EP 1 002 566 B12510152025303540455055Description[0001] The present invention relates to a filter for ad-sorbing heparin and/or endotoxins in plasma and/orblood.[0002] In most clinical treatments in which blood or bi-ological fluids must be treated according to specific pro-cedures related to the disease of a patient, the extracor-poreal circuit in which these fluids flow must receive theaddition of anticoagulants, such as for example heparin,in order to contain the allergic reaction which, as it isknown, endogenous fluids develop in contact with foreignsurfaces or materials.[0003] Relatively high doses of this substance aretherefore normally used in treatments such as blood ox-ygenation, in cardiopulmonary bypass, hemodialysis, he-mofiltration, hemoperfusion and plasmapheresis.[0004] In the end of these extracorporeal treatments,or in case of hemorrhages or complications occurred dur-ing the treatment, it is necessary to neutralize as quicklyas possible the heparin that is still circulating in the car-diovascular system and might be present in high concen-trations; protamine sulfate is used in many of these casesas a heparin antagonist.[0005] However, this method has some limitations dueto the patient’s failure to metabolize part of the volumesof heparin used and to a consequent resumption of re-lease of the heparin several hours after its apparent neu-tralization, especially in the case of high administereddoses.[0006] Moreover, the use of heparin is not limited tothe anticoagulant action that it produces; in fact it canalso be employed in an acid environment with a pH be-tween 5.05 and 5.25, for therapeutic purposes for theselective removal of lipoproteins (cholesterol) such asLDL in dislipidemic patients.[0007] In this regard, the prior art describes in detail aprocess for the extracorporeal precipitation and selectiveseparation of low-density lipoproteins (LDL) known asHELP (Heparin Extracorporeal LDL Precipitation) ifheparin is added to the plasma of the patient so as toform complexes of insoluble heparin-LDL aggregateswhich can be filtered.[0008] According to this process, which uses an ace-tate buffer solution containing heparin in an amountequivalent to 100 UI/ml, the plasma of the patient isplaced in contact with this solution in a 1:1 volume ratio,obtaining the precipitation of LDL, fibrinogen, LP(a) andB-100 apoprotein in clinically effective quantities.[0009] Since heparin is added by means of a buffersolution in an amount which exceeds the actual bindingcapacity of these proteins, it is important to remove theexcess quantity in order to re-establish the initial condi-tions of the plasma, avoiding the increase in risk of he-morrhage and the possible above-mentioned complica-tions.[0010] This removal is currently performed by usingfilters which have cellulose or cellulose-based mem-branes and have a substantially bulky structure with re-spect to the actual filtration yield.[0011] These filters have also significant problems asregards sterilization before their use: in fact it is neces-sary to use incompatible liquids for this operation and inorder to keep the filtering membrane intact, and the sub-sequent elimination of these liquids requires washingwith physiological solution, which however does not en-sure full elimination of traces of these toxic liquids, whichmight therefore be infused to the patient.[0012] Finally, another problem shared by all conven-tional filters is the lack of uniform distribution of the bloodor plasma along the filtering surfaces: the flows of bloodor plasma in fact tend to wet only the proximal portionsthereof, whereas the distal ones remain substantially un-affected.[0013] WO-A98/28064 discloses a filter which com-prises in a housing having an inlet port connected to adistribution chamber and an outlet port connected to acollection chamber an arrangement of first and secondhollow-fiber membranes. According to this document,first and second hollow-fiber membranes are embeddedwith their ends in sealing compounds or packing ele-ments such that the ends of the first hollow-fiber mem-branes facing the distribution chamber are embedded ina sealing compound adjourning the distribution chamberat the inlet end of the housing such that they are protrud-ing this sealing compound and are open towards the dis-tribution chamber. The ends of the second hollow-fibermembranes facing the collection chamber are embeddedin a sealing compound adjourning the collection chamberat the outlet end of the housing such that they are pro-truding this sealing compound adjourning the collectionchamber and are open towards the collection chamber.The hollow-fiber membranes may be arranged in multiplelayers which are wrapped concentrically in a roll and maybe modified with ligands such as diethylaminoethylgroups.[0014] The aim of the present invention is to solve theabove-cited problems of the prior art by providing a filterfor adsorbing heparin and/or endotoxins in blood and/orplasma which is capable of eliminating said substancessubstantially completely and allows to optimize the dis-tribution of blood and plasma on the entire area of thefiltering surfaces and at the same time avoid reductionof the filtering action caused by possible clogging.[0015] This aim, object and others are achieved by afilter for adsorbing heparin and/or endotoxins in bloodand/or plasma, comprising an internally hollow cylindricalcontainment body which is provided, at its inlet and outletends, with corresponding access ports formed in endcaps and internally accommodating a filtering mediumcomposed of microporous fibers having open ends andbeing arranged in multiple layers which are wrapped con-centrically in a roll and have groups of diethylaminoethyldeposited thereon, characterized in that the filter acco-modates a single filtering medium only composed of mi-croporous fibers and in that a packing element for stable1 2
