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Heparins Manufacturer: Method for preparing enoxaparin sodium!

  1. Into salt. Weigh the crude heparin sodium 30g and dissolve it in appropriate purified water to get the heparin sodium solution; Benzethonium chloride 75g was weighed and dissolved in purified water to obtain benzethonium chloride solution. Quickly add benzathonium chloride solution to heparin sodium solution, stir while adding, stir evenly, let stand for 2 hours. Then centrifuge was used for centrifuge operation, and the solid obtained by centrifuge was washed with purified water. At first, the wet heparin benzol chloro-ammonium salt obtained was vacuum dried to obtain heparin benzol chloro-ammonium salt.

  2. To the heparin benzyl ammonium chloride in the presence of 5 times the volume of methylene chloride, stir to dissolve and then to the present benzyl heparin in line 1 times the volume of ammonium chloride, benzyl chloride, maintain temperature 35 ℃, stirring reflect 24 hours, reflects the present heparin benzyl cable end 6 times the volume of 10% ammonium chloride sodium acetate methanol solution, stirring for 10 minutes, let stand for 4 hours, The accumulation was filtered and the wet heparin benzyl ester was obtained by washing the filtered accumulation with methanol twice. Add 8% sodium chloride solution 3 times the volume of heparin benzol chloro-ammonium salt to the wet crude heparin benzyl ester, stir until it is completely dissolved, then add methanol 4 times the volume of sodium chloride solution, stir continuously for 10 minutes, stand for 2 hours, filter and repeat this operation three times to obtain the wet heparin benzyl ester. The wet heparin benzyl ester can be obtained by vacuum drying.

Heparins Manufacturer: Method for preparing enoxaparin sodium!

  Heparins Manufacturer: Method for preparing enoxaparin sodium!

  3. The depolymerization. Purified water 20 times its component was added to the heparin benzyl ester, dissolved by stirring, and heated to 60℃ at the same time. Weigh 10% of the heparin benzyl ester sodium hydroxide and dissolve it in purified water, then quickly add it to the heparin benzyl ester solution, maintain the temperature of 60℃, stir the reaction for 2 hours, then use appropriate hydrochloric acid conditioning solution pH6.0~6.5, cool the solution to room temperature, get the depolymerization solution. Add proper sodium chloride to the depolymerization solution, make its concentration 10%, stir until it is completely dissolved, and then add methanol 60 times the volume of heparin benzyl ester in the stirred state. After well-proportioned stirring, stand for 5 hours, and separate the supernatant to prepare enoxaparin sodium wet crude product.

  4. Oxidation alcohol precipitation. Add purified water 3 times of its component to enoxaparin sodium wet crude product, stir until complete dissolution, add purified water to make the solution concentration 20%. Then, the solution volume was 1% sodium chloride, stirred, heated to 35℃, and the solution pH was adjusted to 9.5~10.0 with sodium hydroxide. The solution was then oxidized with 1% hydrogen peroxide (30% concentration) at the temperature and pH for 8 hours to obtain the oxide solution. The oxidized solution was filtered through a 0.45μm filter element, and pH6.0~6.5 was adjusted with hydrochloric acid. Under the agitation state, methanol, 5 times the volume of filtrate, was stirred evenly, and stood for 5 hours. After the supernatant was separated, enoxaparin sodium was prepared to oxidize alcohol precipitate.

  5. Sterilization and filtration. Purify the water in the oxidized alcohol sediment at a concentration of 25%, stir until the solution is completely dissolved, and filter the solution through the filter element. The sterilized filtrate was dried by lyophilizer, crushed and mixed to get enoxaparin sodium boutique.