Catalogue of Polosh Technologies 2012 Part 2 - Polonia

2) Obtaining heparin
Heparin – a sulfonated mucopolysaccharide, derived mainly from animal organs in the form of
crystalline sodium salt.
Sodium, calcium and ammonium salts of heparin are used in the health service. Lithium heparin
is used for test tube coating in biochemical research and in gasometric analysis.
A brief description of the technology
The process involves two stages. The first stage consists of obtaining heparic acid from a
sodium salt of unfractionated heparin. A concentrated sulfuric acid is added to a 10 % aqueous
solution of sodium heparin with pH � 8.3 until pH � 0.5 is reached.
At the second stage, porophores from sulfonyl groups are substituted with metal or ammonium
cations. Then the appropriate hydroxide is introduced into the heparic acid solution, resulting in
full substitution of sulfonyl groups with hydroxide cations. The hydroxide is added until pH �
9.2–10.2 is reached.
If heparin ammonium salt is to be obtained, concentrated aqueous ammonia solution is added
to crystalline heparic acid until pH � 9.5–10 is reached and then full dissolution of the acid
crystals is effected through stirring. Instead of hydroxides may be applied oxides or carbonates
of cations to be introduced.
At the third stage appropriate heparin salt is precipitated with alcohol (methanol or ethanol).
The solution shall be stirred while adding alcohol. After drain-off the heparin salt crystals are
rinsed a few times with alcohol and then dried.
Advantages of the technology offered
The technology does not require any complicated apparatus, is cheap and the product obtained
with 98 % efficiency is very pure (pharmacopeial purity). Currently employed methods to obtain
salts, other than sodium ones, comprise mainly running an aqueous solution of heparin sodium
salts through columns filled with a cation exchange resin filled with appropriate cations, which
substitute sodium cations. The electrodialysis method can also be applied, using appropriate
membranes permeable to cations and anions. Both methods produce good results but the
electrophoresis method requires specialist apparatus, whereas the ion exchange method
causes expansion of the puncture front and hence dilution of solutions, complicating the
precipitation process and lowering its efficiency.
� open agitators,
� vacuum nutsche filters,
� drying chambers,
� pH meter.
Equipment
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