| Identification | More | [Name]
Heparin | [CAS]
9005-49-6 | [Synonyms]
BOVINE HEPARIN SODIUM
ENOXAPARIN SODIUM
HEPARIN
HEPARIN PORCINE SODIUM SALT
HEPARIN SODIUM
HEPARIN SODIUM (BOVINE)
HEPARIN SODIUM LMW
HEPARIN SODIUM, PORCINE
HEPARIN SODIUM SALT
HEPARIN, SODIUM SALT, BOVINE
HEPARIN, SODIUM SALT, PORCINE
HEPARIN, SODIUM SALT, PORCINE INTESTINAL MUCOSA
HEPARIN, SODIUM SALT, PORCINE INTESTINAL MUCOSA, LOW MOLECULAR WEIGHT
HEP, NA, BOVINE
HEP, NA, PORCINE
LOW MOLECULAR WEIGHT HEPARIN SODIUM
PORCINE HEPARIN SODIUM
REVIPARIN SODIUM
SODIUM HEPARIN
SODIUM HEPARINATE | [EINECS(EC#)]
232-681-7 | [Molecular Formula]
C26H41NO34S4 | [MDL Number]
MFCD00081689 | [Molecular Weight]
1134.93 | [MOL File]
9005-49-6.mol |
| Chemical Properties | Back Directory | [Definition]
A complex organic acid (mucopolysaccharide)
present in mammalian tissues; a strong inhibitor of
blood coagulation; a dextrorotatory polysaccharide
built up from hexosamine and hexuronic acid units
containing sulfuric acid ester groups. Precise chemical fo | [Appearance]
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. | [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
| [CAS DataBase Reference]
9005-49-6(CAS DataBase Reference) |
| Hazard Information | Back Directory | [Hazard]
May cause internal bleeding. | [Description]
Parnaparin sodium is a low molecular weight heparin obtained from bovine mucosal
heparin by chemical depolymerization. It has more potent antithrombotic and profibrinolytic
activity than heparin evidenced by its higher activity in inhibiting factor Xa and in reducing
plasma activity of platelet activator inhibitor. It is effective in improving the venous blood
outflow of lower limbs in deep vein thrombosis (DVT) patients in addition to preventing DVT
following orthopaedic surgery, reportedly without causing bleeding complications. Parnaparin
has also shown efficacy in inflammatory occlusive complications of postphlebitic syndrome
and 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), biochemical
research, rodenticides. | [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 10
gallons of chloroform were added. The mixture was agitated, the temperature
was raised to 90°F and the agitation stopped. 5 gallons of toluene was added
and 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 to
9.6 at 80°F and water to make 300 gallons, was added to the tissue. With
agitation, the temperature was raised to 60°C and held there for 2 hours.
Then steam was applied and the temperature was raised to boiling. 200
pounds of coarse filter aid (perlite) was added and the mixture filtered
through a string discharge vacuum filter. The cake was washed with 200
gallons 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 thermostated
water and the temperature set at 95° to 100°F. 24 gallons of pancreatic
extract, prepared as described above, was added in 4-gallon increments every
12 hours for 3 days. The batch was brought to a boil and cooled to room
temperature.
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 to
bring the pH to 6.5. 20 gallons of methyl isobutyl ketone was added and the
whole mixture was vigorously agitated for 1 hour. The mixture was then
allowed to stand overnight. The clear, aqueous phase was drained off and
discarded. The grayish-brown interphase was then removed, together with a
small amount of the ketone phase, and transferred into a small kettle. The
interphase volume was 7 gallons.
30 gallons of methanol was added and the mixture warmed to 120°F and then
the 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 of
methanol. The cake was then suspended in 5 gallons of water and the heparin
precipitated with 10 gallons of methanol. The solids were collected under
vacuum. The dry weight of the cake was 1,000 grams and the total units were
38,000,000, according to US Patent 2,884,358. | [Brand name]
Liquaemin
Sodium (Organon); Panheprin (Hospira);Fluxum. | [Therapeutic Function]
Anticoagulant | [Biological Functions]
Heparin (heparin sodium) is a mixture of highly electronegative
acidic mucopolysaccharides that contain
numerous N- and O-sulfate linkages. It is produced by
and can be released from mast cells and is abundant in
liver, lungs, and intestines. | [Mechanism of action]
The anticoagulation action of heparin depends on
the presence of a specific serine protease inhibitor (serpin)
of thrombin, antithrombin III, in normal blood.
Heparin binds to antithrombin III and induces a conformational
change that accelerates the interaction of
antithrombin III with the coagulation factors. Heparin
also catalyzes the inhibition of thrombin by heparin cofactor
II, a circulating inhibitor. Smaller amounts of
heparin are needed to prevent the formation of free
thrombin than are needed to inhibit the protease activity
of clot-bound thrombin. Inhibition of free thrombin
is the basis of low-dose prophylactic therapy. | [Pharmacokinetics]
The pharmacokinetic profiles of heparin and LMWHs are quite different. Whereas heparin is only
30% absorbed following subcutaneous injection, 90% of LMWH is systemically absorbed. The
binding 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 to
the high negative-charged density of heparin. This high nonspecific binding decreases
bioavailability and patient variability. Additionally, heparin's nonspecific binding may account for
heparin's narrow therapeutic window and heparin-induced thrombocytopenia (HIT), a major limitation
of heparin. These same affinities are quite low, however, in the case of LMWHs. These parameters
explain several of the benefits of the LMWH's. The favorable absorption kinetics and low protein
binding affinity of the LMWHs results in a greater bioavailability compared with heparin. The
lowered affinity of LMWHs for PF4 seems to correlate with a reduced incidence of HIT. Heparin is
subject to fast zero-order metabolism in the liver, followed by slower first-order clearance from the
kidneys. The LMWHs are renally cleared and follow first-order kinetics. This makes the
clearance of LMWHs more predictable as well as resulting in a prolonged half-life. Finally, the
incidence of heparin-mediated osteoporosis is significantly diminished with use of LMWHs as opposed to heparin. | [Pharmacology]
The physiological function of heparin is not completely
understood. It is found only in trace amounts in
normal circulating blood. It exerts an antilipemic effect
by releasing lipoprotein lipase from endothelial cells;
heparinlike proteoglycans produced by endothelial
cells have anticoagulant activity. Heparin decreases
platelet and inflammatory cell adhesiveness to endothelial
cells, reduces the release of platelet-derived growth
factor, inhibits tumor cell metastasis, and exerts an antiproliferative
effect on several types of smooth muscle.
Therapy with heparin occurs in an inpatient setting.
Heparin inhibits both in vitro and in vivo clotting of
blood. Whole blood clotting time and activated partial
thromboplastin time (aPTT) are prolonged in proportion
to blood heparin concentrations. | [Clinical Use]
#N/A | [Side effects]
The major adverse reaction resulting from heparin
therapy is hemorrhage. Bleeding can occur in the urinary
or gastrointestinal tract and in the adrenal gland.
Subdural hematoma, acute hemorrhagic pancreatitis,
hemarthrosis, and wound ecchymosis also occur. The
incidence of life-threatening hemorrhage is low but variable. Heparin-induced thrombocytopenia of immediate
and delayed onset may occur in 3 to 30% of patients.
The immediate type is transient and may not involve
platelet destruction, while the delayed reaction
involves the production of heparin-dependent antiplatelet
antibodies and the clearance of platelets from
the blood. Heparin-associated thrombocytopenia may
be associated with irreversible aggregation of platelets
(white clot syndrome). Additional untoward effects of
heparin 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 of
glyceryl trinitrate.
Use with care in patients receiving oral
anticoagulants, platelet aggregation inhibitors, aspirin
or dextran. | [Metabolism]
Heparin is prescribed on a unit (IU) rather than milligram
basis. The dose must be determined on an individual
basis. Heparin is not absorbed after oral administration
and therefore must be given parenterally.
Intravenous administration results in an almost immediate
anticoagulant effect. There is an approximate 2-hour
delay in onset of drug action after subcutaneous administration.
Intramuscular injection of heparin is to be
avoided because of unpredictable absorption rates, local
bleeding, and irritation. Heparin is not bound to
plasma proteins or secreted into breast milk, and it does
not cross the placenta.
Heparin’s action is terminated by uptake and metabolism
by the reticuloendothelial system and liver and
by renal excretion of the unchanged drug and its depolymerized
and desulfated metabolite. The relative
proportion of administered drug that is excreted as unchanged
heparin increases as the dose increases. Renal
insufficiency reduces the rate of heparin clearance from
the 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] |
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