目的 建立右旋酮洛芬氨丁三醇（DKPF）溫敏水凝膠的含量測定方法，考察其穩(wěn)定性和組織相容性。方法 建立紫外分光光度法測定DKPF溫敏水凝膠中DKPF含量，并考察方法的專屬性、線性關(guān)系、定量限、精密度、回收率；應(yīng)用建立的紫外分光光度法、恒溫振蕩法測定DKPF溫敏水凝膠的釋放度，檢測高濕、光照、低溫條件下的DKPF溫敏水凝膠穩(wěn)定性。隨機選取80只昆明小鼠，分別sc 0.2 mL DKPF溫敏水凝膠、空白水凝膠、DKPF生理鹽水溶液（DKPF濃度同DKPF溫敏水凝膠），于給藥后1、3、6、9、12 d，每組各取5只脫頸處死，剖開注射部位皮膚觀察水凝膠狀態(tài)，并取皮下組織樣本HE染色后光鏡下觀察，評價DKPF溫敏水凝膠組織相容性。結(jié)果 DKPF在260 nm處有最大紫外吸收，DKPF質(zhì)量濃度在1.70~25.56 μg/mL范圍內(nèi)呈良好的線性關(guān)系（r=0.999 9），方法學(xué)的日間、日內(nèi)精密度，加樣回收率均良好；DKPF溫敏水凝膠主要以擴(kuò)散為主，釋放度符合規(guī)定，且工藝重現(xiàn)性好；水凝膠在低溫、濕度75%條件下穩(wěn)定性良好，不耐光照，需避光保存。sc給予小鼠水凝膠后，各組小鼠均成活，且水凝膠在皮下逐漸減小直至消失；病理切片結(jié)果提示，溫敏水凝膠引起輕微炎癥反應(yīng)，隨著時間延長逐漸消失，組織相容性良好。結(jié)論 本研究所建立的紫外分光光度法方法準(zhǔn)確率高，重復(fù)性好，可應(yīng)用于DKPF溫敏水凝膠中DKPF含量測定；DKPF溫敏水凝膠符合生物材料的安全標(biāo)準(zhǔn)。

Objective To establish a method for determining the content of dexketoprofen trometamol (DKPF) temperature sensitive hydrogels, and to study the stability and histocompatibility of it. Methods The content of DKPF temperature sensitive hydrogels was determined by ultraviolet spectrophotometry, and investigated the specificity, linearity, limit of quantification, precision and recovery rate. The release rate of DKPF thermosensitive hydrogel was determined by ultraviolet spectrophotometry and constant temperature oscillation method. The stability of DKPF thermosensitive hydrogel under high humidity, light and low temperature conditions was determined. Randomly selected 80 male Kunming mice were sc 0.2 mL DKPF temperature sensitive hydrogel, blank hydrogel, DKPF saline solution (the concentration of DKPF with DKPF temperature sensitive hydrogel), after administration of 1, 3, 6, 9, and 12 d, each five rats were sacrificed, cut the skin injection site for hydrogel state observation, and the subcutaneous tissue samples were stained with HE and observed under light microscope to evaluate the histocompatibility of DKPF thermosensitive hydrogels. Results DKPF had the maximum ultraviolet absorption at 260 nm. The linear range of dexketoprofen trometamol was 1.70-25.56 μg/mL (r=0.9999). The precision of intra-and intra-day and the recovery rate of the method were all good. The dissolution of DKPF temperature sensitive hydrogels conformed the rules and it had a good process reproducibility. DKPF temperature sensitive hydrogels had a good stability in low temperature and 75% RH, but it had intolerance of light, should be stored in the dark. After giving hydrogel in mice, mice in all groups survived, and the hydrogel gradually decreased and disappeared. The results of pathological sections showed that the mild inflammatory reaction caused by thermosensitive hydrogel disappeared gradually with time, and the histocompatibility was good. Conclusion This study have established an accurate and repeatable method for dexketoprofen trometamol temperature sensitive hydrogels quality control and the hydrogels meet the safety standards of biological materials.

貴州省科技計劃項目（黔科合平臺人才[2017]5601；[2016]5613\5677）；貴陽市科技計劃項目（筑科合同[20141001]05號/筑科合同[2017]30-29號）