To evaluate the efficacy and safety of compound Decumbent Corydalis Rhizome (DCR) in treating patients with knee osteoarthritis (OA). Totally 79 patients with knee osteoarthritis were selected from out-patient and inpatient departments of West China Hospital and randomly divided into the test group and the control group. The test group (n = 41) was given Compound DCR with the dosage of 1.8 g · d(-1), while the control group (n = 38) was administered with diclofenac sodium with the dosage of 75 mg · d(-1). After 12 weeks of treatment, the total efficacy rates based on patients/physicians evaluation for experimental and control groups were 68.29%, 63.41% and 71.05%, 63.16%, respectively, without significant difference between the two groups. Both of the two groups showed significant improvements in the main efficacy indexes (pain on walking 20 m) and minor indexes (tenderness on palpation, Western Ontario and McMaster Universities OA index (WOMAC) and Short-Form Health Survey (SF-36 ), but without significant difference in efficacy between them. The incidence of related adverse events was 24.39% in the test group and 47.37% in the control group, respectively, with significant differences between the two groups (P < 0.05). In the controlled study, compound DCR is as efficient as diclofenac sodium but more tolerable, with a good clinical application prospect.
Adult ; Aged ; Corydalis ; chemistry ; Diclofenac ; administration & dosage ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Male ; Middle Aged ; Osteoarthritis, Knee ; drug therapy ; Rhizome ; chemistry ; Treatment Outcome

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.
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage/*toxicity ; Benzophenones/administration & dosage/toxicity ; Benzopyrans/administration & dosage/toxicity ; Bromobenzenes/administration & dosage/toxicity ; Cell Movement/drug effects ; Cells, Cultured ; Diclofenac/administration & dosage/toxicity ; Epithelial Cells/drug effects/metabolism/ultrastructure ; Epithelium, Corneal/cytology/*drug effects/metabolism ; Fluorometholone/administration & dosage/toxicity ; Humans ; L-Lactate Dehydrogenase/metabolism ; Microscopy, Electron, Transmission ; Ophthalmic Solutions ; Propionates/administration & dosage/toxicity

BACKGROUND/AIMS: Acute pancreatitis is a common complication of endoscopic retrograde cholangiopancreatography (ERCP). Combination therapy w ith ora l udenafil and aceclofenac may reduce the occurrence of post-ERCP pancreatitis by targeting different pathophysiological mechanisms. We investigated whether combining udenafil and aceclofenac reduced the rates of post-ERCP pancreatitis. METHODS: A prospective, randomized, double-blind, placebo-controlled, multicenter study was conducted in four academic medical centers. Between January 2012 and June 2013, a total of 216 patients who underwent ERCP were analyzed for the occurrence of post-ERCP pancreatitis. Patients were determined to be at high risk for pancreatitis based on validated patient and procedure-related risk factors. RESULTS: Demographic features, indications for ERCP, and therapeutic procedures were similar in each group. There were no significant differences in the rate (15.8% [17/107] vs. 16.5% [18/109], p = 0.901) and severity of post-ERCP pancreatitis between the udenafil/aceclofenac and placebo groups. One patient in each group developed severe pancreatitis. Multivariate analyses indicated that suspected dysfunction of the sphincter of Oddi and endoscopic papillary balloon dilation without sphincterotomy were associated with post-ERCP pancreatitis. CONCLUSIONS: Combination therapy with udenafil and aceclofenac is not effective for the prevention of post-ERCP pancreatitis.
Acute Disease ; Administration, Oral ; Adult ; Aged ; Aged, 80 and over ; Anti-Inflammatory Agents, Non-Steroidal/*administration & dosage/adverse effects ; Cholangiopancreatography, Endoscopic Retrograde/*adverse effects ; Diclofenac/administration & dosage/adverse effects/*analogs & derivatives ; Double-Blind Method ; Drug Therapy, Combination ; Female ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Pancreatitis/diagnosis/etiology/*prevention & control ; Phosphodiesterase 5 Inhibitors/*administration & dosage/adverse effects ; Prospective Studies ; Pyrimidines/*administration & dosage/adverse effects ; Republic of Korea ; Risk Factors ; Sulfonamides/*administration & dosage/adverse effects ; Treatment Outcome ; Young Adult

BACKGROUND/AIMS: The use of proton pump inhibitors or misoprostol is known to prevent the gastrointestinal complications of nonsteroidal anti-inflammatory drugs (NSAIDs). Rebamipide is known to increase the mucosal generation of prostaglandins and to eliminate free oxygen radicals, thus enhancing the protective function of the gastric mucosa. However, it is unknown whether rebamipide plays a role in preventing NSAID-induced gastropathy. The aim of this study was to determine the effectiveness of rebamipide compared to misoprostol in preventing NSAID-induced gastrointestinal complications in patients requiring continuous NSAID treatment. METHODS: We studied 479 patients who required continuous NSAID treatment. The patients were randomly assigned to groups that received 100 mg of rebamipide three times per day or 200 microg of misoprostol three times per day for 12 weeks. The primary endpoint of the analysis was the occurrence rate of gastric ulcers, as determined by endoscopy after 12 weeks of therapy. RESULTS: Of the 479 patients in the study, 242 received rebamipide, and 237 received misoprostol. Ultimately, 44 patients (18.6%) withdrew from the misoprostol group and 25 patients (10.3%) withdrew from the rebamipide group. There was a significant difference in withdrawal rate between the two groups (p=0.0103). The per protocol analysis set was not valid because of the dropout rate of the misoprostol group; thus, the intention to treat (ITT) analysis set is the main set for the efficacy analysis in this study. After 12 weeks, the occurrence rate of gastric ulcers was similar in the rebamipide and misoprostol groups (20.3% vs 21.9%, p=0.6497) according to ITT analysis. In addition, the therapeutic failure rate was similar in the rebamipide and misoprostol groups (13.6% vs 13.1%, p=0.8580). The total severity score of the gastrointestinal symptoms was significantly lower in the rebamipide group than in the misoprostol group (p=0.0002). The amount of antacid used was significantly lower in the rebamipide group than in the misoprostol group (p=0.0258). CONCLUSIONS: Rebamipide can prevent gastric ulcers when used with NSAIDs and can decrease the gastrointestinal symptoms associated with NSAID administration. When the possibility of poor compliance and the potential adverse effects of misoprostol are considered, rebamipide appears to be a clinically effective and safe alternative.
Adult ; Aged ; Alanine/administration & dosage/adverse effects/*analogs & derivatives ; Anti-Inflammatory Agents, Non-Steroidal/*adverse effects ; Anti-Ulcer Agents/*administration & dosage/adverse effects ; Arthritis/drug therapy ; Butanones/adverse effects ; Diclofenac/adverse effects/analogs & derivatives ; Double-Blind Method ; Drug Administration Schedule ; Gastric Mucosa ; Humans ; Middle Aged ; Misoprostol/*administration & dosage/adverse effects ; Quinolones/*administration & dosage/adverse effects ; Stomach Ulcer/chemically induced/*prevention & control ; Thiazines/adverse effects ; Thiazoles/adverse effects ; Treatment Outcome

Tepoxalin is a potent inhibitor of both the cyclooxygenase and lipoxygenase pathways of the arachidonic acid cascade, as well as a potent anti-inflammatory and control-pain (postoperation, arthritis et. al.) agent. The new method about the use of novel synthesis reagents and the first using ionic liquid as reactive solvent to synthesize tepoxalin were presented in this paper. The ionic liquid can be easily recycled and reused for several runs efficiently. The analgesic activity of tepoxalin was detected by acetic acid test on mice. The analysis of variance showed that oral administration of tepoxalin could significantly inhibit the number of writhing response within 1 hour and prolong the latent time in a dose dependent manner as compared with CMC control group (P < 0.05). At the same time, tepoxalin had the same analgesic activity as diclofenac sodium.
Administration, Oral ; Analgesics ; administration & dosage ; chemical synthesis ; pharmacology ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; chemical synthesis ; pharmacology ; Cyclooxygenase Inhibitors ; administration & dosage ; chemical synthesis ; pharmacology ; Diclofenac ; pharmacology ; Imidazoles ; chemistry ; Ionic Liquids ; chemistry ; Lipoxygenase Inhibitors ; administration & dosage ; chemical synthesis ; pharmacology ; Mice ; Pain Measurement ; drug effects ; Pyrazoles ; administration & dosage ; chemical synthesis ; pharmacology ; Random Allocation

Two different salts of diclofenac, diclofenac sodium and diclofenac potassium, in tablet dosage form were tested for their bioavailability and disposition kinetics in a group of eighteen rabbits in normal and experimentally induced dehydrated conditions with a wash out period of 7 days between both stages of study. Biochemical and physiological parameters were also measured in both normal and dehydrated states. Diclofenac levels in plasma were determined using a validated reversed phase HPLC method. Primary kinetic parameters i.e. AUC(0-infinity), Cmax, Tmax and other disposition kinetics were obtained with non-compartmental procedure. Biochemical parameters i.e. packed cell volume, plasma glucose and total lipid concentration in dehydrated rabbits increased significantly. Plasma concentration of diclofenac sodium and diclofenac potassium decreased significantly in water deprived rabbits. In comparison, diclofenac potassium in normal and dehydrated state of the same group of rabbits showed a significantly increased plasma concentration when compared with diclofenac sodium.
Administration, Oral ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; blood ; pharmacokinetics ; Area Under Curve ; Biological Availability ; Dehydration ; metabolism ; Diclofenac ; administration & dosage ; analogs & derivatives ; blood ; pharmacokinetics ; Rabbits ; Tablets

Acanthamoeba Keratitis ; diagnosis ; drug therapy ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; Atropine ; administration & dosage ; Cornea ; pathology ; Diagnosis, Differential ; Diclofenac ; administration & dosage ; Drug Administration Schedule ; Drug Therapy, Combination ; Follow-Up Studies ; Humans ; Mydriatics ; administration & dosage ; Ophthalmic Solutions ; Retrospective Studies

BACKGROUND: NSAIDs and methotrexate induce gut damage and bacterial translocation (BT). However, there is no study examining the combined effects of methotrexate and NSAID on gut damage and BT. We examined the combined effects of methotrexate and NSAID-induced enteropathy and bacterial translocation in an experimental animal model. METHODS: Rats received either no drug, NSAID alone (diclofenac 80 mg/kg and 120 mg/kg per os), methorexate alone (20 mg/kg per os) or NSAID with methotrexate. Gut barrier dysfunction, the degree of intestinal adhesion, stool pellet number, bacterial number of total aerobes and Gram negatives in the distal ileal and cecal contents and the number of Gram negatives in the mesenteric lymph nodes, liver, spleen, kidney and heart were measured. RESULTS: Administration of diclofenac or methotrexate alone caused an increase in gut barrier dysfunction and intestinal adhesion and a decrease in stool pellet number. Administration of diclonfenac alone induced enteric bacterial overgrowth and increased BT to the mesenteric lymph nodes, liver, spleen, kidney and heart. Administration of methotrexate alone induced enteric bacterial undergrowth and BT to the mesenteric lymph nodes, liver, spleen but not to the kidney and heart. The supplements with methotrexate increased the NSAID-induced gut barrier dysfunction and intestinal adhesion, and decreased the stool pellet number. However, the reduced NSAID-induced enteric Gram negative bacterial overgrowth (with a dose of diclofenac of 80 mg/kg) and BT to the liver, spleen, kidney and heart. COCNLUSION: Methotrexate increases NSAID-induced intestinal damage, but reduces NSAID-induced BT to the liver, spleen, kidney and heart in experimental animals.
Administration, Oral* ; Animals ; Anti-Inflammatory Agents ; Anti-Inflammatory Agents, Non-Steroidal ; Bacterial Translocation* ; Diclofenac* ; Heart ; Kidney ; Liver ; Lymph Nodes ; Methotrexate* ; Models, Animal* ; Rats* ; Spleen

Hydroxyethyl chitin (HECH) is a water soluble chitin derivative made by etherification of chitin, ethylene chlorohydrin was used as etherification reagent in this reaction. A novel interpenetrating polymer network (IPN) composed of HECH/PAA was prepared. The IR spectra confirmed that HECH/PAA was formed through chemical bond interaction. The sensitivity of this hydrogel to temperature and pH was studied. The swelling ratio of this hydrogel in artificial intestinal juice is much greater than that in artificial gastric juice. The IPN hydrogel exhibited a typical pH-sensitivity, and its degree of swelling ratio increased with the increase of temperature. The sustained-release drug system of Dichlofenac potassium was prepared by using HECH/PAA as the drug carrier. The release experiment showed a perfect release behavior in artificial intestinal juice. This IPN is expected to be used as a good drug delivery system of enteric medicine.
Acrylates ; administration & dosage ; chemistry ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; Chitin ; administration & dosage ; analogs & derivatives ; chemistry ; Delayed-Action Preparations ; Diclofenac ; administration & dosage ; Drug Carriers ; chemical synthesis ; Drug Delivery Systems ; Hydrogel, Polyethylene Glycol Dimethacrylate ; administration & dosage ; chemistry ; Hydrogen-Ion Concentration

AIMTo prepare diclofenac sodium liposomes and observe its ocular pharmacokinetics in rabbits.

METHODSThe diclofenac sodium cationic liposomes were prepared by reverse-phase evaporation methods and the formula of liposome was optimized with uniform design. HPLC method was established and validated for the determination of diclofenac sodium in precornea, cornea and aqueous humor of rabbit eye. Liposome and eyedrop solution 50 microL with total 50 microg diclofenac sodium were instilled to eyes of rabbits, separately. Samples of tear, cornea and aqueous humor were collected at different time intervals after rabbits were sacrificed. The ocular pharmacokinetics was investigated by the concentration-time data of tear, cornea and aqueous humor.

RESULTSThe mean particle size of the diclofenac sodium liposomes was 226.5 nm with zeta potential of + 18. 1 mV. The entrapment efficiency reached 63%. Compared with solution, liposome was characterized by slower clearance in precornea. The concentration of diclotenac in cornea and aqueous humor instilled with liposome were higher than that with eye-drop solution. Cmax of diclofenac sodium in aqueous humor instilled with liposome and eye-drop solution were (0.69 +/- 0.25) and (0.48 +/- 0.19) microg x mL(-1) and (36.68 +/- 11.7) and (21.82 +/- 8.6) microg x g(-1) in cornea, respectively. But no significant difference were found to Tmax in aqueous humor and cornea between liposome and eyedrop, T(1/2) of diclofenac in aqueous humor and cornea with liposoine were longer than that with eye-drop solution. The ocular bioavailability of liposome in aqueous humor was 211% compared with that of eyedrop.

CONCLUSIONDiclofenac sodium cationic liposomes can increase the corneal contact time, enhance the corneal permeability of diclofenac sodium and improve its ocular bioavailability.

Animals ; Anti-Inflammatory Agents, Non-Steroidal ; administration & dosage ; chemistry ; pharmacokinetics ; Aqueous Humor ; metabolism ; Area Under Curve ; Biological Availability ; Chromatography, High Pressure Liquid ; Cornea ; metabolism ; Diclofenac ; administration & dosage ; chemistry ; pharmacokinetics ; Drug Compounding ; Liposomes ; Microscopy, Electron, Transmission ; Particle Size ; Rabbits ; Random Allocation