氯诺昔康有关物质及含量测定方法的建立

目的:考察不同试验条件下氯诺昔康及其杂质的液相色谱行为,建立氯诺昔康有关物质及含量的HPLC测定方法。方法:以C18为色谱柱,0.05mol·L-1磷酸二氢钾溶液（含0.05％四丁基氢氧化铵）-乙腈-甲醇（57:33:10）为流动相,流速1.0mL·min-1,柱温40℃,检测波长264nm。结果:线性关系r=0.9999,重复性实验RSD为0.67％（n=5）。结论:方法简便、准确,适用于该产品的质量检验分析。     

氯诺昔康术后镇痛对上腹部手术患者免疫功能的影响

目的探讨氯诺昔康术后静脉自控镇痛(PCIA)对上腹部手术患者免疫功能的影响。方法40例ASAⅠ～Ⅱ级择期上腹部手术患者采用全身静脉麻醉,随机分为观察组和对照组,各20例。术后观察组给予0.032%氯诺昔康静注,负荷量为0.15 mg·kg~(-1),背景输注为2 mL·h~(-1),单次追加剂量为0.5 mL,锁定时间15 min;对照组在疼痛时[疼痛视觉模拟评分(VAS)>5分],予曲马多1.5mg·kg~(-1),im,并分别于诱导前及术后即刻、24 h、72 h测定血浆IL-2、IL-6、IL-10含量。结果对照组VAS明显高于观察组,2组术后IL-6、IL-10含量均升高,IL-2均下降,但观察组恢复较对照组早,2组间比较差异有统计学意义(P< 0.05)。结论氯诺昔康术后镇痛可控制炎性应激反应,减轻患者术后免疫抑制,有利于机体术后恢复。     

Effects of lornoxicam on the physiology of severe sepsis

Introduction  

The purpose of the present study was to evaluate the effects of intravenous lornoxicam on haemodynamic and biochemical parameters, serum cytokine levels and patient outcomes in severe sepsis.     

Comparison of the effects of lornoxicam versus diclofenac in pain management after cardiac surgery: A single-blind, randomized, active-controlled study

Background:

Inadequate pain management after cardiac surgery may result 10 in increased morbidity and length of hospital stay. Although opioids are the mainstay of postoperative analgesia, nonsteroidal anti-inflammatory drugs (NSAIDs) may be used instead to avoid the adverse effects (AEs) associated with opioids. Lornoxicam is a newly developed NSAID, the use of which is increasing. However, lornoxicam has not been studied for use in pain management after cardiac surgery.

Objective:

The objective of this study was to compare the efficacy and tolerability 10 of lornoxicam and diclofenac sodium, an NSAID well established for use in pain management after major surgery, in pain management after coronary artery bypass grafting (CABG).

Methods:

This single-blind, randomized, active-controlled study was conducted 10 at the Gaziantep University Hospital, Gaziantep, Turkey. Adult patients scheduled to undergo valve or CABG surgery for the first time were included. Patients were premedicated with diazepam 10 mg PO at 10 PM on the evening before surgery. General anesthesia was induced using fentanyl, midazolam, and propofol, and maintained using fentanyl and isoflurane in pure oxygen. After extubation and when they stated that they felt pain, patients were randomly assigned to 1 of 2 treatment groups: lornoxicam 8 mg IM q8h or diclofenac 75 mg IM q12h, for 48 hours. Meperidine 1 mg/kg IM was given for additional analgesia when needed (rescue medication). Pain relief was assessed using an I1-point visual analog scale (0 = no pain to 10 = worst pain imaginable) immediately before the first injection (baseline), and at 15 and 30 minutes and 1, 2, 3, 4, 6, 12, 18, 24, and 48 hours after the first injection. Sedation was assessed using a 5-point scale (0 = awake and alert to 4 = deep sedation) at the same time points. Tolerability was assessed by monitoring of AEs using patient interview and laboratory analyses.

Results:

Forty patients were enrolled in the study (30 men, 10 women; 10 mean [SD] age, 54.4 [11.1 ] years; 20 patients per treatment group). The demographic and clinical characteristics and mean baseline pain relief scores were statistically similar between the 2 treatment groups. The mean pain relief scores at 15 and 30 minutes were statistically similar to baseline values in the 2 treatment groups. However, the mean pain relief scores at ≥1 hour after the first injection were significantly lower compared with baseline values (both groups, P < 0.05 at time points ≥1 hour). No significant between-group differences in mean pain relief scores were found at any time point. The overall mean pain relief scores were statistically similar between the 2 treatment groups. The mean sedation scores were significantly higher at 30 minutes, 1 hour, and 2 hours after the first injection in the diclofenac group compared with the lornoxicam group (all, P < 0.05). No AEs were observed. The need for rescue medication was statistically similar between the 2 treatment groups (lornoxicam, 2 patients; diclofenac, 3 patients).

Conclusions:

In this study of adult patients who underwent CABG, the efficacy 10 of lornoxicam and diclofenac were similar in postoperative pain management. Both study drugs were well tolerated.     

氯诺昔康在乳腺区段切除手术中的应用

目的:探讨氯诺昔康用于乳腺区段切除手术麻醉的有效性及安全性。方法:择期乳腺区段切除手术患者66例,麻醉方式以局麻为主,随机分为氯诺昔康组(n=33)和对照组(n=33)。在切皮前20~30 min氯诺昔康组给予氯诺昔康16 mg静脉注射,而对照组给予生理盐水4 mL静脉推注。临床效果评价标准:(1)视觉模拟(VAS)评分;(2)局麻药和芬太尼的用量;(3)患者对术中镇痛效果总体印象(VRS)评分;(4)术中呼吸循环指标Ramsay镇静评分;(5)术后24 h内不良反应(如恶心呕吐)发生情况。结果:与对照组比较,氯诺昔康组术中血流动力学稳定,术中VAS评分较低,局麻药和芬太尼用量及加药次数显著减少,术后恶心呕吐等不良反应少。结论:氯诺昔康用于乳腺区段切除手术可以提供满意的镇痛效果。     

喷雾干燥氯诺昔康自微乳化制剂在兔体内的生物利用度

以氯诺昔康片剂为参比制剂,考察了自制喷雾干燥氯诺昔康自微乳化制剂在兔体内的相对生物利用度.以吡罗昔康为内标,采用高效液相色谱法测定兔血浆中的氯诺昔康.6只家兔分别灌胃给予氯诺昔康的片剂或喷雾干燥自微乳化制剂,结果显示,其AUC分别为16 304和26 328 ng·h·ml-1,cmax分别为824和1788 ng/ml,tmax分别为7.0和3.0 h.配对t检验分析表明AUC和cmax具有显著性差异(P＜0.05),tmax具有极显著性差异(P＜0.01),自微乳化制剂的相对生物利用度为161.5％.     

氯诺昔康联合地塞米松超前镇痛用于下肢手术的临床观察

目的：研究氯诺昔康联合地塞米松超前镇痛应用于下肢手术的镇痛效果及安全性。方法：将100例骨科下肢择期手术患者随机分为四组,A组：氯诺昔康（8mg溶于2mL注射用水）＋地塞米松（10mg,2mL）组;B组：氯诺昔康（8mg溶于2mL注射用水）＋生理盐水（2mL）组;C组：地塞米松（10mg,2mL）＋生理盐水（2mL）组;D组：单纯生理盐水（4mL）组。各组于术前30min静注相应药物,术中患者采用连续硬膜外麻醉,术后予静脉自控镇痛（PCIA,2mL／h,48h）。记录术后2、4、8、12、24、48h各时点的视觉模拟评分（VAS）与术后48h最痛程度（PD）评分、术后2d平均疼痛程度（MD）评分来评价其镇痛效果,以舒适度分级（BCS）~睡眠障碍度分级（SS）来评价患者对术后镇痛的满意程度,记录术后各组辅助镇痛药物的使用情况,同时观察恶心、呕吐、皮肤瘙痒、嗜睡、切口感染、延迟不愈等相关不良反应。结果：D组术后2、4、8、12、24、48hVAS评分高于A、B两组（P〈0．05）,同时BCS分级低于A、B两组（P〈0．05）：A组术后2j4、8、12h的VAS评分低于B组（P〈0．05）;术后48h内A组的PD、MD、SS评分均低于其他三组（P〈0．05）,A、B两组辅助镇痛药物的使用量明显少于C、D组（P〈0．05）,恶心、呕吐的发生率A组低于其他三组（P〈0．05）。结论：氯诺昔康联合地塞米松超前镇痛用于骨科手术,能有效缓解术后疼痛,提高患者对镇痛的满意程度,同时减少术后辅助镇痛药物的使用及相关不良反应。     

氯诺昔康、右美沙芬与吗啡协同镇痛作用的临床观察

目的:观察小剂量氯诺昔康、右美沙芬复合小剂量吗啡用于上腹部手术后镇痛的效果.方法:择期上腹部手术患者45例,术后使用100mL一次性镇痛泵.所用药物为分别为吗啡50mg(吗啡组,n=14)、吗啡30mg 右美沙芬15mg(右美沙芬组,n=14)、吗啡30mg 氯诺昔康16mg(氯诺昔康组,n=14)和吗啡30mg(对照组,n=6).记录术后3,6,24,48h疼痛视觉模拟评分(VAS)、Ramsay镇静评分、活动后VAS评分和48h内使用吗啡总量并记录可能出现的不良反应.结果:术后6和24h吗啡组、氯诺昔康组VAS明显低于对照组,右美沙芬组6h明显低于对照组.术后6和24h吗啡与氯诺昔康组活动后VAS明显低于对照组,而右美沙芬组与对照组差异无显著性,且在6h显著高于吗啡组.各组术后镇静评分无差异.术后48h吗啡总量吗啡组明显高于其他3组,氯诺昔康与右美沙芬组低于对照组.术后恶心呕吐病例吗啡组明显高于其他3组.右美沙芬组1例眩晕,吗啡组1例皮肤瘙痒,未发现其他不良反应.结论:小剂量非阿片类药物氯诺昔康与右美沙芬与吗啡联合应用可增加吗啡的镇痛效果.     

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。