氟比洛芬酯注射液用于烧伤患者镇痛的研究进展

烧伤疼痛一直是烧伤患者治疗及恢复过程中的一个难题,各种类型烧伤疼痛的性质和强度不同,给烧伤科临床医师对烧伤疼痛的判别和治疗带来了巨大挑战.阿片类药物作为临床治疗烧伤疼痛的首选药,镇痛效果好,但具有不良反应较多、耐药性、成瘾性等问题.氟比洛芬酯是临床上广泛使用的非甾体类抗炎药(NSAID),通过抑制前列腺素(PG)合成,...     

腹腔注射氟比洛芬酯对大鼠骨癌痛的影响

目的:探讨腹腔注射氟比洛芬酯对大鼠骨癌痛的影响.方法:30只雌性SD大鼠,完全随机分为5组(n=6):肿瘤+生理盐水组(C组)、肿瘤+氟比洛芬酯10 mg·kg-1·d-1组(CK10组)、肿瘤+氟比洛芬酯25 mg·kg-1·d-1组(CK25组)、肿瘤+氟比洛芬酯50 mg·kg-1·d-1组(CK50组)和假手术组+生理盐水(sham组).大鼠胫骨接种肿瘤14d后,腹腔分别注射相应剂量氟比洛芬酯及生理盐水,每天两次,连续7d.于造模前、后3、5、7、10d及14、17、21 d给药前、后半小时测量左后足底机械性缩足阈值(paw mechanical withdrawal threshold,PMWT)和行走痛行为评分.结果:在14、17、21d给药后,与C组(2.67±1.03,2.13±0.96,1.73±0.43)相比,CK25组(5.00±1.10,6.00±1.26,6.33±0.82)、CK50组(6.67±1.03,7.00±1.10,7.67±1.51)大鼠PMWT明显增加(P＜0.05)与C组(2.17±0.41,2.50±0.55,3.33±0.52)相比,CK25组(1.50±0.55,1.33±0.52,1.50±0.55)、CK50(1.10±0.63,1.17±0.41,1.00±0.63)大鼠行走痛评分显著减少(P＜0.05)；CK10组PMWT(3.60±0.89)和行走痛评分(2.50±0.55)与C组比较在d21差异有统计学意义(P＜0.05).在17、21d给药前,与C组比较,CK25组(5.33±1.03,6.33±0.82)和CK50组(5.67±0.82,7.00±1.10)PWMT值明显延长(P＜0.05),CK50组(1.67±0.52,2.00±0.63)行走痛评分明显降低(P＜0.05)；CK25组(2.17±0.41)行走痛评分在d21显著减少(P＜0.05).结论:在大鼠骨癌痛模型中,腹腔注射氟比洛芬酯可以剂量依存性缓解骨癌痛,镇痛效果持久.     

Novel dual-reverse thermosensitive solid lipid nanoparticle-loaded hydrogel for rectal administration of flurbiprofen with improved bioavailability and reduced initial burst effect

The purpose of this study was to develop novel solid lipid nanoparticle (SLN)-loaded dual-reverse thermosensitive hydrogel (DRTH) for rectal administration of flurbiprofen with improved bioavailability and reduced initial burst effect. The flurbiprofen-loaded SLNs were prepared by hot homogenisation technique, after optimising the amounts of lipid mixture (tricaprin and triethanolamine in 8:2 weight ratio), drug and surfactant. The flurbiprofen-loaded thermosensitive SLN composed of drug, lipid mixture and surfactant at a weight ratio of 10/15/1.3 was a solid at room temperature, and changed to liquid form at physiological temperature due to its melting point of about 32 °C. This SLN gave the mean particle size of about 190 nm and entrapment efficiency of around 90%. The DRTHs were prepared by adding this flurbiprofen-loaded thermosensitive SLN in various poloxamer solutions. Their rheological characterisation, release and stability were investigated while a morphological and pharmacokinetic study was performed after its rectal administration to rats compared with the drug and hydrogel. Poloxamer 188 and SLN decreased the gelation temperature and gelation time, but increased the viscosity at 25 °C, gel strength and mucoadhesive force of DRTHs. In particular, the DRTH composed of [SLN/P 407/P 188 (10%/15%/25%)] with the gelation temperature of about 35 °C existed as liquid at room temperature, but gelled at 30–36 °C, leading to opposite reversible property of SLN. Thus, it was easy to administer rectally, and it gelled rapidly inside the body. This DRTH gave a significantly increased dissolution rate of the drug as compared to the flurbiprofen, but significantly retarded as compared to the hydrogel, including the initial dissolution rate. Moreover, this DRTH gave significantly higher plasma concentration and 7.5-fold AUC values compared to the drug, and lower initial plasma concentration and C_max value compared to the hydrogel due to reduced initial burst effect. No damage in rectal mucosa was observed after the application of DRTH. Thus, this DRTH system with improved bioavailability and reduced initial burst effect would be recommended as an alternative for the flurbiprofen-loaded rectal pharmaceutical products.