Einsparung von Diclofenac durch B-Vitamine: Ergebnisse einer randomisierten Doppelblindprüfung mit reduzierten Tagesdosierungen von Diclofenac (75 mg Diclofenac versus 75 mg Diclofenac plus B-Vitamine) bei akuten Lendenwirbelsäulensyndromen

Summary Pain syndromes of the lumbar spine are one of the main problems in orthopedic practice. The therapeutic effect of NSAIDs is not subject to doubt in this connection.But considering that the application of NSAIDs is frequently associated with side effects, a reduction of dosage would be to the patient's benefit. Clinical studies have shown that concomitant treatment with vitamins B₁, B₆, B₁₂ and diclofenac leads to a more efficient pain relief than treatment using diclofenac alone and thus provides the possibility of saving NSAIDs.This clinical trial was carried out in order to determine whether these results can also be achieved when a reduced dosage of diclofenac (75 mg daily) is used.123 patients with acute pain syndromes of the lumbar spine were treated with either B-vitamins and diclofenac or diclofenac alone for a maximum of 7 days. There was the option to terminate therapy in the trial after 3–4 days in the case of total pain relief.45 patients could stop the treatment due to remission of symptoms. 30 patients belonged to the combination therapy group, the other 15 took diclofenac alone; this difference is statistically significant (p< 0.05).All parameters concerning pain relief and movement of the vertebral column showed statistically significant differences in favour of the B-vitamin-diclofenac-combination, too.The results document the positive influence of B-vitamins on painful vertebral syndromes and indicate that B-vitamins contribute to saving of NSAIDs by shortening the treatment time and reducing daily NSAID-dosage.

     

双氯酚酸钾片人体生物等效性研究

目的评价双氯酚酸钾实验制剂和参比制剂的生物等效性。方法8名健康男性志愿者交叉单剂量口服双氯酚酸钾实验制剂或参比制剂50mg,采用反相高效液相色谱法测定经时过程血药浓度,血药浓度时间数据用3p97药代动力学实用程序拟合,计算其药代动力学参数。结果实验制剂和参比制剂主要药代动力学参数Ka分别为(3．042±1．356)h     

血浆中双氯芬酸钾含量测定方法学研究

目的 :为了测定血浆双氯芬酸钾特建立反相高效液相色谱测定法。方法 :反相高效液相色谱法。色谱柱 :HypcrsilODSC18柱 ,5μm( 2 50× 4 .6)mmI .D ;流动相 :甲醇— 2 0mmol/L磷酸二氢钾液 ,用磷酸调至 pH 2 .5;流速 :1ml/min ;柱温 :4 3℃ ;检测波长 :2 82nm。结果 :线性方程为As/Ai=2 .881× 1 0 -3C -0 .0 0 2 1 ,r =0 .9998,线性范围为 ( 1 6～ 1 2 80 0 ) μg/L ,高、中、低三种浓度的双氯芬酸钾测得的日内精密度小于 2 .99% ,日间精密度小于 6.67% ,平均回收率为 ( 99.58± 1 .0 9) %。血浆最低检测浓度为 5μg/L。 结论 :该方法简便、准确、稳定 ,可用于测定血浆双氯芬酸钾浓度和该药药代动力学研究。     

Preparation and evaluation of sodium diclofenac controlled-release tablets

The dissolution behaviour of a direct compression compact prepared with sodium diclofenac and dibasic calcium phosphate (DCP) in different weight ratios with or without Biosoluble polymer^® (acrylic-based resin) was investigated in distilled water and in a medium with changing pH. The results indicate that the amount of sodium diclofenac released from the compact was dependent on the amount of drug and DCP used in the compact, and was also controlled by the amount of Biosoluble polymer^® added. A chemical reaction forming diclofenac acid might occur on the surface of the sodium diclofenac compact during exposure to the acidic medium, which was confirmed by diffuse-reflectance spectroscopy. The tablet with a 12 weight ratio of sodium diclofenac to DCP exhibited a sustained-release behaviour, similar to commercial sustained-release products (Voltaren SR-100^® and Grofenac Retard^®), but a lower release rate was found as compared to the commercial products. The dissolution behaviour of the study tablet and the commercial products was found to be dependent on the dissolution medium and the rotating speeds. Glass beads were added to the dissolution assembly to simulate the influence of food, and the enhanced friction between tablet and glass beads might result in a higher dissolution rate of the tablet and the commercial products.     

Additive effect of nitric oxide and prostaglandin-E2 synthesis inhibitors in endotoxin-induced uveitis in the rabbit

The involvement of nitric oxide (NO) and prostaglandin E₂ (PGE₂) was investigated in a model of intraocular inflammation induced by intravitreal injection of endotoxin (lipopolysaccharide, LPS, 10 ng) in rabbits. The severity of uveitis, the myeloperoxidase (MPO) activity in iris-ciliary body, and the protein concentration in aqueous humor were determined. Nitric oxide synthase (NOS) and cyclooxygenase (COX) activities were assessed respectively by nitrite and PGE₂ levels in aqueous humor. Treatment with inhibitors of NOS (N^G-nitro-L-arginine methyl ester, L-NAME, 50 mg/kg i.p.) or COX (diclofenac, 30 g, topically), alone or in combination, were compared to a salinetreated group. Diclofenac or L-NAME alone reduced or delayed the intensity of uveitis, and partially decreased the protein concentration in aqueous humor; diclofenac, but not L-NAME, partially reduced the polymorphonuclear leukocyte infiltration in the iris ciliary body as indicated by the MPO activity. Treatment with both inhibitors in combination diminished the clinical uveitis, the disruption of the blood-aqueous barrier and the MPO activity in the iris-ciliary body. We conclude that NO and PGE₂ have additive effects in endotoxin-induced uveitis in rabbits, and that the inhibition of both pathways would improve the therapeutical management of uveitis.accepted by M. J. Parnham     

人工神经网络紫外光谱法测定氯芬待因片含量

目的:对紫外光谱重叠的氯芬待因片进行多组分不经分离的含量测定.方法:应用前向型误差反向传播人工神经网络对氯芬待因片进行含量测定.结果:3个模拟样品平均回收率和RSD分别为磷酸可待因98.68%,3.40%;双氯芬酸钠100.01%,0.94%.结论:该方法测定结果准确,性能良好,对于吸收光谱重叠的药物含量测定有一定的参考价值.     

A Raman spectroscopic study of the diclofenac sodium–β-cyclodextrin interaction

The inclusion complex of diclofenac sodium (DCFNa) and β-cyclodextrin (βCD) was prepared and analyzed by using Raman and SERS spectroscopy. The interaction between DCFNa and βCD molecules was evidenced by monitoring the change in the peak positions and the widths of some guest molecule bands relative to those observed in the spectra of the free compound and 1:1 DCFNa–βCD physical mixture. Raman data have shown that the interaction between the guest and host molecules in the 1:1 DCFNa–βCD complex is maintained both through the dichlorophenyl ring and the phenylacetate group. SER spectra revealed that depending on the pH value of the solution different isomeric forms of the 1:1 guest–host complex are preferentially adsorbed on the silver surface via the nonbonding electrons of the oxygen atom. The orientation of the adsorbed species with respect to the metal surface was also elucidated.     

伤科接骨片联合双氯芬酸钠治疗闭合性足踝部骨折早期肿胀的疗效观察

目的探讨伤科接骨片联合双氯芬酸钠注射液治疗闭合性足踝部骨折早期肿胀的临床疗效。方法选取2016年12月—2017年12月天全县中医医院收治的100例闭合性足踝部骨折患者,按随机数字法分为对照组和治疗组,每组各50例。对照组患者肌肉注射双氯芬酸钠注射液,50 mg/次,2～3次/d。治疗组在对照组治疗的基础上以温开水或温黄酒送服伤科接骨片,4片/次,3次/d。两组患者均连续治疗4d。观察两组的临床疗效,比较两组的临床症状改善情况和视觉模拟评分法(VAS)评分。结果治疗后,对照组和治疗组的总有效率分别为82.00%、90.00%,两组比较差异具有统计学意义(P0.05)。治疗后,治疗组踝关节背伸、踝关节屈曲均明显大于对照组,消肿止痛时间、住院时间均明显短于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组患者VAS评分均显著降低,同组治疗前后比较差异具有统计学意义(P0.05);且治疗后治疗组患者VAS评分均明显低于对照组,两组比较差异具有统计学意义(P0.05)。结论伤科接骨片联合双氯芬酸钠注射液治疗闭合性足踝部骨折早期肿胀具有较好的临床疗效,可改善临床症状,缓解疼痛,具有一定的临床推广应用价值。     

The Toxicity of Nonsteroidal Anti-inflammatory Eye Drops against Human Corneal Epithelial Cells in Vitro

This study investigated the toxicity of commercial non-steroid anti-inflammatory drug (NSAID) eye solutions against corneal epithelial cells in vitro. The biologic effects of 1/100-, 1/50-, and 1/10-diluted bromfenac sodium, pranoprofen, diclofenac sodium, and the fluorometholone on corneal epithelial cells were evaluated after 1-, 4-, 12-, and 24-hr of exposure compared to corneal epithelial cell treated with balanced salt solution as control. Cellular metabolic activity, cellular damage, and morphology were assessed. Corneal epithelial cell migration was quantified by the scratch-wound assay. Compared to bromfenac and pranoprofen, the cellular metabolic activity of diclofenac and fluorometholone significantly decreased after 12-hr exposure, which was maintained for 24-hr compared to control. Especially, at 1/10-diluted eye solution for 24-hr exposure, the LDH titers of fluorometholone and diclofenac sodium markedly increased more than those of bromfenac and pranoprofen. In diclofenac sodium, the Na⁺ concentration was lower and amount of preservatives was higher than other NSAIDs eye solutions tested. However, the K⁺ and Cl^- concentration, pH, and osmolarity were similar for all NSAIDs eye solutions. Bromfenac and pranoprofen significantly promoted cell migration, and restored wound gap after 48-hr exposure, compared with that of diclofenac or fluorometholone. At 1/50-diluted eye solution for 48-hr exposure, the corneal epithelial cellular morphology of diclofenac and fluorometholone induced more damage than that of bromfenac or pranoprofen. Overall, the corneal epithelial cells in bromfenac and pranoprofen NSAID eye solutions are less damaged compared to those in diclofenac, included fluorometholone as steroid eye solution.     

Understanding the in vivo performance of enteric coated tablets using an in vitro-in silico-in vivo approach: Case example diclofenac

Individual pharmacokinetics after administration of enteric coated tablets are often highly variable and this has been ascribed to the interaction of the dosage form with the physiology of the gastrointestinal tract. This research aimed to explore the influence of interactions between enteric coated tablets and physiological factors such as gastric and intestinal pH as well as gastric emptying on the release of drug from the dosage form and the subsequent plasma profile, using diclofenac as a case example.A physiologically based pharmacokinetic (PBPK) model for monolithic enteric coated dosage forms was designed and coupled with biorelevant dissolution results to predict PK profiles of diclofenac from Voltaren® tablets in both fasted and fed humans. The paddle method was used to obtain the dissolution profiles of diclofenac in biorelevant media. The Noyes–Whitney model was employed to describe the dissolution kinetics. The PBPK model was set up using STELLA® software. A single unit enteric coated tablet was assumed to be emptied from stomach only with the house-keeping wave. Timing of the emptying was simulated using a random number generator to statistically estimate gastric emptying times after ingestion. The lag times and the dissolution rate used as input parameters in the STELLA® model were adjusted according to the pre-exposure period. The oral PK profiles were predicted for each virtual subject individually, and then the mean profiles and standard deviations were calculated.The dissolution profiles were highly affected by the period of pre-exposure in FaSSGF. A long period of pre-exposure of the tablet prolonged the lag time and decreased the dissolution rate. The results of the pharmacokinetic simulations showed that not only the mean profiles in the fasted state but also the variability could be predicted successfully using data generated for the individual virtual subjects. The results emphasize the importance of accounting for the range of pH profiles and gastrointestinal transit in the target population when predicting plasma profiles of enteric coated dosage forms and point to problems in demonstrating bioequivalence for dosage forms of this type.