What Is Fractionated Heparin?

Dalparin sodium is a low-molecular-weight heparin sodium and is a white or off-white powder. It is almost odorless, tasteless and hygroscopic. Soluble in water and saline, but insoluble in ethanol, acetone, benzene, chloroform and ether. 1% aqueous solution pH 6.0 ~ 7.5.

Chinese name: Dalparin sodium

Foreign name: Dalteparin Sodium
CAS number: 9041-08-1

Introduction to Dalparin Sodium Compounds

Dalparin sodium basic information

Chinese name: Dalparin sodium

Chinese synonym: Heparin Sodium; Adiparin Sodium; Enoxaparin Sodium; Heparin Sodium; Prothrombin; Paparin Sodium; Heparin Sodium

English name: Dalteparin Sodium

English synonyms: SODIUM HEPARIN; SODIUM HEPARINATE; REVIPARIN SODIUM; PORCINE HEPARIN SODIUM; BOVINE HEPARIN SODIUM; ENOXAPARIN SODIUM; HEP, NA, BOVINE; HEP, NA, PORCINE

CAS number: 9041-08-1

Molecular formula: (C ₁₂ H ₁₆ NS ₂ Na ₃ ) ₂₀

EINECS number: 232-681-7 ^[1]

Physicochemical Properties of Dalparin Sodium

1. Properties: white or off-white powder. It is almost odorless, tasteless and hygroscopic.

2. Solubility: soluble in water and saline, insoluble in ethanol, acetone, benzene, chloroform and ether. 1% aqueous solution pH 6.0 ~ 7.5. ^[2]

Dalparin sodium synthesis method

1. Heparin was originally proposed from the liver, and is now mostly extracted from the intestinal mucosa of animals such as pigs, sheep, and cattle. It can be extracted from the lungs and liver. Take the fresh intestinal mucosa and put it into the reaction pot, add sodium chloride at 3%, and adjust the pH to 9.5 with 40% sodium hydroxide. Gradually increase the temperature to 60-65 ° C within half an hour, continue to heat and stir for 2h, then raise the temperature to 95 ° C for 10min, cool to 50 ° C and filter. A strongly basic quaternary ammonium salt anion resin was added to the filtrate, stirred and adsorbed for 8 hours, and left to stand over the liquid. The next day, the upper layer was siphoned off. The resin was rinsed with water until the supernatant was clear, filtered to dry, stirred with 2 times the amount of 1.4M sodium chloride for 2 hours, filtered to dry, and the resin was washed once without the amount of 1.4M sodium chloride. Then, the resin was eluted twice with 3M sodium chloride, filtered to dryness, and the filtrates were combined. An equal amount of 95% ethanol was added to precipitate the liquid, and the precipitate was collected and dried with acetone to obtain a crude product. The crude product was dissolved in 1% sodium chloride, adjusted to pHGCF 1.7-1.8 with hydrochloric acid, and filtered. Adjust the pH to 11 with 5N sodium hydroxide, decolorize by adding 30% hydrogen peroxide, and filter. The filtrate was adjusted to pH 6 with hydrochloric acid, and an equal amount of 95% ethanol was added to precipitate. The precipitate was washed with acetone and dried to obtain heparin. ^[2]

2. Enzymolysis-resin method ^[2]

3. Salting-resin method ^[2]

Dalparin sodium ecological data

It is usually slightly hazardous to water. Do not expose undiluted or large quantities of product to groundwater, waterways or sewage systems. Do not discharge materials into the environment without government permission. ^[2]

Dalparin sodium use

Anticoagulants. Can inhibit the blood clotting process. Used to prevent thrombosis. ^[2]

Pharmacological effects of dalteparin sodium

Much larger than ordinary heparin. In clinical application, it shows that its anti-Xa activity is strong and long-lasting, while the effect of prolonging APTT is weak. Therefore, it has the characteristics of strong antithrombotic effect and low risk of bleeding. In addition, dalteparin sodium can also promote fibrinolysis. By binding to vascular endothelial cells, it can protect endothelial cells and enhance antithrombotic effects. It also has less impact on platelet function and lipid metabolism than ordinary heparin. ^[3]

Dalparin sodium pharmacokinetics

Dalparin sodium cannot be absorbed orally. It takes effect 3 minutes after intravenous injection. The maximum effect time is 2 to 4 hours and the half-life is about 2 hours. It takes effect 2 to 4 hours after subcutaneous injection. The maximum effect time is 3 minutes and the peak time is 3 to 4 hours. The half-life is about 3 to 5 hours, and the bioavailability is 87%. After multiple administrations, the effect can be maintained for 10 to 24 hours. The therapeutic concentration of anti-Xa required to fully exert antithrombotic activity in plasma ranges from 0.1 to 0.6 U / ml. When preventing left ventricular thrombosis in patients with acute anterior myocardial infarction, the blood concentration of dalteparin sodium anti-Xa is 0.6 to 1.0 U / ml; the average anti-Xa blood concentration required to treat acute venous thrombosis is 0.5 U / ml. The distribution of dalteparin sodium in the body is not as extensive as that of unfractionated heparin, and its distribution volume (Vd) is 40-60ml / kg or 3-11L. Dalparin sodium is mainly excreted by the kidney, and its renal clearance is 20 to 30 ml per minute. The half-life of patients with renal insufficiency is prolonged. ^[3]

Dalparin sodium indication

1. It can be used in general surgery, total hip or knee replacement, deep vein thrombosis (DVT) and prophylactic pulmonary embolism (PE), disseminated intravascular coagulation (DIC), etc. in patients with long-term bed rest or malignant tumors.

2. For habitual abortion caused by lupus antibody positive.

3. Can significantly reduce the incidence of DVT in patients with acute ischemic stroke.

4. Prevention and treatment of thromboembolic diseases, prevention of blood clot formation during hemodialysis. ^[3]

Contraindications of Dalparin Sodium

1. Patients with bleeding or bleeding tendency (especially caused by lack of certain coagulation factors).

2. Patients with systemic allergy caused by dalteparin sodium.

3. Patients with thrombocytopenia and positive reactions to platelet aggregation induced by heparin sodium in vitro.

4. Patients with acute and subacute bacterial endocarditis.

5. Patients with progressive bleeding injury of organs (such as progressive gastric and duodenal ulcers).

6. Patients with cerebrovascular accident (except with systemic disseminated intravascular coagulation), patients after brain and spinal cord surgery.

7. Enoxaparin in vitro coagulation test is positive, active peptic ulcer, allergy to dalteparin sodium and stroke (except for systemic embolism) are prohibited.

Dalparin sodium precautions

1. (1) liver and kidney dysfunction; (2) uncontrolled severe hypertension; (3) patients with a history of peptic ulcer.

2. The effects of drugs on pregnancy: Dalparin sodium should not be used in the first 3 months of pregnancy.

3. Protamine can be used as an antagonist when dalteparin sodium is excessive.

4. Dalparin sodium should not be injected intramuscularly. A platelet count should be performed before medication.

5. For severe bleeding, slow intravenous injection of protamine 1mg, protamine sulfate 100U. ^[3]

Dalparin sodium adverse reactions

Thrombocytopenia, abnormal liver function, and bleeding and bruising at the injection site are visible. Occasionally changes in transaminase and alkaline phosphatase. It has been reported that intrathecal epidural anesthesia and postoperative placement of epidural catheters while using daparin sodium can cause spinal hemorrhage. Spinal hemorrhage can cause varying degrees of nerve damage, including long-term or permanent paralysis. ^[3]

Dalparin sodium dosage

1. General treatment: 120U / kg each time, 2 times a day.

2. Prevention of deep vein thrombosis after surgery: (1) Dalparin sodium 2500U is given 1 to 2 hours before surgery, and then once a day, the same dose for 5 to 10 days; (2) 12 to 24 hours after surgery Enoxaparin sodium 30 mg once a day for 7 to 10 days.

3. Prevention of blood clot formation during hemodialysis: administration at the beginning of hemodialysis, weight 0.3ml each for patients weighing less than 50kg; 0.4ml each for patients weighing 50-69kg; patients weighing 70kg or more, 0.6ml each time.

4. Prevention of thromboembolic diseases: general prevention, 0.3ml once a day, usually lasting at least 7 days, in all cases, preventive medication should be used throughout the dangerous period until the patient may move. The first dose of general surgery should be administered 2 to 4 hours before surgery. Orthopedics: The first dose should be given 12 hours before and 12 hours after surgery. Once a day thereafter, the total should last at least 10 days. In all cases, prophylactic medication should be used throughout the danger period until the patient can move.

5. Treatment of thromboembolic diseases: subcutaneous injection, twice a day (once every 12 hours), usually lasts 5 to 7 days, the dose can be adjusted according to weight.

6. To prevent blood clots during extracorporeal circulation during dialysis: intravenous injection of daparin sodium 30-40 U / kg; then infusion at a rate of 15 U / h. Those who received dialysis for less than 4h were given a single dose of 5000U. If there are bleeding complications or renal insufficiency, the dose should be reduced. Such patients can be injected intravenously at 5 to 10 U / kg, followed by an infusion of 4 to 5 U / kg per hour.

7. For the treatment of unstable angina pectoris, 120U / kg is given intravenously every 12 hours, and the maximum recommended dose is 10 000U every 12 hours. Combined for 5-8 days, combined with aspirin. ^[3]

Interactions of Dalparin Sodium with Other Drugs

Use with caution with nonsteroidal anti-inflammatory drugs, aspirin, antiplatelet agglutinants, dextran, and anti-vitamin K drugs because of their potential dangers. ^[3]

Dalparin sodium expert review

Dalparin sodium is a low-dose heparin sodium of pig mucosa, with an average molecular weight of 4000 to 6000. It is a new generation of antithrombotic drugs, which has obvious antithrombotic function, especially strong anticoagulant factor Xa, but anticoagulant Weak, antithrombin effect is very weak. At regular doses it does not cause significant changes in overall coagulation, nor does it prolong bleeding time. Compared with conventional heparin, dalteparin sodium has high bioavailability (90%), long duration of action (24h), and stable antithrombotic effect. Dalparin sodium is obtained by depolymerization of ordinary heparin or through the action of enzymes, and has the advantages that ordinary heparin does not have. Recent research results show that its efficacy is higher than that of unfractionated heparin. It is easy to use and relatively safe, and can be used outside the hospital. ^[3]