Aqueous Phase Synthesis And Pharmacodynamics Of Omeprazole Zinc

Objective:To study the aqueous phase synthesis methods of Omeprazole Zinc;to establish the criterion of examination and assaying; to identificate the structure;to compare the stability with Omeprazole;to study the protection and therapeutical effect on gastric ulcer models in rats.Methods:Omeprazole and Zinc chloride reacting at aqueous phase, Omeprazole Zinc were synthesized once when the pH condition was controled strictly;Spectrophotometry analysis with infrared spectrophotometry(IR),ultraviolet spectrophotometry(UV),mass spectrography(MS),atomic absorption spectrum(AAS) and elemental analysis were adopted to identificate the structure of Omeprazole Zinc; Quantitative analysis with high performance liquid chromatography (HPLC) was adopted to determined the content of Omeprazole Zinc; The temperature accelerated test and humidity accelerated test were adopted to examine the stability of Omeprazole Zinc.The experimental gastric ulcer models in rats incluced by water immersion stress,pylorus ligation and salicylic acid/alcohol were adopted to study the protection and therapeutical effect of Omeprazole Zinc on gastric ulcer.Results:The reaction of Omeprazole and Zinc chloride can take place quickly and completely with pH 11.21,The yield of the synthesis reaction is 94.3%,;Omeprazole Zinc with white crystallized powder is detected by physics-chemistry and instrument method;The concentration-peak's linear relationshipin is good in 4.48μg.ml^-1～71.68μg.ml^-1,Y=251293.8C +1320.431(r=0.9999),the content is 99.6%;After temperature accelerated test,Omeprazole Zinc changed into faint yellow,the resolution ratio step down 0.80%.Omeprazole changed into yellow,the resolution ratio step down 2.39%;After humidity accelerated test,Omeprazole Zinc changed into faint yellow,the resolution ratio step down 2.32%.Omeprazole changed into yellow brown,the resolution ratio step down 7.89%;The ulcer indexs were cut down remarkably on three kinds of gastric ulcer model at dose of 2.5mg·kg^-1 to 10.0mg·kg^-1 of Omeprazole Zinc,the inhibition ratio is 13.6%～91.8%on water immersion stress model; 34.4%～81.3%on pylorus ligation model;50.4～90.3%on salicylic acid/alcohol model.In the rat gastric ulcer model of water immersion stress,gastric ulcer healed obviously after giving Omeprazole Zinc 2.5,5.0,10.0mg.kg^-1·d^-1 three days continuously,the inhibition ratio is 61.6%～100.0%and with a better dose-effect relationship.Conclusions:Omeprazole Zinc is a new synthetical Zinc salt of Omeprazole,there is no domestic and overseas correlated report.The aqueous phase synthesis has high yield with few side reaction products; All items of quality analysis are qualified;Omeprazole Zinc is more stable than Omeprazole at the same temperature and humidity in the temperature accelerated test and humidity accelerated test;Omeprazole Zinc has a conspicuous prevent effect and therapeutical effect on gastric ulcer in rats.