氯诺昔康的合成

以2，5－二氯噻吩为原料，经氯磺化、甲胺化、N－烷基化、环合、氨基取代等反应合成氯诺昔康。甲胺化时，以30％甲胺水溶液代替气体甲胺，简化了操作；N－烷基化时以相转移催化剂／氯乙酸甲酯代替钠氢／碘乙酸甲酯，提高了收率；环合反应更换溶剂系统使收率可达77％。工艺操作简便、安全，条件温和，成本低，总收率可由0．45％提高至12．3％。     

芬太尼与氯诺昔康联合用于妇科开腹术后病人PCSA的临床研究

目的 :评价芬太尼与氯诺昔康联合平衡镇痛用于妇科开腹术后病人皮下自控镇痛 (PCSA)的效果。方法 :6 0例在全麻下行开腹妇科手术的患者 ,随机分为芬太尼组 (Ⅰ组 )、芬太尼 +氯诺昔康组 (Ⅱ组 )和氯诺昔康组(Ⅲ组 )各 2 0例行术后镇痛。用双盲法研究。观察用药后 8、12、2 4、4 8h各时间点安静、咳嗽时VAS评分 ,镇静程度 ,病人对疼痛治疗的总体满意度 ,并记录副作用和用药总剂量。结果 :Ⅱ组芬太尼和氯诺昔康的所用剂量分别与Ⅰ组和Ⅲ组比有非常显著性差异 (P <0 .0 1) ,三组安静和咳嗽时VAS评分无显著性差异 (P >0 .0 5 ) ,Ⅱ组消化道副反应发生率 (10 % )比Ⅰ组 (2 5 % )和Ⅲ组 (2 0 % )低 ;Ⅱ组病人满意度 (95 % )比Ⅰ组 (80 % )和Ⅲ组 (85 % )稍高。结论 :芬太尼与氯诺昔康联用平衡镇痛可显著减少每种药的剂量 ,PCSA效果确切 ,副作用较单一用药少 ,可作为术后PCSA的较佳配方选择。     

The analgesic effect of lornoxicam when added to lidocaine for intravenous regional anaesthesia

Background. The aim of the study was to evaluate the effectof lornoxicam (L) on sensory and motor block onset time, tourniquetpain, and postoperative analgesia, when added to lidocaine inintravenous regional anaesthesia (IVRA). Methods. Forty-five patients undergoing hand surgery were randomlyand blindly divided into three groups as to receive either i.v.saline and IVRA with lidocaine 0.5% (Control group, n=15), i.v.saline and IVRA lidocaine 0.5% with lornoxicam (L-IVRA group,n=15), or intravenous lornoxicam and IVRA lidocaine 0.5% (L-IVgroup, n=15). Sensory and motor blocks onset time, and tourniquetpain was measured after tourniquet application at 5, 10, 20,and 30 min, and analgesic use were recorded during operation.After the tourniquet deflation, at 1, 30 min, and 2, 4 h, visualanalogue scales score, the time to first analgesic requirement,total analgesic consumption in first 24 h, and side effectswere noted. Results. Sensory and motor block onset times were shorter andthe recovery time prolonged in the Group L-IVRA compared withthe other group (P=0.001). A decreased tourniquet pain, a prolongedtime first analgesic requirement [229 (85) min vs 28 (20) and95 (24) min, P=0.0038) and less postoperative analgesic requirementsduring 24 h were found in Group L-IVRA compared with the othergroups (P<0.05). Conclusions. The addition of lornoxicam to lidocaine for intravenousregional anaesthesia shortens the onset of sensory and motorblock, decreases tourniquet pain and improves postoperativeanalgesia without causing any side effect.     

Liquid chromatography-electrospray lonization tandem mass spectrometric determination of lornoxicam in human plasma

A rapid, sensitive and selective liquid chromatography-electrospray ionization tandem mass spectrometric (LC-ESI-MS/MS) method for the determination of lornoxicam in human plasma was developed. Lornoxicam and isoxicam (internal standard) were extracted from human plasma with ethyl acetate at acidic pH and analyzed on a Sunfire C18 column with the mobile phase of methanol:ammonium formate (10 mM, pH 3.0) (70:30, v/v). The analyte was detected using a mass spectrometer, equipped with electrospray ion source. The instrument was set in the multiple-reaction-monitoring mode. The standard curve was linear (r = 0.9998) over the concentration range of 0.50-500 ng/mL. The coefficient of variation and relative error for intra- and inter-assay at four QC levels were 0.7 to 4.2% and -4.5 to 5.0%, respectively. The recoveries of lornoxicam and isoxicam were 87.8% and 66.5%, respectively. The lower limit of quantification for lornoxicam was 0.50 ng/mL using a 200 pL plasma sample. This method was successfully applied to a pharmacokinetic study of lornoxicam after oral administration of lornoxicam (8 mg) to humans.     

氟比洛芬酯与氯诺昔康用于膝关节微骨折术超前镇痛的效果对比

目的比较氟比洛芬酯与氯诺昔康用于膝关节微骨折术超前镇痛的临床效果。方法选取2013年1月~2016年1月收治的膝关节软骨损伤患者300例,均行关节镜引导下微骨折术,根据术前应用超前镇痛情况分为三组(各100例),A组采用氟比洛芬酯,B组采用氯诺昔康,C组为对照组未采取超前镇痛。回顾性分析患者的临床资料,比较三组患者术中疼痛视觉模拟评分(VAS评分)、术后VAS评分、术后额外口服非甾体类药物情况及患者对镇痛总体质量的评价。结果术中关节镜清理时三组患者VAS评分差异无统计学意义(P0.05),而微骨折术时A、B两组VAS评分均低于C组,差异有统计学意义(P0.05),A、B两组差异无统计学意义(P0.05)。A、B两组术后1、4、8及24h的VAS评分均低于C组,差异有统计学意义(P0.05)。A组术后1h及4h的VAS评分显著低于B组,差异有统计学意义(P0.05),其余时间点A、B两组VAS评分差异无统计学意义(P0.05)。A、B两组治疗优良率均高于C组,差异有统计学意义(P0.05),A、B两组差异无统计学意义(P0.05)。结论氟比洛芬酯与氯诺昔康用于膝关节微骨折术均有利于减轻患者术中及术后疼痛,安全可靠,但术后早期氟比洛芬酯的镇痛效果更佳。     

高效液相色谱法-二极管阵列检测器考察注射用头孢唑啉钠与注射用氯诺昔康的配伍稳定性

目的考察注射用头孢唑啉钠与注射用氯诺昔康在氯化钠注射液中的配伍稳定性。方法在室温条件下,采用高效液相色谱法-二极管阵列检测器测定头孢唑啉钠与氯诺昔康配伍后0～6 h内的含量变化,并观察和检测此2种药配伍液的外观与pH值变化。结果在室温下,配伍液6 h内的含量、pH及外观均无明显变化。结论室温条件下,注射用头孢唑啉钠与注射用氯诺昔康在氯化钠注射液中6 h内保持稳定。     

Effects of preemptive intravenous lornoxicam on the analgesic efficacy of epidural morphine and expression of chemokines in women undergoing hysterectomy

Background: It is believed that preemptive IV lornoxicam treatment can reduce the consumption of other analgesics, improve analgesic efficacy, and ameliorate immune function during patient-controlled IV analgesia. However, the effects of preemptive IV lornoxicam treatment on the analgesic efficacy of patient-controlled epidural analgesia (PCEA) with morphine and on chemokine expression remain unknown.Objective: The aim of this prospective, randomized, controlled study was to observe the effects of preemptive IV lornoxicam treatment on the analgesic efficacy of PCEA with morphine and on the expression of monocyte chemotactic protein-1 (MCP-1) and stromal cell-derived factor-1α (SDF-1α) in women undergoing hysterectomy.Methods: Patients undergoing elective hysterectomy with combined spinal and epidural anesthesia were randomized to 1 of 3 groups to receive IV lornoxicam 8 mg before anesthesia (group 1), lornoxicam 16-mg injection before anesthesia (group 2), or isotonic saline (control) before anesthesia. PCEA was used to treat postoperative pain, and a visual analog scale (VAS) and the Bruggemann Comfort Scale (BCS) were used to evaluate analgesic efficacy. Morphine consumption was recorded. To measure plasma concentrations of MCP-1 and SDF-1α via enzyme-linked immunosorbent assay, venous blood samples were obtained from patients at 4 separate times: before anesthesia (baseline); 0 (immediately after anesthesia administration); and 24 and 48 hours after surgery.Results: Forty-five patients (mean [SD] age, 41 [5] years; mean [SD] weight, 54 [6] kg) undergoing elective hysterectomy were included in the study. There were no significant differences in VAS scores, BCS scores, or morphine consumption between the 3 groups. Compared with baseline values, MCP-1 and SDF-1α concentrations were increased significantly immediately after surgery in all 3 groups (all, P < 0.01) and returned to near-baseline values at 24 hours postsurgery in groups 1 and 2, and by 48 hours postsurgery in the control group. MCP-1 and SDF-1α concentrations in groups 1 and 2 were significantly lower than those in the control group immediately (all, P < 0.01) and 24 hours postsurgery (all, P < 0.05).Conclusion: Preemptive IV lornoxicam treatment was associated with attenuation of the plasma concentrations of MCP-1 and SDF-1α immediately after and 24 hours after hysterectomy and was associated with more rapid resolution to near-baseline concentrations of both cytokines in these patients compared with controls; however, it was not associated with significantly reducing epidural morphine consumption.     

氯诺昔康用于食管癌术后镇痛对IL-2、IL-6、IL-10的影响

目的观察氯诺昔康用于食管癌术后镇痛对白细胞介素-2(IL-2)、白细胞介素-6(IL-6)、白细胞介素-10(IL-10)的影响。方法根据术后静脉自控镇痛给药方式不同,将24例食管癌根治术患者随机分为两组,L组(氯诺昔康组,n=12):氯诺昔康40 mg+氟哌利多5 mg;M组(吗啡组,n=12):吗啡40 mg+氟哌     

瑞芬太尼全麻患者应用氯胺酮复合芬太尼和氯诺昔康皮下术后镇痛的可行性

目的 观察小剂量NMDA受体拮抗剂氯胺酮复合芬太尼和氯诺昔康皮下镇痛(PCSA)的安全性和有效性。方法 择期在全麻下行椎弓根钉内固定术患者60例,ASAI～II级,术中均用丙泊酚+瑞芬太尼维持麻醉,术后镇痛按药物配伍不同随机分为3组(n=20)：A组芬太尼0.01mg/kg+氯诺昔康0.6mg/kg,B组氯胺酮2mg/kg+芬太尼0.01mg/kg+氯诺昔康0.6mg/kg,C组芬太尼0.02mg/kg+氯诺昔康0.6mg/kg。氯诺昔康用无菌用水稀释,然后用0.9%生理盐水配制成混合药液100mL。应用PCA泵,3组术后经皮镇痛(PCSA)均采用负荷量+持续背景量+PCA量模式：负荷剂量3mL,背景剂量2mL/h,PCA剂量0.5mL,锁定时间15min。观察术后4 h (T1)、8 h (T2)、16 h(T3)、24 h (T4)、48 h(T5)各时点视觉模拟评分(VAS)、Ramsay镇静评分、血压(BP)、心率(HR)、脉搏血氧饱和度(SpO2)、呼吸频率(RR)和患者对PCA综合满意度评价及不良反应。结果 3组患者镇痛效果均良好,在术后镇痛T1时点静息和活动时VAS评分B组和C组均小于A组,差异有统计学意义（P＜0.05）。B组和C组的PCA综合满意度为优的例数显著多于A组（P＜0.05）。3组术后各时点Bp、HR、RR、SpO2均在正常范围内波动,差异无统计学意义(P>0.05)。各组不良反应发生率较低且差异无统计学意义（P＞0.05）。结论 瑞芬太尼全麻患者应用小剂量氯胺酮复合芬太尼和氯诺昔康皮下术后镇痛安全、有效,且不良反应少。     

曲马多和氯诺昔康术后镇痛对血浆胃动素水平的影响

目的探讨曲马多和氯诺昔康对血浆胃动素的影响。方法60例ASAI～II级择期矫形外科手术患者随机分为两组:曲马多组(A组)和氯诺昔康组(B组),每组各30例。采用视觉模拟评分(VAS)评估术后镇痛效果。观察术后恶心呕吐(PONV)发生情况及镇痛药物用量,测定两组患者血浆胃动素的水平。结果A组镇痛效果与B组比较无显著性差异(P>0.05)。与术前比较,A组胃动素水平显著上升(P<0.01),B组胃动素水平上升不明显(P>0.05)。结论选用非甾体类抗炎药不失为一种减少手术后恶性呕吐发生的好方法。