Protamine Sulfate Injection，硫酸鱼精蛋白注射液

Action and mechanism of action
This product has a strong alkaline group, which can bind to the strongly acidic heparin in the body to form a stable complex, thereby making heparin lose its anticoagulant ability. It also has a mild antithrombin kinase effect, and is generally not used clinically to counteract the anticoagulant effect caused by non-heparin. Since this product can bind to some proteins and peptides, it can be used to form complexes with insulin, corticotropin, etc. to prepare long-acting injections.
[Properties] This product is a white or off-white powder; the aqueous solution shows an acidic reaction to litmus paper.
This product is slightly soluble in water and insoluble in ethanol or ether.
[Identification] (1) Take about 5 mg of this product, add 1 ml of water, dissolve it at a slight temperature, add 1 drop of 10% sodium hydroxide solution
and 2 drops of copper sulfate test solution, and the supernatant will appear purple-red.
(2) Take about 1 mg of this product, add 2 ml of water to dissolve, add 5 drops of 70% ethanol solution of 0.1% α-naphthol and sodium hypochlorite test solution, then add sodium hydroxide test solution to make the solution alkaline, that is, pink.
(3) The aqueous solution of this product shows the identification reaction of sulfate (Appendix III).
[Inspection] Nitrogen Take an appropriate amount of this product and determine it according to the nitrogen determination method (Appendix VII D Method 2). Calculated on the basis of the dry product, the nitrogen content should be 21.0% to 25.0%.
Loss on drying Take this product and dry it at 105 ℃ to constant weight. The weight loss shall not exceed 7.0% (Appendix VIII L).
Pyrogen Accurately weigh an appropriate amount of this product and add sodium chloride injection to make a solution containing 1.5 mg per 1 ml. Inspect according to the law (Appendix XI D). The dosage is 1 ml for every 1 kg of rabbit body weight, which should meet the regulations.
[Potency determination] Determine according to the protamine sulfate bioassay method (Appendix Ⅻ J), which should comply with the regulations, and the measured result should be 90% to 110% of the labeled amount.
[Category] Anti-heparin drug.
[Storage] Sealed and stored in a cool and dark place.
[Preparation] Protamine sulfate injection
[Pharmacological action] Protamine sulfate is a strong base that can form a stable salt with strongly acidic heparin sodium or heparin calcium to make heparin lose its anticoagulant effect. This product acts quickly and neutralizes heparin within 5 minutes of intravenous administration. However, some heparin can be dissociated from the complex again. The amount of protamine required to neutralize 1 unit of heparin from different sources is slightly different. 1 mg of this product can neutralize 90 units of heparin sodium prepared from bovine lung or 115 units of heparin sodium prepared from porcine intestinal mucosa, or 100 units of heparin calcium prepared from porcine intestine. The metabolic transformation process of protamine-heparin complex in the body has not yet been elucidated. Protamine is also a weak anticoagulant. Overdose can cause a short and mild prolongation of the coagulation time index.
[Indications] Mainly used for bleeding and spontaneous bleeding caused by severe overdose of heparin sodium or heparin calcium, such as hemoptysis.
[Adverse reactions] ① Rapid intravenous injection of this product can cause hypotension, bradycardia, pulmonary hypertension, dyspnea, transient facial flushing and warm sensation. Slow intravenous injection, no more than 50 mg within 10 minutes, can avoid the above reactions. ② Those who are allergic to fish and have received this product or insulin containing protamine (such as neutral protamine insulin) in the past are prone to anti-protamine IgE-mediated hypersensitivity or allergic reactions. ③ Some people with male infertility or vasectomy are prone to hypersensitivity to protamine. Applying corticosteroids or antihistamines to such patients before infusion of this product can prevent allergies. 5 After sufficient protamine neutralizes heparin, some patients may experience heparin rebound and bleeding 8 to 9 hours, and some after 18 hours.
[Contraindications] Patients with a history of intolerance or adverse reactions to this product are prohibited from using it.
[Usage and Dosage] Anti-heparin overdose: intravenous injection, the dosage is related to the last heparin dosage and interval time. Each 1mg of protamine can antagonize 100 units of heparin. Because heparin degrades rapidly in the body, only 0.5mg of protamine is needed for every 100 units of heparin 30 minutes after the injection of heparin; the dosage does not exceed 50mg each time, and it can be repeated when needed. Anti-spontaneous bleeding: intravenous drip, 5-8mg/kg body weight/day, divided into 2 times, 6 hours apart, each time diluted with 300-500ml of normal saline and used, and changed to half the amount after 3 days.
[Precautions] This product is only for intravenous injection and should be administered slowly. Coagulation function test is required immediately after administration. ① Use this product with caution in patients who are allergic to fish. ② Too fast intravenous injection can cause bradycardia, hypotension, chest tightness, dyspnea, facial flushing, etc. ③ Pregnant and lactating women must have clear indications for the use of this drug. As for the effects of this product on reproductive ability, whether it has teratogenic or carcinogenic effects, whether it is secreted through breast milk, etc., there is a lack of animal experimental data. 5 This product should be administered alone, and is incompatible with the physical and chemical properties of certain antibiotics (such as penicillin, cephalosporin, etc.).
Protamine Sulfate
Liusuan Yujingdanbai
Protamine Sulfate