In this formulation study,biocompatible non steroidal anti-inflammatory(NSAIDs)-loaded nanoparticles were designed as models to be further integrated in a prosthesis surface functionalization.A modified spontaneous em...In this formulation study,biocompatible non steroidal anti-inflammatory(NSAIDs)-loaded nanoparticles were designed as models to be further integrated in a prosthesis surface functionalization.A modified spontaneous emulsion-solvent diffusion methodology was used to produce drug-loaded PLGA nanoparticles without any purification or solvent evaporation requirements.Formulation parameters,such as lactide/glycolide ratio,polymer concentration,solvent/non solvent ratio and non solvent phase,as well as the non ionic tensioactive P188 co-precipitation composition were systematically explored.The optimized formulation(mean size:145 nm,surface charge:-13 m V) was employed to encapsulate various amounts of NSAIDs in a simple and scalable manner.The drug release was characterized in vitro by a complete release for 48 h.These results encourage upcoming preliminary steps for in vivo experiments of prosthesis surface functionalization.展开更多
Selective cyclo-oxygenase-2 (CQX-2) inhibitor, VIOXX (rofecoxib), wasvoluntarily withdrawn worldwide from drugstores by its maker Merck & Co., Inc. on September 30,2004, for its potential lethal side effects of he...Selective cyclo-oxygenase-2 (CQX-2) inhibitor, VIOXX (rofecoxib), wasvoluntarily withdrawn worldwide from drugstores by its maker Merck & Co., Inc. on September 30,2004, for its potential lethal side effects of heart attack or stroke, The Merck' s decision wasbased on new, three-year data from a prospective, multi-center, randomized, placebo-controlled,double-blind clinical trial of VIOXX with an unrelated study, the APPROVe (Adenomatous PolypPrevention on VIOXX) trial. The trial has been enrolling 2 600 patients and comparing 156 weeks(three years) of treatment with VIOXX 25 mg to placebo since 2000.展开更多
Phenyl sulfone-containing 2, 3-diarylindole derivatives were designed and identified to be selective COX-2 inhibitors. A convenient synthetic route was also developed for the synthesis of the novel inhibitors.
Objective： To evaluate the renoprotection effects of non-steroidal anti-inflammatory drugs （NSAIDs） in renal ischemia-reperfusion injury （IRI） and the cyclooxygenase （COX）-1/2 blockade association by indomethac...Objective： To evaluate the renoprotection effects of non-steroidal anti-inflammatory drugs （NSAIDs） in renal ischemia-reperfusion injury （IRI） and the cyclooxygenase （COX）-1/2 blockade association by indomethacin （IMT） in the mice model. Methods： After the left renal pedicle of mice was clamped, IMT was administrated by intraperitoneal injection with four doses： 1, 3, 5, and 7 mg/kg. Blood and kidney samples were collected 24 h after IRI. The renal functions were assayed by the cytokines and serum creatinine （SCr） using enzyme-linked immunosorbent assay （ELISA） kits. Kidney samples were analyzed by hematoxylin and eosin （H＆E） and immunohistochemistry stainings. Results： The mice administered with 5 mg/kg IMT had a marked reduction in SCr and significantly less tubular damage The tumor necrosis factor a （TNF-α） activity in renal homogenates and interleukin 6 （IL-6） activity in serum had a marked reduction at doses of 5 and 7 mg/kg IMT. The administration of 3 and 5 mg/kg IMT had a marked reduction in the ratio of thromboxane B2 to 6-keto-prostaglandin F1α. COX-1 and COX-2 stainings were weaker in 5 mg/kg IMT groups than that in the other groups. Conclusions： There was a dose response in the IMT function of renal IRI in mice, and IMT had a protective effect in a certain dose range. The effect of IMT on mice IRI was related to COX-1/2 blockades.展开更多
A series of new conjugates of indomethacin with phenolic anfioxidants were synthesized for enhanced antiinflammatory activity as well as reduced ulcerogenic potency. It was found that all conjugates were very potent a...A series of new conjugates of indomethacin with phenolic anfioxidants were synthesized for enhanced antiinflammatory activity as well as reduced ulcerogenic potency. It was found that all conjugates were very potent antioxidants in vitro. They could inhibit lipid peroxidafion significantly, while 11b-11e and 13b-13e could also interact with DPPH. However these conjugates showed little inhibition against croton oil induced mouse ear swelling.展开更多
基金financially supported by the European Erasmus program
文摘In this formulation study,biocompatible non steroidal anti-inflammatory(NSAIDs)-loaded nanoparticles were designed as models to be further integrated in a prosthesis surface functionalization.A modified spontaneous emulsion-solvent diffusion methodology was used to produce drug-loaded PLGA nanoparticles without any purification or solvent evaporation requirements.Formulation parameters,such as lactide/glycolide ratio,polymer concentration,solvent/non solvent ratio and non solvent phase,as well as the non ionic tensioactive P188 co-precipitation composition were systematically explored.The optimized formulation(mean size:145 nm,surface charge:-13 m V) was employed to encapsulate various amounts of NSAIDs in a simple and scalable manner.The drug release was characterized in vitro by a complete release for 48 h.These results encourage upcoming preliminary steps for in vivo experiments of prosthesis surface functionalization.
文摘Selective cyclo-oxygenase-2 (CQX-2) inhibitor, VIOXX (rofecoxib), wasvoluntarily withdrawn worldwide from drugstores by its maker Merck & Co., Inc. on September 30,2004, for its potential lethal side effects of heart attack or stroke, The Merck' s decision wasbased on new, three-year data from a prospective, multi-center, randomized, placebo-controlled,double-blind clinical trial of VIOXX with an unrelated study, the APPROVe (Adenomatous PolypPrevention on VIOXX) trial. The trial has been enrolling 2 600 patients and comparing 156 weeks(three years) of treatment with VIOXX 25 mg to placebo since 2000.
基金support for this study was provided by the National Natural Science foundation of China.
文摘Phenyl sulfone-containing 2, 3-diarylindole derivatives were designed and identified to be selective COX-2 inhibitors. A convenient synthetic route was also developed for the synthesis of the novel inhibitors.
基金supported by the National Key Technology R&D Program of China(No.2011BAI10B07)the National Basic Research Program(973)of China(No.2012CB517603)the National High-Tech R&D Program(863)of China(No.2012AA02A512)
文摘Objective： To evaluate the renoprotection effects of non-steroidal anti-inflammatory drugs （NSAIDs） in renal ischemia-reperfusion injury （IRI） and the cyclooxygenase （COX）-1/2 blockade association by indomethacin （IMT） in the mice model. Methods： After the left renal pedicle of mice was clamped, IMT was administrated by intraperitoneal injection with four doses： 1, 3, 5, and 7 mg/kg. Blood and kidney samples were collected 24 h after IRI. The renal functions were assayed by the cytokines and serum creatinine （SCr） using enzyme-linked immunosorbent assay （ELISA） kits. Kidney samples were analyzed by hematoxylin and eosin （H＆E） and immunohistochemistry stainings. Results： The mice administered with 5 mg/kg IMT had a marked reduction in SCr and significantly less tubular damage The tumor necrosis factor a （TNF-α） activity in renal homogenates and interleukin 6 （IL-6） activity in serum had a marked reduction at doses of 5 and 7 mg/kg IMT. The administration of 3 and 5 mg/kg IMT had a marked reduction in the ratio of thromboxane B2 to 6-keto-prostaglandin F1α. COX-1 and COX-2 stainings were weaker in 5 mg/kg IMT groups than that in the other groups. Conclusions： There was a dose response in the IMT function of renal IRI in mice, and IMT had a protective effect in a certain dose range. The effect of IMT on mice IRI was related to COX-1/2 blockades.
文摘A series of new conjugates of indomethacin with phenolic anfioxidants were synthesized for enhanced antiinflammatory activity as well as reduced ulcerogenic potency. It was found that all conjugates were very potent antioxidants in vitro. They could inhibit lipid peroxidafion significantly, while 11b-11e and 13b-13e could also interact with DPPH. However these conjugates showed little inhibition against croton oil induced mouse ear swelling.
