbiprofen (FP) patch, on knee osteoarthritis (OA) symptoms.

Methods: This was a phase III, multi-center, randomized, adequate, and well-controlled trial, both investigators and patients were blinded to the assigned treatment. Enrolled 633 knee OA patients were treated with either SFPP or FP patch for two weeks. The primary endpoint was improvement in knee pain on rising from the chair as assessed by visual analogue scale (rVAS). Safety was evaluated through adverse events (AEs).

Results: The change in rVAS was 40.9?mm in SFPP group and 30.6?mm in FP patch group (p?p?Conclusions: The superiority of SFPP in efficacy was demonstrated. Most of AEs were mild and few AEs led to treatment discontinuation. Therefore, SFPP provides an additional option for knee OA therapy.