MEDICINAL CHEMISTRY

Low-molecular-weight Heparins, B.P. Low molecular-weight heparins are salts of
sulphated glucosaminoglycan having a weight-average molecular weight less than 8,000
and for which at least 60% of the total weight has a molecular weight less than 8,000.
Depending upon the method of production, the resulting low-molecular-weight heparins
display different chemical structures at the reducing or the non-reducing end of the
polysaccharide chain. Low-molecular weight heparins are obtained by fractionation or
depolymerisation of heparin of natural origin. They occur as white or almost white
powders, which are hygroscopic, and are freely soluble in water.
Low-molecular-weight heparins generally have a greater bioavailability after
subcutaneous injection and longer half-life than heparin. Low-molecular-weight heparins
are given parenterally for the treatment and prophylaxis of thrombo-embolic disorders.
Their effects can be partially reversed by protamine sulphate. A possible decreased risk
of bleeding complications compared with heparins has not been established. Proprietary
Names: Fragmin; Fraxiparin; Sandoparine, Dalteparine sodium, Enoxaperine sodium,
Medroparine calcium, Parnaparine sodium, Tinzaparine sodium.
Heparin Antagonist
Heparin can give rise to haemorrhage as a consequence of its action. If the haemorrhage
is severe and is life-threatening, the effect of heparin can be reversed quickly by the
intravenous infusion of protamine sulphate. The protamines are low-molecular-weight
basic proteins isolated from the sperm or the mature testes of fish, usually species of
family Salmonidae and Clupeidae. They combine with heparin to form a stable inactive
complex. Protamine also has an anticoagulant effect of its own as it interacts with
platelets, fibrinogen and other plasma proteins. Therefore, it should be given in minimal
amount just to neutralize the heparin present in plasma.
Official Drugs
Protamine Sulphate, B.P., I.P.: Protamine sulphate is a mixture of the sulphates of basic
peptides prepared from the sperm or mature testes of fish, usually species of Salmonidae
and Clupeidae. It occurs as a white or almost white powder; hygroscopic. It is sparingly
soluble in water. Protamine sulphate is kept in an airtight, temper-evident container. If the
material is sterile the container should also be sterile.
Protamine sulphate is used to neutralize the anticoagulant action of heparin in the
treatment of haemorrhage resulting from severe heparin over dosage. It should be
administered by slow intravenous injection over a period of ten minutes. Protamine
sulphate has weak anticoagulant properties and if given in gross excess its anticoagulant
effect could be significant. Protamine is also used to prolong the effects of insulin.
Preparation: Protamine Sulphate Injection, B.P., I.P. Proprietary Names: Prosulf
Protamine Hydrochloride, B.P.: Protamine hydrochloride is a white or almost white
powder; hygroscopic. It is soluble in water. The condition of storage, actions and uses
are the same as for protamine sulphate.