高效液相色谱法测定人尿中酮洛酸含量

目的建立以高效液相色谱法测定人尿中酮洛酸浓度的方法。方法色谱柱为Waters Sunfire C18,流动相为0.02mol·L-1磷酸二氢钾溶液-乙腈(70∶30,用磷酸调节pH值至4.5),检测波长为315nm,柱温为35℃,流速为1mL.min-1,进样量为20μL,保留时间为9.1min。结果人尿中酮洛酸浓度在0.1～10.0μg·mL-1范围内线性关系良好,日内和日间RSD<10%,最低定量限为0.1μg·mL-1。结论本法简便、快捷、灵敏,适用于酮洛酸人体药动学研究。     

Evaluation of skin permeation and accumulation profiles of a highly lipophilic fatty ester

The aim was to evaluate the skin permeation and accumulation profiles of a highly lipophilic fatty ester using the combination of various permeation enhancing techniques to study the potential of highly lipophilic fatty esters as local topical agents. Permeation and accumulation profiles of ketorolac stearate (C18:0) were studied using solubility improved formulation, supersaturated solution of permeant in enhancer vehicle, lipophilic receptor solution, enhancer pretreatment, and the removal of stratum corneum and delipidization of skins. Impermeability and minimal skin accumulation of ketorolac stearate could delineate a preliminary possibility for designing safer topical agents without systemic absorption.     

酮咯酸通过胰岛素样生长因子2信号通路抑制卵巢癌的生长和转移

目的 探讨酮咯酸对卵巢癌生长、转移影响及机制。方法 实验于2019年8月至2020年3月进行。细胞计数试剂盒（CCK-8）法检测不同剂量（0.10 g/L、0.50 g/L、1.00 g/L、1.50 g/L）酮咯酸对人卵巢癌细胞SKOV3的抑制率,筛选酮咯酸的最佳作用浓度。SKOV3细胞分为NC组、酮咯酸组、DMSO组、Linsitinib组、酮咯酸+pcDNA 3.1组和酮咯酸+pcDNA 3.1-IGF2组,TraNCwell法检测各组细胞迁移和侵袭,蛋白质印迹法（Western blotting）法检测各组细胞中胰岛素样生长因子2(IGF2)、胰岛素样生长因子1受体（IGF1R）的蛋白表达。裸鼠分为NC组和酮咯酸组,每组10只,观察酮咯酸对肿瘤生长及肿瘤组织中IGF2、IGF1R的蛋白表达的影响。结果 与NC组相比,不同剂量（0.10、0.50、1.00、1.50 g/L）酮咯酸组细胞抑制率升高[（6.99±0.06）%、（23.31±2.11）%、（51.39±6.91）%、（76.14±4.36）%比（0.02±0.00）%,P <0.05],选择1.0 g/L酮咯酸...     

Adding propacetamol to ketorolac increases the tolerance to painful pressure.

Combining an NSAID and paracetamol (acetaminophen) has in some studies given superior analgesia compared with the single drugs. In other trials no additive effect has been found. We have investigated the effect of this drug combination on the pressure pain tolerance threshold (PPTT), a reproducible correlate to clinical pain. The aim of this double blind, randomised, placebo controlled, crossover study was to evaluate the effect of i.v. propacetamol 2 g (= paracetamol 1 g) and ketorolac 30 mg, individually and in combination, on PPTT in 16 volunteers on four separate days. PPTT was measured 15 min before and at 45, 60, 90 and 150 min after the start of test drug administration. The pressure stimuli were applied on the base of a fingernail, increasing by 30 kPa/s until the pressure pain tolerance threshold was reached. For the total observation period (150 min), only the combination (propacetamol+ketorolac) increased significantly PPTT compared with baseline (P<0.04), while PPTT decreased significantly after placebo (P<0.01). The combination (propacetamol+ketorolac) and ketorolac alone increased PPTT compared with placebo (combination vs. placebo and ketorolac vs. placebo, P<0.001) and with propacetamol (combination vs. propacetamol and ketorolac vs. propacetamol, P<0.001). The combination was significantly better than ketorolac alone (P<0.04). After propacetamol 2 g, PPTT did not change significantly neither compared with placebo or baseline. CONCLUSIONS: Tolerance to repeated painful pressure (PPTT) decreased after placebo. Ketorolac 30 mg caused an increase in PPTT compared with placebo but not with baseline. Adding propacetamol 2 g to ketorolac 30 mg significantly increased PPTT. These findings support the practice of combining paracetamol with an NSAID for relief of acute pain.     

酮咯酸氨丁三醇注射液治疗急性胆绞痛的疗效观察

目的：观察酮咯酸氨对胆绞痛患者的疗效及不良反应。方法：将180例患者随机分为3组,分别应用酮咯酸氨丁三醇（治疗组）、奈福泮（对照组1）和盐酸哌替啶（对照组2）进行肌内注射,观察比较三种药物的镇痛效果及不良反应。结果：酮咯酸氨丁三醇在镇痛效果与盐酸哌替啶比较,无显著性差异,但优于奈福泮。不良反应比较,酮咯酸氨丁三醇与奈福泮无显著性差异;两者与盐酸哌替啶比较,均有显著性差异,且副作用小。结论：酮咯酸氨丁三醇治疗急性胆绞痛时,镇痛疗效确切,不良反应少,值得临床推广。     

高效液相色谱法测定人血浆中酮咯酸浓度

目的建立测定人血浆中酮咯酸浓度的高效液相色谱法。方法 24例健康志愿者口服单剂量(20 mg)酮咯酸氨丁三醇胶囊试验制剂。以奥硝唑为内标,待测血浆用甲醇沉淀法进行处理,色谱柱采用PlatisilODS柱(250 mm×4.6 mm,5μm),流动相为0.05 mol/L磷酸二氢钠溶液-乙腈(70∶30)(2 mol/L氢氧化钠调节pH值至5.14±0.01),波长为330 nm,进行HPLC分析。结果试验制剂的主要药动学参数:t1/2为(6.08±1.82)h,Cmax为(1 351.7±310.9)ng/mL,Tmax为(1.86±0.58)h,AUC0-t为(7 735±1 718)ng.h/mL,AUC0-∞为(8183±1 939)ng.h/mL,无内源性物质干扰测定,酮咯酸在24.8～2 480.0 ng/mL范围内与内标物峰面积之比线性关系良好,定量下限为24.8 ng/mL。提取回收率为83.9%～94.6%。结论该方法操作简便、准确,灵敏度高,专属性强,适用于人血浆中酮咯酸浓度的测定。     

Tramadol Versus Ketorolac in the Treatment of Postoperative Pain Following Maxillofacial Surgery

Pain plagues daily activity and hence its management would require alleviation at both the mental and physical planes, thus, bringing about comfort. It includes delivering analgesics in parenteral or oral form, or patches depending on the intensity and availability. Best analgesic regimens are ones that offer broad coverage, easy to administer, safe and economical. A drug seemingly appropriate to treat moderate to severe pain would be Tramadol hydrochloride, a centrally acting synthetic opioid analgesic with lower opiate-like dependence than Morphine. Ketorolac, a pyrrolo-pyrrole derivative, possesses analgesic, anti-inflammatory and anti-pyretic activity would also appear equally suitable. Fifty adult ASA grade I and II patients undergoing surgery under GA in the Department of Oral & Maxillofacial Surgery, College of Dental Sciences, Davangere, were included. Ketorolac (30 mg IM) for 25 patients and Tramadol (100 mg IM) for 25 patients were administered at the time of skin closure and repeated after 8 and 16 h from the conclusion of surgery. Pain, using the VAS at the 2nd, 4th, 6th, 12th and 24th post-operative hour, was assessed and compared using χ²-test. Vitals were monitored and adverse events were looked for. Though both the drugs resulted in significant decrease in pain intensity from the 2nd to 24th post-operative hour, Tramadol always resulted in better pain control than Ketorolac at every post-operative hour (P < 0.050). To conclude, intramuscular Tramadol seemed useful in controlling pain following surgery, with better levels of tolerance than intramuscular Ketorolac. However, both the drugs produced mild side effects but did not appear to influence the outcome.     

预防性镇痛和轻度镇静技术应用于口腔门诊治疗的临床观察

目的:研究预防性镇痛和轻度镇静技术应用于口腔门诊的临床效果。方法:纳入龋病、智齿拔除患者40例,随机分2组,每组20例:Ⅰ组使用1%利多卡因浸润麻醉后传统治疗方法;Ⅱ组采用预防性镇痛和轻度镇静技术,静脉滴注酮咯酸氨丁三醇、右美托咪定后1%利多卡因浸润麻醉下手术治疗。记录患者口腔治疗期间镇痛效果及Ramsay镇静评分,电话回访记录患者离院后1、4、8、12、24 h数字疼痛评分。结果:治疗期间及治疗后12 hⅡ组患者镇静、镇痛均明显优于Ⅰ组(P<0.01)且Ⅱ组患者无一例出现明显不良反应。结论:使用酮咯酸氨丁三醇和右美托咪定的预防性镇痛镇静技术可以安全应用于口腔科门诊患者,患者舒适基本无痛且安全。     

Hesperidin produces antinociceptive response and synergistic interaction with ketorolac in an arthritic gout-type pain in rats

Hesperidin occurs in greatest concentration in plants from the Rutaceae and Lamiaceae families. In human nutrition it contributes to the integrity of blood vessels and its deficiency in the diet has been linked to abnormal capillary leakiness as well as pain. In this study, the bioflavonoid hesperidin was identified as an active compound in an ethanol extract of the Rosmarinus officinalis aerial parts tested in the pain-induced functional impairment model in the rat (PIFIR) as an assay of inflammatory and chronic nociception similar to that observed in clinical gout. Hesperidin produced a dose-dependent and significant response with an ED₂₅ = 1666.72 mg/kg in comparison to an ED₂₅ = 302.90 mg/kg for the extract or an ED₂₅ = 0.47 mg/kg for the reference drug ketorolac in the PIFIR model. Although the antinociceptive response of R. officinalis was reverted in presence of the opioid antagonist naloxone (10 mg/kg, s.c.) and the 5HT_1A antagonist WAY100635 (0.12 mg/kg, s.c.), the hesperidin response was not modified by naloxone (10 mg/kg), WAY100635 (0.12 mg/kg), bicuculline (1 mg/kg, s.c.), flumazenil (10 mg/kg, i.p.) or caffeine (1 mg/kg, s.c.). Nevertheless, it was reduced in presence of capsazepine (10 or 20 mg/kg, s.c.) suggesting the participation of the TRPV1 receptor, which was reinforced when hesperidin significantly reduced the capsaicin-induced nociceptive response. A synergistic interaction was also observed when antinociceptive doses of hesperidin were combined with those of ketorolac producing 15 combinations mainly in additive and supra-additive responses. These results provide evidence for the antinociceptive activity of hesperidin and demonstrate synergistic response when combined with ketorolac, possibly by involvement of the TRPV1 receptor, suggesting their clinical potential in pain therapy.     

酮咯酸氨丁三醇与氟比洛芬酯用于骨科膝关节周围手术术后镇痛对比观察

目的:对比观察氟比洛芬酯与酮咯酸氨丁三醇用于骨科膝关节周围手术术后镇痛(PCA)的效果。方法:选择膝关节周围下肢手术120例,随机分为两组,各60例。氟比洛芬酯(F)组:氟比洛芬酯250mg,酮咯酸氨丁三醇(T)组:酮咯酸氨丁三醇150mg,两组均用生理盐水稀释到100mL,手术结束前半小时接静脉自控镇痛泵。观察记录时点为术后1、4、8、12、24、48h的静态和动态VAS评分、PCA按压次数、镇痛满意度及不良反应。结果:两组患者术后各时点的静态VAS评分及按压次数比较差异无统计学意义(P>0.05),静态VAS评分均<4分。F组术后8、12、24h的动态VAS评分明显高于T组(P<0.05),恶心、呕吐总发生率高于T组(P<0.05)。结论:与氟比洛芬酯相比,酮咯酸氨丁三醇用于膝关节周围手术术后镇痛效果满意,且不良反应少,是术后镇痛的良好选择。