Esomeprazole sodium lyophilized powder injection and preparation method thereof

Abstract

The invention provides an esomeprazole sodium lyophilized powder injection for injection and a preparation method thereof. The weight ratio of esomeprazole sodium to edetate disodium and/or sodium calcium edentate is 1:(0.01-0.1), and the pH value of the esomeprazole sodium lyophilized powder injection is between 9.5 and 11.5. The preparation method comprises the following steps of: 1) weighing and dissolving edetate disodium and/or sodium calcium edentate in the prescription amount in injection water, stirring to dissolve, and regulating the pH value of sodium hydroxide liquid to be between 10.5 and 12.5; and 2) weighing esomeprazole sodium in the prescription amount, adding into liquid prepared in the step 1), stirring at room temperature to completely dissolve the liquid, and filling the injection water till full dose is reached; 3) performing ultrafiltration on the liquid medicament prepared in the step 2) to remove pyrogen; 4) sterilizing and filtering the liquid medicament which is subjected to ultrafiltration; and 5) filling and lyophilizing. The product prepared by the preparation method of esomeprazole sodium lyophilized powder injection has low related substances, and the substance does not remarkably increase in the storing process, and the content is not remarkably reduced.

Description

technical field [0001] The invention relates to a freeze-dried powder injection of esomeprazole sodium and a preparation method thereof, belonging to the technical field of medicine preparation. Background technique [0002] The chemical name of esomeprazole sodium is 5-methoxy-2-((S)-((4-methoxy-3,5-dimethyl-2-pyridyl)methyl)sulfinyl- 1H-benzimidazole sodium, the structural formula is: [0003] [0004] Esomeprazole is the (S)-isomer of omeprazole, a proton pump inhibitor (PPI) that was first developed as an isomer. Its mechanism of action is protonation under acidification conditions, and it is transformed into a ＋ / K ＋ -ATPase active compound sulfenamide, rapidly reacts with H ＋ / K ＋ - The sulfhydryl group of cysteine ​​on the ATPase binds to form a disulfide bond, thereby inactivating the enzyme and specifically inhibiting H in parietal cells ＋ / K ＋ -ATPase activity thereby inhibiting gastric acid secretion. Clinical trials have shown that esomeprazole sodium ...

AI Technical Summary

Problems solved by technology

Although the cost of activated carbon adsorption is low, and it can also adsorb colored impurities, the use of activated carbon to remove pyrogens in esomeprazole sodium freeze-dried powder injection has its own defects.

Activated carbon generally has a strong adsorption effect under slightly acidic conditions. Under alkaline conditions, activated carbon may desorb to increase impurities in the liquid, weaken the adsorption capacity, and reduce the effect of removing pyrogens, and activated carbon may change the pH of the solution. Affect the physical and chemical stability of esomeprazole sodium solution

In addition, freeze-dried powder injection is a sterile preparation, which requires a high level of cleanliness in the production workshop, while activated carbon is very easy to pollute the environment, and there are many factors that affect the effect of depyrogenation, so it is not easy to operate

[0010] 3. The patent application CN102357082 mentions the use of nitrogen protection and the control of the solution temperature at -10~20°C for dosing. The patent application CN102512382 mentions that the preparation temperature needs to be controlled at 10±5°C. The use of nitrogen protection and low temperature dosing requires Special and expensive equipment, complex process and equipment system, many influencing factors, easy to introduce pollution, low feasibility

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