病证结合中药组方治疗类风湿性关节炎活动期临床对照试验

目的:探讨在中医辨证的基础上,采用现代药理研究证实具有消炎镇痛或免疫抑制作用的中药进行组方,治疗类风湿性关节炎活动期患者,并与西药甲氨喋呤加尼美舒利作对照,观察其疗效和安全性。方法:选择类风湿性关节炎活动期患者60例,分为试验组30例和对照组30例。试验组采用病证结合方法给予中药煎剂口服,每日1剂;对照组口服甲氨喋呤7.5~10 mg(1次/周) 尼美舒利分散片100 mg(2次/日),分别在治疗后第8周随访,评价两组临床疗效和不良反应。结果:治疗8周后2组疾病疗效比较:试验组有效率为81.5%(22/27),对照组有效率为76.0%(19/25),两组比较差异无统计学意义(P=0.629>0.05)。两组证候疗效比较:试验组有效率为97.0%(26/27),对照组有效率为76.0%(19/25),两组比较差异有统计学意义(P=0.046<0.05)。两组临床观察指标比较,试验组在改善关节肿胀数、双手握力、晨僵时间等方面,疗效优于对照组(P<0.05);在关节疼痛VAS评分、关节压痛数、关节功能分级等方面与对照组比较差异无统计学意义(P>0.05)。两组实验室指标比较,试验组在降低C反应蛋白方面明显优于对照组(P<0.05);在降低血沉和类风湿因子方面与对照组比较差异无统计学意义(P>0.05)。两组不良反应比较,其不良事件发生率差异有统计学意义(P<0.05)。结论:病证结合中药组方治疗类风湿性关节炎与对照组疗效相当;但在改善证候积分、消肿、降低晨僵时间、提高双手握力、降低C反应蛋白等方面明显优于对照组,不良反应明显低于对照组,是值得提倡的治疗类风湿性关节炎活动期的有效方法。     

尼美舒利对人胃癌细胞株MKN28细胞周期和PTEN、mTOR基因表达的影响

背景：环氧合酶-2（COX-2）抑制剂的肿瘤化学预防作用已被广泛研究，但其作用机制仍未明确。胛EN为一多肿瘤抑制基因，对mTOR信号途径起负调控作用。目的：探讨选择性COX-2抑制剂尼美舒利对人胃癌细胞株MKN28细胞周期和PTEN、mTOR基因表达的影响。方法：以不同浓度尼美舒利于预MKN28细胞．甲基噻唑基四唑（MYr）实验检测细胞活力，流式细胞分析检测细胞周期，实时荧光定量聚合酶链反应（PCR）检测胛EN、mTORmRNA表达。结果：200～600μmol／L尼美舒利作用24～60h对MKN28细胞增殖有明显抑制作用，且作用呈时间-浓度依赖性。200μmol／L和400μmol／L尼美舒利作用48h可使MKN28细胞周期阻滞于G0／G1期和G2，M期。400pmloFL尼美舒利作用36h和48h可显著上调MKN28细胞PTENmRNA表达，作用24h和36h可显著下调mTORmRNA表达。结论：尼美舒利可通过阻滞细胞周期、调控胛EN、mTOR基因表达抑制人胃癌细胞生长。mTOR信号途径与COX-2通路之间可能存在交互作用。     

Effect of the NSAID nimesulide on the radical scavenger glutathione S‑transferase in patients with osteoarthritis of the knee

ABSTRACT

Objective: Osteoarthritis (OA) of the knee is a secondary inflammatory, painful disease of the knee joint with increasing destruction of the articular cartilage. In the inflammatory process the formation of free radicals (reactive oxygen species, ROS) plays a major role in progression of disease and in the subsequent destruction of joint cartilage. The aim of this pilot study was to examine the antioxidative potency of the non-steroidal anti-inflammatory drug (NSAID) nimesulide on glutathione S?transferase (GST), an enzymatic free radical scavenger. In addition, the effects on matrix metalloproteinase MMP?3 and its antagonist tissue inhibitor of matrix-metalloproteinase 3 (TIMP-1) were determined.

Research design and methods: This was an open-pilot study on 20 patients (aged 41–71 years old) suffering from painful OA of the knee, treated for 3 weeks with nimesulide 100?mg b.i.d. Twenty-three healthy subjects (aged 23–57 years), not age matched, served as a comparison group. GST, MMP?3 and TIMP?1 were measured by enzyme-immunoassays. Clinical symptoms and joint function were measured using the WOMAC Index.

Results: During the 3-week treatment period with nimesulide 100?mg b.i.d., both scavenger GST and the TIMP?1/MMP?3 ratio significantly increased. This change was accompanied by significant clinical improvement in terms of pain reduction, stiffness and joint function. Two adverse events occurred possibly related to nimesulide treatment: one case of moderate eyelid swelling, and one case of moderate diarrhea with no abnormality in the endoscopic examination.

Conclusions: These results confirm the antioxidative properties of the study drug, indicating that nimesulide, beside its known anti-inflammatory properties, also shows an evident antioxidative activity that adds further supportive evidence to its key role in the treatment of OA patients (thanks to the absence of degenerative effects on cartilage).     

HPLC测定尼美舒利颗粒中的有关物质

摘 要 目的： 建立尼美舒利颗粒有关物质的HPLC测定方法。 方法: 采用Agilent HC C₁₈（250 mm×4.6 mm,5 μm）色谱柱;流动相：乙腈 0.01 mol·L^-1磷酸二氢铵溶液（氨水调pH至7.0）（4060）;检测波长：230 nm;流速：1.0 ml·min^-1;柱温：30℃;进样量：20 μl。结果: 尼美舒利在0.10～0.30 mg·mL^-1（r=0.999 9）浓度范围内线性关系良好,各杂质峰与主峰分离度均大于2.0,检测限为0.3 ng,定量限为1.0 ng。结论:本方法专属性强,准确度高,重现性良好,可用于尼美舒利颗粒的质量控制。     

Efficacy of rofecoxib and nimesulide in controlling post-extraction pain in oral surgery: a randomised comparative study

SUMMARY

Rofecoxib 50?mg?day^?1 for 6 days provided better postoperative analgesia than nimesulide 200?mg?day^?1 in a randomised trial in patients (n?=?130) undergoing surgical extraction of third molars. The superiority of rofecoxib over nimesulide was especially marked during the first 2–3 postoperative days and in patients with fully

impacted molars. The drugs had similar effects on clinical signs of local postoperative inflammation. The effectiveness of rofecoxib in this study, plus considerations of the toxicity profile of nimesulide, support the conclusion that rofecoxib is preferable to nimesulide for relief of post-operative pain in patients undergoing surgical extraction of molars.     

聚维酮K30、S630对尼美舒利分散片分散性能的影响

目的:比较2种聚维酮类亲水性黏合剂对尼美舒利分散片分散性能的影响。方法:分别选择聚维酮S630和K30的5%乙醇溶液及5%水溶液作为亲水性黏合剂制备尼美舒利分散片,通过检测各组分散片的脆碎度、硬度和分散性比较二者对分散片性能的影响。结果:从分散片的脆碎度、硬度和分散性等方面考察,聚维酮S630的乙醇溶液或水溶液与K30的乙醇溶液或水溶液比较性能相同甚至在分散性方面前者更好。结论:聚维酮S630可以作为K30的替代物用作分散片的亲水性黏合剂。     

蠲痹强督汤治疗强直性脊柱炎随机平行对照研究

[目的]观察蠲痹强督汤治疗强直性脊柱炎疗效。[方法]使用随机平行对照方法,将180例随机分为两组,对照组90例尼美舒利口服。治疗组90例蠲痹强督汤加减。均4周为1疗程。统计症候积分变化。治疗1疗程(28d)判定疗效。[结果]治疗组临床痊愈19例,显效34例,有效22例,无效15例,总有效率83.33%。对照组临床痊愈10例,显效15例,有效32例,无效33例,总有效率63.33%。治疗组疗效优于对照组(P<0.01)。[结论]蠲痹强督汤治疗强直性脊柱炎临床疗效肯定。     

尼美舒利含量测定和有关物质检查方法的研究

目的建立高效液相色谱法测定尼美舒利的含量及有关物质。方法色谱柱为Hypersil BDSC18柱（250mm×4.6mm,5μm）,以0.1%三氟乙酸-乙腈（60∶40）为流动相,流速1.0ml/min,检测波长分别为298nm（含量测定）与230nm（有关物质检查）,柱温35℃。结果尼美舒利在10～200μg/ml浓度范围内,线性关系良好（r=0.9999）;杂质邻氨基二苯醚、2-苯氧甲烷磺酰苯胺、邻硝基二苯醚均在0.1～10.0μg/ml浓度范围内,线性关系良好（r=0.9999）,最低检测限分别为0.8、0.9、0.5ng。结论本方法简便、快速,结果准确、可靠,重现性较好,可用于尼美舒利的有关物质检查和含量测定。     

LC-MS法测定人血浆中尼美舒利的浓度

目的:建立以液-质联用法测定人血浆中尼美舒利浓度的方法。方法:色谱柱为Agilent Zorbox SB-Cl8,流动相为乙腈-0.1%甲酸(65∶35),流速为1.0mL·min-1,柱温为35℃,内标为缬沙坦;正离子检测模式,选择m/z309(尼美舒利,[M+H]+)和m/z436(缬沙坦,[M+H]+)进行监测。结果:尼美舒利血药浓度在5～50ng·mL-1范围内线性关系良好(r=0.9989);方法回收率为87.1%～92.9%;日内、日间RSD分别为3.1%～5.8%、6.4%～9.2%。结论:本方法灵敏、简便,结果准确可靠,重复性好,可用于尼美舒利的临床血药浓度监测和药动学研究。