Note: Descriptions are shown in the official language in which they were submitted.
This invention relates to activated carbon useful as
an adsorbent for purification of blood.
Two types of apparatus are currently commonly used for
purification of blood, for treating patients suffering from
disfunction of the kidney or the liver. The two types of
apparatus are the dialysis type which utilizes a dialysis dia-
phragm and the adsorption type which utilizes adsorbents. The
dialysis type is more popularly used at the present time. However,
this type has the drawbacks that the apparatus is so large that
the treatment is difficult and that a long time is required for
the purification of the blood. Studies are therefore now in pro-
gress for developing adsorption type apparatus wherein the above-
mentioned drawbacks are absent. However, such adsorption type
apparatus has drawbacks other than those present in the dialysis
type apparatus. The adsorbents used presently for the adsorption
type apparatus are those which are prepared by coating crushed
carbon originating from plants (hereinafter referred to as
"coated crushed active carbon"), for example, active carbon made
of carbonized coconut sheIl (hereinafter referred to as "coated
coconut active carbon"). Coated crushed active carbon is prepared,
for example, by dipping the initial carbon into an ethyl alcohol-
ethyl ether solution of pyroxylin, and thereafter drying the
carbon. Electromicroscopic observation shows that a coated
crushed active carbon, for example, the active carbon coated by
the pyroxylin solution dissolved in the mixture of ethyl alcohol
and ethyl ether, is not coated uniformly with a pyroxylin film but
has some uncoated areas in which free carbon dust is exposed
because the crushed active carbon has an irregular form with many
sharp edges and strict cleavage surfaces. The edge portions of
such carbon are often broken off, even by slight outer shock,
resulting in free carboncdust being formed. When blood
is treated with such carbon the carbon dust may be
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taken into the blood and deposited on internal organs. The
adsorbent is usually further covered with a film of albumin or
the like over the above-mentioned coating in order to avoid
sticking and coagulating of blood components. When the crushed
carbon is used, however, it is difficult to ensure that this
outer covering is adequate. Also the sticking of blood platelets
and the like often occurs due to the large number of sharp
projections and edges of the carbon. Consequently, a temporary
reduction of the number of blood platelets can not be avoided.
There is also known an improved method, wherein coating of the
active coconut carbon with pyroxylin is carried out by a phase
separation process using dioxan as a solvent. Although this
method may provide a better coating film and a considerably
reduced amount of free carbon dust, the amount of free carbon
dust is still such as to prevent the carbon being used practically,
and in addition, this method has also the drawback that blood
components stick to the carbon. The greatest drawback of this
method is that a large amount of harmful dioxan remains in the
carbbn as residual solvent due to the difficulty of removing it,
resulting in the dioxan inevitably dissolving in the blood.
Further, although the coated crushed carbon exhibits
a high adsorp~ion capacity for materials having low molecular
weights, it shows a lower adsorption capacity for materials
having medium molecular weights.
The so-called "kidney toxin" in the blood of a patient
suffering from kidney failure, whose blood must be purified,
comprises various materials having different molecular weights.
The components of medium molecular weights, having unknown
chemical structure, are more important than those of low molecular
weights.
Thus an important drawback of the coated crushed active
carbon is that the adsorption capacity on the medium molecular
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weight materials is low.
Ther~e is also known a granular active carbon which is
prepared by mixing a powdery carbon with a binder, granulating
the resulting mixture, and carbonizing the resulting granules
to thereby activate them. When such granular active carbon is
coated, the coated granular acti~e carbon is superior to coated
crushed carbon with regard to the free carbon dust, sticking of
blood and facility of coating, but the granular active carbon
has very low adsorption capacity. . This granular active carbon
10. is, for the latter reason, unsuitable to use:for purification of
blood.
Thus hitherto blood purification appar.atus of the
adsorption type has not been .available.
The present inventors have carried out studies on
activated carbon in the form of bead-shaped bodies to determine
whether the such activated carbbn coated with a film can be
employed as an adsorbent .in blood purification. The inventors
have found that activated carbon in the form of bead-shaped
particles can be easily coate:d by a conventional coating method
without using the phase separation method using dioxan and that
the resulting coated activated carbon has superior properties to
the prior adsorbents from the viewpoints of the strength, free
carbon dust, ignited ash, residual solvent and sticking of blood.
It has been further observed that such coated activated carbon
shows high adsorption capacity for materials of medium molecular
weight.
Accordingly the present invention provides activated
carbon for purification of blood prepared by coating, by melt
molding with a film-forming material, bead-shaped particles of
activa*ed carbon obtained from pitch as a source material.
The activated carbon to.be used in the present invention
is preferably an active carbon having a nearly perfect sphere
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form and obtained from pi.tch as a source material by melt molding,
that is, by molding melted` material. Such~activated carbon is
different from conventional crushed or granulated active carbon.
Such activated carbon can be prepared by, for ex`ample, dispersing
pitch in the melted state in water to form spheres, making said
spheres non-fusible and carbonizing the same. For detailed
descriptions of the preparation for such activated carbon refer-
ence is directed to Japanese Patent Publications No. 25117/74
and No. 18879/75. Such:activated carbon is available in the
market under the name of bead-shaped activated carbon (BAC)
[Trade Mark, manufactured and sold by Taiyokaken Kabushiki
Kaisha in Japan].
The film-forming:material is selected from the materials
which may provide a semipermeab.le film. Such materials include
pyroxylin, polypropylene,' copolymer of vinyl chl:oride-vinylidene
chloride, ethylene glycol polymethacrylate and collagen.
The'activated carbon in the form of bead-shaped
particles may be coated wi.th.the film-forming materials by a
conventional process. Examp.les of such processes include pan
coating, air suspension coating and spray drying. As a solvent
to be'employed for dissolving the film-forming material to be
used to coat the particles, it is desirable to use a solvent
which'can be easily remo.ved in a drying step and which has a low
toxicity even if dissolved in the blood.
In view of this,: ethanol is an especially preferred
solvent when pyroxylin is used as the film-forming material.
When the coated activated carbon in the form of bead-
shaped particles is used practically for the purification of the
blood, it is desirable to further coat the particles with a film
of a material such as albumin on the'surface of the first film
described above.for preventing or inhibiting sticking and
coagulating of the blood.
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The coated activated carbon according to the present
invention shows less free carbon dust, ash to be'dissolved out,
residual solvent, and adsorption and coagulation of the blood
components, and high safety, compared with prior coated coconut
active carbon. Moreover, the active carbon according to the
present invention shows a high adsorption capacity for toxic
components in the blood, a high functionality, and a high
facility of coating and operations, compared with coconut active
carbon and granular active carbon.
The purification of blood can be thus carried out safely
and effectively by using the coated activated carbon according
to the present invention.
The accompanying drawing is graph adsorption spectrums
of coated activated carbon according to the pres'ent invention (I)
(shown by solid line), coated coconut active carbon (II) (shown
by dotted line), coated granular active carbon (A) (shown by
broken line) and the coated granular active carbbn (B) (shown
by chain line). In the graph, adsorption capacity is plotted
on the'ordinate and molecular weight is plotted on the abscissa.
This invention is illustrated by the following Examples
and Exper'iments.
Example 1
To 5 g of pyroxylin were added 200 ml of absolute
ethanol, and the mixture was blended with a homogenizer so as to
be micronized. Thereafter, 800 ml of absolute ethanol were added
to the solution. The solution was mixed and allowed to stand for
24 hours to make a 0.5% solution for spraying.
500 g of activated carbon (BAC) in the form of bead-
shaped particles' having an average diameter of 0.6 mm were placed
into a coating pan having a depth of 25 cm, an outside diameter
of 30 cm, and a bore of 17 cm. The active carbon was coated by
spraying 500 ml of said solution into the pan whilst blowing with
rotation. The resulting coated active carbon was then dried at
80C for two days to obtain coated activated carbon in the form
of bead-shaped particles.
The resulting coated activated carbon was dipped in
water to debubble under a reduced pressure and was sterilized
by steam under pressure. The sterilized activated carbon was
then charged into a plastics vessel for the purification of the
blood, the vessel having diameter of 3 cm, a height of 7 cm, and
a volume of 50 ml and equipped with two filters at the upper end
and the lower end thereof respectively. The vessel was charged
with physiological saline water, which was then replaced with
80 ml. of a 0.5% physiological saline solution of albumin. After
standing overnight, the active carbon was washed by a flow of
physiological saline water. The blood was purified by being
passed through the vesseI.
ExampLe 2
The same procedure was repeated, except that ethylene
glycol polymethacrylate (sold under the name of Trade Mark
"HYDRON") was substituted for pyroxylin.
Experiment
The coated particles of bead-shaped activated carbon
obtained as described in Example 1 were tested to determine var-
ious properties thereof.
Coated coconut active carbon used as a control in this
experiment was prepared by coating coconut active carbon available
on the market with pyroxylin according to the phase separation
process. Coated granular active carbons (A) and (B) were res-
pectiveIy prepared by coating two granular active carbons (A) and
(B) selected from those which are available on the market and
offered by different manufacturers, with pyroxylin according to
the method as described in Example 1.
(1) Amount of free carbon ~dust
_
Ten grams of coated activated carbon in the form of
bead-shaped particles were charged into a 200 ml conical flask.
There was added into the flask'physiological saline water which
had been previously filtered twice by a millipore filter of 0.45
~. The contents of the flask were degassed under a reduced
pressure and decanted to remove excess water. An additional 150
ml of filtered physiological saline water were charged into the
flask and the mixture was shaken for 45 minutes at 130 rpm in
an incubator. After the shaking,,the number of the free carbon
dust particles more than 1.2 micron in size were determined by
a coolter counter. Conventional coated crushed coconut active
carbon was selected as a control.
The results are'shown below.
Number of free carbon
dust particles per ml
Coated activated carbon in the form of
bead-shaped particles 0 - 200
Coated crushed coconut active carbon 3000 - 5000
(2) Adsorption capacity
2 gram samples of the coated activated carbon in the
form of bead-shaped particles were`placed in vessels. To each
of the vessels was added 200 ml of physiological phosphoric acid
buffer solution containing 20 mg/ml of materials having various
molecular weights and the respective mixtures were shaken at 115
rpm for 2 hours in an incubator. Thereafter, the adsorption cap-
acity of each'sample was determined. Coated crushed coconut active
carbon and coated granular active carbons (A) and (B) were selected
as the controls. The results of the determinations are recorded
on the graph of the accompanying drawing, with molecular weight
being plotted on the abscissa and adsorbed concentration being
7~
plotted (mg/dl) on the ordinate. As clearly shown in the graph,
the coated activated carbon according to present invention and in
the form of bead-shaped particles has a hiyh adsorption capacity
not only on materials having low molecular weights but also on the
materials having medium molecular weights. ~owever, the coated
crushed coconut active carbon shows a considerably high adsorption
capacity for the former materials but does not show such an
adsorption capacity for the latter materials. The coated granular
active carbons (A) and (B) exhibit low adsorption capacity on
the former materials and scarceIy any adsorption capacity on the
latter materials.
In the kidney toxin present in a patient suffering
from kidney failure, substances of medium molecular weight with
unknown chemical structure~play an essential part, rather than
the substances of relatively low molecular weight, such as urea,
creatine and uric acid. It is considered that marked nervous
lesions are mainly caused by substances of medium molecular
weight. Therefore, it is an important merit of the coated
activated carbon according to the present invention that, in the
purification of the blood, it exhibits high adsorption capacity
for the materials having medium molecular weight.
t3) Sticking of components of the blood
10 g samples of a coated activated carbon in the form
of bead-shaped particles and coated activated carbon in the form
of bead-shaped particles and further covered with albumin were
charged into respective columns. Through each of the columns,
25 ml of the blood were passed at a velocity of 25 ml/min. The
same operation was repeated 25 times. 100 ml of physiological
saline water were passed, followed by each 100 ml of distilled
water. The respective active carbons were taken out from the
columns and lyophilized. The stic]cing of components of the blood
was inspected by observing the surface with an electron
microscope. Both coated crushed coconut active carbon and the
coated crushed coconut active carbon further covered with albumin
were selected as controls.
Sticking of the Sticking of the
blood platelet_ blood corpuscle
Coated activated carbon in the
form of bead-shaped particles +
Ditto, but further coated with
albumin
Coated crushed coconut active
carbon ++ +
Ditto, but further coated with
albumin
In the above table, - represents no sticking, +
represents a little sticking, + represents considerable sticking,
and ++ represents sticking to such an extent that the most of
surface is covered.
(4) Residual solvent
Only an amount of from about 150 to about 200 ppm of
ethanol remained in the coated activated carbon in the form of
bead-shaped particles of Example 1. The ethanol could not be
detected in the blood, after the blood had been treated by this
coated activated carbon. However, in the case o~ the coated
crushed coconut active carbon which is prepared by the phase
separation method using dioxan as a solvent, the residual dioxan
amounted to as much as about 50,000 ppm, notwithstanding thorough
treatments for removing the dioxan, for example, by vacuum-drying
or lyophilization. About 20,000 ppm of the dioxan remains, even
if the active carbon has been dried at a high temperature ranging
from 80C to 120C for 10 days. ~his dioxan will be released
gradually into the blood. When the blood is treated with such
a coated crushed coconut active carbon.
(5~ Priming volume
The larger is the priming volume, the larger is the
amount of the blood which is recycled out of the body and the
risk of failure is increased accordingly. The priming volume
may become as small as from abo:ut 60 to 110 ml when the coated
activated carbon in the form of bead-shaped particles according
to the present invention is used for the adsorbent, while the
amount is about 400 ml when the conventional dialysis type of
artifical kidney is used.
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