Dalteparin belongs to low molecular weight heparin sodium, which is white or quasi-white powder. Almost odorless, tasteless, hygroscopic. Soluble in water and brine, insoluble in ethanol, acetone, benzene, chloroform and ether. The pH value of 1% aqueous solution is 6.0 ~ 7.5.
Dalteparin API Company synthesis method
Dalteparin API was originally derived from the liver and is now derived from the intestinal mucosa of pigs, sheep, cattle and other animals and can be extracted from the lungs and liver. Fresh intestinal mucosa was put into the reactor, 3% sodium chloride was added, and the pH was adjusted to 9.5 with 40% sodium hydroxide. Heat gradually to 60-65℃ within half an hour, keep stirring for 2h, then heat to 95℃, keep for 10 minutes, cool to below 50℃, filter.
The strongly basic quaternary ammonium anion exchange resin was added to the filtrate, stirred and adsorbed for 8 hours, and the filtrate was allowed to stand. The next day, siphon out the supernatant, rinse the resin supernatant with water to clarify, filter and dry, stir with 2 times 1.4M sodium chloride for 2 hours, filter and dry, and wash the resin again without 1.4M sodium chloride. Then, 3M sodium chloride eluting resin was used twice, filtered to dry, combined with the filtrate, adding the same amount of 95% ethanol precipitation, precipitation collection, dehydration and acetone drying, to obtain crude products.
The product was roughly dissolved in 1% sodium chloride, adjusted to pHGCF 1.7-1.8 with hydrochloric acid, and filtered. Adjust pH to 11 with 5N sodium hydroxide, decolorize with 30% hydrogen peroxide and filter. Adjust the ph of the filtrate to 6 with hydrochloric acid, and add the same amount of 95% ethanol to precipitate. The precipitate is washed and dried with acetone to obtain heparin.