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Physical and biological modification of carbonic sorbents
Clinical Materials
I1 (1992) 12s128
Physical and Biological Modification Sorbents V. G. N~ikoPaev, V. V. Sarnatskaya, N. V. Belitser Kavetsky
Institute:
for Oncology
and Radiobiology
E. V. Eretskaya, Problems,
Ukrainian
of Carbonic
E. A. Snezhkova & 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
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 h.ave studied invitro adsorption of non-conjugated bilirubin on fibrous activated carbons with different pore structure.7 Table 1 summarizes the results of this study. As seen in Table 1, 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 affects 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 ar’e 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 3&4O pm) 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 blood components (e.g. fibrinogen, cells, etc.) aggregate and form leaf-like structures in the space between the small particles
Activated carbons are commonly viewed as nonspecific adsorbents,l despite their considerable structural and physical/chemical selectivities.2m4 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 applications57 6 In this paper physical and biological modifications of carbonic sorbents are evaluated. MODIFICATION Activated carbons are prepared by carbonization and activiation 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.5p6 Carbonic sorbents are highly porous materials. They contain pores with different si%es, i.e. micropores (average diameter: up Oto 40 A), mesopores (average diameter : 40-209 A), and macropores (average diameter : > 200 A). High microporosity means high surface area. However, depending upon 125 ClinicalMaterials Q267-6605/92/$05.00 0
1992 Elsevier
Science Publishers
ktd, England
Table 1. Bilirubin
adsorption
on fibrous activated
carbons -_.-. _ ._..._._-__-.___._..__ &tr$zce aredk (m”/g)
Column number
Fig. 1. Leaf-like
Bilirubin adsorption (mg/cm3 of the column)
1
0%
2 3 4
I+?4 288 0.94
structures
Table 2. Biologically
in the caking area observed
modified
sorbents
Total 1243 1443 1533
E4 I.3 rg
h328
i 4.
at the bottom of a carbon flow direction).
and their therapeutic Molecular weight (Q’alton)
Ligand Endotoxin E. Coli E. Co/i
2000000 -
Bacterial bodies Fibrinogen HSA Proteolytic complexes Encephalogeneous protein
M6KYOpOYSS
340 000 69 000 1600O30000 21000
MeSQpQXS
MicroporeL~
620 664 622 662
509 816 896 5.52
hemoperfusion
colnmn
(arrow
shows
the
bhod
applications Ligand content (mg ligand/g carbon) 49 300 68.5 48-100 20-l 00 400
Therapeutic .~~to~rn~~n~ oncological A~~o~rnrn~n~ oncological otoxemia atic
use and diseases and diseases
insuficiency
Wounds, artificial digestion ~ern~e~~~~~~ti~~ diseases
(Fig. 1). This unwanted process, the so-called ‘caking ‘, may occur with less severity when the larger sorbent particles (about 500 pm) are used. BIOLOGICAL
MODIFICATION
Specificity and the effectiveness of the sorbents may be increased by using different bioentities. We have attached a variety of biologically active materials (i.e. ligands) i n t o our highly activated carbon
in usual!y a few n matrix is not a simple carrier in this case. En other terms these sorbents are ~~f~~~t~o~a~.
Physical
and biological
mod$cation
10
5 rng
20
Enzyme / g Sorbent
Fig. 2. Protein sorption capacity of fibrous carbon as a function of amount of immobilized proteolytic enzymes.
Table 3. DNA-Activated
“1 2 3 4 b+++ ++ + +-
carbon
hemoperfusion
treatment
patient initials
Sex
Age
Diagnosis”
S.V.G. G.M.I. I.G.M. M.Q.S. D.E.I. N.L.B. M.S.B. Z.R.A. L.G.V. P.E.G. G.L.D. B.U.G. P.P.B. J.K.N.
M F M M F F F F F F F M M M
48 37 65 51 21 17 49 19 25 46 13 38 57 42
3,2 3,2 4,~ 3,~ 3 3,~ 3,~ 4,~ 3,~ 3 3,~ 3 3
sorbents
127
effectively by the carbon. As seen in Fig. 2, by including more enzymes in the carbon matrices one can increase the protein adsorption capability of the pure carbon sorbents. In our recent studies, we were able to attach thymic DNA in the macropores of both granular and fibrous activated carbon matrices8 These biologically modified sorbents have initially been developed for the therapy of radiation injuries, but later they were successfully applied for the treatment of a number of immuno-dependent diseases and pathological statuses resulting, from the impairment of the cellular division kinetics.’ Table 3 provides the results of treatment of 113patients with severe forms of psoriases by single hemoperfusion through the DNA-containing carbon adsorbents. Table 4 shows the results of the treatment of 36 patients with psoriasis. As seen here, DNA immobilized activated carbon sorbents are much more successful than unmodified ones. As recent data
where proteolytic enzymes are attached to the carbon matrix, immobilized enzymes degrade the protein molecules rather specifically and then the resultant small fragments are adsorbed much more
0
of carbonic
of patients
with psoriasis
Duration of disease (year)
L2
Clinical effect”
Duration of efSect (months)
+++ +++ +++ +++ ++ t+++ ++ +++ ++ + ++ ++ +-
2,4 17 40 22 4 3 16 0,3 1 29 6 I4 12 10
> > > >
> > > > >
7 33 32 31 27 fG 30 31 29 31 11 10
Psoriatic erythroderma Psoriatic Arthritis Vulgar diffuse psoriasis E,xudative diffuse psoriasis Complete remission Improvement h4inimal improvement Without changes Aggravation
Table 4. DNA-Activated
carbon
versus activated
carbon
for treatment
of patients
with psoriasis
Clinical effects (%) Sorbent type DNA-activated carbon Activated carbon
Number of patients
Complete
Objective
Without
21 9
55.5 0
37.0 33.3
7.5 55.5
Aggravation 0 11.2
showed, the DNA combination with deligandizing synthetic adsorbents is one of the most promising in this respect.
REFERENCES Cooney, D. O., Activated charcoal: antidotal and other medical uses. In Drugs and the Pharmaceutical Sciences, Vol. 9. Marcel Dekker, Inc., New York, 1980, p. I. Anderson, A. H., The pharmacology of activated charcoal. I. Adsorption power of charcoal in aqueous solutions. Acta Pharmacol. Toxicol., 2 (1946) 69-78. Strazhesko, D. N. & Tarkovskaya, I. A., The chemical nature of surface selective ion exchange and surface complex formation on oxidic charcoal. Adsorption and Adsorbents, 1 (1972) 7-17. Strazhesko, D. N., Electrophysical properties of active
charcoals and mechanisms of processes rakmg place on their surface. Adsorption and Adsorbents, 4 (1976) 3-1 5. Nikolaev, V. G., ~e~ocarboperf~sio~ in Experiment and CI , Kiev, 1984, p. 360. 6. Nikolaev, V. G., rin, K. E. & Sergeev, V., Theorsorbents a~~~~catio~ in a~ti~c~a~ organs Biomat. Art$ Cells ArtiJ: Organs, IS (1987) 59-77. 7. ~ Sarnatskaya, V. V., Sigai, U. I+ Klevakhorin, K. E. & Yushko, I, A., igh porosity activated carbons for bilirubin removal. ,!%nki J. /&if. orgLZ?rans, 14 (1991) 179-85. Snezhkova, E. A,, Kolyaden Karol, V. PI., Pdijkitin, A. A., Alexeexka, t P.. & Amalyan, V. A., DNA-coated adsorbents: experimental assessment and results of severe psoriasis treatment. Biomat. Art$ CelLells Arl$ Organs (in press). Snezhkova, E. A., DNA-coating carbon hemosorbents. Congress of the World Aphresis Abstract, I si International Association, Tokyo 1986, p. 81.
I1 (1992) 12s128
Physical and Biological Modification Sorbents V. G. N~ikoPaev, V. V. Sarnatskaya, N. V. Belitser Kavetsky
Institute:
for Oncology
and Radiobiology
E. V. Eretskaya, Problems,
Ukrainian
of Carbonic
E. A. Snezhkova & 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
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 h.ave studied invitro adsorption of non-conjugated bilirubin on fibrous activated carbons with different pore structure.7 Table 1 summarizes the results of this study. As seen in Table 1, 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 affects 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 ar’e 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 3&4O pm) 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 blood components (e.g. fibrinogen, cells, etc.) aggregate and form leaf-like structures in the space between the small particles
Activated carbons are commonly viewed as nonspecific adsorbents,l despite their considerable structural and physical/chemical selectivities.2m4 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 applications57 6 In this paper physical and biological modifications of carbonic sorbents are evaluated. MODIFICATION Activated carbons are prepared by carbonization and activiation 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.5p6 Carbonic sorbents are highly porous materials. They contain pores with different si%es, i.e. micropores (average diameter: up Oto 40 A), mesopores (average diameter : 40-209 A), and macropores (average diameter : > 200 A). High microporosity means high surface area. However, depending upon 125 ClinicalMaterials Q267-6605/92/$05.00 0
1992 Elsevier
Science Publishers
ktd, England
Table 1. Bilirubin
adsorption
on fibrous activated
carbons -_.-. _ ._..._._-__-.___._..__ &tr$zce aredk (m”/g)
Column number
Fig. 1. Leaf-like
Bilirubin adsorption (mg/cm3 of the column)
1
0%
2 3 4
I+?4 288 0.94
structures
Table 2. Biologically
in the caking area observed
modified
sorbents
Total 1243 1443 1533
E4 I.3 rg
h328
i 4.
at the bottom of a carbon flow direction).
and their therapeutic Molecular weight (Q’alton)
Ligand Endotoxin E. Coli E. Co/i
2000000 -
Bacterial bodies Fibrinogen HSA Proteolytic complexes Encephalogeneous protein
M6KYOpOYSS
340 000 69 000 1600O30000 21000
MeSQpQXS
MicroporeL~
620 664 622 662
509 816 896 5.52
hemoperfusion
colnmn
(arrow
shows
the
bhod
applications Ligand content (mg ligand/g carbon) 49 300 68.5 48-100 20-l 00 400
Therapeutic .~~to~rn~~n~ oncological A~~o~rnrn~n~ oncological otoxemia atic
use and diseases and diseases
insuficiency
Wounds, artificial digestion ~ern~e~~~~~~ti~~ diseases
(Fig. 1). This unwanted process, the so-called ‘caking ‘, may occur with less severity when the larger sorbent particles (about 500 pm) are used. BIOLOGICAL
MODIFICATION
Specificity and the effectiveness of the sorbents may be increased by using different bioentities. We have attached a variety of biologically active materials (i.e. ligands) i n t o our highly activated carbon
in usual!y a few n matrix is not a simple carrier in this case. En other terms these sorbents are ~~f~~~t~o~a~.
Physical
and biological
mod$cation
10
5 rng
20
Enzyme / g Sorbent
Fig. 2. Protein sorption capacity of fibrous carbon as a function of amount of immobilized proteolytic enzymes.
Table 3. DNA-Activated
“1 2 3 4 b+++ ++ + +-
carbon
hemoperfusion
treatment
patient initials
Sex
Age
Diagnosis”
S.V.G. G.M.I. I.G.M. M.Q.S. D.E.I. N.L.B. M.S.B. Z.R.A. L.G.V. P.E.G. G.L.D. B.U.G. P.P.B. J.K.N.
M F M M F F F F F F F M M M
48 37 65 51 21 17 49 19 25 46 13 38 57 42
3,2 3,2 4,~ 3,~ 3 3,~ 3,~ 4,~ 3,~ 3 3,~ 3 3
sorbents
127
effectively by the carbon. As seen in Fig. 2, by including more enzymes in the carbon matrices one can increase the protein adsorption capability of the pure carbon sorbents. In our recent studies, we were able to attach thymic DNA in the macropores of both granular and fibrous activated carbon matrices8 These biologically modified sorbents have initially been developed for the therapy of radiation injuries, but later they were successfully applied for the treatment of a number of immuno-dependent diseases and pathological statuses resulting, from the impairment of the cellular division kinetics.’ Table 3 provides the results of treatment of 113patients with severe forms of psoriases by single hemoperfusion through the DNA-containing carbon adsorbents. Table 4 shows the results of the treatment of 36 patients with psoriasis. As seen here, DNA immobilized activated carbon sorbents are much more successful than unmodified ones. As recent data
where proteolytic enzymes are attached to the carbon matrix, immobilized enzymes degrade the protein molecules rather specifically and then the resultant small fragments are adsorbed much more
0
of carbonic
of patients
with psoriasis
Duration of disease (year)
L2
Clinical effect”
Duration of efSect (months)
+++ +++ +++ +++ ++ t+++ ++ +++ ++ + ++ ++ +-
2,4 17 40 22 4 3 16 0,3 1 29 6 I4 12 10
> > > >
> > > > >
7 33 32 31 27 fG 30 31 29 31 11 10
Psoriatic erythroderma Psoriatic Arthritis Vulgar diffuse psoriasis E,xudative diffuse psoriasis Complete remission Improvement h4inimal improvement Without changes Aggravation
Table 4. DNA-Activated
carbon
versus activated
carbon
for treatment
of patients
with psoriasis
Clinical effects (%) Sorbent type DNA-activated carbon Activated carbon
Number of patients
Complete
Objective
Without
21 9
55.5 0
37.0 33.3
7.5 55.5
Aggravation 0 11.2
showed, the DNA combination with deligandizing synthetic adsorbents is one of the most promising in this respect.
REFERENCES Cooney, D. O., Activated charcoal: antidotal and other medical uses. In Drugs and the Pharmaceutical Sciences, Vol. 9. Marcel Dekker, Inc., New York, 1980, p. I. Anderson, A. H., The pharmacology of activated charcoal. I. Adsorption power of charcoal in aqueous solutions. Acta Pharmacol. Toxicol., 2 (1946) 69-78. Strazhesko, D. N. & Tarkovskaya, I. A., The chemical nature of surface selective ion exchange and surface complex formation on oxidic charcoal. Adsorption and Adsorbents, 1 (1972) 7-17. Strazhesko, D. N., Electrophysical properties of active
charcoals and mechanisms of processes rakmg place on their surface. Adsorption and Adsorbents, 4 (1976) 3-1 5. Nikolaev, V. G., ~e~ocarboperf~sio~ in Experiment and CI , Kiev, 1984, p. 360. 6. Nikolaev, V. G., rin, K. E. & Sergeev, V., Theorsorbents a~~~~catio~ in a~ti~c~a~ organs Biomat. Art$ Cells ArtiJ: Organs, IS (1987) 59-77. 7. ~ Sarnatskaya, V. V., Sigai, U. I+ Klevakhorin, K. E. & Yushko, I, A., igh porosity activated carbons for bilirubin removal. ,!%nki J. /&if. orgLZ?rans, 14 (1991) 179-85. Snezhkova, E. A,, Kolyaden Karol, V. PI., Pdijkitin, A. A., Alexeexka, t P.. & Amalyan, V. A., DNA-coated adsorbents: experimental assessment and results of severe psoriasis treatment. Biomat. Art$ CelLells Arl$ Organs (in press). Snezhkova, E. A., DNA-coating carbon hemosorbents. Congress of the World Aphresis Abstract, I si International Association, Tokyo 1986, p. 81.