Synthesis and characterization of novel dextran-conjugated macromolecules of aceclofenac

The study involves the condensation of acylimidazole derivatives of acaclofenac (AC) with dextran 10,000 and 20,000 to obtain aceclofenac-dextran prodrugs AC10 and AC20 respectively with an aim to improve aqueous solubility, increase therapeutic efficiency and reduce the gastrointestinal side effects. The structure of synthesized prodrugs was confirmed by IR and NMR spectroscopy. The molecular weight was determined by Mark-Howink Sakurada equation and the degree of substitution was obtained as 13.3 and 16 % for the prodrugs. In vitro hydrolysis carried out in simulated gastric fluid (SGF), simulated intestinal fluid (SIF) and simulated colonic fluid (SCF) showed faster hydrolysis in SIF and SCF. The percentage anti-inflammatory activity of AC was found as 49.56 whereas an improved value of 56.44 and 61.82 % were obtained for AC10 and AC20 respectively. The prodrugs showed improved analgesia and reduced ulcerogenicity than aceclofenac, thereby proving to be better in action than the parent drug(AU)

El estudio se centra en la condensación de acilimidazoles derivados de aceclofenaco (AC) con dextrano 10.000 y 20.000 para obtener los profármacos de aceclofenaco-dextrano AC10 y AC20, respectivamente, con el objetivo de mejorar la hidrosolubilidad, aumentar la eficacia terapéutica y reducir los efectos secundarios gastrointestinales. La estructura de los profármacos sintetizados se ha confirmado a través de espectroscopia IR y RMN. El peso molecular ha sido determinado a través de la ecuación de Mark-Houwink-Sakurada y se ha obtenido un grado de sustitución de 13,3 y 16% para los profármacos. La hidrólisis in vitro llevada a cabo en fluido gástrico simulado (FGS), fluido intestinal simulado (FIS) y fluido colónico simulado (FCS) ha mostrado una hidrólisis más rápida en FIS y FCS. De ello ha resultado un porcentaje de actividad antiinflamatoria de AC de 49,56, mientras que para AC10 y AC20 se ha obtenido un valor aumentado de 56,44 y 61,82% respectivamente. Los profármacos han mostrado una mejor analgesia y una menor ulcerogenicidad que el aceclofenaco, por lo que se demuestra que su acción es mejor que la del fármaco base(AU)

Artemisinins from folklore to modern medicine--transforming an herbal extract to life-saving drugs.

The history of the artemisinins from Ge Hong in China during the 4th century, to the re-discovery of the qing hao derivatives in the 1970s, to the explosion of artemisinin derivatives and combinations throughout the world today is a fascinating story. The central and underappreciated role of the United States Army's 'drug company' known as the Division of Experimental Therapeutics at the Walter Reed Army Institute of Research is a story worth relating. From being the first group outside China to extract the active component of qing hao, to leading the work on neurotoxicity of the class in animals, to bringing a Good Manufacturing Practices intravenous formulation to the worldwide market is traced.

Chemotherapy of colorectal cancer: history and new themes.

Since the clinical introduction of 5-fluorouracil (5-FU) in 1958, improvements in the treatment of advanced colorectal cancer have been modest. However, improvements in response rates have been demonstrated when 5-FU is administered in conjunction with leucovorin, and when methotrexate or trimetrexate is administered preceding 5-FU, indicating that higher response rates could be achieved by biomodulating the activity of 5-FU. Thus, significant emphasis has been placed on designing more effective 5-FU-based combination regimens. Novel agents, including the thymidylate synthase inhibitor raltritrexed and the topoisomerase I inhibitor irinotecan, also have demonstrated activity in colorectal cancer. Other new approaches include the administration of oral 5-FU prodrugs. The development of novel agents, new therapeutic approaches, and the refinement of existing agents and regimens in the clinic will likely improve response rates and, ultimately, patient survival. The history, current treatment options, and future opportunities for advances in chemotherapy for the treatment of colorectal cancer are discussed.