Flow injection chemiluminescence determination of meloxicam using potassium permanganate and formaldehyde system

A simple, rapid and sensitive flow injection chemiluminescence （FI-CL） method has been developed for the determination of meloxicam. The method is based on the CL-emitting reaction between meloxicam and potassium permanganate in a hydrochloric acid medium, enhanced by formaldehyde （HCHO）. Under optimum conditions, calibration curve over the range of 1.0-20.0μg/mL was obtained. The proposed method was successfully applied to the determination of meloxicam in capsules with no evi- dence of interference from common excipients. The detection limit of this method was 25.6 ng/mL. The relative standard deviation was 2.1% for 10.0 μg/mL meloxicam. The sample throughput was found to be 120 samples/h.

Physicochemical Properties and Evaluation of Microemulsion Systems for Transdermal Delivery of Meloxicam

Microemulsion systems, composed of water, isopropyl myristate （IPM）, polyoxyethylene sorbitan trioleate （Tween 85 ）, and ethanol, were investigated as transdermal drug delivery vehicles for a lipophilic model drug（ meloxicam）. The purpose of this study was to investigate the physicochemieal properties of the tested microemulsion and to find the correlation between the physicoehemical properties and the skin permeation rate of the microemulsion. Pseudo-ternary phase diagram of the investigated system at a constant surfactant/cosurfactant mass ratio （ Km = 1 ： 1 ） was constructed by titration at 20℃, and the five fommlations were selected for further research in the o/w microemulsion domains. The values of electrical conductivity and viscosity showed that the selected systems were bicontinuous or non-spherical o/w microemulsion, and the electrical conductivity and viscosity were increased with increasing the content of water. These results suggest that the optimum formulation of microemulsion, containing 0. 375 meloxicam, 5% isopropyl myristate, 25% Tween 85. 25% ethanol, and water, showed the maximum permeation rate. It had a high electrical conductivity, small droplet size, and proper viscocity.

Enhanced transdermal delivery of meloxicam by nanocrystals: Preparation, in vitro and in vivo evaluation

Meloxicam(MLX) is efficient in relieving pain and inflammatory symptoms, which, however, is limited by the poor solubility and gastrointestinal side effects. The objective of this study is to develop a nanocrystal formulation to enhance transdermal delivery of MLX. MLX nanocrystals were successfully prepared by the nanoprecipitation technique based on acidbase neutralization. With poloxamer 407 and Tween 80(80/20, w/w) as mixed stabilizers,MLX nanocrystals with particle size of 175 nm were obtained. The crystalline structure of MLX nanocrystals was confirmed by both differential scanning calorimetry and X-ray powder diffractometry. However, the nanoprecipitation process reduced the crystallinity of MLX.Nanocrystals increased both in vitro and in vivo transdermal permeation of MLX compared with the solution and suspension counterparts. Due to the enhanced apparent solubility and dissolution as well as the facilitated hair follicular penetration, nanocrystals present a high and prolonged plasma MLX concentration. And 2.58-and 4.4-fold increase in AUC0 →2 4 h was achieved by nanocrystals comparing with solution and suspension, respectively. In conclusion, nanocrystal is advantageous for transdermal delivery of MLX.

Effects of Meloxicam on Vascular Endothelial Growth Factor and Angiopoietin-2 Expression in Colon Carcinoma Cell Line HT-29

To investigate the effect of meloxicam, a selected NSAIDs, on cell growth, expression of VEGF and angiopointin-2 （Ang-2） protein in HT-29 cell line, cultured HT-29 cells were treated with meloxicam of various concentrations for various lengths of time. The proliferation of HT-29 was detected by cell counting kit-8 （CCK-8）, the cell cycle was determined by flow cytometer and the levels of VEGF and Ang-2 protein in supernatants were examined by enzyme linked immunosorbent assay （ELISA）. The mRNA expressions of VEGF and Ang-2 in cultured HT-29 were determined by real-time quantitative reverse-transcription polymerase chain reaction. Our results showed that treatment of meloxicam of different concentrations and for various lengths of time had a cytotoxicic effect on the cell proliferation of HT-29 cells in a concentration-dependant and time-dependant manner. Cell cycle analysis showed that the cells were mainly blocked in G0/G1 phase. The VEGF and Ang-2 protein levels in supernatants of the culture medium were decreased gradually in a concentration-dependent or time-dependent fashion. The mRNA expression of cox-2, VEGF and Ang-2 showed a gradual and concentration-dependent reduction. It is concluded that meloxicam can reduce the expression of VEGF and Ang-2 at the protein and mRNA level in colon carcinoma cell line.

Gut-liver axis improves with meloxicam treatment after cirrhotic liver resection

AIM: To investigate the effect of meloxicam on the gut-liver axis after cirrhotic liver resection.

Co-nanoencapsulated meloxicam and curcumin improves cognitive impairment induced by amyloid-beta through modulation of cyclooxygenase-2 in mice

Alzheimer’s disease is a progressive brain disorder and complex mechanisms are involved in the physiopathology of Alzheimer’s disease.However,there is data suggesting that inflammation plays a role in its development and progression.Indeed,some non-steroidal antiinflammatory drugs,such as meloxicam,which act by inhibiting cyclooxygenase-2 have been used as neuroprotective agents in different neurodegenerative disease models.The purpose of this study was to investigate the effects of co-nanoencapsulated curcumin and meloxicam in lipid core nanocapsules(LCN)on cognitive impairment induced by amyloid-beta peptide injection in mice.LCN were prepared by the nanoprecipitation method.Male Swiss mice received a single intracerebroventricular injection of amyloid-beta peptide aggregates(fragment 25–35,3 nmol/3μL)or vehicle and were subsequently treated with curcumin-loaded LCN(10 mg/kg)or meloxicam-loaded LCN(5 mg/kg)or meloxicam+curcumin-co-loaded LCN(5 and 10 mg/kg,respectively).Treatments were given on alternate days for 12 days(i.e.,six doses,once every 48 hours,by intragastric gavage).Our data showed that amyloid-beta peptide infusion caused long-term memory deficits in the inhibitory avoidance and object recognition tests in mice.In the inhibitory avoidance test,both meloxicam and curcumin formulations(oil or co-loaded LCN)improved amyloid-beta-induced memory impairment in mice.However,only meloxicam and curcumin-co-loaded LCN attenuated non-aversive memory impairment in the object recognition test.Moreover,the beneficial effects of meloxicam and curcuminco-loaded LCN could be explained by the anti-inflammatory properties of these drugs through cortical cyclooxygenase-2 downregulation.Our study suggests that the neuroprotective potential of meloxicam and curcumin co-nanoencapsulation is associated with cortical cyclooxygenase-2 modulation.This study was approved by the Committee on Care and Use of Experimental Animal Resources,the Federal University of Pampa,Brazil(approval No.02-2015)on April 16,2015.

Physicochemical characterization, the Hirshfeld surface, and biological evaluation of two meloxicam compounding pharmacy samples

Meloxicam(MLX) is an anti-inflammatory drug susceptible to variations and crystalline transitions. In compounding pharmacies, the complete crystallographic evaluation of the raw material is not a routine procedure. We performed a complete crystallographic characterization of aleatory raw MLX samples from compounding pharmacies. X-ray diffraction indicated the presence of two crystalline forms in one sample. DSC experiments suggested that crystallization, or a crystal transition, occurred differently between samples. The FTIR and ~1H NMR spectra showed characteristic assignments.^(13)C solid-state NMR spectroscopy indicated the presence of more than one phase in a sample from pharmacy B. The Hirshfeld surface analysis, with electrostatic potential projection, allowed complete assignment of the UV spectra in ethanol solution. The polymorph I of meloxicam was more active than polymorph III in an experimental model of acute inflammation in mice. Our results highlighted the need for complete crystallographic characterization and the separation of freely used raw materials in compounding pharmacies,as a routine procedure, to ensure the desired dose/effect.

The Effect of Delivery Method on the Pharmacokinetic Properties of Meloxicam in Pre-Weaned Dairy Calves with Diarrhea

The non-steroidal anti-inflammatory drug meloxicam is commonly used as adjunct therapy for neonatal calf diarrhea to control pain and inflammation. The objective of this study was to compare the pharmacokinetics of meloxicam in diarrheic pre-ruminant dairy calves dosed either orally or subcutaneously. Twelve pre-ruminant male dairy calves with mild to moderate diarrhea were randomly assigned to receive one of four treatments (three per group): subcutaneous meloxicam (SM, 0.5 mg/kg body weight);an oral bolus meloxicam suspension (OM, 1 mg/kg body weight);an oral meloxicam suspension added to a feeding of oral electrolytes (EM, 1 mg/kg body weight);and an oral meloxicam suspension added to a feeding of milk replacer (MM, 1 mg/kg body weight). The predicted pharmacokinetic parameters for OM, MM, EM, and SM groups were: half-life (56.8 ± 21.7 vs. 136.0 ± 26.6 vs. 85.2 ± 21.7 vs. 36.3 ± 21.7 h), Cmax (4.3 ± 0.4 vs. 3.7 ± 0.4 vs. 3.9 ± 0.4 vs. 2.1 ± 0.4 μg/mL), Tmax (13.3 ± 4.0 vs. 10.7 ± 4.0 vs. 13.3 ± 4.0 vs. 2.7 ± 4.0 h), and AUC0-∞ (383.4 ± 126.8 vs. 877.8 ± 155.3 vs. 457.1 ± 126.8 vs. 126.4 ± 126.8 h * μg/mL). Oral meloxicam, especially MM, had extended elimination phases relative to SM. All meloxicam therapies provided effective therapeutic levels but all oral therapies (1 mg/kg) provided longer durations of activity than injectable meloxicam (0.5 mg/kg).

Simple Spectrophotometric Methods for the Determination of Meloxicam in Presence of Its Degradation Products

To develope two simple and accurate spectrophotometric methods for the determination of meloxicam( I )in presence of its degradation products, 5 -methyl -2 -aminothiazole ( II )and benzothiazine carboxylic acid( Ill ). Method:Both methods are based on the formation of chelate complexes of the studied drug with uranyl acetate and ferric chloride at room temperature in a methanolic medium. Results:The resulting complexes are stable for 24 hrs and show absorption maxima at 406 nm and 580 nm for uranyl and ferric complexes respectively. These methods are applicable over the concentration ranges of 10 -100 and 37.5 -300 p^g ~ mL-1 with mean recoveries of (99.44 ~ 0. 48 ) % and (99. 42 ~ 0. 45 ) %, and molar absorptivity of 4.67 x 103 and 1. 029 x 103 respectively. Conclusion:Both methods are proved to be stability indicating as no interference was observed with the degradation products. The proposed methods were successfully applied to the determination of the frug in bulk powder, laboratory prepared mixtures containing different percentages of degradation products of the drug in bulk powand pharmaceutical dosage

Physical characterization of meloxicam-β-cyclodextrin inclusion complex pellets prepared by a fluid-bed coating method

Meloxicam-β-cyclodextrin （ME-β-CD） inclusion complex was prepared by a fluid-bed coating technique upon solvent removal and simultaneous depositing onto the surface of nonpareil pellets and using PVP K30 as a binding agent to facilitate good coating. The resultant pellets were spherical and intact in shape with good flowability and friability. SEM analysis showed that the pellets were smooth and had a tightly coated inclusion complex layer. In vitro dissolution of the inclusion complex pellets in pH 7.4 phosphate buffer was dramatically enhanced at an ME/CD ratio of 1/1. DSC and powder X-ray diffractometry proved the absence of crystallinity in the ME/CD inclusion complexes. Moreover, Fourier transform-infrared spectrometry together with Raman spectrometry indicated that the thiazole ring of ME was possibly included in the cavity of β-CD.

Evaluation on monoamine neurotransmitters changes in depression rats given with sertraline, meloxicam or/and caffeic acid

Inflammation drives the development of depression and may affect neurotransmitters and thus neurocircuits increase the risk of depression.To investigate the influence of inhibition of inflammatory pathways on the biogenic amine neurotransmitters metabolism in depressive rats,sertraline,and meloxicam,the inhibitors of arachidonic acid-cyclooxygenase-2/lipoxygenase(AA-COX-2/5-LO)pathways,were given to depressive rats.After the development of depression model by chronic unpredictable mild stress(CUMS)for 6 weeks,Successful modeling rats were selected and randomly divided into CUMS group and medication administration group.After given medicine,The biogenic amine neurotransmitters in rat cortex and hippocampus were measured by high-performance liquid chromatography equipped with an electrochemical detector(HPLC-ECD).Compared with the normal group,the concentration of norepinephrine(NE)significantly decreased and the concentrations of Tyrosine(Tyr),Tryptophan(Trp),3,4-dihydroxyphenyl acetic acid(DOPAC),3-methoxy-4-hydroxyphenylglycol(MHPG),homovanillic acid(HVA)and 5-hydroxyindoleacetic acid(5-HIAA)significantly increased in the CUMS group.Sertraline significantly inhibited the elevation of 5-HIAA.Meloxicam inhibited the decrease of NE level in CUMS-induced rat and the increase of Trp,MHPG,and 5-HIAA level in a dose-dependent manner.Caffeic acid inhibited the decrease of NE and the increase of Trp and MHPG in a dose-dependent manner.The inhibition of AA-COX-2/5-LO pathways can improve the behaviors of depression rats and suppress CUMSinduced changes in biogenic amines.Compared with the single-dose lipoxygenase(5-LO)or Cyclooxygenase-2(COX-2)inhibitor,the combination treatment with meloxicam 1 mg/kg and caffeic acid 10 mg/kg have no significant improvement in CUMS-induced depression behavior and the level of cortical monoamine neurotransmitters and their metabolites.

揿针联合常规西药治疗坐骨神经痛的效果分析

目的:探讨揿针联合常规西药治疗坐骨神经痛的效果。方法:选取2019年1—12月中国中医科学院广安门医院南区收治的坐骨神经痛患者96例作为研究对象,按随机数字表法分为观察组和对照组,各48例。对照组采用常规西药治疗,观察组在对照组基础上加施揿针埋针治疗。比较两组疼痛情况、腰椎功能、临床疗效。结果:治疗前,两组疼痛评分比较,差异无统计学意义(P>0.05);治疗2周后、随访3个月后,两组疼痛评分均低于治疗前,且观察组低于对照组(P<0.05)。治疗前,两组腰椎功能评分比较,差异无统计学意义(P>0.05);治疗2周后、随访3个月后,两组腰椎功能评分均低于治疗前,且观察组低于对照组(P<0.05)。观察组治疗总有效率高于对照组,差异有统计学意义(P=0.021)。结论:揿针联合常规西药治疗坐骨神经痛的临床效果显著,可减轻患者疼痛,改善腰椎功能。

超长效局麻药的研究进展

多模式镇痛是术后疼痛管理的金标准,以超声引导下的神经阻滞为基础辅以少阿片类药物和足量全程使用的非甾体类抗炎药是目前最主流的多模式镇痛方案。但超声引导下神经阻滞受限于局麻药作用时间,往往为外科手术患者提供不超过8 h的有效术后镇痛,使外科手术患者术后镇痛满意率不高。随着快速康复理念的不断深入研究,如何延长局麻药的作用时间是研究的重点和热点。超长效局麻药包括已经应用于临床的布比卡因脂质体、HTX-011,以及仍处于研究阶段的季铵盐类衍生物等。本文将从具有缓释系统的超长效局麻药、超长效局麻药的新作用通路及靶点、开发全新化合物形式的超长效局麻药进行综述,为后续超长效局麻药的研究与临床应用提供新的思路。

美洛昔康对荷瘤BALB/c小鼠的围手术期镇痛效果

目的为了降低肿瘤切除术过程中小鼠的围手术期疼痛,保障动物福利最大化和研究数据的准确性,本研究探究美洛昔康对荷瘤小鼠的围手术期镇痛作用。方法所有BALB/c小鼠均采用舒泰和右美托嘧啶的麻醉方案,分为对照组(A组)和美洛昔康注射组(B组)。采用面部表情评分系统和疼痛行为频率评估小鼠的疼痛程度;监测小鼠的体质量以及脏器的组织病理学方法评估其围手术期安全性。结果B组小鼠的麻醉诱导时间较A组缩短,苏醒时间较A组显著延长(P<0.01);术后3 d内,B组小鼠的面部表情评分和疼痛行为频率较A组显著降低;两组小鼠的主要脏器和肠道组织在组织病理学上均无明显病变,体质量无显著差异,B组小鼠全部存活。结论舒泰和右美托嘧啶麻醉方案联合美洛昔康可以缩短BALB/c小鼠的麻醉诱导时间并使其缓慢苏醒,显著地降低了小鼠的围手术期疼痛,且是安全的。

硫酸氨基葡萄糖联合美洛昔康对膝骨关节炎患者血清FGF-2、TGF-β、IGF-1水平及膝关节运动功能的影响

目的 探究硫酸氨基葡萄糖联合美洛昔康对膝骨关节炎患者血清成纤维细胞生长因子-2(fibroblast growth factor-2, FGF-2)、转化生长因子-β(transforming growth factor-β, TGF-β)、胰岛素样生长因子-1(insulin-like growth factor-1, IGF-1)水平及膝关节运动功能的影响。方法 选择2021年6月-2023年6月就诊的膝骨关节炎114例,以随机数字表法分为联合组和美洛昔康组各57例。美洛昔康组予美洛昔康片治疗,联合组在美洛昔康组基础上加用硫酸氨基葡萄糖胶囊治疗,均治疗6周后观察疗效,比较2组治疗前、治疗6周后膝关节运动功能、炎性因子、生长因子水平及治疗期间安全性。结果 治疗6周后,联合组总有效率为91.23%(52/57)高于美洛昔康组的73.68%(42/57)(P<0.05)。治疗6周后,2组5次坐立试验、2.4 m起立行走试验所需时间短于治疗前,且联合组短于美洛昔康组(P<0.05,P<0.01);西安大略和麦克马斯特大学骨关节炎指数评分及血清前列腺素E2、白细胞介素-17、基质金属蛋白酶-3水平低于治疗前,且联合组低于美洛昔康组(P<0.05,P<0.01)。治疗6周后,2组血清FGF-2、TGF-β、IGF-1水平均高于治疗前,且联合组高于美洛昔康组(P<0.05,P<0.01)。2组治疗期间总不良反应发生率比较差异无统计学意义(P>0.05)。结论 硫酸氨基葡萄糖联合美洛昔康可有效升高膝骨关节炎患者血清FGF-2、TGF-β、IGF-1水平,延缓软骨退行性病变,控制机体炎症反应,进而有效改善患者膝关节运动功能,疗效显著,安全性良好。

骨痛灵酊联合美洛昔康片治疗对膝骨关节炎患者预后的影响

目的:探讨骨痛灵酊联合美洛昔康片治疗对膝骨关节炎患者预后的影响。方法:回顾性选取2020年2月—2023年2月临邑县中医院临盘院区收治的100例膝骨关节炎患者,依据用药方法分为联合治疗组、单独治疗组,各50例。联合治疗组给予骨痛灵酊联合美洛昔康片治疗,单独治疗组给予单独美洛昔康片治疗。统计分析两组中医症候积分、疼痛程度、膝关节功能、步态功能、健康状况、生活质量、骨代谢指标、氧化应激指标、炎症因子、临床疗效。结果:治疗后,联合治疗组各项中医症候积分及总分、西安大略和麦克马斯特大学(WOMAC)骨关节炎指数各项评分及总分、奎森运动功能指数(Lequesne评分)、视觉模拟评分法(VAS)评分、健康评价调查表(HAQ)评分、丙二醛(MDA)、一氧化氮(NO)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、白细胞介素-17(IL-17)均低于单独治疗组,6分钟步行试验(6MWT)距离长于单独治疗组,Berg平衡量表(BBS)评分、生活质量评价简表(SF-36)评分、骨钙素(BGP)、骨保护素(OPG)、谷胱甘肽(GSH)、超氧化物歧化酶(SOD)均高于单独治疗组,差异有统计学意义(P<0.05)。联合治疗组治疗总有效率为96.00%,高于单独治疗组的78.00%,差异有统计学意义(P<0.05)。结论:膝骨关节炎患者采用骨痛灵酊联合美洛昔康片治疗效果更好,可缓解疼痛,改善膝关节功能、步态功能,提高生活质量、优化健康状况,调节骨代谢指标、氧化应激指标及炎症因子。

高效液相色谱法测定犬血浆中美洛昔康含量及其在生物等效性研究上的应用

建立沉淀蛋白法结合高效液相色谱法灵敏检测犬血浆中美洛昔康含量的分析方法,并将此方法成功应用于美洛昔康在犬体内的药动学和生物等效性研究。血浆样品采用乙腈沉淀蛋白处理后,采用Agilent SB C18(150 mm×4.6 mm,5μm)色谱柱进行分离,以乙腈-1%甲酸水(80∶20,V∶V)为流动相进行梯度洗脱,检测波长为355 nm。应用该方法测定18只比格犬随机交叉进行颈部皮下注射0.2 mg/kg·bw的国产制剂和进口制剂的美洛昔康注射剂后的血药浓度,并计算药动学参数。结果显示:美洛昔康在0.050~3.2μg/mL的浓度范围内呈现良好线性关系(R^(2)≥0.999),回收率在98.7%~108.2%以内,批内、批间精密度均小于12%,样品稳定性良好,均满足分析检测要求。单剂量皮下注射美洛昔康注射液受试制剂AUC0-t、AUC0-∞、Cmax的90%CI为参比制剂相应参数的80.00%~125.00%范围内,受试制剂和参比制剂具有生物等效性。结果表明,建立的犬血浆中美洛昔康浓度测定方法准确、灵敏、选择性好、重现性高,可用于美洛昔康注射液在犬体内的生物等效性研究。

活血益气通经汤联合美洛昔康对腰椎间盘突出症患者炎症反应及下腰痛的影响

目的:探讨活血益气通经汤联合美洛昔康在腰椎间盘突出症(LDH)患者中的应用价值。方法:选择2020年1月—2023年1月吉安市第一人民医院收治的LDH患者60例,按随机数字表法分为两组。对照组(n=30)采用美洛昔康治疗,观察组(n=30)采用活血益气通经汤联合美洛昔康治疗,两组均治疗14 d。对比分析两组炎症反应、下腰痛程度、腰椎功能、临床疗效、不良反应。结果:治疗后,观察组C反应蛋白(CRP)[(7.53±0.86)mg/L]、白介素(IL)-6[(92.43±10.07)μg/L]、IL-1β[(5.17±0.94)ng/L]、肿瘤坏死因子-α(TNF-α)[(1.14±0.21)ng/L]及视觉模拟评分法(VAS)评分[(2.75±0.69)分]均低于对照组[(9.03±1.04)mg/L、(107.03±14.25)μg/L、(6.04±1.13)ng/L、(1.87±0.29)ng/L、(4.30±1.18)分],日本骨科协会评估治疗分数(JOA)评分中主观症状评分[(7.59±0.67)分]、客观体征评分[(5.20±0.41)分]、日常生活受限度评分[(12.07±0.84)分]及总分[(24.86±2.01)分]均高于对照组[(6.63±1.04)、(4.31±0.54)、(10.23±1.26)、(21.17±2.86)分],差异均有统计学意义(P<0.05);观察组治疗总有效率为93.33%,高于对照组的73.33%,差异有统计学意义(P<0.05);两组治疗期间均未出现不良反应。结论:活血益气通经汤联合美洛昔康可下调LDH患者CRP、IL-6、IL-1β、TNF-α水平,减轻下腰痛,改善腰椎功能,且安全可靠。