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Carbon Sorbents in Medicine and Proteomics
Carbon Sorbents in Medicine and Proteomics
UDC 541.1:542.98
L. G. PYANOVA
Abstract
Hemosorption (purifying the blood outside an organism) and enterosorption (detoxification of an organism
through the gastrointestin al tract) are the most promising methods of the sorption al medicine. As far as the
adsorption of toxic substances with different molecular mass and n ature is concerned, carbon sorbents are
of interest to meet the requirements of medicine. Sorbents of different nature and structure are described.
Methods for controlling the adsorption activity of the sorbent are indicated. A particular attention is paid to
the development of selective sorbents for using in sorption al medicine and proteomics.
However, this results in decreasing the strength er than 500 D. The granules of coal are of ar-
of the sorbent granules. bitrary shape with a rough surface, they are
The second way to control the adsorption fragile to be destroyed in the course of chemi-
properties of adsorbents consists in changing the sorption with releasing fine dust into the blood.
surface chemistry of sorbents, the creation of As the result, the blood cells are injured, and
chemically bound functional groups on the sur- the number of platelets and white blood cells
face of the sorbent to be capable of sorbing the after contact with the sorbent could be reduced
pathologic substances of different n ature. by 80 %. The coals contain mineral impurities
Currently an issue is topical concerning an in great amounts (compounds of potassium,
increase in the efficiency of sorbing the patho- calcium, sodium, magnesium, iron, aluminum,
logical substances of certain n ature aimed at silicon, etc.) those not only impair the adsorp-
developing selective sorbents for subsequent use tion and structural properties of coal, but also
in the sorption al medicine and proteomics (the may pass into the blood [2].
science concerning the development of meth- Introducing the operations of reducing the
ods for the isolation and separation of proteins content of mineral impurities (demineralization),
from biological media, and their identification). of increasing the strength of granules and of
improving the surface relief (encapsulation and
additional processing of grains) to the technol-
REQUIREMENTS FOR MEDICAL SORBENTS ogy allow improving some properties of coal,
but this worsens the sorption characteristics.
Medical sorbents directly contacting with the This situation stimulated research work
biological fluid of an organism are made with aimed at developing novel sorbents on the ba-
special demands for quality: a high level of sis of high quality raw materials and special
chemical purity, minimal content of impurities, technologies. With regard to the medical prac-
non-toxicity, high mechanical strength and tice, the main attention is focused on the devel-
smooth surface relief of granules, the absence opment of carbon sorbents those have a num-
of dust formation (separation of ultrafine par- ber of special and unique properties: a high com-
ticles), high sorption capacity with respect to patibility level with respect to blood and other
removing substances, compatibility with blood organismal fluids, an ability to absorb hydro-
and inert properties with respect to blood cor- phobic toxic substances those almost cannot be
puscles [1]. removed by the sorbents of another nature, an
inertness with respect to the tissues of internal
TECHNOLOGY FOR OBTAINING ACTIVE COAL organs; a wide range of pore structure and sur-
face physicochemical properties [3].
The main properties of industrial activated In our country there are synthetic carbon
carbons commonly used in medicine are adsorbents based on polymer resins developed
determined both by the n ature of source raw and introduced into medical practice (SKN,
materials, and the production technology. SUGS, FAS, SKS, Simplex) as well as a car-
The technology for producing activated car- bon-mineral sorbent (SUMS-1) based on a min-
bons involves three stages: the initial stage con- eral matrix such as γ-alumin a, etc. (Fig. 1) [35].
sists in the preparing raw materials; it is fol- The sorbents developed exhibit a different ac-
lowed by the two stages of thermal processing tivity level with respect to substances caused
such as carbonization (pyrolysis) and activation by the chemical n ature and porous structure
(gasification) those provide an increase in car- of the surface of the sorbent granules, which
bon content and the creation of a porous sur- narrows the range of their application. In ad-
face structure. dition, in recent years the production of these
Activated carbon species produced via this hemosorbents in Russia and Ukraine was for
technology from n atural materials (wood, peat various reasons ceased or reduced.
and fossil coal) have mainly microporous struc- In Japan synthetic sorbents BAC-MU and
ture, which limits their adsorption activity with the BAC-LG from petroleum pitch were de-
respect to substances with the molecular high- veloped those consist of solid grains with a
CARBON SORBENTS IN MEDICINE AND PROTEOMICS 109
smooth surface topography. In the USA, he- Blood Transfusion, the Lomonosov Moscow
mosorbents Ambersorb XE-336, XE-344 with State University developed a biospecific anti-
heavy duty spherical granules those almost do protease hemosorbent Ovosorb based on the
not emit dust were obtained from polymeric ovomucoid protein of duck eggs (n aturally oc-
materials (see Fig. 1). curring protease inhibitor) [7].
Carbon synthetic sorbents became an excel-
lent template for the creation of specific sor-
bents and immunosorbents via chemical modi- CARBON-CARBON COMPOSITE MATERIALS
A NEW GENERATION OF HEMOSORBENTS
fying the surface. Basing on carbon adsorbents
SKN, SUGS, KAU a number of biospecific
adsorbents were developed: GSGD a deligan- At the IHPP, SB RAS (Omsk), technologi-
dization sorbent for the purification of proteins cal approaches were developed to the targeted
and blood cell membranes of blood GUDS a synthesis of a new class of porous carbon-car-
biospecific DNA-containing sorbent, VUDS bon materials based on the globular n anodis-
DNA-containing plasma immunosorbent, and persed carbon, and medical sorbents on this
others (Fig. 2) [6]. basis: a sterile carbon hemosorbent in physio-
The Belarusian State Medical University in logical salt solution VNIITU-1 and a carbon
cooperation with the Belarusians Center of enterosorbent VNIITU-2 [8, 9].
Sorption Detoxification Methods, the Belaru- Basing on the studies concerning the mech-
sian Research Institute of Hematology and anism and kinetics of the thermal decomposi-
Fig. 2 Modified carbon sorbents based on synthetic carbon sorbents SKN, SUGS, KAU.
110 L. G. PYANOVA
tion of hydrocarbons on the surface of dis- butane and other gaseous hydrocarbons on the
persed carbon particles with the formation of surface of carbon n anoparticles at the temper-
pyrolytic carbon performed at the IHPP, a con- ature of 750900 °Ñ. This composite (porous
cept of the template synthesis of porous carbon carbon material) at the stage of activation by
materials was created. The synthesis is based on steam at 700950 °Ñ converts into a mesopo-
a two stage carbon transformation into nanodis- rous carbon material (see Fig. 3, positions 35).
persed carbon particles and pyrocarbon [811]. The technological process of obtaining med-
The feedstock is presented by n atural gas ical sorbents from a matrix such as porous car-
and oil-refining gases, as well as petroleum and bon material with certain porosity includes the
coal tar. At the first stage of the synthesis car- operation aimed at providing its compatibility
ried out in the gas phase at the temperature with blood, sterility and apyrogenicity.
of 12501500 °Ñ, nanodispersed pseudo-spher- The basic operation consists in pneumo hy-
ical carbon particles are formed with the size dromechanical treatment of the porous carbon
of 4060 nm. The process is accompanied by material in a fluidized-bed mode. This opera-
the separation of mineral impurities and re- tion allows one to remove dust carbon particles
moving ash components via the use of special from the surface and pores of the sorbent, to
devices and desalinated quenching water. These bring the pH of the sorbent to physiological
nanoparticles are grouped into aggregates with standard, to improve the overall strength of
carbon-carbon bonds, after the granulation with granules due to the destruction of the weak
a binder form a carbon skeleton of a spherical granules and to remove any surface irregulari-
shape (Fig. 3, position 1, 2). ties (polishing the granules) [8]. The subse-
At the second stage, a granular carbon-car- quent process steps consist in drying the sor-
bon composite consisting of n anosized carbon bent, sterilization by air at 200 °Ñ, packing in
particles and pyrocarbon is formed resulting medical bottles under physiological solution lay-
from the decomposition reaction of propane, er, steam sterilization.
The aim of the new direction in the syn-
thesis of carbon hemo- and enterosorbents was
the creation of medical sorbents free from all
the above-mentioned disadvantages those ex-
hibit a good compatibility with blood.
HEMOSORBENTS
TABLE 1
Physicochemical and biomedical characteristics of the sterile carbon hemosorbent
in physiological salt solution VNIITU-1
Parameters Values
Ash content (%), less than 0.15
Mass fraction of total sulphur (%), less than 0.30
Specific surface area via nitrogen adsorption, m2/g 300400
2
Specific surface area for CTAB adsorption*, m /g 65125
Iodine number, mg/g 175245
Number of granules (0.51.0) mm in diameter (%), more than 90
Number of granules with the diameter less than 0.5 mm (%), less than 10
Strength of the granules under abrasion (%/min), less than 0.30
3
Concentration of NaCl solution, in equilibrium with hemosorbent, mol/dm 0.140.15
pH of NaCl solution in equilibrium with hemosorbent 6.07.8
Impact on blood corpuscles under blood supply
of 80120 mm/min to 350 cm3 of the sorbent:
reduction in the number of leukocytes (%), less than 10
reduction in the number of platelets (%), less than 15
increase in free hemoglobin (%), less than 6
TABLE 2
Porous structure of some carbon sorbents
TABLE 3
Physicochemical and biological characteristics of hemosorbents
Parameters Hemosorbents
SUMS-1 VNIITU-1 FAS SKN-1K SKN-4M ADSORBA 300C
Grain size, mm 0.51.0 0.51.0 0.55.0 0.51.0 0.61.0 0.51.0
Ash content (%), less than 0.15 0.10 2.0 2.0 1.53.0
pH of physiological salt solution
in the equilibrium phase 68 6.07.8 6.07.5 6.57.0 68 6.57.0
Adsorption surface, m2/g 200300 300400 10001100 10001200 1100 320
Regression of total protein and blood cells
after perfusion (mg/L), less than 1520 1015 520 1520 20
Extraction coefficient for toxins
with the average molecular mass, % 33 7795 6070 5570 5060
to exhibit a high adsorption capacity with re- tent of dust whereby they penetrate into the
spect to toxins removed, to have a convenient bloodstream through the walls of organs; an
dosage form, with no causing any adverse or- inconvenient dosage form that requires for pre-
ganoleptic responses. paring the sorbent to introduce into an organ-
In order to produce enterosorbents one uses car- ism, the presence of odor, a high content of
bonaceous materials of different nature: naturally impurities (ash).
occurring, synthetic ones, and others (Fig. 4). The technology of matrix synthesis based
Enterosorbents are available in the form of on globular carbon allowed one to create en-
pastes, granules, powders, tablets, fibre. They terosorbent VNIITU-2, the pharmaceutical
are characterized by a high adsorption surface preparation of high quality that completely
area (up to 1250 m2/g and higher), with the meets the requirements of medicine (Table 4).
total pore volume of 0.41.2 cm3/g, with the It represents a chemically pure sorbent (with
grain size ranging within 0.11.0 mm. carbon content of at least 99.5 %, mineral im-
However, it should be noted that there are purities not exceeding 0.5 %), solid granules,
following disadvantages observed for the en- rounded, 0.51.0 mm in size, being not destroyed
terosorbents: swelling in organismal fluids, a in the course of passing through digestive or-
small size of sorbent particles, or a high con- gans, those do not injure the mucous tunic. The
TABLE 4
Physicochemical and biomedical properties of carbon enterosorbent VNIITU-2
sorbent has neither smell nor taste. Mesoporous Requirements for quality enterosorbents for ani-
nature of the sorbent surface allows the removal mals should not be worse than the demands concern-
of toxic substances with low and medium mo- ing enterosorbents designed for a human organism.
lecular mass from a human organism [8, 13]. According to the technology of matrix syn-
thesis, enterosorbent Zookarb was developed
Enterosorbents for animals that is not inferior in quality comparing to en-
terosorbent VNIITU-2 (Table 5) and is efficient
A considerable part of foreign compounds for the detoxification of animals (cattle, hors-
penetrate in the human organism with food, es, pigs, chickens, fur-bearing animals (mink),
especially with animal products. home animals) and poultry; it is widely used at
Within the framework of the problem of livestock farms.
protecting the intern al environment of humans,
increasing the quality and safety of animal
DIRECTIONS OF DEVELOPING SELECTIVE SORBENTS
products is considered to be of crucial impor-
tance. For this purpose, of wide application are
enterosorbents (Polyisorb, Polyphepan, En- Creating materials with high adsorption ac-
terosgel, activated carbon, etc.) those allow one tivity with respect to toxic substances of pro-
to perform detoxifying an animal organism and tein nature by controlling the chemical n ature
remove hazardous substances those can be via adjusting the chemical nature of their sur-
transferred into a human organism together face (chemical modification) is of considerable
with the production of livestock. interest because it allows one to develop a wide
114 L. G. PYANOVA
TABLE 5
Physicochemical and biomedical properties of carbon enterosorbent Zookarb
range of efficient sorbents for using them the 4) The ability of organic compounds to en-
fields of medicine and proteomics. As a carrier ter into polycondensation reaction with the for-
for obtaining a selective sorbent, carbon he- mation of polymer chains, which provides a
mosorbents with unique properties are consid- low mobility of the modifier.
ered promising. The main idea of the chemical modification
There are several directions of creating se- consists in the fact that multifunction al inter-
lective sorbents: action (involved in the formation of bonds of
The creation of chemically bonded func- several reactive groups) plays an important role
tional groups on the surface of the matrix (car- in the sorption of large organic molecules. Of
boxyl, carbonyl, ester, etc.) capable of cova- greatest interest for modifying the carbon sur-
lent interaction with a variety of biologically face are organic substances those have nitro-
active substances (amino acids, enzymes, anti- gen- and oxygen-containing groups in their
bodies, antigens, etc.). structure. The interaction between the com-
The introduction of nitrogen, sulphur and pounds of protein n ature with the function al
other heteroatoms to the matrix. groups of the surface of the sorption material
Coating the surface of the matrix with a could result in the formation of covalent bonds
according to the donor-acceptor mechanism.
polymer film which has functional groups suitable
Thereby, OH and NH2 can serve as the do-
for covalent binding bioligands in its structure.
nor groups, as well as Ñ=Î and ÑÎÎÍ
groups can serve as acceptor groups.
CHOICE OF MODIFIER The IHPP of the SB RAS developed a set
of methods for chemical function alization of
The choice of a modifier (monomer) con- the surface of carbon adsorbents with a strong
taining functional groups (nitrogen and oxygen), fixation of nitrogen- and oxygen-containing
is vindicated by its chemical likeness to the func- groups to give them selective adsorption prop-
tion al groups of a protein. The modifier should erties concerning various toxic substances of
exhibit a number of specific properties: protein n ature. There were used a variety of
1) Non-toxicity, modifiers [14, 15]. Of greatest interest are sor-
2) Solubility in aqueous solutions, bents modified with the polymer of aminocap-
3) The presence of nitrogen- and oxygen- roic acid [15]. The choice of the modifier is
containing groups, caused by the presence of two chemically dif-
CARBON SORBENTS IN MEDICINE AND PROTEOMICS 115
At the present time, sorbents with different 11 Surovikin V. F., Surovikin Yu. V., Tsekhanovich M. S.,
Ros. Khim. Zh., 4 (2007) 111.
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Rekomendatsii), Minsk, 2001.
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