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How to prepare enoxaparin sodium?

  Enoxparin sodium is a low molecular weight anticoagulant used for the prevention and treatment of deep vein thrombosis or pulmonary embolism as well as heparin. Enoxparin sodium is white or white as powder, tasteless, moisture-inducing, soluble in water, insoluble in ethanol, acetone and other organic chemical solvents. It has strong negative charge in aqueous solution and can combine with some cations to form molecular complexes. The solution is stable at pH 7.

  1. Into salt. Weigh 30g of crude heparin sodium, add to it and dissolve it with purified water to obtain heparin sodium solution; 75g benzsoxol ammonium chloride was weighed, and different purified water was added to dissolve it to obtain benzsoxol ammonium chloride solution. Benzsoxol ammonium chloride solution was slowly added to the heparin sodium solution, stirring while adding, stirring and mixing evenly, and left for 2 hours. Then a high-speed centrifuge needs to be used for research centrifugation technology operation. The solid obtained from centrifugation treatment is fully washed with purified water. Finally, the obtained wet product and heparin benzyl ammonium chloride are analyzed and dried in vacuum environment to obtain heparin benzyl ammonium chloride.

  2. The esterification. To the heparin benzyl ammonium chloride to add 5 times the volume of methylene chloride, stir to dissolve to join heparin benzyl again after 1 times the volume of benzyl chloride ammonium chloride, maintain temperature 35 ℃, mixing reaction for 24 hours, end of the reaction to join heparin benzyl line 6 times the volume of 10% ammonium chloride sodium acetate methanol solution, stirring for 10 minutes, let stand for 4 hours, The precipitate was filtered and washed twice with methanol to obtain wet crude heparin benzyl ester. Add heparin benzyl acetate wet crude product 8% sodium chloride solution with the weight of 3 times the volume of heparin benzyl chloride ammonium salt, stir until completely dissolved, then add methanol with the volume of 4 times the volume of sodium chloride solution, continue stirring for 10 minutes, stand for 2 hours, filter and repeat this operation three times, to obtain the wet heparin benzyl acetate. The wet product of heparin benzyl ester was vacuum dried to obtain heparin benzyl ester.

How to prepare enoxaparin sodium?

  3. The depolymerization. Pure water 20 times its weight was added to benzyl heparin ester, stirring while dissolving, and heating to 60℃. Sodium hydroxide, which accounted for 10% of the weight of heparin benzyl ester, was dissolved in pure water, and then slowly added to the heparin benzyl ester solution, the temperature was kept at 60℃, stirring for 2 hours, and then the pH value of the solution was adjusted to 6.0~6.5 with an appropriate amount of hydrochloric acid, cooled to room temperature, and the depolymerization solution was obtained. Add an appropriate amount of sodium chloride to the depolymerization solution, make its concentration 10%, stir until it is completely dissolved, then add methanol 60 times the weight of benzyl heparin while stirring, stir evenly, then stand for 5 hours, separate the supernatant, and get the wet crude enoxaparin sodium.

  4. Oxidation and alcohol precipitation. Add 3 times the weight of enoxaparin sodium in pure water to the wet crude product and stir until it is completely dissolved. Add pure water to achieve a solution concentration of 20%. Then add 1% of the solution volume of sodium chloride, stirring, heating to 35℃, with sodium hydroxide to adjust the pH of the solution to 9.5-10.0; Hydrogen peroxide, which is 1% of the volume of the solution (30% in concentration), is then added and oxidized for 8 hours while maintaining temperature and pH to obtain an oxidized solution. The oxidized solution was filtered through a 0.45μm filter core, and the pH was adjusted to 6.0~6.5 with hydrochloric acid. Methanol 5 times the volume of the filtrate was added while stirring, and the supernatant was separated after stirring evenly. After standing for 5 hours, the oxidized alcohol precipitation of enoxparin sodium was obtained.

  5. Sterilize and filter. An appropriate amount of purified water is added to the oxidized alcohol precipitation product to make it have a concentration of 25%. After stirring until it can be completely dissolved, the solution is passed through the filter core and filtration. Enoxaparin sodium can be obtained after the sterilized filtrate is dried under the control of lyophilizer and mixed with crushing technology.

  This is Heparin Manufacturer's introduction to the preparation method of enoxaparin sodium. If you want to know the Heparin sodium price, please come to consult!