Heparin CAS 9005-49-6
Introduction：Basic information about Heparin CAS 9005-49-6, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Heparin Basic information
| Product Name: | Heparin |
| Synonyms: | HEPARIN SODIUM (BOVINE);HEPARIN SODIUM LMW;HEPARIN SODIUM, PORCINE;HEPARIN SODIUM SALT;HEPARIN PORCINE SODIUM SALT;LOW MOLECULAR WEIGHT HEPARIN SODIUM;PORCINE HEPARIN SODIUM;SODIUM HEPARIN |
| CAS: | 9005-49-6 |
| MF: | C26H41NO34S4 |
| MW: | 1134.93 |
| EINECS: | 232-681-7 |
| Product Categories: | |
| Mol File: | 9005-49-6.mol |
Heparin Chemical Properties
| Melting point | 250 °C (decomp) |
| alpha | D20 +55° |
| storage temp. | Store at -20°C, sealed storage, protect from light |
| solubility | H2O: 50 mg/mL, clear, faintly yellow |
| form | crystalline (fine) |
| color | white |
| Optical Rotation | +45～+53 |
| Cosmetics Ingredients Functions | SKIN CONDITIONING |
| CAS DataBase Reference | 9005-49-6(CAS DataBase Reference) |
Safety Information
| Safety Statements | 24/25 |
| WGK Germany | 2 |
| RTECS | MI0850000 |
| F | 3-10 |
| Hazardous Substances Data | 9005-49-6(Hazardous Substances Data) |
| Toxicity | LD50 oral in rat: 1950mg/kg |
| Description | Parnaparin sodium is a low molecular weight heparin obtained from bovine mucosalheparin by chemical depolymerization. It has more potent antithrombotic and profibrinolyticactivity than heparin evidenced by its higher activity in inhibiting factor Xa and in reducingplasma activity of platelet activator inhibitor. It is effective in improving the venous bloodoutflow of lower limbs in deep vein thrombosis (DVT) patients in addition to preventing DVTfollowing orthopaedic surgery, reportedly without causing bleeding complications. Parnaparinhas also shown efficacy in inflammatory occlusive complications of postphlebitic syndromeand in acute myocardial infarction. |
| Chemical Properties | White or pale-colored amorphous powder; nearly odorless; hygroscopic. Soluble in water;insoluble in alcohol, benzene, acetone, chloroform,and ether; pH in 17% solution between 5.0 and 7.5. |
| Originator | Opocrin (Italy) |
| Occurrence | Heparin is a complex organic acid (mucopolysaccharide) present in mammalian tissues and a strong inhibitor of blood coagulation. Although the precise formula and structure of heparin are uncertain, it has been suggested that the formula for sodium heparinate, generally the form of the drug used in anticoagulant therapy, is (C12H16N2Na3)20 with a molecular weight of about 12,000. The commercial drug is derived from animal livers or lungs. |
| Uses | Medicine (anticoagulant), biochemicalresearch, rodenticides. |
| Definition | A complex organic acid (mucopolysaccharide)present in mammalian tissues; a strong inhibitor ofblood coagulation; a dextrorotatory polysaccharidebuilt up from hexosamine and hexuronic acid unitscontaining sulfuric acid ester groups. Precise chemical fo |
| Definition | A POLYSACCHARIDEthat inhibits the formation of thrombinfrom prothrombin and thereby preventsthe clotting of blood. It is used in medicineas an anticoagulant. |
| Definition | heparin: A glycosaminoglycan (mucopolysaccharide)with anticoagulantproperties, occurring in vertebratetissues, especially the lungs andblood vessels. |
| Manufacturing Process | 5,000 pounds of beef intestine was introduced into a stainless steel reactor,jacketed with thermostated water and steam. 200 gallons of water and 10gallons of chloroform were added. The mixture was agitated, the temperaturewas raised to 90°F and the agitation stopped. 5 gallons of toluene was addedand the vessel closed. Autolysis was continued for 17 hours. The extractant solution, consisting of 30 gallons of glacial acetic acid, 35 gallons of 30% aqueous ammonia, 50% sodium hydroxide to adjust the pH to9.6 at 80°F and water to make 300 gallons, was added to the tissue. Withagitation, the temperature was raised to 60°C and held there for 2 hours.Then steam was applied and the temperature was raised to boiling. 200pounds of coarse filter aid (perlite) was added and the mixture filteredthrough a string discharge vacuum filter. The cake was washed with 200gallons of hot water on the filter. The filtrate was allowed to stand overnight and the fat skimmed off the top.After cooling to 100°F, the filtrate was transferred to a tank with thermostatedwater and the temperature set at 95° to 100°F. 24 gallons of pancreaticextract, prepared as described above, was added in 4-gallon increments every12 hours for 3 days. The batch was brought to a boil and cooled to roomtemperature. The batch was then filtered into a vessel and assayed for heparin content.40,000,000 units were found in 1,000 gallons of filtrate. 20 kg of noctylamine was added and 105 pounds of glacial acetic acid was added tobring the pH to 6.5. 20 gallons of methyl isobutyl ketone was added and thewhole mixture was vigorously agitated for 1 hour. The mixture was thenallowed to stand overnight. The clear, aqueous phase was drained off anddiscarded. The grayish-brown interphase was then removed, together with asmall amount of the ketone phase, and transferred into a small kettle. Theinterphase volume was 7 gallons. 30 gallons of methanol was added and the mixture warmed to 120°F and thenthe pH was adjusted to 9.0. The mixture was then allowed to settle overnight.The solids were collected with vacuum and washed with 5 gallons ofmethanol. The cake was then suspended in 5 gallons of water and the heparinprecipitated with 10 gallons of methanol. The solids were collected undervacuum. The dry weight of the cake was 1,000 grams and the total units were38,000,000, according to US Patent 2,884,358. |
| Brand name | LiquaeminSodium (Organon); Panheprin (Hospira);Fluxum. |
| Therapeutic Function | Anticoagulant |
| Biological Functions | Heparin (heparin sodium) is a mixture of highly electronegativeacidic mucopolysaccharides that containnumerous N- and O-sulfate linkages. It is produced byand can be released from mast cells and is abundant inliver, lungs, and intestines. |
| Hazard | May cause internal bleeding. |
| Mechanism of action | The anticoagulation action of heparin depends onthe presence of a specific serine protease inhibitor (serpin)of thrombin, antithrombin III, in normal blood. Heparin binds to antithrombin III and induces a conformationalchange that accelerates the interaction ofantithrombin III with the coagulation factors. Heparinalso catalyzes the inhibition of thrombin by heparin cofactorII, a circulating inhibitor. Smaller amounts ofheparin are needed to prevent the formation of freethrombin than are needed to inhibit the protease activityof clot-bound thrombin. Inhibition of free thrombinis the basis of low-dose prophylactic therapy. |
| Pharmacology | The physiological function of heparin is not completelyunderstood. It is found only in trace amounts innormal circulating blood. It exerts an antilipemic effectby releasing lipoprotein lipase from endothelial cells;heparinlike proteoglycans produced by endothelialcells have anticoagulant activity. Heparin decreasesplatelet and inflammatory cell adhesiveness to endothelialcells, reduces the release of platelet-derived growthfactor, inhibits tumor cell metastasis, and exerts an antiproliferativeeffect on several types of smooth muscle. Therapy with heparin occurs in an inpatient setting.Heparin inhibits both in vitro and in vivo clotting ofblood. Whole blood clotting time and activated partialthromboplastin time (aPTT) are prolonged in proportionto blood heparin concentrations. |
| Pharmacokinetics | The pharmacokinetic profiles of heparin and LMWHs are quite different. Whereas heparin is only30% absorbed following subcutaneous injection, 90% of LMWH is systemically absorbed. Thebinding affinity of heparin to various protein receptors, such as those on plasma proteins,endothelial cells, platelets, platelet factor 4 (PF4), and macrophages, is very high and is related tothe high negative-charged density of heparin. This high nonspecific binding decreasesbioavailability and patient variability. Additionally, heparin's nonspecific binding may account forheparin's narrow therapeutic window and heparin-induced thrombocytopenia (HIT), a major limitationof heparin. These same affinities are quite low, however, in the case of LMWHs. These parametersexplain several of the benefits of the LMWH's. The favorable absorption kinetics and low proteinbinding affinity of the LMWHs results in a greater bioavailability compared with heparin. Thelowered affinity of LMWHs for PF4 seems to correlate with a reduced incidence of HIT. Heparin issubject to fast zero-order metabolism in the liver, followed by slower first-order clearance from thekidneys. The LMWHs are renally cleared and follow first-order kinetics. This makes theclearance of LMWHs more predictable as well as resulting in a prolonged half-life. Finally, theincidence of heparin-mediated osteoporosis is significantly diminished with use of LMWHs as opposed to heparin. |
| Side effects | The major adverse reaction resulting from heparintherapy is hemorrhage. Bleeding can occur in the urinaryor gastrointestinal tract and in the adrenal gland.Subdural hematoma, acute hemorrhagic pancreatitis,hemarthrosis, and wound ecchymosis also occur. Theincidence of life-threatening hemorrhage is low but variable. Heparin-induced thrombocytopenia of immediateand delayed onset may occur in 3 to 30% of patients.The immediate type is transient and may not involveplatelet destruction, while the delayed reactioninvolves the production of heparin-dependent antiplateletantibodies and the clearance of platelets fromthe blood. Heparin-associated thrombocytopenia maybe associated with irreversible aggregation of platelets(white clot syndrome). Additional untoward effects ofheparin treatment include hypersensitivity reactions(e.g., rash, urticaria, pruritus), fever, alopecia, hypoaldosteronism,osteoporosis, and osteoalgia. |
| Drug interactions | Potentially hazardous interactions with other drugs Analgesics: increased risk of bleeding with NSAIDs- avoid concomitant use with IV diclofenac;increased risk of haemorrhage with ketorolac -avoid. Nitrates: anticoagulant effect reduced by infusions ofglyceryl trinitrate. Use with care in patients receiving oralanticoagulants, platelet aggregation inhibitors, aspirinor dextran. |
| Metabolism | Heparin is prescribed on a unit (IU) rather than milligrambasis. The dose must be determined on an individualbasis. Heparin is not absorbed after oral administrationand therefore must be given parenterally.Intravenous administration results in an almost immediateanticoagulant effect. There is an approximate 2-hourdelay in onset of drug action after subcutaneous administration.Intramuscular injection of heparin is to beavoided because of unpredictable absorption rates, localbleeding, and irritation. Heparin is not bound toplasma proteins or secreted into breast milk, and it doesnot cross the placenta. Heparin’s action is terminated by uptake and metabolismby the reticuloendothelial system and liver andby renal excretion of the unchanged drug and its depolymerizedand desulfated metabolite. The relativeproportion of administered drug that is excreted as unchangedheparin increases as the dose increases. Renalinsufficiency reduces the rate of heparin clearance fromthe blood. |
| Purification Methods | Most likely contaminants are mucopolysaccharides including heparin sulfate and dermatan sulfate. Purify heparin by precipitation with cetylpyridinium chloride from saturated solutions of high ionic strength. [Cifonelli & Roden Biochemical Preparations 12 12 1968, Wolfrom et al. J Org Chem 29 540 1946, Huggard Adv Carbohydr Chem 10 336-368 1955] |
Heparin Preparation Products And Raw materials
| Raw materials | Ethanol-->Hydrogen peroxide-->Water-->Chloroform-->Toluene |
