One, raw material processing:Heparin Sodium API supplier (Heparin sodium API supplier) introduces Heparin sodium from fresh pig lung (or frozen pig lung after natural thawing), and then rinses it with water carefully to remove internal and external dirt and skin fat, grind it to shreds, and mix it with equal amount of water and preservative with a solubility of.01% after stirring it thoroughly.
Two extraction, enzyme solution: first of all the above fully mixing raw materials, use a small amount of dilute alkali liquor (through the corresponding precision determination of PH test paper, similarly hereinafter) fine-tuning to PH value of 8 to 9, then add the ground fresh pancreatic juice as enzyme agent in advance (add pig pancreatic juice should be raw material liquid actual weight of 1% to 1.5%), stir well, slowly heat up to 40 degrees or so, Maintain the PH value of the feed solution and continue to stir, maintain the temperature of the feed solution at 37-40℃ for 3-4 hours, then heat up to 47-50℃, maintain the PH value =8.0-8.5, add a little pancreatic juice as appropriate, and continue the enzymatic hydrolysis for 4-5 hours. In the enzymatic hydrolysis process, if the ph value of the enzymatic hydrolysis material decreases, it should be treated with a small amount of dilute alkali (5%-8% NaOH) in time, adjust the pH value to 5.5-6 with hydrochloric acid, and then heat up to 80℃. After full stirring, add about 5% of the total weight of the feed solution (containing NaCL≥95% and calcium magnesium calcium salt < 0.5%), and then heat up to 90℃ for 30 minutes, stop stirring, and remove impurities while hot. When the filtrate was cooled to 37℃, the pH of the filtrate was adjusted to 10.5 with dilute alkali solution, and the filtrate was adjusted to pH =9.0-9.5 for ion exchange adsorption treatment.
Three, ion exchange adsorption: first, the enzyme extract is cooled to room temperature, carefully remove the thin layer of oil floating on the liquid surface, control the temperature to 45 degrees, stop heating, when the pretreatment D-254 resin is added to stir, the content of heparin sodium in the solution is 2.55-3% of the solution. If necessary, the amount of heparin sodium should be increased in the solution. After stirring and adsorption treatment for 3 hours, the filtrate can be used as raw material for the production of the new drug Careshu for the treatment of coronary artery disease.
Four, refining:Crude heparin sodium was completely dissolved in 2% sodium chloride solution to obtain a solution with a solubility of about 8%. The above substances are carefully adjusted to ph = 8.0-8.2 in 5mol/ L sodium hydroxide solution at night, and the temperature is raised to 78-80 ° C. When the purple color is no longer fading, 0.15-0.2 mol/ L potassium permanganate solution is added per 100 million units at the end of the first oxidation operation. Add a small amount of saturated sodium sulfite solution when the red color has just faded. After proper cooling, the feed liquid is filtered once, and the filtrate is filtered again when the temperature of the filtrate is lowered to 36 ℃. The pH value of the filtrate is adjusted to 10.5-11.0 with a little saturated sodium hydroxide solution, and a little 3%-5% hydrogen peroxide solution is slowly added under full stirring, for secondary oxidation at 25-27 ℃ for 16-24 hours. After the oxidation process is completed, Add the feed solution, collect the above precipitate, dissolve with a small amount of 10% sodium chloride solution, add 3-4 times 95% ethanol precipitate, collect the precipitate (1 precipitate with anhydrous ethanol dehydration, grinding, dewatering with acetone, grinding, dewatering with acetone, vacuum drying with far infrared (50-60℃), get refined heparin sodium.