RESUMO
Introduction: beeswax alcohols, consisting in a reproducible mixture of six primary fatty alcohols from 24 to 34 carbon atoms purified from Apis mellifera beeswax, has been shown to produce antioxidant and gastroprotective effects. This substance is used to manufacture Abexol® 50 mg tablets, the finished form used in clinical studies and in routine practice. Objective: to determine the stability of 50 mgâBeeswax alcohols tablets (Abexol®) packed in highâdensity polyethylene flasks. Methods: samples from three batches of Abexol® 50 mg tablets packed in white high density polyethylene flasks (Rainbow & Nature, Sydney, Australia) were put into cardboard boxes and kept under climatic conditions of the zone IV (30±2 ºC, 70±5 percent of relative humidity) for five years. Results: all parameters tested were within specifications throughout the whole study: appearance (white round tablets with intact surfaces), average weight (initial average weight±7,5 percent), total content of the six fatty alcohols (50±3.75 mg), disintegration time (<15 min), hardness (Ë3 kg/cm2) and microbiological content (≤1 000 bacteria/g and ≤100 fungi/g, absence of E. coli,S. aureus, Pseudomonas, Salmonella and C. albicans). This result is consistent with the data of a previous stability study of Abexol® 50 mg tablets manufactured in Cuba and packed in blisters of polyvinyl chloride and aluminum. Conclusions: the results of the present study support that Abexol®50mg tablets packed in white high density polyethylene flasks and stored at the conditions of the climatic zone IV have a shelf life of 5 years(AU)
Introducción: los alcoholes de la cera de abejas constituyen una mezcla reproducible de seis alcoholes grasos primarios de 24 a 34 átomos de carbono purificados de la cera de Apis mellifera. Esta sustancia, con efectos antioxidantes y gastroprotectores, es empleada para la elaboración de las tabletas de Abexol® con dosis de 50 mg de alcoholes, forma farmacéutica terminada utilizada en los ensayos clínicos y en la práctica de rutina. Objetivo: determinar la estabilidad de las tabletas con 50 mg de alcoholes de cera de abejas (Abexol®) en frascos de polietileno de alta densidad. Métodos: muestras de tres lotes de tabletas de Abexol® con dosis de 50 mg envasadas en frascos de polietileno de alta densidad ( Rainbow & Nature, Sydney, Australia) se pusieron en cajas de cartón y se mantuvieron en las condiciones de la zona climática IV (30±2 ºC, 70±5 por ciento de humedad relativa) durante cinco años. Resultados: los parámetros evaluados se mantuvieron dentro de sus especificaciones de calidad durante todo el estudio: apariencia (tabletas blancas redondas con superficies enteras), peso promedio (inicial±7,5 por ciento), contenido total de los seis alcoholes grasos (50±3,75 mg), tiempo de desintegración (<15 min), dureza (Ë3 kg/cm2) y contenido microbiológico (≤1 000 bacterias/g y ≤100 hongos/g, ausencia de E. coli, S. aureus, Pseudomonas, Salmonella y C. albicans). Este resultado es consistente con los datos de un estudio previo de estabilidad de tabletas de Abexol® con dosis de 50 mg, fabricadas en Cuba y envasadas en blísteres de cloruro de polivinilo y aluminio. Conclusiones: los resultados del presente estudio sustentan que las tabletas de Abexol® con dosis de 50 mg, envasadas en frascos de polietileno de alta densidad y almacenadas en las condiciones de la zona climática IV, presentan un tiempo de vida útil de cinco años(AU)
Assuntos
Humanos , Ceras/uso terapêutico , Estabilidade Enzimática , Comprimidos , Cuba , Álcoois GraxosRESUMO
Nonsteroidal antiinflammatory drugs include the traditional drugs and more selective COX-2 inhibitors. Traditional nonsteroidal antiinflammatory drug use is hampered by their gastrotoxicity, while COX-2-inhibitors increase the cardiovascular risk. The search of safer substances for managing inflammatory conditions is updated, a challenge wherein dual COX/5-LOX inhibitors have a place. This review summarizes the benefits of D-002, a mixture of higher aliphatic beeswax alcohols, on joint health and gastric mucosa. D-002 elicits gastroprotection through a multiple mechanism that involves the increased secretion and improved quality of the gastric mucus, the reduction of hydroxyl radical, lipid peroxidation, protein oxidation, neutrophil infiltration and the increase of antioxidant enzymes on the gastric mucosa. Consistently, D-002 inhibits NSAIDs, ethanol, pylorus-ligation and acetic acid-induced gastric ulceration in rats, and has reduced gastrointestinal symptoms in clinical studies. Early results found that D-002 was effective in the cotton pellet-induced granuloma and carrageenan-induced pleurisy model in rats, lowering pleural leukotriene B4 levels without causing gastrointestinal ulceration. However, D-002 effects on inflammation received little attention for years. Recent data have shown that D-002 inhibited both COX and 5-LOX activities with a greater affinity for 5-LOX and could act as a dual COX/5-LOX inhibitor. This mechanism might explain efficacy in experimental inflammatory and osteoarthritic models as well as clinical efficacy in osteoarthritic patients while supporting the lack of D-002 gastrotoxicity, but not the gastroprotective effects, which appear to be due to multiple mechanisms. In summary oral D-002 intake could help manage inflammatory conditions that impair joint health, while offering gastroprotection.
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BACKGROUND/AIMS: Nonsteroidal anti-inflammatory drugs relieve osteoarthritis (OA) symptoms but cause adverse effects. D-002, a mixture of beeswax alcohols, is effective against experimental OA. A pilot study found that D-002 (50 mg/day) for 8 weeks improves OA symptoms. The aim of this study was to investigate the effects of D-002 (50 to 100 mg/day) administered for 6 weeks on OA symptoms. METHODS: Patients with OA symptoms were double-blindly randomized to D-002 (50 mg) or placebo for 6 weeks. Symptoms were assessed by the Western Ontario and McMaster Individual Osteoarthritis Index (WOMAC) and the visual analog scale (VAS) scores. Patients without symptom improvement at week 3 were titrated to two daily tablets. The primary outcome was the total WOMAC score. WOMAC pain, joint stiffness and physical function scores, VAS score, and use of rescue medications were secondary outcomes. RESULTS: All randomized patients (n = 60) completed the study, and 23 experienced dose titration (two in the D-002 and 21 in the placebo groups). At study completion, D-002 reduced total WOMAC (65.4%), pain (54.9%), joint stiffness (76.8%), and physical function (66.9%) WOMAC scores, and the VAS score (46.8%) versus placebo. These reductions were significant beginning in the second week, and became enhanced during the trial. The use of rescue medication by the D-002 (6/30) group was lower than that in the placebo (17/30) group. The treatment was well tolerated. Seven patients (two in the D-002 and five in the placebo group) reported adverse events. CONCLUSIONS: These results indicate that D-002 (50 to 100 mg/day) for 6 weeks ameliorated arthritic symptoms and was well tolerated.
Assuntos
Anti-Infecciosos/uso terapêutico , Álcoois Graxos/uso terapêutico , Osteoartrite/tratamento farmacológico , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/efeitos adversos , Cuba , Método Duplo-Cego , Esquema de Medicação , Álcoois Graxos/administração & dosagem , Álcoois Graxos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/diagnóstico , Osteoartrite/fisiopatologia , Medição da Dor , Inquéritos e Questionários , Comprimidos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
AIM: To investigate the effects of beeswax alcohols (D-002) on the esophageal damage induced by gastroesophageal reflux (GER) in rats. METHODS: Sixty male rats were randomized into six groups (10 rats/group): a negative control and five groups with experimentally induced GER: a positive vehicle control, three treated with D-002 (25, 100 and 200 mg/kg, respectively), and one with omeprazole 10 mg/kg. All treatments were given by gastric gavage. One hour after dosing, GER was produced by simultaneous ligation of the pyloric end and the forestomach. Esophageal lesions index (ELI), gastric secretion volume and acidity, and esophageal malondialdehyde (MDA) and sulfhydryl (SH) group concentrations were measured. Statistical significance was considered at P < 0.05. RESULTS: As compared to the negative control, the positive control group exhibited increased ELI (5.2 ± 0.33 vs 0 ± 0, P = 0.0003), gastric secretion volume (2.69 ± 0.09 vs 0.1 ± 0.0, P = 0.0003) and acidity (238 ± 19.37 vs 120.0 ± 5.77, P = 0.001), and esophageal concentrations of MDA (2.56 ± 0.1 vs 1.76 ± 0.28, P = 0.001) and SH groups (1.02 ± 0.05 vs 0.56 ± 0.08, P = 0.0003). D-002 (25, 100 and 200 mg/kg) reduced ELI (3.36 ± 0.31, 2.90 ± 0.46 and 2.8 ± 0.23, respectively) vs the positive control (5.2 ± 0.33) (P = 0.004; P = 0.002; P = 0.001, respectively). There were no significant changes in acidity with D-002 treatment, and only the highest dose reduced the volume of the gastric secretion (1.92 ± 0.25) vs the positive control (2.69 ± 0.09, P = 0.013). D-002 (25, 100 and 200 mg/kg) lowered the esophageal MDA (2.05 ± 0.16, 1.98 ± 0.22 and 1.93 ± 0.22, respectively) (P = 0.01; P = 0.03; P = 0.03, respectively) and SH group concentration (0.87 ± 0.06, 0.79 ± 0.08 and 0.77 ± 0.06, respectively) (P = 0.04; P = 0.04; P = 0.02) vs the positive control (2.56 ± 0.10 and 1.02 ± 0.05, respectively). Omeprazole decreased ELI (2.54 ± 0.47), gastric secretion volume (1.97 ± 0.14) and acidity (158.5 ± 22.79), esophageal MDA (1.87 ± 0.13) and SH group (0.72 ± 0.05) concentrations vs the positive control (P = 0.002; P = 0.001; P = 0.02; P = 0.003; P = 0.002, respectively). CONCLUSION: Acute oral administration of D-002 decreased macroscopic esophageal lesions and oxidative stress in rats with experimentally induced GER, without modifying gastric secretion acidity.