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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.


Equipment

  • open agitators,
  • vacuum nutsche filters,
  • drying chambers,
  • pH meter.


Patents

Patent application P-386 867 (2008) „Method to obtain other heparin salts from sodium heparin”.


References

The technology has been developed on a laboratory scale. It has not been implemented.


Information

Irena Grzywa-Niksińska, Ph.D., Chem. Eng.

phone: + 48 22 568 20 05