Polymer material based on modified polysaccharides for heparin removal and neutralisation in medical applications (removal of heparin from blood and body fluids)

Summary of the technology

Heparin has many clinical applications due to potent activity for inhibition of blood clotting. Heparin is a drug of choice when quick anticoagulant effect is required, e.g. during surgical procedures, and especially to prevent clotting of blood in devices for extracorporeal therapy, like dialysers and cardiopulmonary bypasses.

The use of heparin carries a risk of serious side-effects, among of which bleedings, thrombocytopenia and osteoporosis are most frequent. Due to the side-effects heparin should be removed from the bloodstream as soon as the anticoagulant effect is no longer needed. The most common method is administration of protamine, a small protein that is a heparin antagonist. Another polymer used to inactivate heparin is poly-L-lysine, also applied to enhance the effect of protamine. Moreover, heparin can be neutralised by enzymatic degradation with immobilised heparinase.
However, the current methods of heparin removal themselves can produce side-effects. For example, as many as 10% of patients suffer from unwanted reactions caused by protamine that can have severe consequences, including fatal events. Among the side-effects there are: pulmonary hypertension, arterial hypertension, anaphylactic crisis, thrombocytopenia, granulocytopenia, complement activation and release of cytokines. Furthermore, protamine-induced heparin neutralisation is incomplete and followed by allergic reaction. Poly-L-lysine, on the other hand, is a relatively expensive polymer.

Description of the technology

The subject of the offer is an application of modified natural polysaccharides, in water solutions or in the cross-linked form of microspheres, for removal of heparin from blood and body fluids. The offered method allows for heparin neutralisation in the patient’s organism, but could be also used for constructions of devices for extracorporeal heparin removal.


The subject of this licensing offer is a method for removal or neutralization of heparin in blood and body fluids by application of modified polysaccharides, especially hydroxypropyl cellulose, dextran and chitosan. The polymer can be used both in soluble form and in microsphere or film design. Hydroxypropyl cellulose is a physiologically inert compound with well-documented lack of toxicity; it is used by pharmaceutical industry as a binder and coating in manufacturing of tablets and capsules. Dextran has a long record of medical uses, e.g. as an anti-platelet agent and a blood substitute. Chitosan is a natural, biodegradable and biocompatible polysaccharide used in medical applications in a form of solution, films and microspheres. The key advantages of chitosan are: affordable cost and lack of toxicity. Genipin used for microspheres cross-linking is also a natural and non-toxic substance isolated from fruit of evergreen tropical plant Gardenia jasminoides.

Main advantages of its use

  • Experimental data proved that the polymers are capable of heparin binding and can neutralise its anticoagulant activity with efficiency similar to protamine sulphate, which is routinely used for heparin inactivation in medical procedures. Comparing to the protamine polysaccharides included in the offer have advantageous safety profile. Furthermore, the modified chitosan has antibacterial and antifungal properties that are an additional advantage of the offered material. Supplementary method has been developed for desorption of heparin from the polymer, so that the material can be easily regenerated and re-used for heparin removal.


  • The method has the following biomedical applications: 1.Using the polymer in solution allows for quick administration to the patient (e.g. as an intravenous formulation) and neutralisation of heparin anticoagulant activity. 2.Material in the form of microspheres and/or film can be used for construction of devices for extracorporeal heparin removal, mostly from blood and plasma.

Related Keywords

  • Industrial Technologies
  • Biological Sciences
  • Drug delivery and other equipment (including kidney dialysis machines)
  • Heparin
  • dialysers
  • cardiopulmonary bypasses
  • blood clotting
  • plasma
  • bleedings
  • thrombocytopenia
  • Anticoagulant
  • protamine
  • medical devices

About Jagiellonian University

Jagiellonian University, founded 1364, is the oldest university in Poland and one of the oldest worldwide. The research and teaching activities are conducted at 15 faculties, including the Medical College (Collegium Medicum). Over 3,700 researchers work at the university and the total number of students is about 50,000.

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