as hemoperfusion, the particle size may be a limiting factor. In this later case, the ~lood components (e.g. fibrinogen, cells, etc.) aggregate and form leaf-like.
ClinicalMaterials 11 (1992) 125-128
Physical and Biological Modification of Carbonic Sorbents ~
V. G. Nikolaev, V. V. Sarnatskaya, E. V. Eretskaya, E. A. Snezhkova & N. V. Belitser Kavetsky Institute for Oncology and Radiobiology Problems, Ukrainian Academy of Sciences, Kiev, Ukraine
Abstract: Activated carbons are usually considered as non-specific sorbents. However, their specificity and effectiveness may be increased by physical and biological modifications. This paper gives our approach and discusses the results of some related recent studies.
INTRODUCTION Activated carbons are commonly viewed as non-
specificadsorbents, 1 despitetheir considerablestructural and physical/chemical selectivities..2-4 Recently, activated carbons based on synthetic polymers (the so-called carbon pyropolymers) and their . biologically modified forms have been evaluated by us as specific sorbents and have been used in many diverse clinical applications. 5,6 In this paper physical and biological modifications of carbonic sorbents are evaluated. PHYSICAL MODIFICATION Activated carbons are prepared by carbonization and activation of different raw materials. Depending on the raw material and also the processing conditions, activated carbons with different internal .structures may be obtained. In our studies, we have used basically polymeric materials in spherical or fibre forms to prepare activated carbon sorbents for different medical applications. In order to adjust the specificity of the resultant matrix we have changed both material and also processing conditions. 5,6 . Carbonic sorbents are highly porous materials. They contain pores with different sizes, i.e. micropores (average diameter: up to 40 A), mesopores .(average diameter: 40--200 A), and macro pores (average diameter: > 200 A). High microporosity means high surface area. However, depending upon Clinical Materials 0267-6605/92/$05.00
the size and the shape of the molecules to be adsorbed, not all pores may be available. In other words, by changing the pore structure,' the specificity of the sorbent can be tailored. In order to discuss this effect, we have studied invitro adsorption of non-conjugated bilirubin on fibrous activated carbons with different pore struc. ture.? Table I summarizes the results of this study. As seen in Table I, the extent 'of bilirubin adsorption is significantly changed with the internal structure of the carbonic sorbent. By increasing the microporosity bilirubin adsorption can be increased about five times. The size of the spherical carbonic .sorbents is another important parameter that a~ects mainly the kinetic properties. Higher adsorption rates can be achieved by using smaller particles. This is because of the shorter diffusional pathways (low mass transfer resistance in the particle) in the smaller ones. Smaller particles are preferred to prepare biologically modified sorbents, because the large biomolecules are attached mostly at the outer . surface or in the macropores. The smaller particles (about 30--40pin) can be used effectively in plasma sorption devices where sorbent particles contact with plasma (not blood). However, in direct blood-contacting devices, such as hemoperfusion, the particle size may be a limiting . factor. In this later case, the ~lood components (e.g. fibrinogen, cells, etc.) aggregate and form leaf-like structures in the space between the small particl~s 125
@ 1992 Elsevier Science Publishers Ltd, England
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V. G. Nikolaev et ill.
Table 1. Bilirubin adsorption on fibrous activated carbons
Column number
Surface area (m2fg) Bilirubin adsorption (mgfcm3 of the column)
1 2 3 4
---T 0,53 1.84 2-88
0,94
Total
Macropores
Mesopores
Micropores
1243 1493 ]533 1328
14 13 15 14
620 664 622 662
609 816 896 652
,1 .
Fig. 1. Leaf-like structures in the caking area observed at the bottom of a carbon hemoperfusion column (arrow shows the blood, flow direction).
Table 2. Biologically modified sorbents and their therapeutic applications
Ligand Endotoxin E. Coli E. Coli Bacterial ,bodies Fibrinogen HSA Proteolytic complexes Encephalogeneous protein'
Molecular weight (dallon)
2000000
Ligand content (mg ligandfg carbon) 4,9
300 340000 69000 16000-30000 21000
(Fig. I). This unwanted process, the so-called 'caking', may occur with less severity when the' larger sorbent particles (about 500,um) are used. BIOLOGICAL MODIFICATION SpecifiCityand the effectiveness of the sorbents may be increasc:d by using different bioentities. We have attached a variety of biologically active materials (i.e'. ligands) into. our highly activated carbon.
68'5 40-100 20-100 400
'
Therapeutic
use
Autoimmune and oncological diseases Autoimmune and oncological diseases Endotoxemia Hepatic insufficiency Wounds, artificial digestion Demyelinizating diseases'
sorbents and have applied them in many diverse applications, as exemplified in Table 2. These biologically modified sorbents can be prepared from two separately stored components, namely carbon matrix and biologically active materials. Ligands are immobilized on carbon surfaces by physical adsorption in usually a few minutes to some hours. A carbon matrix is not a simple carrier in this case. In other terms, these sorbents are bifunctional. For example, in the case,
Physical and bio/'ogical modification
where proteolytic enzymes are attached to the carbon matrix, immobilized enzymes degrade the protein molecules rather specifically
