Preparation and characterization of solidified SMEDDS containing flurbiprofen by spray drying method

Flurbiprofen, a non-steroidal anti-inflammatory agent, is used to treat rheumatoid arthritis and sore throat (1)However, it gave poor water solubility, and various solubilization technique such as self-microemulsifying drug delivery system(SMEDDS) has been used to improve the solubility, dissolution and oral bioavailability [2].The objective of this work was to develop redispersible solidified SMEDDS containing water-insoluble flurbiprofen with enhanced solubility.

The Extent of Solubilization of Flurbiprofen and Ketoprofen by Cetyltrimethylammonium Micelles Using Semi-Equilibrium Dialysis

The partitioning of two non-steroidal anti-inflammatory drugs (NSAIDs), flurbiprofen and ketoprofen, into cationic cetyltrimethylammonium micelles was investigated using semi-equilibrium dialysis at 37℃ in phosphate buffered saline. The micellar-water solubilization equilibrium constants for both NSAIDs, in their deprotonated forms, were observed to decrease linearly with increasing mole fraction of drug in micelles. For flurbiprofen, the solubilization constant in the limit as mole fraction of drug in micelles approaches zero was found to be 11,200 (co = 1 M), while for ketoprofen the value was 1950 (co = 1 M). Using 1H-NMR and UV spectroscopic techniques, the locus of solubilization for ketoprofen was found to be towards the charged exterior of the micelles, in the Stern layer, whereas flurbiprofen was found to solubilize more in the micellar interior.

Effect of flurbiprofen axetil analgesia after knee replacement on the cytokine contents in serum and joint fluid as well as HPA axis activity

Objective: To investigate the effect of flurbiprofen axetil analgesia after knee replacement on the cytokine contents in serum and joint fluid as well as HPA axis activity. Methods: Patients who underwent knee replacement in People's Hospital of Dongxihu District between April 2015 and January 2018 were selected as the research subjects and randomly divided into the experimental group who accepted flurbiprofen axetil combined with patient-controlled intravenous analgesia and the control group who accepted patient-controlled intravenous analgesia alone. The contents of cytokines and HPA axis-related hormones in serum were measured before surgery as well as 1 d and 3 d after surgery;the contents of cytokines in joint fluid were measured 1 d and 3 d after surgery. Results: Compared with those of same group before surgery, NGF, NPY, TNF-α, IL-2, IL-4, IL-10, ACTH, COR, INS, GH and PRL levels of both groups were increasing 1 d and 3 d after surgery, and NGF, NPY, TNF-α, IL-2, IL-4, IL-10, ACTH, COR, INS, GH and PRL levels in serum as well as PGE2, OPN, TGF-β1, FGF21, CXCL12 and YKL-40 in joint fluid of experimental group 1 d and 3 d after surgery were lower than those of control group. Conclusion: Flurbiprofen axetil analgesia after knee replacement can reduce the release of cytokines in serum and joint fluid, and inhibit the activity of HPA axis, and its analgesic effect is exact.

Effect of flurbiprofen axetil intervention before induction on incision pain and inflammatory stress response after orthopedic surgery

Objective:To study the effect of flurbiprofen axetil intervention before induction on incision pain and inflammatory stress response after orthopedic surgery.Methods: A total of 86 cases of elderly patients who underwent operative treatment of femoral neck fracture in Guangyuan Hospital of Traditional Chinese Medicine between March 2014 and December 2017 were selected as the research subjects. All patients were randomly divided into the experimental group who accepted flurbiprofen axetil intervention before induction + routine anesthesia induction and maintenance, and the control group who accepted routine anesthesia induction and maintenance, and each group included 43 cases. The pain levels of the two groups were assessed 24 h after surgery;the levels of pain mediators and inflammatory stress molecules in serum as well as the expression intensity of inflammatory stress molecules in peripheral blood were determined before surgery and 24 h after surgery.Results:24 h after surgery, serum SP, NPY, PGE2, TNF-α, IL-1β, IL-18, ACTH, COR and NE levels as well as peripheral blood NF-κB, NLRP3, Caspase-1, GLUT4 and FOXP3 expression intensity of both groups were significantly higher than those before surgery, and NRS pain score, serum SP, NPY, PGE2, TNF- , IL-1β, IL-18, ACTH, COR and NE levels as well as peripheral blood NF-κB, NLRP3, Caspase-1, GLUT4 and FOXP3 expression intensity of experimental group 24 h after surgery were significantly lower than those of control group.Conclusions:Flurbiprofen axetil intervention before induction can improve and inhibit the incision pain and inflammatory stress response after orthopedic surgery.

S(+)-Flurbiprofen Shows Potent PGE2 Inhibitory Activity in Inflammatory Cells, Superior Cell Transport Activity and Skin Permeability

We developed a novel topical non-steroidal anti-inflammatory drug (NSAID)patch, S(+)-flurbiprofen plaster, (SFPP), containing S(+)-flurbiprofen (SFP), an enantiomer of flurbiprofen (FP). In a previous study conducted in an animal model, we showed good skin absorption and potent analgesic efficacy of SFPP. In this study, to examine the superior features, as an NSAID patch, of SFP as compared to FP and R(-)-flurbiprofen (RFP), we tested the stereospecificity of SFP actions on Prostaglandin E2 (PGE2) inhibition in rat inflammatory leukocytes and in the binding activity of the drug to cells, and also the in vitro skin permeability of the drug in the Yucatan micropig (YMP). SFP showed potent inhibitory activity on PGE2 production from peritoneal leukocytes stimulated with a bacterial suspension, as compared to RFP and FP. The half maximal (50%) inhibitory concentration (IC50) values were 14 nM for SFP, 52 nM for FP, and 17,000 nM for RFP. In the cell binding study, significant and rapid increase of SFP binding to polymorphonuclear leucocytes (PMNs) was observed at 5 min after incubation, eventually reaching a steady state. SFP showed significantly higher binding activity for the inflammatory leucocytes as compared to RFP, suggesting its superior transfer potency. The skin permeability profile of SFP, RFP and FP in the YMP model showed that the rank order of the cumulative amount of permeated compounds in the skin was SFP > RFP > FP. The steady-state permeation rate (Flux) of SFP was significantly higher than that of FP (4.89 and 1.55 mg/cm2/h, respectively, p = 0.0068), indicating the remarkably superior skin permeability of SFP. SFP exerted potent inhibitory activity on PGE2 production and superior binding activity to the PMNs and skin permeability, as compared to FP and RFP. These results suggest that SFP possesses favorable characteristics for use as an active ingredient in the NSAID patch.

Effect of flurbiprofen axetil pretreatment on the pain degree as well as stress hormone and mediator secretion after abdominal surgery

Objective:To study the effect of flurbiprofen axetil pretreatment on the pain degree as well as stress hormone and mediator secretion after abdominal surgery.Methods: Patients undergoing abdominal surgery in our hospital between May 2015 and March 2017 were selected and randomly divided into two groups, intervention group received flurbiprofen axetil pretreatment combined with routine intravenous anesthesia, and the control group only accepted conventional intravenous anesthesia. The levels of pain neurotransmitters and cytokines, stress hormones and mediators in serum were detected before operation as well as 12 h and 24 h after operation.Results: 12 h and 24 h after operation, serum NPY, SP, Glu, TNF-α, IL-2, IL-6, IL-10, ACTH, Cor, Ins, NE and E levels of both groups of patients were significantly higher than those before operation while SOD, GHS-Px and HO-1 levels were significantly lower than those before operation, and serum NPY, SP, Glu, TNF-α, IL-2, IL-6, IL-10, ACTH, Cor, Ins, NE and E levels of intervention group 12 h and 24 h after operation were significantly lower than those of control group while SOD, GHS-Px and HO-1 levels were significantly higher than those of control group.Conclusion:Flurbiprofen axetil pretreatment can reduce the pain degree and stress response after abdominal surgery.

Synthesis of Flurbiprofen via Suzuki Reaction Catalyzed by Palladium Charcoal in Water

Flurbiprofen 1，优秀 nonsteroidal 反煽动性的药，在 69% 总收率在 5 步被综合。构造双性人芳基碎片的关键步成功地作为 phenylation 试剂用 sodiumtetraphenylborate 在水里经由 Pd/C-catalyzed 铃木偶合反应被完成。

Efficacy and safety of flurbiprofen cataplasms versus loxoprofen sodium cataplasms in knee osteoarthritis:a randomized controlled trial

Background:Clinical trial evidence is limited to identify better topical non-steroidal anti-inflammatory drugs(NSAIDs)for treating knee osteoarthritis(OA).We aimed to compare the clinical efficacy and safety of flurbiprofen cataplasms(FPC)with loxoprofen sodium cataplasms(LSC)in treating patients with knee OA.Methods:This is an open-label,non-inferiority randomized controlled trial conducted at Peking University Shougang Hospital.Overall,250 patients with knee OA admitted from October 2021 to April 2022 were randomly assigned to FPC and LSC treatment groups in a 1:1 ratio.Both medications were administered to patients for 28 days.The primary outcome was the change of pain measured by visual analog scale(VAS)score from baseline to day 28(range,0-10 points;higher score indicates worse pain;non-inferiority margin:1 point;superiority margin:0 point).There were four secondary outcomes,including the extent of pain relief,the change trends of VAS scores,joint function scores measured by the Western Ontario and McMaster University Osteoarthritis Index(WOMAC),and adverse events.Results:Among 250 randomized patients(One patient without complete baseline record in the flurbiprofen cataplasms was excluded;age,62.8±10.5 years;61.4%[153/249]women),234(93.6%)finally completed the trial.In the intention-to-treat analysis,the decline of the VAS score for the 24-h most intense pain in the FPC group was non-inferior,and also superior to that in the LSC group(differences and 95%confidence interval,0.414(0.147-0.681);P<0.001 for non-inferiority;P=0.001 for superiority).Similar results were observed of the VAS scores for the current pain and pain during exercise.WOMAC scores were also lower in the FPC group at week 4(12.50[8.00-22.50]vs.16.00[11.00-27.00],P=0.010),mainly driven by the dimension of daily activity difficulty.In addition,the FPC group experienced a significantly lower incidence of adverse events(5.6%[7/124]vs.33.6%[42/125],P<0.001),including irritation,rash and pain of the skin,and sticky hair uncovering pain.Conclusions:This study suggested that FPC is superior to LSC for treating patients with knee OA in pain relief,joint function improvement,and safety profile.Trial Registration:ChiCTR.org.cn,ChiCTR2100054822.

氟比洛芬酯对胸腔镜右肺叶切除术患者单肺通气期间肺功能的影响

目的观察氟比洛芬酯对胸腔镜右肺叶切除术患者采用封堵器行单肺通气期间肺氧合功能、呼吸力学及肺部并发症的影响。方法选择择期全麻下行胸腔镜右肺叶切除术采用封堵器行单肺通气的患者60例,男25例,女35例,年龄35~64岁,BMI 18~28 kg/m^(2),ASAⅠ或Ⅱ级。采用随机数字表法将患者分为两组:氟比洛芬酯组(F组)和对照组(C组),每组30例。F组在麻醉诱导前15 min静注氟比洛芬酯1.0 mg/kg,C组不予处理。于麻醉诱导前20 min(T_(0))、单肺通气30 min(T_(1))、单肺通气60 min(T_(2))、双肺通气15 min(T_(3))时抽取桡动脉血行血气分析,计算氧合指数(OI)并记录SpO_(2)。记录T_(1)、T_(2)时的气道峰压(Ppeak)、气道平台压(Pplat)、肺动态顺应性(Cdyn)和无效腔气量与潮气量之比(V_(D)/V_(T))。记录单肺通气期间低氧血症发生情况、补救例数、术后转ICU例数、术后72 h内肺不张、急性肺损伤和肺炎发生情况。结果与C组比较,F组T_(1)时SpO_(2)、T_(1)—T_(3)时PaO_(2)和OI、T_(1)、T_(2)时Cdyn明显升高(P<0.05);T_(1)、T_(2)时Ppeak和V_(D)/V_(T)、T_(2)时Pplat明显降低(P<0.05)。两组无一例单肺通气期间发生低氧血症和补救、术后转入ICU、术后72 h内发生肺不张、急性肺损伤和肺炎。结论对胸腔镜右肺叶切除术采用封堵器行单肺通气的患者,麻醉诱导前静注氟比洛芬酯有助于改善单肺通气期间肺氧合功能,优化呼吸力学参数。

Preemptive analgesic effects of flurbiprofen axetil in patients undergoing radical resection of esophageal carcinoma via the left thoracic approach

Background Systemic non-steroidal anti-inflammatory drugs have been evaluated for their possible preemptive analgesic effects.The efficacy of flurbiprofen axetil for preemptive analgesia in patients undergoing radical resection of esophageal carcinoma via the left thoracic approach needs further investigation.The aim of this study was to research the preemptive analgesic effects of flurbiprofen axetil in thoracic surgery,and the influence of preoperative administration on postoperative respiratory function.Methods This randomized,double-blind,controlled trial enrolled 60 patients undergoing radical resection of esophageal carcinoma via the left thoracic approach.Anesthesia management was standardized.Each patient was randomly assigned to receive either 100 mg flurbiprofen axetil intravenously 15 minutes before incision （PA group） or intravenous normal saline as a control （C group）.Postoperative analgesia was with sufentanil delivered by patient-controlled analgesia pump.Postoperative sufentanil consumption,visual analog scale pain scores,plasma levels of interleukin-8,and oxygenation index were measured.Results Compared with the preoperative baseline,postoperative patients in the PA group had no obvious increase in pain scores （P 〉0.05）,but patients in the C group had significantly increased pain scores （P〈0.05）.Pain scores in the C group were significantly higher at 24 hours postoperatively than preoperatively.Intergroup comparisons showed lower visual analog scale scores at 2-24 hours postoperatively in the PA group than the C group （P 〈0.05）.Sufentanil consumption and plasma interleukin-8 levels at 2 and 12 hours postoperatively were significantly lower in the PA group than the C group （P 〈0.05）.The oxygenation index at 2 and 12 hours postoperatively was significantly higher in the PA group than the C group （P〈0.05）.Conclusions Intravenous flurbiprofen axetil appears to have a preemptive analgesic effect in patients undergoing radical resection of esophageal carcinoma via the left thoracic approach,and appears to contribute to recovery of respiratorv function and to reduction of the postoperative inflammatory reaction.

Analgesic effect of parecoxib and flurbiprofen axetil for patients undergoing laparoscopic cholecystectomy and their influences on platelet aggregation

It is known that opioids produce postoperative analgesia, while it can also cause, especially in large doses, side effects like nausea, vomiting, constipation, syncope, skin itching, urinary retention and even respiratory inhibition. These factors have all greatly limited its clinical use for treating postoperative pain. Meanwhile, non-steroidal anti-inflammatory drugs （NSAIDs） play an increasingly important role in postoperative analgesia. Some studies suggest that NSAIDS may be neural protective in cerebral ischemic conditions.

Therapeutic time window of flurbiprofen axetil＇s neuroprotective effect in a rat model of transient focal cerebral ischemia

Background The neuroprotective effect of the cyclooxygenase （COX） inhibitor has been demonstrated in acute and chronic neurodegenerative processes. But its function under cerebral ischemic conditions is unclear. This study was designed to evaluate the neuroprotective efficacy of emulsified flurbiprofen axetil （FA, COX inhibitor） and its therapeutic time window in a model of transient middle cerebral artery occlusion （MCAO） in rats. Methods Forty-eight male SD rats were randomly assigned into six groups （n=8 in each group）; three FA groups, vehicle, sham and ischemia/reperfusion （I/R） groups. Three doses of FA （5, 10 or 20 mg/kg, intravenous infusion） were administered just after cerebral ischemia/reperfusion （I/R）. The degree of neurological outcome was measured by the neurologic deficit score （NDS） at 24, 48 and 72 hours after I/R. Mean brain infarct volume percentage （MBIVP） was determined with 2,3,5-triphenyltetrazolium chloride （TTC） staining at 72 hours after I/R. In three other groups （n=8 in each group）, the selected dosage of 10 mg/kg was administrated intravenously at 6, 12 and 24 hours after I/R. Results The three different doses of FA improved NDS at 24, 48 and 72 hours after I/R and significantly reduced MBIVP. However, the degree of MBIVP in the FA 20 mg/kg group differed from that in FA 10 mg/kg group. Of interest is the finding that the neuroprotective effect conferred by 10 mg/kg of FA was also observed when treatment was delayed until 12-24 hours after ischemia reperfusion. Conclusion COX inhibitor FA is a promising therapeutic strategy for cerebral ischemia and its therapeutic time window could last for 12-24 hours after cerebral ischemia reperfusion, which would help in lessening the initial ischemic brain damage.

镇痛药物在膝关节置换术后的应用效果与经济学评价

目的探讨膝关节置换术后镇痛的药物疗效与经济学评价。方法选取2021年1月至2022年12月于新乡市中心医院接受膝关节置换术治疗患者180例作为研究对象,按照随机数字表法分为A组(术后接受氟比洛芬酯镇痛)、B组(术后接受帕瑞昔布镇痛)及C组(术后接受酮咯酸氨丁三醇镇痛),各60例。对比镇痛效果、视觉模拟疼痛评分(VAS)、术后首次下床时间、48 h内PCIA按压次数、膝关节活动度及不良反应发生率。结果重复测量方差分析显示,3组静息、咳嗽状态下VAS评分、膝关节活动度时间、组间及交互效应有统计学意义(P<0.05);C组T_(1)、T_(2)、T_(3)、T_(4)时点的静息、咳嗽状态下VAS评分分别低于A组和B组,而T_(0)、T_(1)、T_(2)、T_(3)、T_(4)、T_(5)时点的膝关节活动度均高于A组和B组(P<0.05)。C组镇痛总满意度高于A组和B组(P<0.05)。C组的术后首次下床时间、48 h内PCIA按压次数均低于A组和B组(P<0.05)。C组的住院时间均短于A组和B组(P<0.05);B组和C组的住院费用、镇痛医疗成本均低于A组(P<0.05);B组的住院费用、镇痛医疗成本与C组差异无统计学意义(P>0.05)。3组不良反应总发生率差异无统计学意义(P>0.05)。结论酮咯酸氨丁三醇镇痛用于膝关节置换术后有利于减轻患者疼痛和缩短首次下床时间。

Flurbiprofen axetil promotes neuroprotection by activation of cerebral peroxisome proliferator-activated receptor gamma after focal cerebral ischemia in rats

Background Our previous papers indicate that flurbiprofen axetil （FA）, a cyclooxygenase inhibitor, is a promising therapeutic strategy for cerebral ischemia in rats. This study aimed to investigate whether FA could promote a neuroprotective effect by activation of peroxisome proliferator-activated receptor-y （PPAR-y） after focal cerebral ischemia in rats. Methods Totally 48 male Sprague-Dawley （SD） rats were randomly assigned into six groups （n=8 in each group）： animals in group ischemia/reperfusion （I/R） only received 120-minute transient middle cerebral artery occlusion （tMCAO）; animals in group I/R ＋FA were administered FA （10 mg/kg） by caudal vein just after 120-minute tMCAO; animals in group I/R ＋FA＋GW9662 were administered GW9662 （a PPAR-Y inhibitor, 1 mg/kg） intraperitoneally 30 minutes before cerebral ischemia onset and FA （10 mg/kg） by caudal vein just after 120-minute tMCAO; animals in group I/R ＋GW9662 were administered GW9662 （1 mg/kg） intraperitoneally 30 minutes before cerebral ischemia onset; animals in group I/R ＋DMSO were administered 3% DMSO （vehicle of GW9662, 1 ml/kg） intraperitoneally 30 minutes before cerebral ischemia onset; animals in sham group experienced the identical surgery apart from the insertion of the nylon filament. The neurologic deficit score （NDS） were performed at 72 hours after reperfusion, and then mean brain infarct volume percentage （MBIVP） was determined with 2,3,5-triphenyltetrazolium chloride （TTC） 10 g/L staining. Results NDS was significantly increased in group I/R＋FA （12.0 （10.0-15.0））, group I/R＋FA＋GW9662 （10.0 （8.0-12.0））, and in group I/R＋FA＋DMSO （12.0 （9.0-14.0）） at 72 hours after reperfusion compared with those in group I/R （7.5 （6.0-10.0））. NDS was conspicuously different between group I/R＋FA （12.0 （10.0-15.0）） and group I/R＋FA＋GW9662 （10.0 （8.0-12.0））. MBIVP in group I/R （（45.82±8.83）%） was significantly greater than that in group I/R＋FA （（23.52±9.90）%）, group I/R＋FA＋GW9662 （（33.17±7.15）%）; MBIVP in group I/R＋FA （（23.52±9.90）%） was significantly smaller than that in group I/R＋FA＋GW9662 （（33.17±7.15）%）. Conclusions FA confers the neuroprotective effect on tMCAO in rats and the selective PPAR-Y antagonist GW9662 attenuates the effect of FA. FA could promote a neuroprotective effect by, or in part, activation of PPAR-y after focal cerebral ischemia in rats.

氟比洛芬酯复合利多卡因用于妇科腹腔镜手术的麻醉效果研究

目的:探讨氟比洛芬酯复合利多卡因用于妇科腹腔镜手术的麻醉效果。方法:选取2020年10月至2022年10月于四川绵阳四〇四医院择期行腹腔镜手术的132例患者,采用单双号法分为对照组和联合组,各66例。麻醉诱导前10 min,对照组患者静脉注射0.9%氯化钠注射液10 mL,联合组患者双通道泵入氟比洛芬酯1.0 mg/kg+利多卡因1.0 mg/kg,术中持续输注利多卡因1.0 mg/(kg·h)至手术结束。比较两组患者术中用药剂量、脑电双频指数,术后(4、6和12 h)镇痛质量,术后12 h血清应激反应指标[肾上腺素(E)、去甲肾上腺素(NE)和皮质醇(Cor)]水平及术后24 h内不良反应发生情况。结果:联合组患者瑞芬太尼、丙泊酚总用量显著低于对照组;联合组患者插管前1 min、插管后1 min及插管后5 min的脑电双频指数显著低于对照组;术后4、6和12 h,联合组患者疼痛程度评分显著低于对照组,舒适度评分显著高于对照组;术后12 h,两组患者E、NE及Cor水平均较术前显著升高,但联合组患者的E、NE及Cor水平显著低于对照组,上述差异均有统计学意义(P<0.05)。术后24 h内,联合组、对照组患者的不良反应总发生率分别为4.55%(3/66)、7.58%(5/66),差异无统计学意义(P>0.05)。结论:氟比洛芬酯复合利多卡因预防性镇痛可有效提高妇科腹腔镜手术患者的麻醉镇痛质量,减轻机体围手术期应激反应,且使用安全。

氟比洛芬酯与丙泊酚复合麻醉对老年肺癌肺叶切除术患者肺氧合功能、血流动力学及呼吸顺应性的影响

目的分析氟比洛芬酯与丙泊酚复合麻醉对老年肺癌肺叶切除术患者围术期肺氧合功能、血流动力学及呼吸顺应性的影响。方法选取2020年1月—2022年6月行肺叶切除术的老年肺癌100例为研究对象,根据围术期麻醉方式的不同分为观察组和对照组,每组50例。观察组在单肺通气前实施氟比洛芬酯与丙泊酚复合麻醉,对照组在单肺通气前实施丙泊酚全凭静脉麻醉。比较2组术中丙泊酚用量,不同时间点[麻醉诱导前(T1)、单肺通气30 min(T2)、单肺通气60 min(T3)及术毕(T4)]肺氧合功能指标[氧分压(PaO_(2))、二氧化碳分压(PaCO_(2))、氧合指数(OI)]、血流动力学指标[平均动脉压(MAP)、心率(HR)]及呼吸顺应性指标[动态肺顺应性(Cdyn)]的变化情况,以及术后并发症发生情况。结果观察组术中丙泊酚用量(110.32±3.89)mg明显少于对照组(168.21±4.86)mg(P<0.01)。T1和T4时,2组PaO_(2)、PaCO_(2)、OI、MAP、HR、Cdyn比较差异均无统计学意义(P>0.05);与T1时比较,2组在T2和T3时PaO_(2)、PaCO_(2)、OI、HR及Cdyn均明显降低,MAP明显升高(P<0.05);其中观察组T2和T3时PaO_(2)、OI及Cdyn高于对照组,MAP、HR明显低于对照组(P<0.05,P<0.01)。观察组术后并发症总发生率18.00%(9/50)低于对照组54.00%(27/50)(P<0.01)。结论对行单肺通气下肺癌肺叶切除术的老年患者应用氟比洛芬酯与丙泊酚复合麻醉效果确切,可明显减少术中丙泊酚用量,改善患者围术期肺氧合功能及血流动力学,提高患者呼吸顺应性,有效保护肺功能,且安全性较好。

高效液相色谱法测定氟比洛芬中4种基因毒性杂质

目的建立高效液相色谱法测定氟比洛芬中基因毒性杂质:2-氟苯胺、4-溴-2-氟乙酰苯胺、4-溴-2-氟苯胺和4-溴-2-氟联苯。方法采用Phenomenex Kinetex F5100A(250 mm×4.6 mm,5μm)色谱柱,乙腈-水-冰醋酸(体积比30∶65∶5)为流动相A,乙腈为流动相B,梯度洗脱,流速为1.2 mL·min^(-1),检测波长为254 nm,进样体积10μL,柱温为35℃。结果2-氟苯胺、4-溴-2-氟乙酰苯胺、4-溴-2-氟苯胺和4-溴-2-氟联苯的检测下限分别为5.987、3.198、6.408,3.199 mg·L^(-1),分别在质量浓度19.96~2235(r=0.993)、10.66~2387(r=0.999)、21.36~2392(r=0.999)和10.66~2388 mg·L^(-1)(r=0.999)内与峰面积呈良好线性关系,平均加样回收率分别为100.5%、100.2%、101.4%和97.9%(n=9),加样回收率良好,对照品和供试品加标溶液在24 h内稳定性良好。三批次样品中基因毒性杂质均符合限度要求。结论所建立的方法简单,定量准确,专属性较好,适用于氟比洛芬中基因毒性杂质2-氟苯胺、4-溴-2-氟乙酰苯胺、4-溴-2-氟苯胺和4-溴-2-氟联苯的测定。

氟比洛芬酯预处理对于羟考酮复合丙泊酚在无痛纤维支气管镜检查术中应激反应的影响研究

目的研究氟比洛芬酯预处理对于羟考酮复合丙泊酚在无痛纤维支气管镜检查术中血流动力学以及应激反应的影响。方法90例无痛纤维支气管镜检查者,采用前瞻性研究方法,按随机数字表法分为A、B、C组,每组30例。A组:检查前5 min静脉滴注5 ml生理盐水,检查前静脉注射羟考酮0.1 mg/kg,丙泊酚2 mg/kg;B组:检查前5 min静脉滴注5 ml生理盐水,检查前静脉注射羟考酮0.08 mg/kg,丙泊酚2 mg/kg;C组:检查前5 min静脉滴注50 mg氟比洛芬酯,检查前静脉注射羟考酮0.06 mg/kg,丙泊酚2 mg/kg。三组术中丙泊酚恒定输注,若术中患者体动则静脉追加丙泊酚30~50 mg。比较三组患者不同时间点[麻醉诱导前5 min(T0)、用药后即刻(T1)、喉罩置入后1 min(T2)、插入纤维支气管镜后1 min(T3)、纤维支气管镜取出后1 min(T4)、完成检查后5 min(T5)]血流动力学指标[经皮血氧饱和度(SpO_(2))、舒张压(DBP)、收缩压(SBP)、心率(HR)],不同时间点(T0、插入纤维支气管镜后3 min、T5)应激以及炎症反应指标[白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、肾上腺素(E)、去甲肾上腺素(NE)],不良反应(呛咳、低氧血症及喉、支气管痉挛)发生情况。结果T0、T4、T5时,三组SBP、DBP、HR、SpO_(2)比较差异无统计学意义(P>0.05);T2时,三组SpO_(2)比较差异无统计学意义(P>0.05);T1、T3时,三组SpO_(2)比较差异有统计学意义(P<0.05);T1、T2、T3时,三组SBP、DBP、HR比较差异有统计学意义(P<0.05)。T0时,三组NE、E、TNF-α、IL-6比较差异无统计学意义(P>0.05);插入纤维支气管镜后3 min、T5时,B组NE、E、TNF-α、IL-6均高于A组、C组,差异有统计学意义(P<0.05)。A组低氧血症、呛咳及喉、支气管痉挛发生率分别为20.00%、6.67%、3.33%,B组分别为3.33%、20.00%、6.67%,C组分别为3.33%、3.33%、3.33%。与A组比较,B组、C组低氧血症发生率明显降低,差异有统计学意义(P<0.05);与B组相比,C组呛咳发生率明显降低,差异有统计学意义(P<0.05);三组喉、支气管痉挛发生率比较,差异无统计学意义(P>0.05)。结论氟比洛芬酯预处理对羟考酮复合丙泊酚在无痛纤维支气管镜检查术中有助于缓解患者的应激反应,术中血流动力学更稳定,可使不良反应和麻醉药物剂量减少。

舒芬太尼联合氟比洛芬酯在功能性内窥镜鼻窦手术后患者静脉自控镇痛中的应用效果观察

目的探讨舒芬太尼联合氟比洛芬酯在功能性内窥镜鼻窦手术(FESS)后患者静脉自控镇痛(PCIA)中的应用效果。方法选取78例FESS患者为研究对象,按随机数字表法分为对照组和观察组,各39例。对照组行舒芬太尼PCIA,观察组行舒芬太尼联合氟比洛芬酯PCIA。对比两组镇痛效果、镇静效果、应激反应、PCIA使用情况及不良反应发生率。结果观察组术后3、6、12 h时视觉模拟评分法(VAS)评分为(3.58±0.42)、(2.39±0.32)、(1.85±0.24)分,Ricker镇静-躁动评分(SAS评分)为(4.24±0.45)、(3.46±0.37)、(2.83±0.22)分,均低于对照组的(4.12±0.51)、(3.08±0.41)、(2.31±0.29)分和(4.95±0.59)、(4.01±0.38)、(3.39±0.35)分(P<0.05);观察组术后24 h时皮质醇(COR)、去甲肾上腺素(NE)、促肾上腺皮质激素(ACTH)水平分别为(181.62±18.74)μg/L、(230.14±25.59)ng/L、(10.12±1.53)ng/L,均低于对照组的(204.36±19.75)μg/L、(251.52±26.43)ng/L、(12.96±1.62)ng/L(P<0.05);观察组按压次数、实际有效进药次数分别为(7.41±1.12)、(4.15±0.67)次/24 h,少于对照组的(9.69±1.27)、(5.25±1.05)次/24 h(P<0.05);两组不良反应发生率对比差异无统计学意义(P>0.05)。结论舒芬太尼联合氟比洛芬酯在FESS患者术后PCIA中应用价值高,可提高患者镇痛、镇静效果,减轻机体应激反应,减少PCIA按压次数,安全可靠。

氟比洛芬酯联合地佐辛对老年全髋关节置换术患者的疗效研究

目的 探讨氟比洛芬酯联合地佐辛对老年全髋关节置换术患者应激反应和炎症因子的影响。方法 根据随机抽签法将2021年3月—2023年3月武夷山市立医院收治的130例老年全髋关节置换术患者分为观察组(n=65)与对照组(n=65)。2组均采用静脉全身麻醉,对照组以地佐辛超前镇痛,观察组采取氟比洛芬酯联合地佐辛超前镇痛。对比2组患者的术后苏醒质量、疼痛程度、应激反应指标、炎症反应指标和不良反应。结果 观察组术后2、6、12、24 h的视觉模拟评分量表(visual analogue scale,VAS)分别为(6.09±0.98)分、(4.12±0.80)分、(2.29±0.57)分、(1.26±0.33)分,低于对照组的(6.85±1.03)分、(4.79±0.85)分、(2.80±0.62)分、(1.71±0.42)分(P <0.05)。观察组术后苏醒质量指标均优于对照组(P<0.05)。术后24 h,观察组应激反应肾上腺素(adrenaline,AD)、去甲肾上腺素(norepinephrine,NE)、皮质醇(cortisol,Cor)水平均低于对照组(P<0.05)。术后24 h,观察组炎症因子白介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、超敏C反应蛋白(hypersensitive C-reactive protein,hs-CRP)水平均低于对照组(P<0.05)。2组不良反应总发生率比较,差异无统计学意义(P>0.05)。结论 老年全髋关节置换术患者采用氟比洛芬酯联合地佐辛具有良好的镇痛效果,能够提高患者苏醒质量,抑制应激反应水平,改善炎症反应,安全性良好。