Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

OBJECTIVE:To prepare Clopidogrel bisulfate tablets,and to optimize its formulation and technology. METHODS:The single factor test and compatibility test were used to optimize the fillers,disintegrating agents,adhesive,lubricants and prepa-ration technology;using sticking situation and disintegration time as indexes,the orthogonal test was used to optimize the amount of disintegrating agents [low substituted hydroxypropyl cellulose(L-HPC)],lubricants(hydrogenated vegetable oil and PEG6000), and the optimal technology was validated. The dissolution of prepared tablet and imported tablet(Plavix)in water,pH 2.0 hydro-chlorate buffer,pH 4.5 phosphate buffer(PBS)and pH 6.8 PBS were investigated,and influential factor test was conducted. RE-SULTS:Clopidogrel bisulfate tablets were prepared with dry granulating. The optimal formulation (1 000 tablets) was as follows as clopidogrel bisulfate 97.8 g,mannitol 84 g,amylum pregelatinisatum 36 g,L-HPC 8 g,hydrogenated vegetable oil 8 g, PEG6000 6 g;no tablet compressing sticking situation was found in prepared tablets and it owned medium disintegration time;ac-cumulative dissolution curves of prepared tablets in 4 kinds of medium were similar to those of Plavix;there were no significant dif-ference in results of influential factor test between prepared tablet and Plavix. CONCLUSIONS:Clopidogrel bisulfate tablets are prepared successfully,and the formulation is reasonable,practical,stable and controllable in quality.

OBJECTIVETo study the pharmacokinetics and bioavailability of ginkgolides sustained-release tablet and conventional tablet in Beagle dogs.

METHODThe concentrations of ginkgolides in plasma were determined by LC-MS. The main pharmacokinetic parameters of ginkgolides sustained-release tablet and conventional tablet in vivo were obtained using Pharmacokinetic software DAS 2.0.

RESULTThe C(max) of grinkgolide A in ginkgolide sustained-release tablet and conventional tablet were 443.51, 1 039.30 microg x L(-1), respecitvely. t(max) were 2.92, 1.08 h, respectively. AUC(0-12h) were 1 808.21, 2 041.37 h x microg(-1) x L(-1), respectively. MRT were 5.18, 3.18 h, respectively. The relative bioavailability of ginkgolides A was 88.58%. The C(max) of ginkgolide B in ginkgolide sustained-release tablet and conventional tablet were 407.13, 547.38 microg x L(-1), respectively. t(max) were 2.92, 1.08 h, respectively. AUC(01-12 h) were 1 987.31, 1 748.04 h x microg(-1) x L(-1), respectively. MRT were 6.05, 4.98 h, respectively. The relative bioavailability of ginkgolides B was 113.69%.

CONCLUSIONThe ginkgolides sustained-release tablets have good sustained release characteristics and are bioequivalent to the reference formulation.

Animals ; Area Under Curve ; Biological Availability ; Chromatography, High Pressure Liquid ; methods ; Delayed-Action Preparations ; administration & dosage ; pharmacokinetics ; Dogs ; Ginkgolides ; administration & dosage ; analysis ; pharmacokinetics ; Lactones ; analysis ; Male ; Mass Spectrometry ; methods ; Quality Control ; Tablets ; administration & dosage ; pharmacokinetics ; Therapeutic Equivalency

Objective To investigate the expression of vascular endothelial growth factor-C(VEGF-C) in human non-small cell lung cancer(NSCLC) and to elucidate its roles in lymph node metastasis and prognosis evaluation. Methods The expression of VEGF-C was examined in 50 NSCLC specimens and 20 archival surgical specimens of human pulmonary inflammatory pseudotumor tissues by immunohistochemistry. Results The positive rate of VEGF-C expression in NSCLC and inflammatory pseudotumor was 44% and 5% respectively. There was significant difference in VEGF-C expression between the two groups. The expression rate of VEGF-C in NSCLC was significantly higher in the patients with lymph node metastasis (66 7%) than that in the patients without lymph node metastasis (23 1%, P